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Cetinalp NE, Akkus G, Seydaoglu G, Ozsoy KM, Akbaba M, Baykara O, Oktay K, Erman T. Early Predictors of Remission in Acromegaly Patients after Pure Endoscopic Endonasal Transsphenoidal Surgery. J Neurol Surg B Skull Base 2025; 86:303-312. [PMID: 40351877 PMCID: PMC12064305 DOI: 10.1055/a-2319-0344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 04/23/2024] [Indexed: 07/03/2024] Open
Abstract
Objective Surgery is the first-line treatment in acromegaly but it takes months to confirm remission. It is crucial to determine remission early in order to inform the patient and plan further treatment options. We aimed to evaluate the predictors of remission at the early phase after endoscopic endonasal pituitary surgery in acromegaly patients. Methods Fifty-four growth hormone (GH)-adenoma patients operated via pure endoscopic endonasal approach were analyzed in this observational study. We compared the basic clinical, radiological characteristics, and the preoperative and postoperative hormone levels in terms of remission according to current guidelines. Results The surgical remission rate was 61.1%. When the patients were compared according to surgical remission, the age, gender, and immunohistochemical granulation type were found to be nonsignificant, while diabetes mellitus was more common (55.6 vs. 44.4%). The preoperative tumor volume (1.2 ± 0.9 vs. 4.1 ± 4.2 cm 3 ) and postoperative GH and insulin-like growth factor-1 (IGF-1) levels were higher in the nonremission group ( p < 0.05). We defined a number of cut-off values of both GH and IGF-1 levels to predict remission at the postoperative phase. Age standardized regression analyses showed that postoperative day 1 (POD-1) GH levels (odds ratio [OR]: 8.9; 95% confidence interval [CI]: 1.99-40.0, p = 0.004) and tumor volume (OR: 3.14; 95% CI: 1.09-9.0, p = 0.034) were found to be significant independent predictors for remission. Conclusion We demonstrated that tumor volume and POD-1 GH levels are independent predictors of remission in acromegaly patients operated via the pure endoscopic endonasal technique and may be used as an early marker of remission, and this may lead to taking adjuvant medical therapies early into account to improve prognosis.
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Affiliation(s)
- Nuri Eralp Cetinalp
- Department of Neurosurgery, Cukurova University Faculty of Medicine, Balcali, Adana, Türkiye
| | - Gamze Akkus
- Division of Endocrinology, Department of Internal Medicine, Cukurova University Faculty of Medicine, Adana, Türkiye
| | - Gulsah Seydaoglu
- Department of Biostatistics, Cukurova University Faculty of Medicine, Adana, Türkiye
| | - Kerem Mazhar Ozsoy
- Department of Neurosurgery, Cukurova University Faculty of Medicine, Balcali, Adana, Türkiye
| | - Mevlana Akbaba
- Department of Neurosurgery, Cukurova University Faculty of Medicine, Balcali, Adana, Türkiye
| | - Okay Baykara
- Department of Neurosurgery, Cukurova University Faculty of Medicine, Balcali, Adana, Türkiye
| | - Kadir Oktay
- Department of Neurosurgery, Cukurova University Faculty of Medicine, Balcali, Adana, Türkiye
| | - Tahsin Erman
- Department of Neurosurgery, Cukurova University Faculty of Medicine, Balcali, Adana, Türkiye
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Losa M, Garbin E, Calcagnile R, Voltan G, Ceccato F, Scaroni C, Occhi G, Mortini P. The Preoperative Paradoxical GH Response to Oral Glucose Load Predicts a Low Risk of Recurrence in Acromegaly. J Clin Endocrinol Metab 2025; 110:1404-1409. [PMID: 38878276 DOI: 10.1210/clinem/dgae410] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Indexed: 04/24/2025]
Abstract
CONTEXT A paradoxical growth hormone (GH) response to oral glucose load (oral glucose tolerance test [OGTT]) in acromegaly is associated with a milder phenotype. OBJECTIVE To study whether the GH response to the OGTT predicts the risk of recurrence after initial surgical cure. METHODS Retrospective, observational study at 2 tertiary care centers. We investigated 254 patients with acromegaly who were cured by surgery. All patients underwent an OGTT at diagnosis before pituitary surgery. A peak to basal GH ratio ≥120% within 90 minutes was used to distinguish paradoxical (GH-Par) from nonparadoxical responses (GH-NPar) in patients with acromegaly. Cox analysis was used to investigate whether the paradoxical GH response to OGTT was associated with the risk of disease recurrence. RESULTS A paradoxical GH response to OGTT occurred in 87 patients (34.3%, termed GH-Par group). Recurrence of acromegaly occurred in 3 patients in the GH-Par group (3.4%) and in 20 patients in the GH-NPar group (12.0%). In the multivariate analysis, the paradoxical GH response to OGTT was significantly associated with a low risk of recurrence (HR 0.18, 95% CI 0.05-0.63; P = .007). Basal GH level at diagnosis was the only other variable associated with the risk of disease recurrence (HR 1.58, 95% CI 1.01-2.47; P = .04). CONCLUSION Our study demonstrates that a paradoxical GH response to OGTT in the preoperative setting predicts a lower risk of disease recurrence after initial surgical cure. The pattern of GH responsiveness to OGTT is, therefore, useful to predict the long-term outcome of patients with acromegaly.
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Affiliation(s)
- Marco Losa
- Department of Neurosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute University, 20132 Milan, Italy
| | - Enrico Garbin
- Department of Neurosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute University, 20132 Milan, Italy
| | - Riccardo Calcagnile
- Department of Neurosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute University, 20132 Milan, Italy
| | - Giacomo Voltan
- Department of Medicine DIMED, University of Padua, 35128 Padua, Italy
- Endocrine Unit, University-Hospital of Padua, 35128 Padua, Italy
| | - Filippo Ceccato
- Department of Medicine DIMED, University of Padua, 35128 Padua, Italy
- Endocrine Unit, University-Hospital of Padua, 35128 Padua, Italy
| | - Carla Scaroni
- Department of Medicine DIMED, University of Padua, 35128 Padua, Italy
- Endocrine Unit, University-Hospital of Padua, 35128 Padua, Italy
| | - Gianluca Occhi
- Department of Biology, University of Padua, 35131 Padua, Italy
| | - Pietro Mortini
- Department of Neurosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute University, 20132 Milan, Italy
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Alvarez M, Donato A, Rincon J, Rincon O, Lancheros N, Mancera P, Guzman I. Evaluation of pituitary tumor volume as a prognostic factor in acromegaly: A cross-sectional study in two centers. World J Radiol 2025; 17. [DOI: pmid: 40176958 pmcid: pmc11959620 doi: 10.4329/wjr.v17.i3.100168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND
Acromegaly is caused by a pituitary neuroendocrine tumor (PitNET) with excessive production of growth hormone (GH), leading to multisystem complications. Previous studies have identified predictors of disease persistence following surgery and poor response to medical treatment, including tumor size, vertical and horizontal extensions of the adenoma, hyperintensity in T2-weighted magnetic resonance imaging, granulation density, and pre- and postoperative GH and insulin-like growth factor 1 (IGF-1) levels.
AIM
To evaluate PitNET volume as a complementary prognostic factor in patients with acromegaly.
METHODS
This is a retrospective descriptive study with an analytical component evaluating the correlation between the volumetric analysis of GH-producing PitNETs, IGF-1 levels before and after surgery, disease control during follow-up, and the line of therapy required for disease control in a cohort of patients treated at two centers: Endocrinology Department of the Central Military Hospital and Centros Médicos Colsanitas, Bogotá, Colombia.
RESULTS
A total of 77 patients with acromegaly (42 men, 35 women) were included in this study. The mean age at diagnosis was 42 years (standard deviation [SD]: 12), with a mean disease duration of 9.9 years (SD: 7.2). The mean pituitary tumor volume was 4358 mm³ (SD: 6291, interquartile range [IQR]: 13602). Patients with controlled acromegaly had a mean PitNET volume of 3202 mm³ (SD: 4845, 95%CI: 621-5784) compared to 5513 mm³ (SD: 7447, 95%CI: 1545-9482) in the uncontrolled group (P = 0.15). A PitNET volume exceeding 3697 mm³ was associated with a higher likelihood of requiring third or fourth-line therapy (50% vs 36%; P = 0.03).
CONCLUSION
PitNET volume was associated with the need for higher-line therapy to manage acromegaly but did not correlate with long-term disease control or with pre- or postsurgical IGF-1 levels. Nevertheless, a trend towards an inverse relationship between tumor volume and future disease control was observed. While macroadenoma classification remains crucial, among patients with macroadenomas, those with a volume exceeding 3697 mm³ could have worse prognosis.
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Alvarez M, Donato A, Rincon J, Rincon O, Lancheros N, Mancera P, Guzman I. Evaluation of pituitary tumor volume as a prognostic factor in acromegaly: A cross-sectional study in two centers. World J Radiol 2025; 17:100168. [PMID: 40176958 PMCID: PMC11959620 DOI: 10.4329/wjr.v17.i3.100168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 01/14/2025] [Accepted: 02/14/2025] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Acromegaly is caused by a pituitary neuroendocrine tumor (PitNET) with excessive production of growth hormone (GH), leading to multisystem complications. Previous studies have identified predictors of disease persistence following surgery and poor response to medical treatment, including tumor size, vertical and horizontal extensions of the adenoma, hyperintensity in T2-weighted magnetic resonance imaging, granulation density, and pre- and postoperative GH and insulin-like growth factor 1 (IGF-1) levels. AIM To evaluate PitNET volume as a complementary prognostic factor in patients with acromegaly. METHODS This is a retrospective descriptive study with an analytical component evaluating the correlation between the volumetric analysis of GH-producing PitNETs, IGF-1 levels before and after surgery, disease control during follow-up, and the line of therapy required for disease control in a cohort of patients treated at two centers: Endocrinology Department of the Central Military Hospital and Centros Médicos Colsanitas, Bogotá, Colombia. RESULTS A total of 77 patients with acromegaly (42 men, 35 women) were included in this study. The mean age at diagnosis was 42 years (SD: 12), with a mean disease duration of 9.9 years (SD: 7.2). The mean pituitary tumor volume was 4358 mm³ (SD: 6291, interquartile range [IQR]: 13602). Patients with controlled acromegaly had a mean PitNET volume of 3202 mm³ (SD: 4845, 95%CI: 621-5784) compared to 5513 mm³ (SD: 7447, 95%CI: 1545-9482) in the uncontrolled group (P = 0.15). A PitNET volume exceeding 3697 mm³ was associated with a higher likelihood of requiring third or fourth-line therapy (50% vs 36%; P = 0.03). CONCLUSION PitNET volume was associated with the need for higher-line therapy to manage acromegaly but did not correlate with long-term disease control or with pre- or postsurgical IGF-1 levels. Nevertheless, a trend towards an inverse relationship between tumor volume and future disease control was observed. While macroadenoma classification remains crucial, among patients with macroadenomas, those with a volume exceeding 3697 mm³ could have worse prognosis.
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Affiliation(s)
- Mauricio Alvarez
- Department of Endocrinology, Hospital Militar Central, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Angel Donato
- Department of Neuroradiology, Hospital Militar Central, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Juliana Rincon
- Department of Epidemiology, Fundación Universitaria Sanitas, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Oswaldo Rincon
- Department of Endocrinology, Hospital Militar Central, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Natalia Lancheros
- Department of Clinical Medicine, Centros Médicos Colsanitas, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Pedro Mancera
- Department of Endocrinology, Universidad Militar Nueva Granada, Bogota 110221, Distrito Capital de Bogotá, Colombia
| | - Isaac Guzman
- Department of Endocrinology, Hospital Militar Central, Bogota 110221, Distrito Capital de Bogotá, Colombia
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Vouzouneraki K, Nylén F, Holmberg J, Olsson T, Berinder K, Höybye C, Petersson M, Bensing S, Åkerman AK, Borg H, Ekman B, Robért J, Engström BE, Ragnarsson O, Burman P, Dahlqvist P. Digital Voice Analysis as a Biomarker of Acromegaly. J Clin Endocrinol Metab 2025; 110:983-990. [PMID: 39363748 PMCID: PMC11913075 DOI: 10.1210/clinem/dgae689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 09/10/2024] [Accepted: 10/02/2024] [Indexed: 10/05/2024]
Abstract
CONTEXT There is a considerable diagnostic delay in acromegaly, contributing to increased morbidity. Voice changes due to orofacial and laryngeal changes are common in acromegaly. OBJECTIVE Our aim was to explore the use of digital voice analysis as a biomarker for acromegaly using broad acoustic analysis and machine learning. METHODS Voice recordings from patients with acromegaly and matched controls were collected using a mobile phone at Swedish university hospitals. Anthropometric and clinical data and the Voice Handicap Index (VHI) were assessed. Digital voice analysis of a sustained and stable vowel [a] resulted in 3274 parameters, which were used for training of machine learning models classifying the speaker as "acromegaly" or "control." The machine learning models were trained with 76% of the data and the remaining 24% was used to assess their performance. For comparison, voice recordings of 50 pairs of participants were assessed by 12 experienced endocrinologists. RESULTS We included 151 Swedish patients with acromegaly (13% biochemically active and 10% newly diagnosed) and 139 matched controls. The machine learning model identified patients with acromegaly more accurately (area under the receiver operating curve [ROC AUC] 0.84) than experienced endocrinologists (ROC AUC 0.69). Self-reported voice problems were more pronounced in patients with acromegaly than matched controls (median VHI 6 vs 2, P < .01) with higher prevalence of clinically significant voice handicap (VHI ≥20: 22.5% vs 3.6%). CONCLUSION Digital voice analysis can identify patients with acromegaly from short voice recordings with high accuracy. Patients with acromegaly experience more voice disorders than matched controls.
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Affiliation(s)
| | - Fredrik Nylén
- Department of Clinical Sciences, Umeå University, SE-901 87 Umeå, Sweden
| | - Jenny Holmberg
- Department of Clinical Sciences, Umeå University, SE-901 87 Umeå, Sweden
| | - Tommy Olsson
- Department of Public Health and Clinical Medicine, Umeå University, SE-901 87 Umeå, Sweden
| | - Katarina Berinder
- Department of Endocrinology, Karolinska University Hospital and Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden
| | - Charlotte Höybye
- Department of Endocrinology, Karolinska University Hospital and Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden
| | - Maria Petersson
- Department of Endocrinology, Karolinska University Hospital and Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden
| | - Sophie Bensing
- Department of Endocrinology, Karolinska University Hospital and Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden
| | - Anna-Karin Åkerman
- Department of Internal Medicine, Örebro University Hospital and Faculty of Health and Medical Sciences, Örebro University, SE-171 76 Örebro, Sweden
| | - Henrik Borg
- Department of Endocrinology, Skåne University Hospital, Lund University, SE-205 02 Malmö, Sweden
| | - Bertil Ekman
- Department of Endocrinology and Department of Health, Medicine and Caring Sciences, Linköping University, SE-581 85 Linköping, Sweden
- Department of Endocrinology and Department of Health, Medicine and Caring Sciences, Linköping University, SE-601 81 Norrköping, Sweden
| | - Jonas Robért
- Department of Endocrinology and Department of Health, Medicine and Caring Sciences, Linköping University, SE-581 85 Linköping, Sweden
| | - Britt Edén Engström
- Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
| | - Oskar Ragnarsson
- Department of Endocrinology, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
- Wallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, SE-413 45 Gothenburg, Sweden
| | - Pia Burman
- Department of Endocrinology, Skåne University Hospital, Lund University, SE-205 02 Malmö, Sweden
| | - Per Dahlqvist
- Department of Public Health and Clinical Medicine, Umeå University, SE-901 87 Umeå, Sweden
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Gezer E, Çetinarslan B, Cantürk Z, Selek A, Sözen M, Köksalan D, Bekiroğlu A, Anik I, Ceylan S. May the SAGIT® instrument be used as a preoperative prognostic tool in patients with acromegaly? Minerva Endocrinol (Torino) 2025; 50:24-31. [PMID: 36285746 DOI: 10.23736/s2724-6507.22.03888-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/18/2024]
Abstract
BACKGROUND The SAGIT® instrument has been developed for acromegaly to assist clinicians in staging the disease accurately, assessing the response to therapy, and adjusting the treatment. We aimed to evaluate the preoperative utility of the SAGIT® instrument and to discover a cut-off value for predicting the surgery outcome and long-term prognosis of patients with acromegaly. METHODS A total of 832 patients with acromegaly were identified from the medical record system. Acromegaly diagnosis was confirmed by elevated IGF-1 levels according to the age-adjusted upper limit of normal, lack of suppression of GH concentration to <0.4 µg/L following a 75 g oral glucose tolerance test, and the existence of a pituitary adenoma demonstrated by MRI. The SAGIT® instrument comprises five key components of acromegaly: signs and symptoms (S), associated comorbidities (A), GH levels (G), IGF-1 levels (I), and the features of the tumor (T). The initial postoperative remission was evaluated 3 months after surgery. RESULTS A final cohort of 132 patients has been included in our study. Median preoperative SAGIT scores were significantly different (10.00 [9.00-11.00] to 11.00 [10.00-13.00], [P=0.002]) between patients who achieved initial remission at 3 months and those who were not in remission. The threshold SAGIT score distinguishing between initial remission and nonremission groups was 10 with an AUC of 0.660 (P<0.001). CONCLUSIONS In our retrospective cohort study, the findings suggested that the SAGIT® instrument may be a beneficial preoperative tool to predict the initial remission postoperatively and long-term prognosis of the patients with acromegaly.
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Affiliation(s)
- Emre Gezer
- Department of Endocrinology and Metabolism, Darica Farabi Training and Research Hospital, Kocaeli, Türkiye -
| | - Berrin Çetinarslan
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Kocaeli, Kocaeli, Türkiye
| | - Zeynep Cantürk
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Kocaeli, Kocaeli, Türkiye
| | - Alev Selek
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Kocaeli, Kocaeli, Türkiye
| | - Mehmet Sözen
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Kocaeli, Kocaeli, Türkiye
| | - Damla Köksalan
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Kocaeli, Kocaeli, Türkiye
| | - Aylin Bekiroğlu
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Kocaeli, Kocaeli, Türkiye
| | - Ihsan Anik
- Department of Neurosurgery, Faculty of Medicine, University of Kocaeli, Kocaeli, Türkiye
| | - Savaş Ceylan
- Department of Neurosurgery, Faculty of Medicine, University of Kocaeli, Kocaeli, Türkiye
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Golub D, White TG, Shah HA, Khaleghi M, Huntoon KM, Zandbergen IM, Bakker LEH, Ghalib LM, Pelsma ICM, Dowlati E, Chaskes MB, Fastenberg JH, Verstegen MJT, Biermasz NR, Prevedello DM, Dehdashti AR. Outcomes in surgical management of microprolactinomas: an international multi-institutional series. Pituitary 2025; 28:28. [PMID: 39900842 DOI: 10.1007/s11102-025-01497-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/01/2025] [Indexed: 02/05/2025]
Abstract
BACKGROUND Prolactinomas represent the most common pituitary adenoma subtype, the majority of which are microprolactinomas. Dopamine agonists (DAs) remain the first-line intervention for microprolactinomas, however, many patients either cannot tolerate DAs or require lifelong therapy to maintain hormonal control. As endoscopic endonasal surgery (EES) continues to revolutionize the surgical management of sellar lesions, we sought to reassess the feasibility and efficacy of early surgical resection for microprolactinoma. METHODS Retrospective chart review from 2010 to 2021 of adults who underwent EES for microprolactinoma was performed across three medical centers. Surgical failure was defined as a need to restart DAs, a serum prolactin level greater than 30ng/mL at last follow-up, tumor recurrence, or a need for reoperation. RESULTS A total of 56 patients were identified with a mean age of 32.9 years and an average of 26.4 months of follow-up. The majority had been on DAs preoperatively (98.2%). The most common surgical indications were DA intolerance (73.2%), tumor unresponsiveness (19.6%), and desire for pregnancy (7.1%). Gross total resection was achieved in 51 (91.1%) cases. The overall surgical remission rate was approximately 70% with failures observed in 17 (30.4%) patients. Multivariate logistic regression identified subtotal resection as the only independent predictor of surgical failure (p = 0.038*). The most common postoperative complication was transient arginine vasopressin deficiency (AVP-D) (21.4%). There were no cases of permanent AVP-D, new visual deficits, or cerebrospinal fluid leak. CONCLUSIONS With a surgical remission rate of nearly 70%, EES represents a safe and viable alternative strategy to long-term DA treatment for microprolactinomas.
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Affiliation(s)
- Danielle Golub
- Department of Neurosurgery, Northwell Health, Manhasset, NY, USA.
- Department of Neurosurgery, North Shore University Hospital, Northwell Health, 300 Community Drive, Suite 10 Monti, Manhasset, NY, 11030, USA.
| | - Timothy G White
- Department of Neurosurgery, Northwell Health, Manhasset, NY, USA
| | - Harshal A Shah
- Department of Neurosurgery, Northwell Health, Manhasset, NY, USA
| | - Mehdi Khaleghi
- Department of Neurosurgery, Wexner Medical Center, The Ohio State University, Columbus, OH, USA
| | - Kristin M Huntoon
- Department of Neurosurgery, Wexner Medical Center, The Ohio State University, Columbus, OH, USA
| | - Ingrid M Zandbergen
- Department of Neurosurgery, Center for Endocrine Tumors, Leiden University Medical Center, Leiden, The Netherlands
- Department of Medicine, Division of Endocrinology, Center for Endocrine Tumors, Leiden University Medical Center, Leiden, The Netherlands
| | - Leontine E H Bakker
- Department of Medicine, Division of Endocrinology, Center for Endocrine Tumors, Leiden University Medical Center, Leiden, The Netherlands
| | - Luma M Ghalib
- Department of Endocrinology, Wexner Medical Center, The Ohio State University, Columbus, OH, USA
| | - Iris C M Pelsma
- Department of Medicine, Division of Endocrinology, Center for Endocrine Tumors, Leiden University Medical Center, Leiden, The Netherlands
| | - Ehsan Dowlati
- Department of Neurosurgery, Northwell Health, Manhasset, NY, USA
| | - Mark B Chaskes
- Department of Otolaryngology-Head and Neck Surgery, Northwell Health, Manhasset, NY, USA
| | - Judd H Fastenberg
- Department of Otolaryngology-Head and Neck Surgery, Northwell Health, Manhasset, NY, USA
| | - Marco J T Verstegen
- Department of Neurosurgery, Center for Endocrine Tumors, Leiden University Medical Center, Leiden, The Netherlands
| | - Nienke R Biermasz
- Department of Medicine, Division of Endocrinology, Center for Endocrine Tumors, Leiden University Medical Center, Leiden, The Netherlands
| | - Daniel M Prevedello
- Department of Neurosurgery, Wexner Medical Center, The Ohio State University, Columbus, OH, USA
| | - Amir R Dehdashti
- Department of Neurosurgery, Northwell Health, Manhasset, NY, USA
- Department of Otolaryngology-Head and Neck Surgery, Northwell Health, Manhasset, NY, USA
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8
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Balagurunath K, Chrenek R, Gerstl J, Corrales CE, Laws ER, Mekary RA, Smith TR, Hong CS. Predictors of biochemical remission after transsphenoidal surgery in a large cohort of acromegaly patients. Pituitary 2024; 28:2. [PMID: 39708072 DOI: 10.1007/s11102-024-01472-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/09/2024] [Indexed: 12/23/2024]
Abstract
PURPOSE The objective of this study was to characterize the clinical characteristics and factors predictive of biochemical remission in patients with symptomatic acromegaly undergoing transsphenoidal surgery (TSS) at an academic tertiary care center, as defined by the 2022 Acromegaly Consensus Conference guidelines. METHODS In this single institution, longitudinal, retrospective study, a large cohort of 158 patients with a preoperative diagnosis of acromegaly undergoing surgery at a large, academic, tertiary care center were examined. We excluded 38 patients as IGF-1 testing was performed less than 12 weeks postoperatively. RESULTS The majority of tumors were intrasellar macroadenomas (75%), receiving endoscopic surgery (98.3%). Patients who failed remission appeared to have higher raw IGF-1 levels preoperatively (732 ± 313 ng/mL) compared to those who attained remission (278 ± 313 ng/mL), and trended towards higher rates of GH hypersecretion (93.1% vs. 78.4%). Patients failing remission had higher GH levels and IGF-1 levels postoperatively and experienced a lower percentage reduction in raw IGF-1 levels. Multivariable logistic regression demonstrated that the magnitude of preoperative IGF-1 (OR: 1.001, 95% CI: 1.00, 1.003) and the percentage change in IGF-1 (OR: 1.021, 95% CI: 1.01, 1.04) were predictive of remission failure. Radiographic characteristics such as tumor size, suprasellar extension, and location were not necessarily predictive of worse postoperative outcomes. CONCLUSIONS Lesions which failed to achieve biochemical remission appeared to display distinctive preoperative endocrinological characteristics, with preoperative IGF-1 levels and percentage changes in IGF-1 levels being predictive of biochemical remission status.
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Affiliation(s)
- Kaasinath Balagurunath
- Computational Neuroscience Outcomes Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Ryan Chrenek
- Computational Neuroscience Outcomes Center, Harvard Medical School, Boston, Massachusetts, USA
- Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jakob Gerstl
- Computational Neuroscience Outcomes Center, Harvard Medical School, Boston, Massachusetts, USA
| | - C Eduardo Corrales
- Computational Neuroscience Outcomes Center, Harvard Medical School, Boston, Massachusetts, USA
- Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, Massachusetts, USA
| | - Edward R Laws
- Computational Neuroscience Outcomes Center, Harvard Medical School, Boston, Massachusetts, USA
- Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Rania A Mekary
- Computational Neuroscience Outcomes Center, Harvard Medical School, Boston, Massachusetts, USA
- School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences (MCPHS) University, Boston, Massachusetts, USA
| | - Timothy R Smith
- Computational Neuroscience Outcomes Center, Harvard Medical School, Boston, Massachusetts, USA
- Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Christopher S Hong
- Computational Neuroscience Outcomes Center, Harvard Medical School, Boston, Massachusetts, USA.
- Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
- Department of Neurosurgery, VA Boston Healthcare System, Boston, United States of America.
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9
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Tosaka M, Yamaguchi R, Horiguchi K, Ozawa A, Matsumoto S, Honda F, Hokama Y, Yoshida T, Okano M, Tsukada A, Ishiuchi S, Yamada M, Yoshimoto Y. Outcome of endoscopic transsphenoidal surgery for acromegaly: Comparison of using and not using the floor standing pneumatic powered endoscope-holder system. Heliyon 2024; 10:e35647. [PMID: 39170435 PMCID: PMC11336817 DOI: 10.1016/j.heliyon.2024.e35647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 07/31/2024] [Accepted: 08/01/2024] [Indexed: 08/23/2024] Open
Abstract
Introduction Endoscopic transsphenoidal surgery can be performed by two surgeons, including an endoscopist (PE/2S), and by a single surgeon with an endoscope-holder system (PE/1S + H). We analyzed the surgical outcome, and outcome predictors in acromegaly patients in endoscopic transsphenoidal surgery using floor standing pneumatic endoscope-holder system. Methods Endoscopic transsphenoidal surgery was performed with PE/1S+H (n = 51) and PE/2S (n = 20). Postoperative remission was evaluated by the 2010 consensus criteria for acromegaly. We compared the surgical results of PE/2S style and PE/1S+H style, and investigated the factors associated with favorable surgical outcomes. Results There was no difference in clinical background between the PE/2S and the PE/1S + H groups. The remission rates for PE/2S and PE/1S+H were 65.0% and 82.4%, respectively, with no significant difference (p = 0.128). In consecutive 71 cases, statistically useful predictors of remission were low preoperative growth hormone (GH) level (<12 ng/mL), low Knosp grade (0-2), and low revised Knosp grade (0-3A). In the conventional Knosp grade 0-2 and 3/4, the sensitivity was 0.76 and the specificity was 0.81. In the revised Knosp grade 0-3A and 3B/4, the sensitivity was 0.96 and the specificity was 0.44. Conclusion The outcome of GH-producing pituitary neuroendocrine tumors surgically removed by PE/1S+H could be almost equivalent to that by PE/2S. Preoperative low GH level and Knosp grades, including revised Knosp grades, are useful preoperative predictors for surgical remission of acromegaly.
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Affiliation(s)
- Masahiko Tosaka
- Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Rei Yamaguchi
- Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Kazuhiko Horiguchi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Atsushi Ozawa
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Shunichi Matsumoto
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Fumiaki Honda
- Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Yohei Hokama
- Department of Neurosurgery, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan
| | - Takaaki Yoshida
- Department of Neurosurgery, Saku Central Hospital Advanced Care Center, Saku, Nagano, Japan
| | - Mitsuko Okano
- Department of Neurosurgery, Hokushin General Hospital, Nakano, Nagano, Japan
| | - Akihiro Tsukada
- Department of Neurosurgery, Hokushin General Hospital, Nakano, Nagano, Japan
| | - Shogo Ishiuchi
- Department of Neurosurgery, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan
| | - Masanobu Yamada
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Yuhei Yoshimoto
- Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
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10
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Geng Y, Dong Q, Cong Z, Zhu J, Li Z, Du C, Yuan F, Zeng X, Ali A, Yang J, Tang C, Ma C. Endocrine Outcomes and Associated Predictive Factors for Somatotrophin Pituitary Adenoma after Endoscopic Endonasal Transsphenoidal Surgery: 10 Years of Experience in a Single Institute. J Neurol Surg B Skull Base 2024; 85:389-396. [PMID: 38966302 PMCID: PMC11221908 DOI: 10.1055/a-2081-1427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 04/22/2023] [Indexed: 07/06/2024] Open
Abstract
Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas. Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order. Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level ( p = 0.166), basal GH level ( p = 0.001), and nadir GH level ( p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891-0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery. Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission.
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Affiliation(s)
- Yuanming Geng
- Department of Neurosurgery, Jinling Hospital, Nanjing Medical University, Nanjing, People's Republic of China
| | - Qian Dong
- School of Nursing, Bengbu Medical College, Anhui, People's of Republic of China
- Department of Neurosurgery, Jinling Hospital, Nanjing, People's Republic of China
| | - Zixiang Cong
- Department of Neurosurgery, Jinling Hospital, Nanjing, People's Republic of China
| | - Junhao Zhu
- Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Zhenxing Li
- Department of Neurosurgery, Jinling Hospital, Nanjing Medical University, Nanjing, People's Republic of China
- Department of Neurosurgery, Jinling Hospital, Nanjing, People's Republic of China
| | - Chaonan Du
- Department of Neurosurgery, Jinling Hospital, Nanjing Medical University, Nanjing, People's Republic of China
| | - Feng Yuan
- Department of Neurosurgery, Jinling Hospital, Nanjing Medical University, Nanjing, People's Republic of China
| | - Xinrui Zeng
- Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Alleyar Ali
- Department of Neurosurgery, Jinling Hospital, Nanjing Medical University, Nanjing, People's Republic of China
| | - Jin Yang
- Department of Neurosurgery, Jinling Hospital, Nanjing, People's Republic of China
| | - Chao Tang
- Department of Neurosurgery, Jinling Hospital, Nanjing, People's Republic of China
| | - Chiyuan Ma
- Department of Neurosurgery, Jinling Hospital, Nanjing Medical University, Nanjing, People's Republic of China
- Department of Neurosurgery, Jinling Hospital, Nanjing, People's Republic of China
- Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
- School of Medicine, Southeast University, Nanjing, People's Republic of China
- Department of Neurosurgery, Jinling Hospital, the First School of Clinical Medicine, Southern Medical University, Nanjing, People's Republic of China
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11
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Unal TC, Aydoseli A, Ozgen U, Dolas I, Sabanci PA, Aras Y, Ozturk M, Ozata MS, Gul N, Kubat Uzum A, Mutlu U, Bilgic B, Saka E, Yarman S, Sencer A. A single-center experience of transsphenoidal endoscopic surgery for acromegaly in 73 patients: results and predictive factors for remission. Br J Neurosurg 2024; 38:648-653. [PMID: 34241568 DOI: 10.1080/02688697.2021.1947977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 05/29/2021] [Accepted: 06/22/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Transsphenoidal endoscopic surgery is the first-line treatment for growth hormone-secreting adenomas. OBJECTIVE To analyse the results of the transsphenoidal endoscopic approach for acromegaly and to determine the predictive factors of remission. METHODS A single-centre retrospective review was performed in patients who underwent endoscopic transsphenoidal surgery for acromegaly between January 2009 and January 2019. Demographic features, clinical presentation, histopathology records, complications and pre- and postoperative radiologic and endocrinological assessments were evaluated. The factors that influenced the remission rates were investigated. RESULTS A total of 73 patients underwent surgery via the transsphenoidal endoscopic approach. Cavernous sinus invasion was detected in 32 patients (43.8%); and macroadenoma, in 57 (78%). The pathology specimens of the 27 patients (36.9%) showed dual-staining adenomas with prolactin. A total of 51 patients (69.8%) attained biochemical remission 1 year after surgery. A second operation was performed in 10 patients (13.6%) with residual tumours without biochemical remission in the first year. Six (60%) of the patients attained remission at the last follow-up. Transient diabetes insipidus was observed in 18 patients (24.6%); and rhinorrhoea, which was resolved with conservative treatment, in 4 (5.4%). None of the patients developed panhypopituitarism. The presence of cavernous sinus invasion and preoperative IGF-1, immediate postoperative GH and third-month IGF-1 levels were predictive of remission. CONCLUSION Transsphenoidal endoscopic surgery is a safe and effective treatment for acromegaly. Reoperation should be considered in patients with residual tumours without remission.
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Affiliation(s)
- Tugrul Cem Unal
- Department of Neurosurgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Aydin Aydoseli
- Department of Neurosurgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Utku Ozgen
- Department of Neurosurgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ilyas Dolas
- Department of Neurosurgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Pulat Akin Sabanci
- Department of Neurosurgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Yavuz Aras
- Department of Neurosurgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Metehan Ozturk
- Department of Neurosurgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Musa Samet Ozata
- Department of Neurosurgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Nurdan Gul
- Department of Internal Medicine, Division of Endocrinology and Metabolism, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ayse Kubat Uzum
- Department of Internal Medicine, Division of Endocrinology and Metabolism, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ummu Mutlu
- Department of Internal Medicine, Division of Endocrinology and Metabolism, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Bilge Bilgic
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Esra Saka
- Department of Anesthesiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Sema Yarman
- Department of Internal Medicine, Division of Endocrinology and Metabolism, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Altay Sencer
- Department of Neurosurgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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12
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Giustina A, Biermasz N, Casanueva FF, Fleseriu M, Mortini P, Strasburger C, van der Lely AJ, Wass J, Melmed S. Consensus on criteria for acromegaly diagnosis and remission. Pituitary 2024; 27:7-22. [PMID: 37923946 PMCID: PMC10837217 DOI: 10.1007/s11102-023-01360-1] [Citation(s) in RCA: 44] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/17/2023] [Indexed: 11/06/2023]
Abstract
PURPOSE The 14th Acromegaly Consensus Conference was convened to consider biochemical criteria for acromegaly diagnosis and evaluation of therapeutic efficacy. METHODS Fifty-six acromegaly experts from 16 countries reviewed and discussed current evidence focused on biochemical assays; criteria for diagnosis and the role of imaging, pathology, and clinical assessments; consequences of diagnostic delay; criteria for remission and recommendations for follow up; and the value of assessment and monitoring in defining disease progression, selecting appropriate treatments, and maximizing patient outcomes. RESULTS In a patient with typical acromegaly features, insulin-like growth factor (IGF)-I > 1.3 times the upper limit of normal for age confirms the diagnosis. Random growth hormone (GH) measured after overnight fasting may be useful for informing prognosis, but is not required for diagnosis. For patients with equivocal results, IGF-I measurements using the same validated assay can be repeated, and oral glucose tolerance testing might also be useful. Although biochemical remission is the primary assessment of treatment outcome, biochemical findings should be interpreted within the clinical context of acromegaly. Follow up assessments should consider biochemical evaluation of treatment effectiveness, imaging studies evaluating residual/recurrent adenoma mass, and clinical signs and symptoms of acromegaly, its complications, and comorbidities. Referral to a multidisciplinary pituitary center should be considered for patients with equivocal biochemical, pathology, or imaging findings at diagnosis, and for patients insufficiently responsive to standard treatment approaches. CONCLUSION Consensus recommendations highlight new understandings of disordered GH and IGF-I in patients with acromegaly and the importance of expert management for this rare disease.
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Affiliation(s)
- Andrea Giustina
- San Raffaele Vita-Salute University and IRCCS Hospital, Milan, Italy
| | | | | | | | - Pietro Mortini
- San Raffaele Vita-Salute University and IRCCS Hospital, Milan, Italy
| | | | | | | | - Shlomo Melmed
- Cedars-Sinai Medical Center, 8700 Beverly Blvd, NT 2015, Los Angeles, CA, 90048, USA.
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13
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Cohen-Cohen S, Rindler R, Botello Hernandez E, Donegan D, Erickson D, Meyer FB, Atkinson JL, Van Gompel JJ. A Novel Preoperative Score to Predict Long-Term Biochemical Remission in Patients with Growth-Hormone Secreting Pituitary Adenomas. World Neurosurg 2024; 182:e882-e890. [PMID: 38123128 DOI: 10.1016/j.wneu.2023.12.076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 12/12/2023] [Accepted: 12/13/2023] [Indexed: 12/23/2023]
Abstract
OBJECTIVE Transsphenoidal surgery (TSS) is considered the treatment of choice in most patients with growth hormone (GH)-secreting pituitary adenomas. Several preoperative factors have been studied to predict postsurgical remission. Our objective was to design a score that could be used in the preoperative setting to identify patients that will achieve long-term biochemical remission after TSS. METHODS A retrospective analysis of consecutive patients with GH-secreting pituitary adenomas that underwent TSS in our institution from 2000 to 2015 who fulfilled prespecified criteria were included. Logistic regression methods were used to evaluate independent preoperative variables predicting long-term remission. Beta coefficients were used to create a scoring system for clinical practice. RESULTS Sixty-eight patients were included, with a mean follow-up time of 87 months. Twenty (29%) patients had tumors with a Knosp grade ≥ 3A. Gross-total resection was achieved in 43 (63%) patients. Thirty-three (48%) patients had long-term biochemical remission after TSS. In a multivariate analysis, the following variables were statistically significantly associated with long-term biochemical remission: age, adenoma size (diameter), Knosp grade, GH level, and insulin growth-factor 1index 1 at diagnosis. A score of <3 out of 8 total points was identified as a cutoff associated with long-term remission, with a sensitivity of 91.4% and specificity of 72.7% (AUC 0.867, OR 28.44, 95% CI 6.94-116.47, P = < 0.001). CONCLUSIONS A novel, simple, easy-to-use scoring system was created to identify patients with the highest chances of long-term biochemical remission following TSS. This scale should be prospectively validated in a multicenter study before widespread adoption.
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Affiliation(s)
| | - Rima Rindler
- Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Diane Donegan
- Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota, USA; Division of Endocrinology, Diabetes and Metabolism, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Dana Erickson
- Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota, USA
| | - Fredric B Meyer
- Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - John L Atkinson
- Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Jamie J Van Gompel
- Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota, USA.
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14
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Tomasik A, Stelmachowska-Banaś M, Maksymowicz M, Czajka-Oraniec I, Raczkiewicz D, Zieliński G, Kunicki J, Zgliczyński W. Pathologic Characteristics of Somatotroph Pituitary Tumors-An Observational Single-Center Study. Biomedicines 2023; 11:3315. [PMID: 38137536 PMCID: PMC10741635 DOI: 10.3390/biomedicines11123315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 11/26/2023] [Accepted: 12/04/2023] [Indexed: 12/24/2023] Open
Abstract
The pathologic evaluation of a tumor tissue is an essential part of an acromegaly patient's assessment. This study aimed to analyze the pathologic characteristics of pituitary tumors in patients with acromegaly. The demographic data, in addition to the hormonal, imaging, and pathologic results of 120 patients with acromegaly after pituitary surgery, were extracted from the Polish Acromegaly Registry. We compared sparsely and densely granulated tumors, GH(+), mixed GH(+)/PRL(+) and plurihormonal tumors, α-subunit-positive and α-subunit-negative tumors, and tumors of various Ki-67 indices in terms of the abovementioned features. Sparsely granulated tumors were more frequent in women than in men (p = 0.001) and in younger patients (p = 0.011), and they were larger (p < 0.001) compared to densely granulated tumors. Tumors with positive α-subunit were smaller (p = 0.013), showed extrasellar extension less often (p = 0.039), and were more often densely granulated (p < 0.001) compared to α-subunit-negative tumors. Patients with a higher Ki-67 index were younger (p < 0.001) and more often diagnosed with genetic syndromes (p = 0.02); they had higher GH concentrations (p = 0.007), larger tumors (p = 0.006), and cavernous sinus invasions more frequently (p = 0.022). Conclusions: The pathologic characteristics of somatotroph pituitary tumors are associated with patient's age, sex, hormonal results, tumor size, and the degree of extrasellar expansion.
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Affiliation(s)
- Agnieszka Tomasik
- Department of Endocrinology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
| | | | - Maria Maksymowicz
- Department of Cancer Pathomorphology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Izabella Czajka-Oraniec
- Department of Endocrinology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
| | - Dorota Raczkiewicz
- Department of Medical Statistics, School of Public Health, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
| | - Grzegorz Zieliński
- Department of Neurosurgery, Military Institute of Medicine, 04-141 Warsaw, Poland
| | - Jacek Kunicki
- Department of Neurosurgery, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Wojciech Zgliczyński
- Department of Endocrinology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
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15
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Zhao M, Li K, Niu H, Zhao Y, Lu C. Perioperative hormone level changes and their clinical implications in patients with pituitary adenoma: a retrospective study of 428 cases at a single center. Front Endocrinol (Lausanne) 2023; 14:1286020. [PMID: 37964947 PMCID: PMC10642766 DOI: 10.3389/fendo.2023.1286020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 10/13/2023] [Indexed: 11/16/2023] Open
Abstract
Objective This study employs case data analysis to elucidate alterations in hormone levels pre and post-surgery among patients with pituitary adenoma. Moreover, it investigates the influence of various associated factors on endocrine function. Methods A retrospective analysis was conducted on clinical data from 428 patients who underwent surgical treatment within a short period at a single center. Statistical methods were employed to examine detailed hormone level fluctuations before and after surgery in patients with pituitary adenoma, along with their interrelations with different factors. Results Between January 2016 and October 2022, a total of 428 consecutive patients with pituitary adenoma underwent surgical treatment. Of these, 232 were males and 196 were females, with an average age of 45.91 years (range: 16-84, standard deviation: 12.18). Univariate analysis indicated that females exhibited a higher susceptibility to preoperative endocrine dysfunction (p < 0.05). Conversely, males, patients with larger tumor volumes, and older patients were more prone to preoperative pituitary insufficiency. Postoperatively, the most substantial remission rate occurred in prolactin (77.4%), followed by growth hormone (GH) (71.8%) and cortisol (4/6). The highest recovery rate in functions was observed in growth hormone secretion function (80%), followed by pituitary-adrenal axis hormone secretion function (56.3%) and pituitary-thyroid axis hormone secretion function (47.5%). The most noteworthy incidence of newly developed postoperative endocrine deficiencies was found in the pituitary-adrenal axis (31.8%), while the occurrence rates of deficiencies in other axes were relatively low. The elevated postoperative remission rate of growth hormone correlated with a higher surgical resection rate and lower preoperative growth hormone levels. Additionally, lower preoperative prolactin levels corresponded to a higher remission rate of prolactin postoperatively. Furthermore, the restoration of postoperative thyroid hormone secretion function was associated with higher preoperative free thyroxine levels. Reduced postoperative cortisol secretion function was linked to multiple surgeries and an extended interval between hormone retesting and surgery. Conclusion Surgical intervention effectively ameliorates endocrine disorders in pituitary adenoma patients, thereby mitigating symptoms and enhancing their quality of life. Preoperative management of growth hormone and prolactin levels facilitates an increased remission rate of these hormones post pituitary adenoma surgery. Patients displaying preoperative thyroid hormone secretion dysfunction should be considered for active supplementation therapy. Whenever feasible, complete tumor resection is recommended. For patients undergoing reoperation or multiple surgeries, vigilant postoperative cortisol monitoring and supplementation should be thoughtfully administered.
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Affiliation(s)
| | - Kai Li
- Department of Neurosurgery, Peking University International Hospital, Beijing, China
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16
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Vassilyeva N, Mena N, Kirov K, Diatlova E. Comparative effectiveness of endoscopic and microscopic adenoma removal in acromegaly. Front Endocrinol (Lausanne) 2023; 14:1128345. [PMID: 37766690 PMCID: PMC10519786 DOI: 10.3389/fendo.2023.1128345] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 08/16/2023] [Indexed: 09/29/2023] Open
Abstract
Introduction Somatotropinomas are the main cause of acromegaly. Surgery is the primary and most efficient method of treatment. The study aimed to compare the radicality of small-sized and medium (<30 mm) somatotropinoma removal and the incidence of postoperative complications in patients with acromegaly when using microscopic and endoscopic techniques. Methods In this randomized controlled trial, a total of 83 patients with acromegaly underwent transspheroidal endoscopy or microscopic surgery. Somatotropinoma was the cause of acromegaly in all cases. Patients were randomly divided into two comparison groups depending on the applied surgical technique. Group 1 (n = 40) consisted of patients who underwent adenomectomy with transnasal transsphenoidal access by a microscope. Group 2 (n = 43) included patients who underwent the same surgical procedure with an endoscope. The following indicators were assessed: radicality of tumor removal, treatment effectiveness, postoperative complications, and remission rate. Results The study has shown that removal of somatotropinoma in patients with acromegaly using endoscopic technique increases the radicality of tumor removal in comparison with microscopic technique. Total removal of somatotropinoma was successful in 88.4% of cases when using the endoscopic technique. Secondly, the segmentation of patients according to their tumor characteristics poses challenges, primarily owing to the rarity of acromegaly as a disease. The difference between groups was not statistically significant (p=1.02). There were no statistically significant differences in basal GH level and IGF-1 level between groups (p=0.546 and p=0.784, respectively). Discussion Endonasal transsphenoidal endoscopic adenomectomy is proven efficacy, a less traumatic degree, and higher somatotropinoma removal radicality. Both surgical methods lead to disease remission.
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Affiliation(s)
- Natalya Vassilyeva
- Department Emergency Medicine, Anesthesiology and Resuscitation, Karaganda Medical University, Karaganda, Kazakhstan
| | - Natmir Mena
- Department of General Surgery, Medical University Pleven, Pleven, Bulgaria
| | - Kiril Kirov
- Research Institute, Medical University Pleven, Pleven, Bulgaria
| | - Ekaterina Diatlova
- Department of Nursing Management and Social Work, Sechenov First Moscow State Medical University, Moscow, Russia
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17
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Theiler S, Hegetschweiler S, Staartjes VE, Spinello A, Brandi G, Regli L, Serra C. Influence of gender and sexual hormones on outcomes after pituitary surgery: a systematic review and meta-analysis. Acta Neurochir (Wien) 2023; 165:2445-2460. [PMID: 37555999 PMCID: PMC10477253 DOI: 10.1007/s00701-023-05726-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 07/07/2023] [Indexed: 08/10/2023]
Abstract
BACKGROUND Although there is an increasing body of evidence showing gender differences in various medical domains as well as presentation and biology of pituitary adenoma (PA), gender differences regarding outcome of patients who underwent transsphenoidal resection of PA are poorly understood. The aim of this study was to identify gender differences in PA surgery. METHODS The PubMed/MEDLINE database was searched up to April 2023 to identify eligible articles. Quality appraisal and extraction were performed in duplicate. RESULTS A total of 40 studies including 4989 patients were included in this systematic review and meta-analysis. Our analysis showed odds ratio of postoperative biochemical remission in males vs. females of 0.83 (95% CI 0.59-1.15, P = 0.26), odds ratio of gross total resection in male vs. female patients of 0.68 (95% CI 0.34-1.39, P = 0.30), odds ratio of postoperative diabetes insipidus in male vs. female patients of 0.40 (95% CI 0.26-0.64, P < 0.0001), and a mean difference of preoperative level of prolactin in male vs. female patients of 11.62 (95% CI - 119.04-142.27, P = 0.86). CONCLUSIONS There was a significantly higher rate of postoperative DI in female patients after endoscopic or microscopic transsphenoidal PA surgery, and although there was some data in isolated studies suggesting influence of gender on postoperative biochemical remission, rate of GTR, and preoperative prolactin levels, these findings could not be confirmed in this meta-analysis and demonstrated no statistically significant effect. Further research is needed and future studies concerning PA surgery should report their data by gender or sexual hormones and ideally further assess their impact on PA surgery.
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Affiliation(s)
- Sven Theiler
- Machine Intelligence in Clinical Neuroscience (MICN) Laboratory, Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Frauenklinikstrasse 10, 8091, Zurich, Switzerland
| | - Saskia Hegetschweiler
- Machine Intelligence in Clinical Neuroscience (MICN) Laboratory, Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Frauenklinikstrasse 10, 8091, Zurich, Switzerland
| | - Victor E Staartjes
- Machine Intelligence in Clinical Neuroscience (MICN) Laboratory, Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Frauenklinikstrasse 10, 8091, Zurich, Switzerland
| | - Antonio Spinello
- Machine Intelligence in Clinical Neuroscience (MICN) Laboratory, Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Frauenklinikstrasse 10, 8091, Zurich, Switzerland
| | - Giovanna Brandi
- Institute for Intensive Care, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Luca Regli
- Machine Intelligence in Clinical Neuroscience (MICN) Laboratory, Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Frauenklinikstrasse 10, 8091, Zurich, Switzerland
| | - Carlo Serra
- Machine Intelligence in Clinical Neuroscience (MICN) Laboratory, Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Frauenklinikstrasse 10, 8091, Zurich, Switzerland.
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Cavalcante RADC, Vieira LA, Peres LFA, Zaccariotti AJ, Alencar HDS, Jatene EM, Camargo LA, Rodrigues MLD. Endoscopic endonasal approach for acromegaly: surgical outcomes using 2018 consensus criteria for remission. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2023; 67:e000650. [PMID: 37364152 PMCID: PMC10661002 DOI: 10.20945/2359-3997000000650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 03/13/2023] [Indexed: 06/28/2023]
Abstract
Objective The primary aim is to analyze the endoscopic endonasal surgical results in short-term and two-year follow-ups according to the 11th Acromegaly Consensus statement (2018). Indeed, prognostic factors and complications were analyzed. Subjects and methods 40 patients who underwent endoscopic endonasal surgery by acromegaly between 2013 to 2020 was analyzed. Patients were considered in remission if an upper limit of normal (ULN) IGF-1 was less than 1.0 at the six-month and two-year follow-ups. Moreover, we assessed the Knosp grade, tumor volumetry, ULN, T2 signal in MRI, reoperation, and complications. Results The mean age of admission was 46.7 years. Thirty-two patients were in remission after six months of surgery (80%), decreasing to 76.32% at the two-year follow-up. All microadenomas presented remission (n = 6). Regarding the complications, three patients had permanent panhypopituitarism (7.5%); postoperative cerebrospinal fluid (CSF) leaks did not occur in this series. The hyperintense signal on the T2 MRI and a higher tumor volumetry were the single predictor's factors of non-emission in a multivariate regression logistic analysis (p < 0.05). Preoperative hormone levels (GH and IGF-1) were not a prognostic factor for remission. The re-operated patients who presented hypersignal already had a high predictor of clinical-operative failure. Conclusion The endoscopic endonasal surgery promotes high short-term and two-year remission rates in acromegaly; the tumor's volumetry and the T2 hypersignal were statistically significant prognostic factors in non-remission - the complications presented at similar rates in comparison to the literature. In invasive GH-secreting tumors, we should offer these patients a multi-disciplinary approach to improve acromegalic patients' remission rates.
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Affiliation(s)
- Rodrigo Alves de Carvalho Cavalcante
- Universidade Federal de GoiásFaculdade de MedicinaHospital das ClínicasGoiâniaGOBrasilDepartamento de Cirurgia Neurológica, Hospital das Clínicas, Faculdade de Medicina, Universidade Federal de Goiás, Goiânia, GO, Brasil
- Hospital do Câncer Araújo JorgeGoiâniaGOBrasilServiço de Cirurgia Neurológica, Hospital do Câncer Araújo Jorge, Goiânia, GO, Brasil
| | - Luiz Alves Vieira
- Universidade Federal de GoiásFaculdade de MedicinaGoiâniaGOBrasilFaculdade de Medicina, Universidade Federal de Goiás, Goiânia, GO, Brasil
| | - Luís Felipe Araújo Peres
- Universidade Federal de GoiásFaculdade de MedicinaGoiâniaGOBrasilFaculdade de Medicina, Universidade Federal de Goiás, Goiânia, GO, Brasil
| | - Alice Jardim Zaccariotti
- Universidade Federal de GoiásFaculdade de MedicinaGoiâniaGOBrasilFaculdade de Medicina, Universidade Federal de Goiás, Goiânia, GO, Brasil
| | - Helioenai de Sousa Alencar
- Universidade Federal de GoiásFaculdade de MedicinaHospital das ClínicasGoiâniaGOBrasilDepartamento de Cirurgia Neurológica, Hospital das Clínicas, Faculdade de Medicina, Universidade Federal de Goiás, Goiânia, GO, Brasil
| | - Estela Muszkat Jatene
- Universidade Federal de GoiásFaculdade de MedicinaHospital das ClínicasGoiâniaGOBrasilDepartamento de Endocrinologia, Hospital das Clínicas, Faculdade de Medicina, Universidade Federal de Goiás, Goiânia, GO, Brasil
| | - Leandro Azevedo Camargo
- Universidade Federal de GoiásFaculdade de MedicinaHospital das ClínicasGoiâniaGOBrasilDepartamento de Otorrinolaringologia, Hospital das Clínicas, Faculdade de Medicina, Universidade Federal de Goiás, Goiânia, GO, Brasil
| | - Monike Lourenço Dias Rodrigues
- Universidade Federal de GoiásFaculdade de MedicinaHospital das ClínicasGoiâniaGOBrasilDepartamento de Endocrinologia, Hospital das Clínicas, Faculdade de Medicina, Universidade Federal de Goiás, Goiânia, GO, Brasil
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Molteni G, Caiazza N, Fulco G, Sacchetto A, Gulino A, Marchioni D. Functioning Endocrine Outcome after Endoscopic Endonasal Transsellar Approach for Pituitary Neuroendocrine Tumors. J Clin Med 2023; 12:jcm12082986. [PMID: 37109322 PMCID: PMC10145377 DOI: 10.3390/jcm12082986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 04/15/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND The endoscopic endonasal approach (EEA) is a well-established technique for the treatment of pituitary neuroendocrine tumor Preservation of normal gland tissue is crucial to retain effective neuroendocrine pituitary function. The aim of this paper is to analyze pituitary endocrine secretion after EEA for pituitary neuroendocrine tumor to identify potential predictors of functioning gland recovery. METHODS Patients who underwent an exclusive EEA for pituitary neuroendocrine tumors between October 2014 and November 2019 were reviewed. Patients were divided into groups according to postoperative pituitary function (Group 1, unchanged; group 2, recovering; group 3, worsening). RESULTS Among the 45 patients enrolled, 15 presented a silent tumor and showed no hormonal impairment, and 30 patients presented pituitary dysfunction. A total of 19 patients (42.2%) were included in group 1, 12 (26.7%) patients showed pituitary function recovery after surgery (group 2), and 14 patients (31.1%) exhibited the onset of new pituitary deficiency postoperatively (group 3). Younger patients and those with functioning tumor were more likely to have complete pituitary hormonal recovery (p = 0.0297 and p = 0.007, respectively). No predictors of functional gland worsening were identified. CONCLUSION EEA for pituitary neuroendocrine tumor is a reliable and safe technique regarding postoperative hormonal function. Preserving pituitary function after tumor resection should be a primary goal in a minimally invasive approach.
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Affiliation(s)
- Gabriele Molteni
- Division of Otorhinolaryngology, Department of Surgery, Dentistry, Gynecology, and Pediatrics, University of Verona, University Hospital of Verona, Piazzale L.A. Scuro, 10, 37134 Verona, Italy
| | - Nicole Caiazza
- Division of Otorhinolaryngology, Department of Surgery, Dentistry, Gynecology, and Pediatrics, University of Verona, University Hospital of Verona, Piazzale L.A. Scuro, 10, 37134 Verona, Italy
| | - Gianfranco Fulco
- Division of Otorhinolaryngology, Department of Surgery, Dentistry, Gynecology, and Pediatrics, University of Verona, University Hospital of Verona, Piazzale L.A. Scuro, 10, 37134 Verona, Italy
| | - Andrea Sacchetto
- Division of Otorhinolaryngology, Department of Surgery, Dentistry, Gynecology, and Pediatrics, University of Verona, University Hospital of Verona, Piazzale L.A. Scuro, 10, 37134 Verona, Italy
| | - Antonio Gulino
- Division of Otorhinolaryngology, Department of Surgery, Dentistry, Gynecology, and Pediatrics, University of Verona, University Hospital of Verona, Piazzale L.A. Scuro, 10, 37134 Verona, Italy
| | - Daniele Marchioni
- Division of Otorhinolaryngology, Department of Surgery, Dentistry, Gynecology, and Pediatrics, University of Verona, University Hospital of Verona, Piazzale L.A. Scuro, 10, 37134 Verona, Italy
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20
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Nie D, Fang Q, Wong W, Gui S, Zhao P, Li C, Zhang Y. The effect of endoscopic transsphenoidal somatotroph tumors resection on pituitary hormones: systematic review and meta-analysis. World J Surg Oncol 2023; 21:71. [PMID: 36859291 PMCID: PMC9976528 DOI: 10.1186/s12957-023-02958-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 02/22/2023] [Indexed: 03/03/2023] Open
Abstract
PURPOSE Currently, endoscopic transsphenoidal surgery is the main treatment for pituitary neuroendocrine tumors (PitNETs). Excision of the tumor may have positive or negative effects on pituitary endocrine function, and the pituitary function of somatotroph tumors is a point of particular concern after the operation. This study aimed to conduct a meta-analysis on the effect of endoscopic transsphenoidal somatotroph tumor resection on pituitary function. METHODS A systematic literature search was conducted for articles that included the evaluation of pituitary target gland before and after endoscopic transsphenoidal pituitary tumor resection and were published between 1992 and 2022 in PubMed, Cochrane, and Ovid MEDLINE. RESULTS Sixty-eight studies that included biochemical remission rates in 4524 somatotroph tumors were concluded. According to the 2000 consensus, the biochemical remission rate after transsphenoidal endoscopic surgery was 66.4% (95% CI, 0.622-0.703; P = 0.000), the biochemical remission rate was 56.2% according to the 2010 consensus (95% CI, 0.503-0.620; P = 0.041), and with the rate of biochemical remission ranging from 30.0 to 91.7% with investigator's definition. After endoscopic resection, adrenal axis dysfunction was slightly higher than that before surgery, but the difference was not statistically significant. Hypothyroidism was 0.712 times higher risk than that before surgery (OR = 0.712; 95% CI, 0.527-0.961; P = 0.027). Hypogonadism was 0.541 times higher risk than that before surgery (OR = 0.541; 95% CI, 0.393-0.746; P = 0.000). Hyperprolactinemia was 0.131 times higher risk than that before surgery (OR = 0.131; 95% CI, 0.022-0.783; P = 0.026). The incidence of pituitary insufficiency was 1.344 times the risk before surgery after endoscopic resection of somatotroph tumors, but the difference was not statistically significant. CONCLUSIONS In patients with somatotroph tumors after undergoing endoscopic surgery, the risk of dysfunction and pituitary insufficiency tend to increase, while preoperative thyroid insufficiency, gonadal insufficiency, and hyperprolactinemia will be partially relieved.
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Affiliation(s)
- Ding Nie
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Qiuyue Fang
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Wakam Wong
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Songbai Gui
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Peng Zhao
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Chuzhong Li
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Yazhuo Zhang
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
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21
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Papaioannou C, Druce M. Preoperative medical treatments and surgical approaches for acromegaly: A systematic review. Clin Endocrinol (Oxf) 2023; 98:14-31. [PMID: 35726150 PMCID: PMC10084190 DOI: 10.1111/cen.14790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 06/12/2022] [Accepted: 06/19/2022] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Acromegaly is a condition characterized by an overproduction of growth hormone which infers high morbidity and mortality if left untreated. The objective of this review is to analyse and appraise the current evidence for the generalized use of preoperative medications and the various surgical approaches as described in the literature. DESIGN A thorough search from MEDLINE via PubMed, EMBASE, and Cochrane Library has been performed which identified a total of 37 papers. CONCLUSION The preoperative use of somatostatin receptor agonists (SAs) in acromegaly is a controversial topic with current guidelines suggesting against their generalized routine use. Most authors noticed an insignificant long-term remission of acromegaly when given SAs compared with nil preoperative therapy, except for invasive macroadenomas as SAs have been found to reduce the tumour volume and aid towards the total resection of the adenoma. Furthermore, according to the evidence available, endoscopic transsphenoidal surgery is the optimum method for hypophysectomy in terms of its remission and safety profile.
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Affiliation(s)
- Christos Papaioannou
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK
| | - Maralyn Druce
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK
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22
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Astafyeva LI, Shkarubo AN, Chernov IV, Ibrahim SR, Badmaeva IN, Strunina YV, Ilovayskaya IA, Pronin VS, Sidneva YG, Kalinin PL. [Predictors of postoperative remission of acromegaly. (Experience of the Burdenko Neurosurgical Center)]. ZHURNAL VOPROSY NEIROKHIRURGII IMENI N. N. BURDENKO 2023; 87:76-84. [PMID: 38054230 DOI: 10.17116/neiro20238706176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/07/2023]
Abstract
BACKGROUND Treatment of acromegaly is still an unresolved problem. Overall postoperative remission rate ranges from 34 to 85%. These values are better for microadenomas (75-90%) and worse for macroadenomas (45-70%). Identification of predictors of acromegaly remission after surgical treatment is an urgent objective to improve the quality of medical care for these patients. OBJECTIVE To analyze postoperative freedom from acromegaly and predictors of remission. MATERIAL AND METHODS A retrospective single-center study included 227 patients with acromegaly who underwent resection of pituitary adenoma between August 2018 and August 2021. RESULTS Remission (normalization of serum IGF-1) was achieved in 65 (55%) patients. Growth hormone and IGF-1 index decreased after surgery in all patients. Mean preoperative serum growth hormone was 12.45 [6.88, 29.85] ng/ml, early postoperative concentration - 1.54 [0.80, 3.38] ng/ml, in delayed period - 1.15 [0.57, 3.80] ng/ml. Mean IGF-1 index was 2.18 [1.69, 2.71], 1.47 [0.99, 1.90] and 0.99 [0.74, 1.43], respectively. CONCLUSION Significant predictors of acromegaly remission after neurosurgical treatment were age, preoperative level of growth hormone, tumor size and location, growth hormone and IGF-1 index in early postoperative period and residual tumor after surgery. Multivariate analysis revealed a significant association of acromegaly remission with small tumor size, low postoperative level of growth hormone and no residual tumor within 3-6 month after surgery.
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Affiliation(s)
| | | | - I V Chernov
- Burdenko Neurosurgical Center, Moscow, Russia
| | - S R Ibrahim
- People's Friendship University of Russia, Moscow, Russia
| | | | | | - I A Ilovayskaya
- Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia
| | - V S Pronin
- Russian Medical Academy of Continuing Professional Education, Moscow, Russia
| | - Yu G Sidneva
- Burdenko Neurosurgical Center, Moscow, Russia
- Research Institute for Emergency Pediatric Surgery and Traumatology, Moscow, Russia
| | - P L Kalinin
- Burdenko Neurosurgical Center, Moscow, Russia
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23
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The Prognostic-Based Approach in Growth Hormone-Secreting Pituitary Neuroendocrine Tumors (PitNET): Tertiary Reference Center, Single Senior Surgeon, and Long-Term Follow-Up. Cancers (Basel) 2022; 15:cancers15010267. [PMID: 36612263 PMCID: PMC9818833 DOI: 10.3390/cancers15010267] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/25/2022] [Accepted: 12/27/2022] [Indexed: 01/03/2023] Open
Abstract
Postoperative deserved outcomes in acromegalic patients are to normalize serum insulin-like growth factor (IGF-1), reduce the tumoral mass effect, improve systemic comorbidities, and reverse metabolic alterations. Pituitary neuroendocrine tumors (PitNET) are characterized to present a heterogeneous behavior, and growth hormone (GH)-secreting PitNET is not an exception. Promptly determining which patients are affected by more aggressive tumors is essential to guide the optimal postoperative decision-making process [prognostic-based approach]. From 2006 to 2019, 394 patients affected by PitNET were intervened via endoscopic endonasal transsphenoidal approach by the same senior surgeon. A total of 44 patients that met the criteria to be diagnosed as acromegalic and were followed up at least for 24 months (median of 66 months (26-156) were included in the present study. Multiple predictive variables [age, gender, preoperative GH and IGF-1 levels, maximal tumor diameter, Hardy's and Knosp's grade, MRI. T2-weighted tumor intensity, cytokeratin expression pattern, and clinicopathological classification] were evaluated through uni- and multivariate statistical analysis. Sparse probability of long-term remission was related to younger age, higher preoperative GH and- or IGF-1, group 2b of the clinicopathological classification, and sparsely granulated cytokeratin expression pattern. Augmented recurrence risk was related to elevated preoperative GH levels, tumor MRI T2-weighted hyperintensity, and sparsely granulated cytokeratin expression pattern. Finally, elevated risk for reintervention was related to group 2b of the clinicopathological classification, Knosp's grade IV, and tumor MRI T2-weighted hyperintensity. In this study, the authors determined younger age, higher preoperative GH and- or IGF-1 levels, group 2b of the clinicopathological classification, Knosp's grade IV, MRI T2-weighted tumor hyperintensity and sparsely granulated cytokeratin expression pattern are related to worse postoperative outcomes in long-term follow-up patients affected with GH-secreting PitNET.
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24
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Луценко АС, Белая ЖЕ, Пржиялковская ЕГ, Лапшина АМ, Никитин АГ, Азизян ВН, Иващенко ОВ, Григорьев АЮ, Мельниченко ГА. [Short-term and long-term remission after endoscopic transnasal adenomectomy in patients with acromegaly]. PROBLEMY ENDOKRINOLOGII 2022; 68:67-75. [PMID: 36689713 PMCID: PMC9939963 DOI: 10.14341/probl13192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/05/2022] [Accepted: 12/05/2022] [Indexed: 01/25/2023]
Abstract
BACKGROUND Neurosurgery is the most effective treatment for acromegaly. As most of the patients present with macroadenomas, surgical treatment is not always successful, even with the expert level of a neurosurgeon. Assessment of the postoperative remission rates in acromegaly preoperative predictors of treatment efficacy is an urgent task of modern research. AIM To assess the short-term and long-term remission of acromegaly after endoscopic transnasal adenomectomy in a tertiary medical center and assess preoperative predictors of the treatment effectiveness. MATERIALS AND METHODS A single-center, prospective, uncontrolled study was conducted. We included patients with active acromegaly who did not receive medical therapy with somatostatin analogues and were referred for endoscopic transsphenoidal adenomectomy. Plasma miRNA expression was assessed by quantitative reverse transcription PCR. Postoperative samples of adenomas were sent for study, with the determination of the immunohistochemical staining for somatostatin receptors 2 and 5 subtypes and morphology was performed on postoperative adenoma samples. RESULTS The study included 44 patients: 32.8% men, median age 47.0 [34.0; 55.0], IGF-1 744.75 ng/ml [548.83;889.85], growth hormone 9.5 ng/ml [4.94; 17.07]. Tumor volume 832 mm3 [419.25; 2532.38]. Early postoperative remission was achieved in 35 patients (79.5%). Patients who achieved short-term remission had higher IGF-1 and basal growth hormone levels. Median follow-up was 19.0 months [12.5;29.0]. Long-term remission was achieved in 61.4% (27 patients), no remission in 9 (20.5%), recurrency in 2 patients (4.5%), 6 patients were to follow-up (13.6%). In patients with long-term remission, we observed lower growth hormone and IGF-1 levels. No differences in miRNA expression was observesd. The predictive value of basal GH before surgery for long-term remission was assessed: area under the curve 0.811 (95% CI: 0.649; 0.973). A cut-off value of 15.55 ng/mL corresponded to a sensitivity of 70.0% (34.8%; 93.3%), a specificity of 85.7% (67.3%; 96.0%), an accuracy of 81.6% (65 .7%; 92.3%), PPV 63.6% (39.3%; 82.5%), NPV 88.9% (75.4%; 95.4%). CONCLUSION Rates of short-term and long-term remission after endoscopic transsphenoidal adenomectomy in our cohort is 79,5% и 61,4%, respectively, and is comparable with literature data for expert pituitary centers. Preoperative GH shows potential value in predicting the long-term remission of acromegaly, but further studies in a larger sample are needed to obtain more accurate cut-off values.
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Affiliation(s)
- А. С. Луценко
- Национальный медицинский исследовательский центр эндокринологии
| | - Ж. Е. Белая
- Национальный медицинский исследовательский центр эндокринологии
| | | | - А. М. Лапшина
- Национальный медицинский исследовательский центр эндокринологии
| | | | - В. Н. Азизян
- Национальный медицинский исследовательский центр эндокринологии
| | - О. В. Иващенко
- Национальный медицинский исследовательский центр эндокринологии
| | - А. Ю. Григорьев
- Национальный медицинский исследовательский центр эндокринологии
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Mamelak A. Surgery as a first-line option for prolactinomas. Expert Rev Endocrinol Metab 2022; 17:485-498. [PMID: 36200144 DOI: 10.1080/17446651.2022.2131531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 09/28/2022] [Indexed: 01/05/2023]
Abstract
INTRODUCTION Treatment of prolactinomas with dopamine agonists has been the established first-line treatment option for many years, with surgery reserved for refractory cases or medication intolerance. This approach may not be the best option in many cases. AREAS COVERED Review of the epidemiology, biology, and treatment options available for prolactinomas, including best available data on outcomes, costs, and morbidities for each therapy. These data are then used to propose a 'surgery-first' treatment approach for a subset of prolactinomas as an alternative to primary medical management. EXPERT OPINION Based on the available data, there is a strong rationale that transsphenoidal surgery should be considered a first-line treatment option for both micro- and macro-prolactinomas that do not demonstrate high grade cavernous sinus invasion on MRI imaging, with dopamine agonists administered as a secondary therapy for tumors not in remission following surgery, and for giant tumors. This 'surgery-first' approach assumes the availability of skilled and experienced pituitary surgeons to ensure optimal outcomes. This approach should result in high cure rates and reduced DA requirements for patients not cured from initial surgery. Further, it will reduce medical costs over a patient's lifetime and the chronic morbidities associated with protracted dopamine agonist usage.
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Affiliation(s)
- Adam Mamelak
- Surgical Director, Pituitary Center & Center for Minimally Invasive Skull Base Surgery, Cedars-Sinai Medical Center, Los Angeles
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26
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Chhabra R, Kumar A, Virk RS, Dutta P, Ahuja C, Mohanty M, Dhandapani S. Outcomes in pituitary adenoma causing acromegaly following endoscopic endonasal transsphenoidal surgery. J Neurosci Rural Pract 2022; 13:696-704. [PMID: 36743751 PMCID: PMC9894003 DOI: 10.25259/jnrp-2022-3-28-r1-(2453)] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 09/20/2022] [Indexed: 12/10/2022] Open
Abstract
Objectives The objectives of the study were to study the analysis of outcomes after endoscopic endonasal transsphenoidal surgery (EETSS) in acromegaly in terms of surgical complications, clinical improvement, endocrinological remission, achievement of prognostically critical growth hormone (GH) level, and requirement of additional treatment. Materials and Methods The study included 28 acromegaly patients, who underwent EETSS. A 2010 consensus criterion was used for defining remission. Assessment of prognostically critical GH level (random value <2.5 ng/ml), the extent of resection and additional treatment, was done at post-operative week (POW) 12. Results All adenomas were macroadenomas; with a mean volume of 16.34 cm3 (range, 0.4-99 cm3). Most adenomas had high-grade extensions. Most common suprasellar, infrasellar, anterior, and posterior extension grades were 3 (n = 13), 1 (n = 16), 1 (n = 14), and 0 (n = 20), respectively. Knosp Grade 3 was common on both sides (right, n = 9 and left, n = 8). One patient had already been operated on with EETSS, 1.5 years back from current surgery. Sixteen patients were on hormonal support, preoperatively. Four patients died during follow-up. Post-operative common complications were diabetes insipidus (DI, n = 18), cerebrospinal fluid rhinorrhea (n = 10), surgical site hematoma (n = 3), meningitis (n = 3), hydrocephalus (n = 2), and syndrome of inappropriate antidiuretic hormone (n = 1). The mean hospital stay was 11.62 days and 12.17 months were the mean follow-up period. At 12 POW, no improvement was seen in body enlargement and visual complaints, but all other complaints improved significantly except perspiration. Adenomas were decreased in all extensions except posterior and mean adenoma volume was reduced from 16.34 cm3 to 2.92 cm3 after surgery. Sub-total resection (STR, n = 10), near-total resection (NTR, n = 7), gross-total resection (GTR, n = 5), and partial resection (PR, n = 2) were achieved. Endocrinological remission and prognostically critical GH levels were attained in 29.17% (n = 7) and 66.67% (n = 16), respectively. NTR, GTR, STR, and PR were associated with 57.14%, 40%, 10%, and 0% endocrinological remission, respectively. Additional treatment was required in a total of 17 patients, three in GTR, nine in STR, three in NTR, and two in PR. Ten were treated with Gamma Knife radiosurgery along with medical treatment and seven with medical treatment alone. Conclusion A successful EETSS can reduce adenoma volume to achieve clinical improvement, endocrinologic remission, and prognostically critical GH level with some complications related to surgery. Pre-operative larger volume and higher extension grades affect these outcomes adversely.
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Affiliation(s)
- Rajesh Chhabra
- Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashwani Kumar
- Department of Neurosurgery, Government Medical College and Hospital, Chandigarh, India
| | - R. S. Virk
- Department of Otorhinolaryngology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pinaki Dutta
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Chirag Ahuja
- Department of Neuroradiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Manju Mohanty
- Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sivashanmugam Dhandapani
- Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Crisafulli S, Fontana A, L'Abbate L, Ientile V, Gianfrilli D, Cozzolino A, De Martino MC, Ragonese M, Sultana J, Barone-Adesi F, Trifirò G. Development and testing of diagnostic algorithms to identify patients with acromegaly in Southern Italian claims databases. Sci Rep 2022; 12:15843. [PMID: 36151305 PMCID: PMC9508179 DOI: 10.1038/s41598-022-20295-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 09/12/2022] [Indexed: 12/05/2022] Open
Abstract
Acromegaly is a rare disease characterized by an excessive production of growth-hormone and insulin-like growth factor 1, typically resulting from a GH-secreting pituitary adenoma. This study was aimed at comparing and measuring accuracy of newly and previously developed coding algorithms for the identification of acromegaly using Italian claims databases. This study was conducted between January 2015 and December 2018, using data from the claims databases of Caserta Local Health Unit (LHU) and Sicily Region in Southern Italy. To detect acromegaly cases from the general target population, four algorithms were developed using combinations of diagnostic, surgical procedure and co-payment exemption codes, pharmacy claims and specialist’s visits. Algorithm accuracy was assessed by measuring the Youden Index, sensitivity, specificity, positive and negative predictive values. The percentage of positive cases for each algorithm ranged from 7.9 (95% CI 6.4–9.8) to 13.8 (95% CI 11.7–16.2) per 100,000 inhabitants in Caserta LHU and from 7.8 (95% CI 7.1–8.6) to 16.4 (95% CI 15.3–17.5) in Sicily Region. Sensitivity of the different algorithms ranged from 71.1% (95% CI 54.1–84.6%) to 84.2% (95% CI 68.8–94.0%), while specificity was always higher than 99.9%. The algorithm based on the presence of claims suggestive of acromegaly in ≥ 2 different databases (i.e., hospital discharge records, copayment exemptions registry, pharmacy claims and specialist visits registry) achieved the highest Youden Index (84.2) and the highest positive predictive value (34.8; 95% CI 28.6–41.6). We tested four algorithms to identify acromegaly cases using claims databases with high sensitivity and Youden Index. Despite identifying rare diseases using real-world data is challenging, this study showed that robust validity testing may yield the identification of accurate coding algorithms.
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Affiliation(s)
| | - Andrea Fontana
- Unit of Biostatistics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Luca L'Abbate
- Department of Diagnostics and Public Health, University of Verona, P.le L.A. Scuro 10, 37134, Verona, Italy
| | - Valentina Ientile
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
| | - Daniele Gianfrilli
- Section of Medical Pathophysiology and Endocrinology, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Alessia Cozzolino
- Section of Medical Pathophysiology and Endocrinology, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | | | - Marta Ragonese
- Department of Human Pathology of Adulthood and Childhood "G. Barresi" DETEV, University of Messina, Messina, Italy
| | - Janet Sultana
- College of Medicine and Health, University of Exeter, Exeter, UK
| | - Francesco Barone-Adesi
- Department of Translational Medicine, University Piemonte Orientale, Novara, Italy.,Research Center in Emergency and Disaster Medicine (CRIMEDIM), University Piemonte Orientale, Novara, Italy
| | - Gianluca Trifirò
- Department of Diagnostics and Public Health, University of Verona, P.le L.A. Scuro 10, 37134, Verona, Italy.
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Guo X, Zhang R, Zhang D, Wang Z, Gao L, Yao Y, Deng K, Bao X, Feng M, Xu Z, Yang Y, Lian W, Wang R, Ma W, Xing B. Determinants of immediate and long-term remission after initial transsphenoidal surgery for acromegaly and outcome patterns during follow-up: a longitudinal study on 659 patients. J Neurosurg 2022; 137:618-628. [PMID: 35171834 DOI: 10.3171/2021.11.jns212137] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 11/04/2021] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Treatment outcomes following initial transsphenoidal surgery (TSS) for acromegaly are erratic. Identifying outcome patterns can assist in informing patients about possible treatment outcomes and planning for individualized adjuvant treatments in advance. In this study, the authors aimed to investigate the immediate and long-term endocrine remission rates following initial TSS for acromegaly, identify clinical determinants of treatment outcomes, and explore outcome patterns during a long-term follow-up and the pattern-specific patient features. METHODS This prospective, single-center, longitudinal cohort study enrolled patients with acromegaly who underwent TSS in the period from 2015 to 2018 at the authors' institution. Immediate remission, assessed on the 2nd postoperative morning, and long-term remission, assessed at least 18 months after TSS, were evaluated according to the strict 2010 consensus criteria (random growth hormone [GH] < 1 ng/ml or GH nadir < 0.4 ng/ml after oral glucose tolerance test, and age- and sex-normalized insulin-like growth factor 1). Univariate and bivariate regression analyses were used to identify determinants of remission. RESULTS A total of 659 patients with acromegaly (average age 42 years, 44% males) underwent TSS for pituitary adenomas (macroadenomas, 85%; invasive tumors, 35%) and were followed up during a median of 51 months. Immediate and long-term remission rates after initial TSS were 37% and 69%, respectively. Older age at diagnosis (OR 1.7), male sex (OR 1.6), smaller tumors (OR 2.0), noninvasive tumors (OR 4.8), and tumors positive for follicle-stimulating hormone/luteinizing hormone (OR 1.5) were predictors of immediate surgical remission. In addition to the above predictors, lower preoperative GH (OR 2.4), absence of preoperative central hypothyroidism (OR 2.6), and endoscopic TSS (OR 10.6) were predictors of long-term remission. Regression analyses revealed that endoscopic TSS (OR 2.8, 95% CI 1.524-5.291, p = 0.001), absence of cavernous sinus invasion (OR 4.1, 95% CI 2.522-6.613, p < 0.001), older age (OR 1.03, 95% CI 1.006-1.048, p = 0.013), and male sex (OR 2.0, 95% CI 1.224-3.247, p = 0.006) were independent determinants of long-term remission. Five outcome patterns were identified based on the changes in hormonal results during follow-up, including continuous remission (34%), refractory acromegaly (28%), delayed remission (21%), remission after adjuvant therapy (14%), and recurrence after initial remission (3%). The clinical characteristics of each subgroup were identified. CONCLUSIONS Cavernous sinus invasion, age at diagnosis, and sex are the best determinants of immediate and long-term remission after initial TSS for acromegaly. Endoscopic TSS predicts a higher long-term remission rate than that with microscopic TSS. The authors identified five outcome patterns in acromegaly and group-specific patient characteristics for clinical decision-making.
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Affiliation(s)
- Xiaopeng Guo
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 3China Pituitary Disease Registry Center, Beijing
- 4China Pituitary Adenoma Specialist Council, Beijing; and
| | - Ruopeng Zhang
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 5Peking Union Medical College, Tsinghua University, Beijing, China
| | - Duoxing Zhang
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 5Peking Union Medical College, Tsinghua University, Beijing, China
| | - Zihao Wang
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 3China Pituitary Disease Registry Center, Beijing
- 4China Pituitary Adenoma Specialist Council, Beijing; and
| | - Lu Gao
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 3China Pituitary Disease Registry Center, Beijing
- 4China Pituitary Adenoma Specialist Council, Beijing; and
| | - Yong Yao
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 3China Pituitary Disease Registry Center, Beijing
- 4China Pituitary Adenoma Specialist Council, Beijing; and
| | - Kan Deng
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 3China Pituitary Disease Registry Center, Beijing
- 4China Pituitary Adenoma Specialist Council, Beijing; and
| | - Xinjie Bao
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 3China Pituitary Disease Registry Center, Beijing
- 4China Pituitary Adenoma Specialist Council, Beijing; and
| | - Ming Feng
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 3China Pituitary Disease Registry Center, Beijing
- 4China Pituitary Adenoma Specialist Council, Beijing; and
| | - Zhiqin Xu
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 3China Pituitary Disease Registry Center, Beijing
- 4China Pituitary Adenoma Specialist Council, Beijing; and
| | - Yi Yang
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 3China Pituitary Disease Registry Center, Beijing
- 4China Pituitary Adenoma Specialist Council, Beijing; and
| | - Wei Lian
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 3China Pituitary Disease Registry Center, Beijing
- 4China Pituitary Adenoma Specialist Council, Beijing; and
| | - Renzhi Wang
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 3China Pituitary Disease Registry Center, Beijing
- 4China Pituitary Adenoma Specialist Council, Beijing; and
| | - Wenbin Ma
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 3China Pituitary Disease Registry Center, Beijing
- 4China Pituitary Adenoma Specialist Council, Beijing; and
| | - Bing Xing
- 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 2Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
- 3China Pituitary Disease Registry Center, Beijing
- 4China Pituitary Adenoma Specialist Council, Beijing; and
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Neidert MC, Zeitlberger AM, Leske H, Tschopp O, Sze L, Zwimpfer C, Wiesli P, Bellut D, Bernays RL, Rushing EJ, Schmid C. Association of pre- and postoperative αKlotho levels with long-term remission after pituitary surgery for acromegaly. Sci Rep 2022; 12:14765. [PMID: 36042253 PMCID: PMC9428163 DOI: 10.1038/s41598-022-19078-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 08/24/2022] [Indexed: 11/13/2022] Open
Abstract
Soluble αKlotho (sKl) is a disease-specific biomarker that is elevated in patients with acromegaly and declines after surgery for pituitary adenoma. Approximately 25% of patients do not achieve remission after surgery, therefore a risk stratification for patients early in the course of their disease may allow for the identification of patients requiring adjuvant treatment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have been assessed as biomarker for disease activity, however the value of sKl as a predictive biomarker of surgical success has not been evaluated yet. In this study, we measured serum biomarkers before and after transsphenoidal pituitary surgery in 55 treatment-naïve patients. Based on biochemical findings at follow-up (7–16 years), we divided patients into three groups: (A) long-term cure (defined by normal IGF-1 and random low GH (< 1 μg/l) or a suppressed GH nadir (< 0.4/μg/l) on oral glucose testing); (B) initial remission with later disease activity; (C) persistent clinical and/or biochemical disease activity. sKl levels positively related to GH, IGF-1 levels and tumor volume. Interestingly, there was a statistically significant difference in pre- and postoperative levels of sKl between the long-term cure group and the group with persistent disease activity. This study provides first evidence that sKl may serve as an additional marker for surgical success, decreasing substantially in all patients with initial clinical remission while remaining high after surgery in patients with persistent disease activity.
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Affiliation(s)
- Marian Christoph Neidert
- Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland. .,Department of Neurosurgery, Kantonsspital St.Gallen, Rohrschacher Strasse 95, 9007, St. Gallen, Switzerland.
| | - Anna Maria Zeitlberger
- Department of Neurosurgery, Kantonsspital St.Gallen, Rohrschacher Strasse 95, 9007, St. Gallen, Switzerland
| | - Henning Leske
- Department of Neuropathology, University Hospital Zurich, Zurich, Switzerland.,Department of Pathology, Oslo University Hospital, Oslo, Norway.,University of Oslo (UiO), Oslo, Norway
| | - Oliver Tschopp
- Division of Endocrinology and Diabetes, University Hospital Zurich, Zurich, Switzerland
| | - Lisa Sze
- Division of Endocrinology and Diabetes, Kantonsspital Winterthur, Winterthur, Switzerland
| | - Cornelia Zwimpfer
- Division of Endocrinology and Diabetes, University Hospital Zurich, Zurich, Switzerland
| | - Peter Wiesli
- Department of Internal Medicine, Kantonsspital Frauenfeld, Frauenfeld, Switzerland
| | - David Bellut
- Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland
| | | | | | - Christoph Schmid
- Division of Endocrinology and Diabetes, University Hospital Zurich, Zurich, Switzerland
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30
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Chhabra R, Kumar A, Virk RS, Dutta P, Ahuja C, Mohanty M, Dhandapani S. Outcomes in Pituitary Adenoma Causing Acromegaly Following Endoscopic Endonasal Transsphenoidal Surgery. J Neurosci Rural Pract 2022. [DOI: 10.1055/s-0042-1751226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
Abstract
Abstract
Objectives The objective of this study was the analysis of outcomes after endoscopic endonasal transsphenoidal surgery (EETSS) in acromegaly in terms of surgical complications, clinical improvement, endocrinological remission, achievement of prognostically critical growth hormone (GH) level, and requirement of additional treatment.
Materials and Methods The study included 28 acromegaly patients, who underwent EETSS. 2010 consensus criterion was used for defining remission. Assessment of prognostically critical GH level (random value less than 2.5 ng/mL), the extent of resection, and additional treatment was done at postoperative week (POW) 12.
Results All adenomas were macroadenomas, with the mean volume of 16.34 cm3 (range, 0.4–99 cm3). Most adenomas had high-grade extensions. Most common suprasellar, infrasellar, anterior, and posterior extension grades were 3 (n = 13), 1(n = 16), 1(n = 14), and 0 (n = 20), respectively. Knosp grade 3 was common on both sides (right, n = 9 and left, n = 8). One patient had already been operated on with EETSS, 1.5 years back from current surgery. Sixteen patients were on hormonal support, preoperatively. Four patients died during follow-up. Postoperative common complications were diabetes insipidus (n = 18), cerebrospinal fluid rhinorrhea (n = 10), surgical site hematoma (n = 3), meningitis (n = 3), hydrocephalus (n = 2), and syndrome of inappropriate antidiuretic hormone (n = 1). The mean hospital stay was 11.62 days, and 12.17 months was the mean follow-up period. At 12 POW, no improvement was seen in body enlargement and visual complaints, but all other complaints improved significantly except perspiration. Adenomas were decreased in all extensions except posterior, and mean adenoma volume was reduced from 16.34 to 2.92 cm3 after surgery. Subtotal resection (STR, n = 10), near-total resection (NTR, n = 7), gross-total resection (GTR, n = 5), and partial resection (PR, n = 2) were achieved. Endocrinological remission and prognostically critical GH levels were attained in 29.17% (n = 7) and 66.67% (n = 16), respectively. NTR, GTR, STR, and PR were associated with 57.14, 40, 10, and 0% endocrinological remission, respectively. Additional treatment was required in a total of 17 patients: 3 GTR, 9 STR, 3 NTR, and 2 PR patients. Ten patients were treated with gamma knife radiosurgery along with medical treatment and seven with medical treatment alone.
Conclusion A successful EETSS can reduce adenoma volume to achieve clinical improvement, endocrinological remission, and prognostically critical GH level with some complications related to surgery. Preoperative larger volume and higher extension grades affect these outcomes adversely.
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Affiliation(s)
- Rajesh Chhabra
- Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashwani Kumar
- Department of Neurosurgery, Government Medical College and Hospital, Chandigarh, India
| | - R S Virk
- Department of Otorhinolaryngology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pinaki Dutta
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Chirag Ahuja
- Department of Neuroradiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Manju Mohanty
- Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sivashanmugam Dhandapani
- Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Sulu C, Bektaş AB, Şahin S, Durcan E, Kara Z, Demir AN, Özkaya HM, Tanrıöver N, Çomunoğlu N, Kızılkılıç O, Gazioğlu N, Gönen M, Kadıoğlu P. Machine learning as a clinical decision support tool for patients with acromegaly. Pituitary 2022; 25:486-495. [PMID: 35435565 DOI: 10.1007/s11102-022-01216-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/10/2022] [Indexed: 10/18/2022]
Abstract
OBJECTIVE To develop machine learning (ML) models that predict postoperative remission, remission at last visit, and resistance to somatostatin receptor ligands (SRL) in patients with acromegaly and to determine the clinical features associated with the prognosis. METHODS We studied outcomes using the area under the receiver operating characteristics (AUROC) values, which were reported as the performance metric. To determine the importance of each feature and easy interpretation, Shapley Additive explanations (SHAP) values, which help explain the outputs of ML models, are used. RESULTS One-hundred fifty-two patients with acromegaly were included in the final analysis. The mean AUROC values resulting from 100 independent replications were 0.728 for postoperative 3 months remission status classification, 0.879 for remission at last visit classification, and 0.753 for SRL resistance status classification. Extreme gradient boosting model demonstrated that preoperative growth hormone (GH) level, age at operation, and preoperative tumor size were the most important predictors for early remission; resistance to SRL and preoperative tumor size represented the most important predictors of remission at last visit, and postoperative 3-month insulin-like growth factor 1 (IGF1) and GH levels (random and nadir) together with the sparsely granulated somatotroph adenoma subtype served as the most important predictors of SRL resistance. CONCLUSIONS ML models may serve as valuable tools in the prediction of remission and SRL resistance.
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Affiliation(s)
- Cem Sulu
- Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes, Cerrahpasa Medical School, Istanbul University-Cerrahpaşa, Kocamustafapaşa Street No:53, 34098 Fatih, Istanbul, Turkey
| | - Ayyüce Begüm Bektaş
- Graduate School of Sciences and Engineering, Koç University, Istanbul, Turkey
| | - Serdar Şahin
- Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes, Cerrahpasa Medical School, Istanbul University-Cerrahpaşa, Kocamustafapaşa Street No:53, 34098 Fatih, Istanbul, Turkey
| | - Emre Durcan
- Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes, Cerrahpasa Medical School, Istanbul University-Cerrahpaşa, Kocamustafapaşa Street No:53, 34098 Fatih, Istanbul, Turkey
| | - Zehra Kara
- Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes, Cerrahpasa Medical School, Istanbul University-Cerrahpaşa, Kocamustafapaşa Street No:53, 34098 Fatih, Istanbul, Turkey
| | - Ahmet Numan Demir
- Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes, Cerrahpasa Medical School, Istanbul University-Cerrahpaşa, Kocamustafapaşa Street No:53, 34098 Fatih, Istanbul, Turkey
| | - Hande Mefkure Özkaya
- Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes, Cerrahpasa Medical School, Istanbul University-Cerrahpaşa, Kocamustafapaşa Street No:53, 34098 Fatih, Istanbul, Turkey
- Pituitary Center, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Necmettin Tanrıöver
- Pituitary Center, Istanbul University-Cerrahpasa, Istanbul, Turkey
- Department of Neurosurgery, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Nil Çomunoğlu
- Department of Medical Pathology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Osman Kızılkılıç
- Pituitary Center, Istanbul University-Cerrahpasa, Istanbul, Turkey
- Department of Radiology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Nurperi Gazioğlu
- Pituitary Center, Istanbul University-Cerrahpasa, Istanbul, Turkey
- Department of Neurosurgery, Istinye University, Istanbul, Turkey
| | - Mehmet Gönen
- Department of Industrial Engineering, College of Engineering, Koç University, Istanbul, Turkey
- School of Medicine, Koç University, Istanbul, Turkey
| | - Pınar Kadıoğlu
- Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes, Cerrahpasa Medical School, Istanbul University-Cerrahpaşa, Kocamustafapaşa Street No:53, 34098 Fatih, Istanbul, Turkey.
- Pituitary Center, Istanbul University-Cerrahpasa, Istanbul, Turkey.
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Vergeer RA, Theunissen REP, van Elk T, Schmidt I, Postma MR, Tamasi K, van Dijk JMC, Kuijlen JMA. Fluorescence-guided detection of pituitary neuroendocrine tumor (PitNET) tissue during endoscopic transsphenoidal surgery available agents, their potential, and technical aspects. Rev Endocr Metab Disord 2022; 23:647-657. [PMID: 35344185 PMCID: PMC9156450 DOI: 10.1007/s11154-022-09718-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/03/2022] [Indexed: 10/29/2022]
Abstract
Differentiation of pituitary neuroendocrine tumor (PitNET) tissue from surrounding normal tissue during surgery is challenging. A number of fluorescent agents is available for visualization of tissue discrepancy, with the potential of improving total tumor resection. This review evaluates the availability, clinical and technical applicability of the various fluorescent agents within the field of pituitary surgery. According to PRISMA guidelines, a systematic review was performed to identify reports describing results of in vivo application of fluorescent agents. In this review, 15 publications were included. Sodium Fluorescein (FNa) was considered in two studies. The first study reported noticeable fluorescence in adenoma tissue, the second demonstrated the strongest fluorescence in non-functioning pituitary adenomas. 5-Aminolevulinic acid (5-ALA) was investigated in three studies. One study compared laser-based optical biopsy system (OBS) with photo-diagnostic filter (PD) and found that the OBS was able to detect all microadenomas, even when MRI was negative. The second study retrospectively analyzed twelve pituitary adenomas and found only one positive for fluorescence. The third investigated fifteen pituitary adenomas of which one displayed vague fluorescence. Indocyanine green (ICG) was researched in four studies with variable results. Second-Window ICG yielded no significant difference between functioning and non-functioning adenomas in one study, while a second study displayed 4 times higher fluorescence in tumor tissue than in normal tissue. In three studies, OTL38 showed potential in non-functioning pituitary adenomas. At present, evidence for fluorescent agents to benefit total resection of PitNETs is lacking. OTL38 can potentially serve as a selective fluorescent agent in non-functioning pituitary adenomas in the near future.
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Affiliation(s)
- Rob A Vergeer
- Department of Neurosurgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
| | - Robin E P Theunissen
- Department of Neurosurgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Theodora van Elk
- Department of Neurosurgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Iris Schmidt
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Mark R Postma
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Katalin Tamasi
- Department of Neurosurgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - J Marc C van Dijk
- Department of Neurosurgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Jos M A Kuijlen
- Department of Neurosurgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Kizilgul M, Duger H, Nasiroglu NI, Sencar E, Hepsen S, Akhanli P, Berker D, Cakal E, Bostan H, Ucan B. Efficacy of cabergoline add-on therapy in patients with acromegaly resistance to somatostatin analogs treatment and the review of literature. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2022; 66:278-285. [PMID: 35612842 PMCID: PMC9832853 DOI: 10.20945/2359-3997000000481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 03/02/2022] [Indexed: 11/23/2022]
Abstract
Objective It is reported that adding cabergoline to somatostatin analog (SSA) normalizes IGF-1 levels approximately in one-third of patients with acromegaly. We investigated the effect of combination therapy and potential predictors of response in patients with acromegaly who do not respond to SSA therapy alone. Methods Fifty acromegaly patients (M/F 23/27, mean age 50.88 ± 12.34 years) were divided into two groups as the active and control groups in this connection. Before and after treatment, we not only evaluated serum GH and IGF-1 levels and tumor size but also analyzed the factors relevant to the effect of the combined therapy. Results Adding cabergoline to SSA treatment led to IGF-1 normalization in 42% (21/50) of patients. Mean GH levels decreased from 2.64 ± 1.79 to 1.34 ± 0.99 ng/mL (p < .0001) and IGF-1 levels decreased from 432.92 ± 155.61 to 292.52 ± 126.15 ng/mL (p < .0001). GH and IGF-1 reduction in percent (%) were significantly higher in the controlled group (63% to 40%, p = 0.023 and 45% to 19%, p = 0.0001). Moreover, tumor size decrease was significantly higher in controlled group (-3.6 cm to -1.66 cm, p = 0.005). Conclusion According to the results of our study, the addition of cabergoline to SSA normalized IGF-1 levels in a considerable amount of acromegaly patients with a moderately elevated IGF-1 level, regardless of serum PRL levels. Besides, cabergoline treatment was also influential in patients with higher IGF-1 levels despite a lower remission rate.
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Affiliation(s)
- Muhammed Kizilgul
- University of Health Sciences, Diskapi Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey, ;
| | - Hakan Duger
- University of Health Sciences, Diskapi Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - Narin Imga Nasiroglu
- University of Health Sciences, Numune Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - Erkam Sencar
- University of Health Sciences, Diskapi Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - Sema Hepsen
- University of Health Sciences, Diskapi Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - Pinar Akhanli
- University of Health Sciences, Diskapi Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - Dilek Berker
- University of Health Sciences, Numune Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - Erman Cakal
- University of Health Sciences, Diskapi Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - Hayri Bostan
- University of Health Sciences, Diskapi Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - Bekir Ucan
- University of Health Sciences, Diskapi Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
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Kelly AP, Greenfield JP, Dobri GA, Schwartz TH. Pediatric pituitary adenomas are more aggressive, more likely to be hormone producing and are more difficult to cure than adult pituitary adenomas: case series and systematic literature review. Childs Nerv Syst 2022; 38:729-738. [PMID: 35048170 DOI: 10.1007/s00381-022-05445-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 01/06/2022] [Indexed: 11/29/2022]
Abstract
PURPOSE Pediatric pituitary adenomas (pPAs) are uncommon. Thus, their presentation and outcomes after treatment are less well-understood than those of pituitary adenomas in adulthood (aPAs). METHODS A retrospective chart review was conducted for all patients who underwent endoscopic endonasal transsphenoidal surgery (EETS) for pPA at NewYork-Presbyterian Hospital/Weill Cornell Medicine (NYP/WCM) from 2005-2020. Eleven patients were identified, and information pertaining to age, sex, adenoma characteristics, procedural details, and outcomes was reviewed. A systematic review of the literature was also performed to compare outcomes of EETS versus microscopic endonasal transsphenoidal surgery (METS) for pPA. RESULTS From 2005-2020, 11 patients underwent EETS for pPA at NYP/WCM. Mean age at operation was 14.9 ± 2.7 years, and 5 patients (45.5%) were male. 10 adenomas (90.9%) were hormone-producing. Of the functional adenomas, 8 (80.0%) were PRL-secreting and 2 (20.0%) were GH-secreting. Maximum adenoma diameter (MAD) ranged from 1.2-5.1 cm, with a median of 1.55 cm. Cavernous sinus invasion (CSI) occurred in 2 patients with macroprolactinoma. Gross total resection (GTR) was achieved in 10 (90.9%). Biochemical remission occurred in 5/10 (50.0%). Post-operative complications were documented in 8 cases (72.7%) and included diabetes insipidus, hypopituitarism, sinusitis, weight gain, cerebrospinal fluid leak, meningitis, and hydrocephalus. Systematic literature review of 105 microscopic and 175 endoscopic cases revealed high frequency of hormone-producing tumors (83.6%) and similar rates of GTR (82.4% vs 85.1%) and biochemical cure (75.8% vs 64.3%). CONCLUSIONS pPAs are more likely to be hormone producing and may be more aggressive and difficult to cure than aPAs. EETS is an effective treatment, although complication rates may be higher than in adult populations.
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Affiliation(s)
- Alexander P Kelly
- Weill Cornell Medical College, Weill Cornell Medicine, New York, NY, USA
| | - Jeffrey P Greenfield
- Department of Neurological Surgery, Weill Cornell Medicine/NewYork-Presbyterian Hospital, New York, NY, USA
| | - Georgiana A Dobri
- Department of Neurological Surgery, Weill Cornell Medicine/NewYork-Presbyterian Hospital, New York, NY, USA
| | - Theodore H Schwartz
- Department of Neurological Surgery, Weill Cornell Medicine/NewYork-Presbyterian Hospital, New York, NY, USA.
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Donegan D, Algeciras-Schimnich A, Ashrafzadeh-Kian S, Erickson D. Insulin-Like Growth Factor 1 in the Early Postoperative Assessment of Acromegaly. Am J Clin Pathol 2022; 157:595-601. [PMID: 34665848 DOI: 10.1093/ajcp/aqab168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 08/31/2021] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES Assessment of surgical outcome in acromegaly is typically recommended at 3 to 6 months following surgery. The purpose of this study was to determine if insulin-like growth factor 1 (IGF-1) concentrations at 6 weeks were equally predictive of surgical outcomes compared with IGF-1 concentrations at 3 to 6 months postoperatively applying newer IGF-1 assays. METHODS Retrospective review of patients with newly diagnosed acromegaly who had surgery between 2013 and 2020 and had postoperative IGF-1 measured by 6 weeks and 3 to 6 months. RESULTS At 6 weeks, 20 (35%) of the total 57 had normal IGF-1 and became abnormal in 1 at 3 to 6 months, whereas 37 (65%) of 57 had abnormal IGF-1 concentrations at 6 weeks, which normalized in 1 patient by 3 to 6 months. In patients who changed clinical status, IGF-1 at 6 weeks was within ±0.1-fold of normal. Although a difference was seen between median IGF-1 concentrations (286 vs 267 ng/mL, P = .009) at 6 weeks and 3 to 6 months, the mean reduction was small (-19.9 ng/mL). CONCLUSIONS Compared with 3 to 6 months, use of IGF-1 at 6 weeks was associated with a change in clinical status in 3.5% of patients. Therefore, in most patients, IGF-1 at 6 weeks can be used to assess clinical outcome via newer assays.
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Affiliation(s)
- Diane Donegan
- Department of Endocrinology Diabetes and Metabolism, Indiana University School of Medicine, Indianapolis, IN, USA
- Department of Endocrinology, Diabetes and Metabolism, Mayo College of Medicine, Rochester, MN, USA
| | | | | | - Dana Erickson
- Department of Endocrinology, Diabetes and Metabolism, Mayo College of Medicine, Rochester, MN, USA
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Giantini-Larsen AM, Uribe-Cardenas R, Juthani RG. Acromegaly. Otolaryngol Clin North Am 2022; 55:331-341. [DOI: 10.1016/j.otc.2021.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Ganz JC. Pituitary adenomas. PROGRESS IN BRAIN RESEARCH 2022; 268:191-215. [PMID: 35074080 DOI: 10.1016/bs.pbr.2021.10.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Pituitary adenomas produce a complex collection of disorders. Some are incidental findings. Some distort local anatomical structures which can lead to disorders of vision or hormone production. Some produce excesses of hormones which can be either life threatening or clinically distressing. The management requires the expertise of a variety of experts who plan together. No single treatment is universally successful in controlling these conditions. Medical, biochemical, surgical and radiosurgical management can all have parts to play. Coordinate co-operation between specialists will provide patients with the best available treatment.
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Affiliation(s)
- Jeremy C Ganz
- Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway.
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Ting Lim DS, Fleseriu M. Personalized Medical Treatment in Patients with Acromegaly: A Review. Endocr Pract 2022; 28:321-332. [PMID: 35032649 DOI: 10.1016/j.eprac.2021.12.017] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 12/22/2021] [Accepted: 12/23/2021] [Indexed: 12/23/2022]
Abstract
Acromegaly is associated with significant morbidity and mortality if not appropriately treated. In addition to insulin-like growth factor 1 (IGF-1) and growth hormone (GH) normalization, and tumor shrinkage, treatment goals include symptom relief, managing complications and improving quality of life. Surgical resection is a first-line treatment in most patients, with few being pretreated pre-operatively with medications. Somatostatin receptor ligands (SRLs), injectable and more recently oral capsules, have been the cornerstone of first-line medical therapy for persistent disease. However, several factors, including sparsely granulated adenomas, absent/low somatostatin receptor (SSTR2) status, imaging T2-hyperintensity, young age and aryl hydrocarbon receptor interacting protein mutations could predict first-generation SRL resistance. Patients with these characteristics may be better candidates for the GH receptor antagonist, pegvisomant, or in cases of large tumors the second-generation SRL, pasireotide. Combination therapy should be further pursued in patients who remain biochemically uncontrolled or have high remnant tumor after monotherapy. An efficacious and cost-effective pegvisomant dose-sparing effect of SRLs when used in combination has been demonstrated. With such a wide array of medical treatment options, it is increasingly important to tailor treatment to patients' unique characteristics as well as preferences, with a goal of personalizing management to achieve high quality outcomes.
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Affiliation(s)
| | - Maria Fleseriu
- Pituitary Center, and Departments of Medicine (Endocrinology, Diabetes and Clinical Nutrition) and Neurological Surgery, Oregon Health & Science University, Portland, Oregon, USA.
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Tomasik A, Stelmachowska-Banaś M, Maksymowicz M, Czajka-Oraniec I, Raczkiewicz D, Zieliński G, Kunicki J, Zgliczyński W. Clinical, hormonal and pathomorphological markers of somatotroph pituitary neuroendocrine tumors predicting the treatment outcome in acromegaly. Front Endocrinol (Lausanne) 2022; 13:957301. [PMID: 36187106 PMCID: PMC9523725 DOI: 10.3389/fendo.2022.957301] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 08/29/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Transsphenoidal adenomectomy (TSS) of somatotroph pituitary neuroendocrine tumor (PitNET) is the first-line treatment of acromegaly. Pharmacological treatment is recommended if surgery is contraindicated or did not lead to disease remission. The choice of treatment best fitting each patient should be based on thorough investigation of patients' characteristics. The current analysis attempts to create a tool for personalized treatment planning. AIM This study aimed to assess whether clinical, biochemical, imaging and pathological characteristics can predict surgical remission and response to first-generation somatostatin receptor ligands (SRLs) and pasireotide-LAR in acromegaly. PATIENTS AND METHODS A retrospective study of 153 acromegaly patients, treated in the Department of Endocrinology in Bielanski Hospital in Warsaw, Poland was performed. Data on demographics, hormonal and imaging results, pathological evaluation, and treatment outcome was extracted from the Polish Acromegaly Registry collecting information from 11 endocrinology centers in Poland and analyzed. RESULTS Patients with surgical remission had lower GH and IGF-1 concentrations at diagnosis (median GH 5.5 µg/L [IQR: 3.1-16.0] vs. 19.9 µg/L [IQR: 9.8-42.4], p=<0.001 and mean IGF-1 3.1xULN ± SD=1.2 vs. 3.7xULN ± SD=1.2, p=0.007, respectively) and smaller tumors (median 12.5mm [IQR: 9-19] vs. 23mm [IQR: 18-30], p<0.001). These tumors were more often densely granulated (DG) (73.2% vs. 40.0%, p=0.001) with positive staining for alpha-subunit (α-SU) (58.3% vs. 35.5%, p=0.021) and lower Ki-67 index (p=0.002). Patients responding well to SRLs were more often male (55.6% vs 44.4%, p=0.026), presented lower GH concentration (median GH 17.2 µg/L [IQR: 6.2-29.0] vs. 23.8 µg/L [IQR: 11.2-49.5], p=0.048) and had more often DG tumors (63.0% vs. 14.3%, p<0.001). No significant differences between good and poor-response to pasireotide-LAR groups were found. In multivariate logistic regression analysis fasting GH concentration <8.63 µg/L, maximal tumor diameter <15.5mm, normoprolactinemia and DG tumor turned out to be independent predictors of surgical remission (OR=0.92, p=0.026; OR=0.87, p=0.069, OR=3.86, p=0.096 and OR=3.05, p=0.181, respectively). Fasting GH concentration <36.6 µg/L and DG tumor turned out to be independent predictors of good response to first-generation SRLs (OR=0.96, p=0.06 and OR=10.68, p=0.002, respectively). CONCLUSIONS Younger age at diagnosis, male sex, lower GH, IGF-1 and PRL concentrations, smaller tumor size at diagnosis as well as positive α-SU staining, lower Ki-67 index and DG tumors predicted better treatment outcome in acromegaly patients.
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Affiliation(s)
- Agnieszka Tomasik
- Department of Endocrinology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Maria Stelmachowska-Banaś
- Department of Endocrinology, Centre of Postgraduate Medical Education, Warsaw, Poland
- *Correspondence: Maria Stelmachowska-Banaś,
| | - Maria Maksymowicz
- Department of Cancer Pathomorphology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | | | - Dorota Raczkiewicz
- Department of Medical Statistics, School of Public Health, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Grzegorz Zieliński
- Department of Neurosurgery, Military Institute of Medicine, Warsaw, Poland
| | - Jacek Kunicki
- Department of Neurosurgery, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Wojciech Zgliczyński
- Department of Endocrinology, Centre of Postgraduate Medical Education, Warsaw, Poland
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Cambria V, Beccuti G, Prencipe N, Penner F, Gasco V, Gatti F, Romanisio M, Caputo M, Ghigo E, Zenga F, Grottoli S. First but not second postoperative day growth hormone assessments as early predictive tests for long-term acromegaly persistence. J Endocrinol Invest 2021; 44:2427-2433. [PMID: 33837920 PMCID: PMC8502138 DOI: 10.1007/s40618-021-01553-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 03/10/2021] [Indexed: 10/24/2022]
Abstract
PURPOSE Postoperative assessment of acromegaly activity is typically performed at least 3 months after neurosurgery (NS). Few studies have evaluated the use of early postoperative growth hormone (GH) levels as a test to predict short- and long-term remission of acromegaly. Our objective was to evaluate the diagnostic performance of serum random GH on a postoperative day one (D1-rGH) and two (D2-rGH), particularly in predicting long-term disease persistence. MATERIALS AND METHODS Forty-one subjects with acromegaly who were undergoing NS were enrolled (mean age ± SD 47.4 ± 13.1 years at diagnosis; women 54%; macroadenomas 71%). The final assessment of disease activity was performed one year after NS. ROC curves were used to evaluate the diagnostic performance of D1-rGH and D2-rGH. RESULTS After a 1-year follow-up, the overall remission rate was 55%. ROC analysis identified an optimal D1-rGH cut-off value of 2.1 ng/mL for diagnosing long-term disease persistence (55.6% SE; 90.9% SP). The cut-off point became 2.5 ng/mL after maximizing specificity for disease persistence (yielding a 100% positive predictive value) and 0.3 ng/mL after maximizing sensitivity for disease remission. The optimal D2-rGH cut-off value was 0.6 ng/mL (81.8% SE; 50% SP); the cut-off point became 2.9 ng/mL after maximizing specificity and 0.1 ng/mL after maximizing sensitivity, with no clinical utility. CONCLUSIONS D1-rGH could be a highly specific test for the early diagnosis of long-term acromegaly persistence, which is predicted by a value > 2.5 ng/mL with a great degree of certainty. The diagnostic performance of D2-rGH was insufficient. Further research is required to validate these preliminary results prior to modifying the postoperative management of acromegaly.
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Affiliation(s)
- V. Cambria
- Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy
| | - G. Beccuti
- Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy
| | - N. Prencipe
- Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy
| | - F. Penner
- Division of Neurosurgery, Department of Neurosciences “Rita Levi Montalcini”, University of Turin, Turin, Italy
| | - V. Gasco
- Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy
| | - F. Gatti
- Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy
| | - M. Romanisio
- Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy
| | - M. Caputo
- Division of Endocrinology, Department of Translational Medicine, University of Eastern Piedmont “Amedeo Avogadro”, Novara, Italy
| | - E. Ghigo
- Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy
| | - F. Zenga
- Division of Endocrinology, Department of Translational Medicine, University of Eastern Piedmont “Amedeo Avogadro”, Novara, Italy
| | - S. Grottoli
- Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy
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Asa SL, Mete O, Cusimano MD, McCutcheon IE, Perry A, Yamada S, Nishioka H, Casar-Borota O, Uccella S, La Rosa S, Grossman AB, Ezzat S. Pituitary neuroendocrine tumors: a model for neuroendocrine tumor classification. Mod Pathol 2021; 34:1634-1650. [PMID: 34017065 DOI: 10.1038/s41379-021-00820-y] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 03/25/2021] [Accepted: 03/25/2021] [Indexed: 02/06/2023]
Abstract
The classification of adenohypophysial neoplasms as "pituitary neuroendocrine tumors" (PitNETs) was proposed in 2017 to reflect their characteristics as epithelial neuroendocrine neoplasms with a spectrum of clinical behaviors ranging from small indolent lesions to large, locally invasive, unresectable tumors. Tumor growth and hormone hypersecretion cause significant morbidity and mortality in a subset of patients. The proposal was endorsed by a WHO working group that sought to provide a unified approach to neuroendocrine neoplasia in all body sites. We review the features that are characteristic of neuroendocrine cells, the epidemiology and prognosis of these tumors, as well as further refinements in terms used for other pituitary tumors to ensure consistency with the WHO framework. The intense study of PitNETs has provided information about the importance of cellular differentiation in tumor prognosis as a model for neuroendocrine tumors in different locations.
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Affiliation(s)
- Sylvia L Asa
- Department of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA.
| | - Ozgur Mete
- Department of Pathology, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Michael D Cusimano
- Department of Neurosurgery, Saint Michael's Hospital, University of Toronto, Toronto, ON, Canada
| | - Ian E McCutcheon
- Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Arie Perry
- Department of Pathology, University of California San Francisco, San Francisco, CA, USA
| | - Shozo Yamada
- Hypothalamic and Pituitary Center, Moriyama Neurological Center Hospital, Tokyo, Japan
| | - Hiroshi Nishioka
- Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Tokyo, Japan
| | - Olivera Casar-Borota
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
| | - Silvia Uccella
- Department of Pathology, University of Insubria, Varese, Italy
| | - Stefano La Rosa
- Institute of Pathology, University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Ashley B Grossman
- Department of Endocrinology, University of Oxford, London, UK.,Royal Free London, London, UK.,Barts and the London School of Medicine, London, UK.,London Clinic Centre for Endocrinology, London, UK
| | - Shereen Ezzat
- Department of Medicine, University Health Network, University of Toronto, Toronto, ON, Canada
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Yang J, Wen G, Tang C, Zhong C, Zhu J, Cong Z, Ma C. Evaluation of Surgical Freedom for One-and-a-Half Nostril, Mononostril, and Binostril Endoscopic Endonasal Transsphenoidal Approaches. J Neurol Surg B Skull Base 2021; 82:383-391. [PMID: 35573921 DOI: 10.1055/s-0040-1701526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 12/11/2019] [Indexed: 10/24/2022] Open
Abstract
Objective This article determines which of the one-and-a-half nostril, mononostril, and binostril endoscopic endonasal transsphenoidal approaches provide a superior manipulation during surgery. Methods The three approaches were orderly performed on 10 silicon-injected cadaveric heads to quantitatively assess surgical freedom and attack angle for sella. Measurements were determined with a standardized method under neuronavigation system using data of computed tomography. Results The one-and-a-half nostril endoscopic transsphenoidal approach (OETA) offered superior exposed area than that of the mononostril approach (META), and similar to that of the binostril approach (BETA). For surgical freedom at anatomic targets, the OETA showed greater surgical flexibility at pituitary center, the right medial optic carotid recess (R-mOCR), the left mOCR, the medial intersection of the right cavernous internal carotid artery, and extension line of upper margin of the clivus (R-mICC) than those of the META, and similar to those of the BETA. For sagittal angle of attack to the R-mOCR, R-mICC, and L-mOCR, the OETA can provide better angular freedom for surgeon than that of the META, and similar to that of the BETA. The OETA had the same axial attack to the pituitary center with the BETA. The OETA and the META had limited surgical freedom at L-mICC, and both inferior to the BETA. Conclusion The OETA has similar exposed area, surgical freedom, and attack angle for most anatomic targets to the BETA without resecting contralateral nasal septal mucosa, and obviously superior to the META.
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Affiliation(s)
- Jin Yang
- Jinling Hospital, Nanjing Medical University, Nanjing, People's Republic of China
| | - Guodao Wen
- Department of Neurosurgery, Tungwah Hospital of Sun Yat-Sen University, Dongguan, People's Republic of China
| | - Chao Tang
- Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, People's Republic of China
| | - Chunyu Zhong
- Jinling Hospital, Nanjing Medical University, Nanjing, People's Republic of China
| | - Junhao Zhu
- Jinling Hospital, Nanjing Medical University, Nanjing, People's Republic of China
| | - Zixiang Cong
- Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, People's Republic of China
| | - Chiyuan Ma
- Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, People's Republic of China
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Torres A, Sanmillan JL, Lau R, Gabarros A. Final Outcome in Growth Hormone-Secreting Adenomas After Combination of Maximal Tumor Resection and Medical Treatment. World Neurosurg 2021; 154:e292-e301. [PMID: 34252630 DOI: 10.1016/j.wneu.2021.07.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 07/04/2021] [Accepted: 07/05/2021] [Indexed: 01/19/2023]
Abstract
OBJECTIVE Gross total resection (GTR) is not always possible in acromegalic patients, especially in patients with invasive growth hormone-secreting adenomas. We analyzed the biochemical remission outcome in relation to extent of tumor resection and effectiveness of medical treatment in cases of remnant tumor. METHODS Retrospective analysis was performed of acromegalic patients operated on between 2002 and 2017. Preoperative imaging, tumor invasiveness, extent of resection, and biochemical remission were collected. Patients with tumor remnant not amenable to second surgery began medical treatment. The relationship between pituitary adenoma remnant volume and final biochemical outcome was analyzed. RESULTS Of 120 acromegalic patients operated on, 82 underwent transsphenoidal microsurgery and 38 underwent endonasal endoscopic approach. GTR was achieved in 72 cases (60%); subtotal resection (STR), 21 (17.5%) cases; and partial resection, 27 (22.5%) cases. There was a nonsignificant higher rate of GTR/STR in patients who underwent endonasal endoscopic approach. However, a significantly higher remission rate (89.45% vs. 67.1%) was achieved in these patients (P < 0.01). Greater tumor volume and invasiveness were associated with a lower remission (P < 0.05). Patients with tumor remnant who achieved biochemical remission with added medical therapy had a significantly smaller tumor volume (P < 0.001). CONCLUSIONS The more aggressive surgical resection is, the greater the chance of attaining final biochemical remission, whether or not GTR is achieved. Medical therapy effectiveness is enhanced in cases with STR. Invasive growth hormone-secreting macroadenomas that are not surgically amenable to total resection are best managed with a combination of safe STR and medical treatment.
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Affiliation(s)
- Alberto Torres
- Department of Neurological Surgery, Bellvitge University Hospital, Barcelona, Spain.
| | - Jose Luis Sanmillan
- Department of Neurological Surgery, Bellvitge University Hospital, Barcelona, Spain
| | - Ruth Lau
- Department of Neurological Surgery, Bellvitge University Hospital, Barcelona, Spain
| | - Andreu Gabarros
- Department of Neurological Surgery, Bellvitge University Hospital, Barcelona, Spain
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Cardinal T, Rutkowski MJ, Micko A, Shiroishi M, Jason Liu CS, Wrobel B, Carmichael J, Zada G. Impact of tumor characteristics and pre- and postoperative hormone levels on hormonal remission following endoscopic transsphenoidal surgery in patients with acromegaly. Neurosurg Focus 2021; 48:E10. [PMID: 32480366 DOI: 10.3171/2020.3.focus2080] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 03/31/2020] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Acromegaly is a disease of acral enlargement and elevated serum levels of insulin-like growth factor-1 (IGF-1) and growth hormone (GH), usually caused by a pituitary adenoma. A lack of consensus on factors that reliably predict outcomes in acromegalic patients following endoscopic endonasal transsphenoidal surgery (EETS) warrants additional investigation. METHODS The authors identified 52 patients with acromegaly who underwent an endoscopic endonasal approach (EEA) for resection of a GH-secreting pituitary adenoma. Preoperative and postoperative tumor and endocrinological characteristics such as tumor size, invasiveness, and GH/IGF-1 levels were evaluated as potential indicators of postoperative hormonal remission. Endocrinological remission was defined as postoperative IGF-1 levels at or below the age- and sex-normalized values. RESULTS The 52 patients had a mean age of 50.7 ± 13.4 years and a mean follow-up duration of 24.4 ± 19.1 months. Ten patients (19%) had microadenomas and 42 (81%) had macroadenomas. Five patients (9.6%) had giant adenomas. Forty-four tumors (85%) had extrasellar extension, with 40 (77%) exhibiting infrasellar invasion, 18 (35%) extending above the sella, and 7 (13%) invading the cavernous sinuses. Thirty-six patients (69%) underwent gross-total resection (GTR; mean maximal tumor diameter 1.47 cm), and 16 (31%) underwent subtotal resection (STR; mean maximal tumor diameter 2.74 cm). Invasive tumors were significantly larger, and Knosp scores were negatively correlated with GTR. Thirty-eight patients (73%) achieved hormonal remission after EEA resection alone, which increased to 87% with adjunctive medical therapy. Ninety percent of patients with microadenomas and 86% of patients with macroadenomas achieved hormonal remission. Preoperative IGF-1 and postoperative day 1 (POD1) GH levels were inversely correlated with hormonal remission. Postoperative CSF leakage occurred in 2 patients (4%), and none experienced vision loss, death, or injury to internal carotid arteries or cranial nerves. CONCLUSIONS Endoscopic transsphenoidal resection of GH-secreting pituitary adenomas is a safe and highly effective treatment for achieving hormonal remission and tumor control in up to 87% of patients with acromegaly when combined with postoperative medical therapy. Patients with lower preoperative IGF-1 and POD1 GH levels, with less invasive pituitary adenomas, and who undergo GTR are more likely to achieve postoperative biochemical remission.
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Affiliation(s)
- Tyler Cardinal
- 1Department of Neurosurgery, USC Pituitary Center, Keck School of Medicine of University of Southern California, Los Angeles, California
| | - Martin J Rutkowski
- 1Department of Neurosurgery, USC Pituitary Center, Keck School of Medicine of University of Southern California, Los Angeles, California
| | - Alexander Micko
- 1Department of Neurosurgery, USC Pituitary Center, Keck School of Medicine of University of Southern California, Los Angeles, California.,2Department of Neurosurgery, Medical University of Vienna, Austria
| | - Mark Shiroishi
- 3Department of Radiology, Division of Neuroradiology, Keck School of Medicine of University of Southern California
| | - Chia-Shang Jason Liu
- 3Department of Radiology, Division of Neuroradiology, Keck School of Medicine of University of Southern California
| | - Bozena Wrobel
- 5Department of Otolaryngology, Keck School of Medicine of University of Southern California, Los Angeles, California
| | - John Carmichael
- 1Department of Neurosurgery, USC Pituitary Center, Keck School of Medicine of University of Southern California, Los Angeles, California.,4Department of Medicine, Division of Endocrinology and Diabetes, Keck School of Medicine of University of Southern California; and
| | - Gabriel Zada
- 1Department of Neurosurgery, USC Pituitary Center, Keck School of Medicine of University of Southern California, Los Angeles, California
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Bashari WA, Senanayake R, Koulouri O, Gillett D, MacFarlane J, Powlson AS, Fernandez-Pombo A, Bano G, Martin AJ, Scoffings D, Cheow H, Mendichovszky I, Tysome J, Donnelly N, Santarius T, Kolias A, Mannion R, Gurnell M. PET-guided repeat transsphenoidal surgery for previously deemed unresectable lateral disease in acromegaly. Neurosurg Focus 2021; 48:E8. [PMID: 32480379 DOI: 10.3171/2020.3.focus2052] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Accepted: 03/03/2020] [Indexed: 11/06/2022]
Abstract
OBJECTIVE The object of this study was to determine if revision transsphenoidal surgery (TSS), guided by 11C-methionine PET/CT coregistered with volumetric MRI (Met-PET/MRCR), can lead to remission in patients with persistent acromegaly due to a postoperative lateral disease remnant. METHODS The authors identified 9 patients with persistent acromegaly following primary intervention (TSS ± medical therapy ± radiotherapy) in whom further surgery had initially been discounted because of equivocal MRI findings with suspected lateral sellar and/or parasellar disease (cases with clear Knosp grade 4 disease were excluded). All patients underwent Met-PET/MRCR. Scan findings were used by the pituitary multidisciplinary team to inform decision-making regarding repeat surgery. Revision TSS was performed with wide lateral exploration as guided by the PET findings. Endocrine reassessment was performed at 6-10 weeks after surgery, with longitudinal follow-up thereafter. RESULTS Met-PET/MRCR revealed focal tracer uptake in the lateral sellar and/or parasellar region(s) in all 9 patients, which correlated with sites of suspected residual tumor on volumetric MRI. At surgery, tumor was identified and resected in 5 patients, although histological analysis confirmed somatotroph tumor in only 4 cases. In the other 4 patients, no definite tumor was seen, but equivocal tissue was removed. Despite the uncertainty at surgery, all patients showed immediate significant improvements in clinical and biochemical parameters. In the 8 patients for whom long-term follow-up data were available, insulin-like growth factor 1 (IGF-1) was ≤ 1.2 times the upper limit of normal (ULN) in all subjects and ≤ 1 times the ULN in 6 subjects, and these findings have been maintained for up to 28 months (median 8 months, mean 13 months) with no requirement for adjunctive medical therapy or radiotherapy. No patient suffered any additional pituitary deficit or other complication of surgery. CONCLUSIONS This study provides proof of concept that Met-PET/MRCR can be helpful in the evaluation of residual lateral sellar/parasellar disease in persistent acromegaly and facilitate targeted revision TSS in a subgroup of patients.
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Affiliation(s)
- Waiel A Bashari
- 1Cambridge Endocrine Molecular Imaging Group.,2Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science; Departments of
| | - Russell Senanayake
- 1Cambridge Endocrine Molecular Imaging Group.,2Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science; Departments of
| | - Olympia Koulouri
- 1Cambridge Endocrine Molecular Imaging Group.,2Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science; Departments of
| | - Daniel Gillett
- 1Cambridge Endocrine Molecular Imaging Group.,3Nuclear Medicine
| | - James MacFarlane
- 1Cambridge Endocrine Molecular Imaging Group.,2Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science; Departments of
| | - Andrew S Powlson
- 1Cambridge Endocrine Molecular Imaging Group.,2Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science; Departments of
| | - Antia Fernandez-Pombo
- 1Cambridge Endocrine Molecular Imaging Group.,2Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science; Departments of
| | | | - Andrew J Martin
- 8Neurosurgery, St George's University Hospital, London, United Kingdom
| | | | - Heok Cheow
- 1Cambridge Endocrine Molecular Imaging Group.,3Nuclear Medicine.,4Radiology
| | | | - James Tysome
- 1Cambridge Endocrine Molecular Imaging Group.,5Otolaryngology, and
| | - Neil Donnelly
- 1Cambridge Endocrine Molecular Imaging Group.,5Otolaryngology, and
| | - Thomas Santarius
- 1Cambridge Endocrine Molecular Imaging Group.,6Neurosurgery, University of Cambridge and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Hills Road, Cambridge; and Departments of
| | - Angelos Kolias
- 1Cambridge Endocrine Molecular Imaging Group.,6Neurosurgery, University of Cambridge and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Hills Road, Cambridge; and Departments of
| | - Richard Mannion
- 1Cambridge Endocrine Molecular Imaging Group.,6Neurosurgery, University of Cambridge and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Hills Road, Cambridge; and Departments of
| | - Mark Gurnell
- 1Cambridge Endocrine Molecular Imaging Group.,2Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science; Departments of
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Expression of Transforming Growth Factor β1, Smad3, and Phospho-Smad3 in Somatotropinomas and Their Relationship to Tumor Behavior. World Neurosurg 2021; 153:e20-e27. [PMID: 34087455 DOI: 10.1016/j.wneu.2021.05.088] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 05/21/2021] [Accepted: 05/22/2021] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To investigate the role of transforming growth factor β1 (TGF-β1), Smad3, and phospho-Smad3 (p-Smad3) in the invasion of somatotropinomas. METHODS In total, 45 somatotropinomas were obtained from patients who underwent surgery for the first time between 2011 and 2015 at Beijing Tiantan Hospital. The expression of TGF-β1, Smad3, and p-Smad3 was examined by western blot, quantitative reverse transcription polymerase chain reaction, and immunohistochemistry in somatotropinomas, and factors correlated with tumor invasion were analyzed. RESULTS A total of 13 invasive somatotropinomas and 32 noninvasive somatotropinomas were enrolled in the study. TGF-β1 protein (P < 0.01) and mRNA (P < 0.01) levels were significantly less in the invasive somatotropinomas than noninvasive somatotropinomas. There was no significant difference in Smad3 protein level or Smad3 mRNA level between invasive somatotropinomas and noninvasive somatotropinomas. However, the p-Smad3 protein level was significantly less in the invasive somatotropinomas than noninvasive somatotropinomas (P < 0.01). Univariate analysis demonstrated that TGF-β1 (P < 0.01) and p-Smad3 scores (P < 0.01) were associated with invasion. In multivariate analysis, p-Smad3 scores remained a significantly independent predictor of invasion (odds ratio 0.897, 95% confidence interval 0.834-0.964, P < 0.05). CONCLUSIONS Low expression of p-Smad3 is correlated with invasion of somatotropinomas.
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Utility of intraoperative ultrasonography for resection of pituitary adenomas: a comparative retrospective study. Acta Neurochir (Wien) 2021; 163:1725-1734. [PMID: 33403430 DOI: 10.1007/s00701-020-04674-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 12/04/2020] [Indexed: 10/22/2022]
Abstract
BACKGROUND The evolution of pituitary surgery has made it a safe and effective form of treatment; however, risks of inadequate tumor resection, cerebrospinal fluid (CSF) leak, pituitary dysfunction, and vascular injury still exist. The use of intraoperative ultrasonography (IOUS) in pituitary surgery has been well described. Recent advancements in ultrasound technology have allowed for expanded utility as described here. METHODS A retrospective review was performed between January 2016 and December 2019. One hundred thirty-eight patients (mean age 53.7 years, 47% females) were identified undergoing transsphenoidal surgery for pituitary tumors. Thirty-four patients had IOUS performed using a side-firing ultrasound probe, while 104 did not. Data was analyzed for preoperative (demographics, clinical, and radiographic features), perioperative (blood loss, operative time), and postoperative (complications, length of stay, hormone remission, and extent of resection) outcomes. RESULTS There were no significant differences in patient age, gender, tumor volume, Knosp grade, and hormone-secreting status between the two groups. Patients treated using IOUS had significantly higher rates of gross total resection (79% vs. 44%, p = 0.0008), shorter operative times (74 vs. 146 min, p < 0.0001), lower blood loss (119 vs. 284 cc, p < 0.0001), and hospital stays (2.9 vs. 4.2 days, p = 0.001). Overall complication rates were lower in the IOUS group compared to standard pituitary surgery but did not reach significance. CONCLUSIONS Recent improvements in ultrasound technology have allowed for miniaturization of probes capable of delivering high-resolution images. The use of IOUS in transsphenoidal pituitary surgery may significantly increase rates of gross total resection, while decreasing blood loss, hospital LOS, and operative time.
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48
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Goyal-Honavar A, Sarkar S, Asha HS, Kapoor N, Thomas R, Balakrishnan R, Chacko G, Chacko AG. Impact of Experience on Outcomes After Endoscopic Transsphenoidal Surgery for Acromegaly. World Neurosurg 2021; 151:e1007-e1015. [PMID: 34023462 DOI: 10.1016/j.wneu.2021.05.030] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 05/10/2021] [Accepted: 05/11/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Acromegaly is a syndrome of metabolic alterations secondary to increased growth hormone levels from a somatotroph pituitary adenoma. A multidisciplinary approach beginning with surgery, followed by adjuvant radiation or medical therapy for residual disease, is considered standard of care. Several factors affect the likelihood of remission after surgery, but the impact of surgical experience on remission rates has not been adequately assessed. METHODS Retrospective review of 203 patients, divided into 2 eras (era 1, 102 patients; era 2, 101 patients) of patients who underwent transsphenoidal surgery for acromegaly by a single surgeon over 11 years, was performed, determining the effect of surgical experience on rates of remission and various complications. Remission was defined according to the 2014 Endocrine Society Clinical Practice Guideline. RESULTS The rate of surgical remission was 40.6% (62.9% among noninvasive adenomas). Rates of surgical remission significantly improved in the latter half of this cohort (31.2% in the first half vs. 50% in the second half), despite other factors being comparable. On multivariate analysis, surgeon experience, cavernous sinus invasion, and preoperative growth hormone levels affected the rates of surgical remission. Rates of cerebrospinal fluid leak and hypopituitarism were lower in the second half, whereas resolution of acromegaly-associated comorbidities was increased. CONCLUSIONS We report, in this large single-surgeon review of endoscopically operated acromegaly cases, increased rates of surgical remission and reduced complications with increasing surgeon experience. The overall experience of the treating team in dealing with perioperative and intraoperative factors also contributes to improved outcomes.
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Affiliation(s)
| | - Sauradeep Sarkar
- Department of Neurosurgery, Christian Medical College, Vellore, Tamil Nadu, India
| | | | - Nitin Kapoor
- Department of Endocrinology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Regi Thomas
- Department of Otorhinolaryngology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Rajesh Balakrishnan
- Department of Radiation Oncology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Geeta Chacko
- Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Ari G Chacko
- Department of Neurosurgery, Christian Medical College, Vellore, Tamil Nadu, India. ]
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Shen M, Chen Z, Shou X, He W, Qiao N, Ma Z, Ye Z, Zhang Y, Zhang Q, Zhou X, Cao X, Zhang Z, Ye H, Li Y, Zhao Y, Li S, He M, Wang Y. 2010 versus the 2000 consensus criteria in patients with normalised insulin-like growth factor 1 after transsphenoidal surgery has high predictive values for long-term recurrence-free survival in acromegaly. J Neuroendocrinol 2021; 33:e12958. [PMID: 33998086 DOI: 10.1111/jne.12958] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 01/31/2021] [Accepted: 02/09/2021] [Indexed: 01/15/2023]
Abstract
The present study investigated the factors associated with recurrence during long-term follow-up in acromegaly and compared the recurrence rate between patients in remission with 2010 vs 2000 consensus criteria. We retrospectively recruited 133 adult acromegalic patients who had undergone transsphenoidal surgery (TSS) from January 2013 to December 2014 and assessed their clinical characteristics, surgical outcomes and recurrence. Surgical remission was defined as normalised insulin-like growth factor 1 (IGF-1) with nadir growth hormone (GH) during an oral glucose tolerance test (OGTT) < 1 μg/ L no less than 3 months after TSS without adjuvant therapy. Recurrence was defined as persistently reelevated IGF-1 after surgical remission. Cox regression analysis and Kaplan-Meier survival analysis were performed to evaluate the factors associated with recurrence. Remission was achieved in 77 cases (57.9%) after TSS alone. Recurrence was seen in five cases (6.5%) at 12, 12, 12, 36 and 54 months, respectively, after surgery. Cox regression analysis showed that a nadir GH < 0.4 μg /L (vs 0.4-1.0 μg /L) at surgical remission (odds ratio [OR] = 0.106; 95% confidence interval [CI] = 0.017-0.645; P = 0.015) and Ki-67 index (OR = 2.636; 95% CI = 1.023-6.791; P = 0.045) were independent factors influencing recurrence. Kaplan-Meier survival analysis showed that the median recurrence-free survival was 36 months (95% CI = 20-52) for patients with nadir GH 0.4-1.0 μg /L at surgical remission. The median recurrence-free survival for patients with nadir GH < 0.4 μg /L at surgical remission was much longer (ie, required further follow-up to estimate). A failure of GH suppression under 0.4 μg /L during an OGTT in patients with normalised IGF-1 and a higher Ki-67 index are independent predictors of recurrence after surgical remission in GH-secreting pituitary adenomas. Compared to patients with nadir GH < 0.4 μg /L, those with nadir GH 0.4-1.0 μg /L appear to have a significantly higher risk of recurrence.
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Affiliation(s)
- Ming Shen
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
- Research Units of New Technologies of Micro-Endoscopy Combination in Skull Base Surgery (2018RU008), Chinese Academy of Medical Sciences, Shanghai, China
| | - Zhengyuan Chen
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Xuefei Shou
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
- Research Units of New Technologies of Micro-Endoscopy Combination in Skull Base Surgery (2018RU008), Chinese Academy of Medical Sciences, Shanghai, China
| | - Wenqiang He
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Nidan Qiao
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Zengyi Ma
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Zhao Ye
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Yichao Zhang
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Qilin Zhang
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Xiang Zhou
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
- Research Units of New Technologies of Micro-Endoscopy Combination in Skull Base Surgery (2018RU008), Chinese Academy of Medical Sciences, Shanghai, China
| | - Xiaoyun Cao
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Zhaoyun Zhang
- Shanghai Pituitary Tumor Center, Shanghai, China
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Hongying Ye
- Shanghai Pituitary Tumor Center, Shanghai, China
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yiming Li
- Shanghai Pituitary Tumor Center, Shanghai, China
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yao Zhao
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
- Research Units of New Technologies of Micro-Endoscopy Combination in Skull Base Surgery (2018RU008), Chinese Academy of Medical Sciences, Shanghai, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shiqi Li
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
| | - Min He
- Shanghai Pituitary Tumor Center, Shanghai, China
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yongfei Wang
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Shanghai Pituitary Tumor Center, Shanghai, China
- Research Units of New Technologies of Micro-Endoscopy Combination in Skull Base Surgery (2018RU008), Chinese Academy of Medical Sciences, Shanghai, China
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50
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Swanson AA, Erickson D, Donegan DM, Jenkins SM, Van Gompel JJ, Atkinson JLD, Erickson BJ, Giannini C. Clinical, biological, radiological, and pathological comparison of sparsely and densely granulated somatotroph adenomas: a single center experience from a cohort of 131 patients with acromegaly. Pituitary 2021; 24:192-206. [PMID: 33074402 DOI: 10.1007/s11102-020-01096-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/13/2020] [Indexed: 01/01/2023]
Abstract
PURPOSE Growth hormone-producing pituitary adenomas are divided into two clinically relevant histologic subtypes, densely (DG-A) and sparsely (SG-A) granulated. Histologic subtype was evaluated in a large cohort of patients with acromegaly, separating DG-A and SG-A, and correlated with clinicopathological characteristics. METHODS Patients with acromegaly undergoing surgery as initial therapy between 1995 and 2015 were identified. Histologic subtype was determined by keratin expression pattern with CAM5.2 and correlated with clinical and imaging parameters, somatostatin receptor subtype 2 (SST2) expression, post-surgical remission rate, and application of a prognostic scoring system incorporating proliferation and invasiveness. RESULTS One hundred thirty-one patients were included. Tumors were classified as DG-A (75, 57.3%), SG-A (29, 22.1%), intermediate (I-A) (9, 6.9%), and unclassified (18, 13.7%) when CAM5.2 was negative. DG-A and I-A were combined for analysis (DG/I-A) and compared to SG-A. Age, gender, proliferation, and post-surgical remission did not differ. SG-A were larger [2 vs. 1.5 cm (median), p = 0.03], more frequently invasive [65.5% vs. 32.9%, p = 0.004], associated with higher MRI T2-weighted signal ratio [1.01 vs. 0.82 (median), p = 0.01], showed lower SST2 expression (p < 0.0001), and scored higher in the prognostic classification (p = 0.004). Surgical remission occurred in 41.7% DG/I-A and 41.4% SG-A (p = 1.0). On multivariate analysis, absence of invasion (p = 0.009) and lower pre-operative IGF-1 index (p = 0.0002) were associated with post-surgical remission. CONCLUSION CAM5.2 allowed distinction between DG/I-A and SG-A in most but not all cases. Histologic subtype did not predict surgical outcome. Absence of invasion and lower pre-operative IGF-1 index were the only significant predictors of post-surgical remission in this cohort.
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Affiliation(s)
- Amy A Swanson
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA
| | - Dana Erickson
- Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA
| | - Diane Mary Donegan
- Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA
- Division of Endocrinology, Diabetes and Metabolism, Indiana University, Indianapolis, IN, USA
| | - Sarah M Jenkins
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | | | | | | | - Caterina Giannini
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
- Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
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