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Aluyi-Osa G, Suleman A, Salati C, Spadea L, Gagliano C, Musa M, Zeppieri M. Multidisciplinary management of pituitary macroadenoma. World J Methodol 2025; 15:97694. [DOI: 10.5662/wjm.v15.i3.97694] [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: 06/05/2024] [Revised: 11/18/2024] [Accepted: 12/03/2024] [Indexed: 03/06/2025] Open
Abstract
BACKGROUND Pituitary macroadenomas represent a significant challenge in clinical management due to their variable presentations and complex treatment considerations. This manuscript explores the multidisciplinary approach to understanding and managing pituitary macroadenomas, integrating neurosurgery, endocrinology, radiology, and pathology perspectives.
AIM To summarize the literature on pituitary macroadenoma and outline the possible multidisciplinary approach in the diagnosis, management, and rehabilitation of individuals with pituitary adenomas, to add to already preexisting knowledge, in managing these cases enhancing better ocular and systemic outcomes.
METHODS A search was conducted on an online publication database (PubMed) using the term “pituitary adenoma” including all results published over twenty years (2004-2024). Results were sorted for relevance, language, and completeness.
RESULTS A total of 176 records were returned. The guidelines of the PRISMA 2020 statement were followed in this study. A total of 23 records were excluded due to being out of scope while a further 13 records were duplicates. Another 17 records were not available as full-length articles and were also excluded. The references of each included record was further searched for relevant publications. A total of 141 records were therefore used in this minireview.
CONCLUSION Pituitary macroadenomas pose substantial clinical challenges due to their size and potential for significant hormonal and neurological impact, modern therapeutic strategies offer effective management options. Early detection and comprehensive treatment are essential for optimizing patient outcomes and maintaining quality of life. Continued research and advancements in medical technology are likely to further enhance the management and prognosis of this condition in the future
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Affiliation(s)
- Gladness Aluyi-Osa
- Department of Ophthalmology, Africa Eye Laser Center, Km 7, Benin 300105, Nigeria
| | - Ayuba Suleman
- Department of Ophthalmology, Africa Eye Laser Center, Km 7, Benin 300105, Nigeria
| | - Carlo Salati
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
| | - Leopoldo Spadea
- Eye Clinic, Policlinico Umberto I, "Sapienza" University of Rome, Rome 00142, Italy
| | - Caterina Gagliano
- Department of Medicine and Surgery, University of Enna "Kore", Enna 94100, Italy
- Mediterranean Foundation "G.B. Morgagni", 95125 Catania, Italy
| | - Mutali Musa
- Department of Ophthalmology, Africa Eye Laser Center, Km 7, Benin 300105, Nigeria
- Department of Optometry, University of Benin, Benin 300283, Nigeria
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
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Huang Y, Guo J, Han X, Zhao Y, Li X, Xing P, Liu Y, Sun Y, Wu S, Lv X, Zhou L, Zhang Y, Li C, Xie W, Liu Z. Splicing diversity enhances the molecular classification of pituitary neuroendocrine tumors. Nat Commun 2025; 16:1552. [PMID: 39934142 PMCID: PMC11814191 DOI: 10.1038/s41467-025-56821-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 02/03/2025] [Indexed: 02/13/2025] Open
Abstract
Pituitary neuroendocrine tumors (PitNETs) are one of the most common intracranial tumors with diverse clinical manifestations. Current pathological classification systems rely primarily on histological hormone staining and transcription factors (TFs) expression. While effective in identifying three major lineages, molecular characteristics based on hormones and TFs lack sufficient resolution to fully capture the complex tumor heterogeneity. Transcriptional diversity by alternative splicing (AS) offered additional insight to address this challenge. Here, we perform bulk and full-length single-cell RNA sequencing to comprehensively investigate AS dysregulation across all PitNET lineages. We reveal pervasive splicing dysregulations that better depict tumor heterogeneity. Additionally, we delineate fundamental splicing heterogeneity at single-cell resolution, confirming bulk findings and refining splicing dysregulation varying among tumor cell types. Notably, we effectively distinguish the silent corticotroph subtype and define a distinct TPIT lineage subtype, which is associated with worse clinical outcomes and increased splicing abnormalities driven by altered ESRP1 expression. In conclusion, our results characterize the subtype specific AS landscape in PitNETs, enhancing the understanding of the PitNETs subtyping.
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Affiliation(s)
- Yue Huang
- China National Center for Bioinformation, Beijing, China
- Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Jing Guo
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Xueshuai Han
- China National Center for Bioinformation, Beijing, China
- Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
| | - Yang Zhao
- China National Center for Bioinformation, Beijing, China
- Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
| | - Xuejing Li
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Peiqi Xing
- China National Center for Bioinformation, Beijing, China
- Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
| | - Yulou Liu
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Yingxuan Sun
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Song Wu
- University of Chinese Academy of Sciences, Beijing, China
- National Genomics Data Center, China National Center for Bioinformation, Beijing, China
| | - Xuan Lv
- China National Center for Bioinformation, Beijing, China
- Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Lei Zhou
- China National Center for Bioinformation, Beijing, China
- Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Yazhuo Zhang
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Chuzhong Li
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
- Department of Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China.
| | - Weiyan Xie
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
| | - Zhaoqi Liu
- China National Center for Bioinformation, Beijing, China.
- Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
- University of Chinese Academy of Sciences, Beijing, China.
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Li Z, Wu Y, He G, Wang R, Bao X. Phenotype Transformation of PitNETs. Cancers (Basel) 2024; 16:1731. [PMID: 38730682 PMCID: PMC11083144 DOI: 10.3390/cancers16091731] [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: 03/15/2024] [Revised: 04/24/2024] [Accepted: 04/26/2024] [Indexed: 05/13/2024] Open
Abstract
Phenotype transformation in pituitary neuroendocrine tumors is a little-known and unpredictable clinical phenomenon. Previous studies have not clearly defined and systematically concluded on the causes of this rare phenomenon. Additionally, the mechanisms of phenotype transformation are not well known. We reviewed cases reported in the literature with the aim of defining phenotype transformation in pituitary neuroendocrine tumors. We present an overview of the wide spectrum of phenotype transformation and its clinical features. We also discuss findings on the potential mechanism of this rare transformation, which may be related to PC1/3, the bioactivity of secretory hormones, gene mutations and the plasticity of pituitary neuroendocrine tumors. Clinicians should be aware of this rare phenomenon and more studies on the underlying mechanisms are required.
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Affiliation(s)
| | | | | | | | - Xinjie Bao
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; (Z.L.); (Y.W.); (G.H.); (R.W.)
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4
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Stratakis CA. An update on, and genetics of refractory adenomas of childhood. Pituitary 2023; 26:281-287. [PMID: 37318708 DOI: 10.1007/s11102-023-01327-2] [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: 05/16/2023] [Indexed: 06/16/2023]
Abstract
Pituitary adenomas in childhood tend to be more frequently due to germline genetic changes and are often diagnosed at late stages due to delayed recognition by pediatricians and other caretakers who are not familiar with this rare disease in childhood. As a result, often, pediatric pituitary adenomas are aggressive or remain refractory to treatment. In this review, we discuss germline genetic defects that account for the most common pediatric pituitary adenomas that are refractory to treatment. We also discuss some somatic genetic events, such as chromosomal copy number changes that characterize some of the most aggressive pituitary adenomas in childhood that end up being refractory to treatment.
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Affiliation(s)
- Constantine A Stratakis
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, 20892, Bethesda, MD, USA.
- Human Genetics & Precision Medicine, IMMB, FORTH, Heraklion, Greece.
- ELPEN Research Institute, Athens, Greece.
- Medical Genetics, H. Dunant Hospital, Athens, Greece.
- Faculty of Medicine, European University of Cyprus, Nicosia, Cyprus.
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5
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Sabahi M, Ghasemi-Nesari P, Maroufi SF, Shahbazi T, Yousefi O, Shahtaheri SA, Bin-Alamer O, Dabecco R, Velasquez N, Arce KM, Adada B, Benjamin CG, Borghei-Razavi H. Recurrent Cushing Disease: An Extensive Review on Pros and Cons of Different Therapeutic Approaches. World Neurosurg 2023; 172:49-65. [PMID: 36739900 DOI: 10.1016/j.wneu.2023.01.108] [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: 01/25/2023] [Accepted: 01/27/2023] [Indexed: 02/05/2023]
Abstract
OBJECTIVE Recurrent Cushing disease (CD) is characterized by the reappearance of clinical and hormonal aspects of hypercortisolism that occur more than 6 months after an initial post-treatment remission. METHODS We performed a systematic review and meta-analysis to synthesize the evidence about remission and complication rates after transsphenoidal surgery (TSS) radiotherapy (RT) and medical therapy (MT) in recurrent CD patients. A quantitative systematic review was performed. Article selection was performed by searching MEDLINE (using PubMed), and Cochrane electronic bibliographic databases through 2020. RESULTS We noted 61 articles described therapeutic management of recurrent CD patients with representative outcome. A total of 723 patients received different therapeutic modality for their recurrent CD. The remission rates were 0.65 (95% confidence interval [CI] 0.60-0.70), 0.57 (95% CI 0.51-0.63), and 0.75 (95% CI 0.60-0.86) in the TSS, RT, and MT subgroups, respectively. The total remission rate after therapeutic approaches on recurrent CD patients was 0.64 (95% CI 0.60-0.68). A test for subgroup differences revealed there was a statistically significant difference between different subgroups (P = 0.01). The post hoc test showed that in comparison with RT, TSS (P = 0.0344) and MT (P = 0.0149) had a higher rate of remission. However, there was no statistically significant difference between separate therapeutic modalities in terms of complications including diabetes insipidus (P = 1.0) and hypopituitarism (P = 0.28). CONCLUSIONS Compared MT and TSS, RT has a statistically lower rate of remission. Although there is robust superiority of surgery over RT, interpretation of MT data must considered with caution due to the small number of included cases and wide CI range.
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Affiliation(s)
- Mohammadmahdi Sabahi
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Paniz Ghasemi-Nesari
- Neurosurgery Research Group (NRG), Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran; Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Farzad Maroufi
- Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Taha Shahbazi
- Neurosurgery Research Group (NRG), Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran; Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Omid Yousefi
- Trauma Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Alireza Shahtaheri
- Neurosurgery Research Group (NRG), Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran; Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Othman Bin-Alamer
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Rocco Dabecco
- Department of Neurological Surgery, Pauline Braathen Neurological Centre, Cleveland Clinic Florida, Weston, Florida, USA
| | - Nathalia Velasquez
- Department of Otolaryngology/Head and Neck Surgery, Cleveland Clinic Florida, Weston, Florida, USA
| | - Karla M Arce
- Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic Florida, Weston, Florida, USA
| | - Badih Adada
- Department of Neurological Surgery, Pauline Braathen Neurological Centre, Cleveland Clinic Florida, Weston, Florida, USA
| | | | - Hamid Borghei-Razavi
- Department of Neurological Surgery, Pauline Braathen Neurological Centre, Cleveland Clinic Florida, Weston, Florida, USA.
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Portovedo S, Neto LV, Soares P, Carvalho DPD, Takiya CM, Miranda-Alves L. Aggressive nonfunctioning pituitary neuroendocrine tumors. Brain Tumor Pathol 2022; 39:183-199. [PMID: 35725837 DOI: 10.1007/s10014-022-00441-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Accepted: 05/31/2022] [Indexed: 11/29/2022]
Abstract
Nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) are tumors that are not associated with clinical evidence of hormonal hypersecretion. According to the World Health Organization (WHO), there are some subtypes of PitNETs that exhibit more aggressive behavior than others. Among the types of potentially aggressive PitNETs, three are nonfunctional: silent sparsely granulated somatotropinomas, silent corticotropinomas, and poorly differentiated PIT-1 lineage tumors. Several biological markers have been investigated in NF-PitNETs. However, there is no single biomarker able to independently predict aggressive behavior in NF-PitNETs. Thus, a more complex and multidisciplinary proposal of a comprehensive definition of aggressive NF-PitNETs is necessary. Here, we suggest a combined and more complete criterion for the NF-PitNETs classification. We propose that aggressiveness is due to a multifactorial combination, and we emphasize the need to include new emerging markers that are involved in the aggressiveness of NF-PitNETs and the need to identify.
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Affiliation(s)
- Sérgio Portovedo
- Laboratório de Endocrinologia Experimental-LEEx, Centro de Ciências da Saúde, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco F - Sala F1-015 - Ilha do Fundão, Rio de Janeiro, RJ, 21941-912, Brazil.,Programa de Pós-Graduação em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Leonardo Vieira Neto
- Programa de Pós-Graduação em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.,Serviço de Endocrinologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Paula Soares
- Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal.,Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, Portugal.,Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (FMUP), Porto, Portugal
| | - Denise Pires de Carvalho
- Programa de Pós-Graduação em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.,Laboratório de Fisiologia Endócrina Doris Rosenthal, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Christina Maeda Takiya
- Laboratório de Imunopatologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Leandro Miranda-Alves
- Laboratório de Endocrinologia Experimental-LEEx, Centro de Ciências da Saúde, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco F - Sala F1-015 - Ilha do Fundão, Rio de Janeiro, RJ, 21941-912, Brazil. .,Programa de Pós-Graduação em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. .,Programa de Pós-Graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. .,Programa de Pós-Graduação em Ciências Morfológicas, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
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7
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Lu L, Wan X, Xu Y, Chen J, Shu K, Lei T. Prognostic Factors for Recurrence in Pituitary Adenomas: Recent Progress and Future Directions. Diagnostics (Basel) 2022; 12:diagnostics12040977. [PMID: 35454025 PMCID: PMC9024548 DOI: 10.3390/diagnostics12040977] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/01/2022] [Accepted: 04/11/2022] [Indexed: 02/04/2023] Open
Abstract
Pituitary adenomas (PAs) are benign lesions; nonetheless, some PAs exhibit aggressive behaviors, which lead to recurrence. The impact of pituitary dysfunction, invasion-related risks, and other complications considerably affect the quality of life of patients with recurrent PAs. Reliable prognostic factors are needed for recurrent PAs but require confirmation. This review summarizes research progress on two aspects—namely, the clinical and biological factors (biomarkers) for recurrent PAs. Postoperative residue, age, immunohistological subtypes, invasion, tumor size, hormone levels, and postoperative radiotherapy can predict the risk of recurrence in patients with PAs. Additionally, biomarkers such as Ki-67, p53, cadherin, pituitary tumor transforming gene, matrix metalloproteinase-9, epidermal growth factor receptor, fascin actin-bundling protein 1, cyclooxygenase-2, and some miRNAs and lncRNAs may be utilized as valuable tools for predicting PA recurrence. As no single marker can independently predict PA recurrence, we introduce an array of comprehensive models and grading methods, including multiple prognostic factors, to predict the prognosis of PAs, which have shown good effectiveness and would be beneficial for predicting PA recurrence.
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Affiliation(s)
| | | | | | | | | | - Ting Lei
- Correspondence: ; Tel./Fax: +86-27-8366-5202
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Taguchi A, Kinoshita Y, Tominaga A, Amatya VJ, Takeshima Y, Yamasaki F. Metachronous Double Pituitary Adenoma with Altered Transcriptional Factor Profile: A Case Report and Literature Review. NMC Case Rep J 2022; 8:657-663. [PMID: 35079531 PMCID: PMC8769424 DOI: 10.2176/nmccrj.cr.2021-0121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 06/17/2021] [Indexed: 11/26/2022] Open
Abstract
Double pituitary adenomas (DPAs), especially metachronous DPAs, are extremely rare and there has been no report about DPAs with altered transcriptional factors. We describe the case of a 25-year-old man who presented with acromegaly 7 years after surgery for a non-functioning pituitary adenoma (NFPA). Before the initial surgery, endocrine evaluation confirmed NFPA or silent somatotroph pituitary adenoma (SPA) because of normal serum levels of insulin-like growth factor-1 (IGF-1) and insufficient suppression of growth hormone (GH) levels in the oral glucose tolerance test (OGTT). Immunohistochemistry of resected tissue obtained from gross total resection (GTR) with transsphenoidal surgery (TSS) was negative for follicle-stimulating hormone, luteinizing hormone, GH, and Pit-1 but positive for GATA3, which confirmed the gonadotroph pituitary adenoma (GPA) diagnosis. Seven years later, follow-up brain MRI revealed a 13.3 × 5.6 × 4.7 mm tumor within the sellar turcica. The endocrine evaluation confirmed acromegaly because of high serum levels of IGF-1 and insufficient suppression of GH levels upon OGTT. GTR with TSS was again performed, and immunohistochemistry was negative for GATA3 but positive for GH and Pit-1. Surprisingly, he showed altered transcription factor expressions between initial and recurrent surgery. Based on the overall clinical course and hormonal secretion findings, we speculated metachronous development of a DPA, i.e., SPA followed by GPA, wherein a few remaining cells of the SPA might have regrown after the initial surgery. We conducted a literature review of cases that documented altered hormone secretion at recurrence and emphasized the necessity of identifying a small adenoma when there is a discrepancy between pathological findings and hormone secretion tests.
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Affiliation(s)
- Akira Taguchi
- Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Hiroshima, Japan
| | - Yasuyuki Kinoshita
- Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Hiroshima, Japan
| | - Atsushi Tominaga
- Department of Neurosurgery and Neuro-Endovascular Therapy, Hiroshima Prefectural Hospital, Hiroshima, Hiroshima, Japan
| | - Vishwa Jeet Amatya
- Department of Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Hiroshima, Japan
| | - Yukio Takeshima
- Department of Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Hiroshima, Japan
| | - Fumiyuki Yamasaki
- Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Hiroshima, Japan
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Lamback EB, Wildemberg LE, Gadelha MR. Current opinion on the diagnosis and management of non-functioning pituitary adenomas. Expert Rev Endocrinol Metab 2021; 16:309-320. [PMID: 34678108 DOI: 10.1080/17446651.2021.1988851] [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: 08/31/2021] [Accepted: 09/30/2021] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Non-functioning pituitary adenomas (NFPAs) are clinically silent tumors and the second most common pituitary adenoma. Surgery is the mainstay of treatment as there is, as yet, no effective medical treatment. AREAS COVERED We present current knowledge on the clinical diagnosis, histopathological classification, molecular data, and management strategies in NFPA. EXPERT OPINION NFPA is a heterogeneous group of tumors, in respect to their origin and clinical course. In recent years, research on pathology and molecular biology have advanced our knowledge of NFPA pathogenesis. NFPA exhibit, in the majority of cases, an indolent behavior, with satisfactory response to treatment. In aggressive cases, multimodal management is needed; however, even this approach may be insufficient, so the development of new treatments is warranted for better management. In this setting, the understanding of the mechanisms involved in the genesis and progression of NFPA is crucial for the identification and development of directed treatments with higher chances of response.
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Affiliation(s)
- Elisa B Lamback
- Neuroendocrinology Research Center/Endocrinology Division, Medical School and Hospital Universitário Clementino Fraga Filho, Rio De Janeiro, Brazil
- Neuropathology and Molecular Genetics Laboratory, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio De Janeiro, Brazil
- Neuroendocrine Unit, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio De Janeiro, Brazil
| | - Luiz Eduardo Wildemberg
- Neuroendocrinology Research Center/Endocrinology Division, Medical School and Hospital Universitário Clementino Fraga Filho, Rio De Janeiro, Brazil
- Neuropathology and Molecular Genetics Laboratory, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio De Janeiro, Brazil
- Neuroendocrine Unit, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio De Janeiro, Brazil
| | - Mônica R Gadelha
- Neuroendocrinology Research Center/Endocrinology Division, Medical School and Hospital Universitário Clementino Fraga Filho, Rio De Janeiro, Brazil
- Neuropathology and Molecular Genetics Laboratory, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio De Janeiro, Brazil
- Neuroendocrine Unit, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio De Janeiro, Brazil
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10
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Popa Ilie IR, Herdean AM, Herdean AI, Georgescu CE. Spontaneous remission of Cushing's disease: A systematic review. ANNALES D'ENDOCRINOLOGIE 2021; 82:613-621. [PMID: 34687655 DOI: 10.1016/j.ando.2021.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 08/28/2021] [Accepted: 10/11/2021] [Indexed: 10/20/2022]
Abstract
Spontaneous remission is rare in Cushing's disease. We describe one illustrative case and provide a systematic review of cases previously reported in the literature. Case report: A 51-year-old woman diagnosed with Cushing's disease underwent 9 months' isolated metyrapone treatment. Two months after end of treatment, she was admitted with acute kidney failure. After another 4 months, in June 2020, there was no evidence of hypercortisolism, either clinically or biochemically, or of hypocortisolism. At the time of writing, 1 year later, she was still in remission. Cases reported in the literature: 23 patients were reported, including the present case. 87% were female with a median age of 32 years. Ten of those with radiologically visible tumors had microadenoma (44%) and 7 had macroadenoma (30%). Mean time from diagnosis to spontaneous remission was 5 months, and was shorter in macroadenoma (1 month) than in microadenoma (13.5 months). Treatments before spontaneous remission were: no treatment (65%), steroidogenesis enzyme inhibitors (22%), bilateral adrenalectomy and adrenal autotransplantation (5%), partial bilateral adrenalectomy (4%), and incomplete pituitary surgery (4%). Pituitary tumor apoplexy was the most frequently incriminated event (91%), radiologically documented in 43% of patients. Mean remission during follow-up was 28 months (range, 6-130 months). Recurrence occurred in 39% (n=9) of patients. Although several mechanisms responsible for this phenomenon have been proposed, clinical or subclinical pituitary tumor apoplexy, the latter sometimes presenting atypically, seems to be the most frequently incriminated event. Doctors should be aware of this, and regular follow-up is mandatory due to its unpredictability.
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Affiliation(s)
- Ioana Rada Popa Ilie
- Department of Endocrinology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 3-5, Louis Pasteur street, 400349 Cluj-Napoca, Romania.
| | - Alina Maria Herdean
- Department of Endocrinology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 3-5, Louis Pasteur street, 400349 Cluj-Napoca, Romania.
| | - Andrei Ioan Herdean
- Department of Anatomy and Embriology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania.
| | - Carmen Emanuela Georgescu
- Department of Endocrinology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 3-5, Louis Pasteur street, 400349 Cluj-Napoca, Romania.
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11
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AKKUŞ G, KARAGÜN B, ÇETİNALP NE, AÇIKALIN A, ODABAŞ F, EVRAN OLGUN M, SERT M, ZORLUDEMİR S, TETİKER BT. Klinik olarak belirgin Cushing hastalığı olan hastalar ile sessiz kortikotrof hücreli adenomu olan hastaların klinik, hormonal, radyolojik ve morfolojik olarak karşılaştırılması. CUKUROVA MEDICAL JOURNAL 2020. [DOI: 10.17826/cumj.783225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
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12
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Abstract
Aggressive pituitary tumors (APTs) represent rare pituitary adenomas (PAs) with local invasion of surrounding tissues, increased risk for multiple recurrence, rapid tumor growth, or resistance to standard therapies. The most common APTs in children and adolescents are giant prolactinomas and somatotropinomas. Few cases of Crooke's cell adenomas, silent corticotroph adenomas and pituitary carcinomas have also been reported in the literature. Pediatric patients with APTs have higher risk of harboring germline genetic defects, most commonly in the MEN1 and AIP genes. Since certain genetic defects confer a more aggressive behavior to PAs, genetic testing should be considered in tumors with young onset and positive family history. The management of pediatric APTs involves usually a combination of standard therapies (surgical, medical, radiation). Newer agents, such as temozolomide, have been used in few cases of pediatric pituitary tumors with promising results. In the elderly, PAs are more commonly non-functioning. Their management often poses dilemmas given the coexistence of age-related comorbidities. However, standard surgical treatment and temozolomide seem to be safe and well tolerated in elderly patients.
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Affiliation(s)
- Christina Tatsi
- Section on Genetics and Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, 10 Center Drive, Building 10, NIH-Clinical Research Center, Room 1-3330, MSC1103, Bethesda, MD, 20892, USA
| | - Constantine A Stratakis
- Section on Genetics and Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, 10 Center Drive, Building 10, NIH-Clinical Research Center, Room 1-3330, MSC1103, Bethesda, MD, 20892, USA.
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13
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Guerrero-Pérez F, Marengo AP, Vidal N, Villabona C. Pituitary Adenomas with Changing Phenotype: A Systematic Review. Exp Clin Endocrinol Diabetes 2020; 128:835-844. [PMID: 32289831 DOI: 10.1055/a-1120-8277] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
PURPOSE AND METHODS Phenotype transformation in pituitary adenomas (PA) is a little known and unexpected clinical phenomenon. We describe two illustrative cases and performed a systematic review of cases reported in literature. RESULTS Case 1: A 24-year-old woman underwent surgery because of Cushing's disease. A complete tumor resection and hypercortisolism resolution was achieved. Two years later, tumor recurred but clinical and hormonal hypercortisolism were absent. Case 2: A 77-year-old woman underwent surgery due to acromegaly. A complete tumor resection and GH excess remission was achieved. Four years later, tumor recurred but clinical and hormonal acromegaly was ruled out. Search of literature: From 20 patients (including our cases), 75% were female with median age 45 (19) years. Ten patients (50%) had initially functioning PA: 8 switched to NFPA (5 ACTH-secreting PA, 2 prolactinomas and 1 acromegaly) and 2 exchanged to acromegaly from TSH-secreting PA and microprolactinoma. One patient developed a pituitary carcinoma from ACTH-secreting PA. Ten patients (50%) initially had NFPA; 9 developed Cushing's disease (4 silent corticotroph adenomas, 4 null cell PA and 1 managed conservatively). One patient with silent somatotroph PA changed to acromegaly. Treatments before transformation were surgery (80%), radiotherapy (40%), pharmacological (40%) and in 2 patients switching happened without any treatment. Median follow-up until transformation was 72 months (range 12-276). CONCLUSION PA can change from functioning to (NF) non-functioning (vice versa) and even exchange their hormonal expression. Clinicians should be aware and a careful lifelong follow-up is mandatory to detect it.
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Affiliation(s)
| | | | - Noemi Vidal
- Department of Pathology; Bellvitge University Hospital, Barcelona, Spain
| | - Carles Villabona
- Department of Endocrinology, Bellvitge University Hospital, Barcelona, Spain
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14
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Zheng G, Lu L, Zhu H, You H, Feng M, Liu X, Dai C, Yao Y, Wang R, Zhang H, Sun X, Lu Z. Clinical, Laboratory, and Treatment Profiles of Silent Corticotroph Adenomas That Have Transformed to the Functional Type: A Case Series With a Literature Review. Front Endocrinol (Lausanne) 2020; 11:558593. [PMID: 33071973 PMCID: PMC7538591 DOI: 10.3389/fendo.2020.558593] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Accepted: 08/13/2020] [Indexed: 12/02/2022] Open
Abstract
Purpose: Silent corticotroph adenoma (SCA) is clinically non-functional pituitary adenoma with expression of corticotropin or Tpit. To further understand the characteristics of this rare type of SCA transforming to a functional SCA, we retrospectively reviewed SCAs that converted to typical Cushing's syndrome at a tertiary medical center and the relevant literature. Methods: Patients were identified based on the diagnosis of pituitary adenoma without symptoms of hypercortisolism at the initial visit with positive Immunohistochemical (IHC) staining for corticotropin or Tpit after surgery and subsequent transformation to functional SCAs during the follow-up period from March 1990 to January 2020 at Peking Union Medical College Hospital and in the literature. The characteristics of the clinical manifestations, biochemical results, imaging findings, pathology findings and outcome were analyzed. Results: Altogether, 16 patients were included in the study with an average age of 42.0 ± 12.48 (18-65) years at the first visit. Females were slightly predominant (F:M = 1.3:1). The median time of conversion from the nonfunctional to the functional type was 30 (13.0, 68.3) months. Once a functional SCA developed, the adrenocorticotropic hormone (ACTH) level and 24-h urine free cortisol were increased 3.8- (2.6, 12.9) and 5.3- (2.6, 19.3) fold, respectively, above the normal range. Approximately 50% of the patients had macrocystic changes on pituitary MRI. All 16 patients experienced 1-5 surgeries with a median of 2.5 (2.0, 4.0) surgeries. The proportion of patients with Ki-67 ≥ 3% increased from 22.2% (2/9) at the beginning to 50% (7/14) at the time of functional SCA diagnosis. Thirteen patients received radiotherapy, and 4 patients (30.8%) achieved remission. Four patients with refractory functional SCAs received temozolomide treatment with the normalization of cortisol in 4 cases and reduced tumor volume in 3 cases. Conclusion: In this study, all cases that transformed to functional SCAs were macroadenomas. Hypercortisolism was more severe in functional SCA patients. The tumors tended to have frequent recurrence and were highly invasive. Temozolomide could be a promising treatment for refractory functional SCA cases. Long-term follow-up is needed for nonfunctional SCAs since some cases have the potential to transform to clinical Cushing's syndrome.
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Affiliation(s)
- Guangyao Zheng
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
- School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Lin Lu
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
- *Correspondence: Lin Lu
| | - Huijuan Zhu
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Hui You
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Ming Feng
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Xiaohai Liu
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Congxin Dai
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Yong Yao
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Renzhi Wang
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Huabing Zhang
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Xu Sun
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Zhaolin Lu
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
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15
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Rotman LE, Vaughan TB, Hackney JR, Riley KO. Long-Term Survival After Transformation of an Adrenocorticotropic Hormone–Secreting Pituitary Macroadenoma to a Silent Corticotroph Pituitary Carcinoma. World Neurosurg 2019; 122:417-423. [PMID: 30447452 DOI: 10.1016/j.wneu.2018.11.011] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 10/31/2018] [Accepted: 11/02/2018] [Indexed: 10/27/2022]
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16
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Prendergast N, Aldana PR, Rotondo RL, Torres-Santiago L, Beier AD. Pediatric silent corticotroph pituitary adenoma and role for proton therapy: case report. J Neurosurg Pediatr 2019; 23:214-218. [PMID: 30497138 DOI: 10.3171/2018.9.peds18107] [Citation(s) in RCA: 3] [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: 04/17/2018] [Accepted: 09/12/2018] [Indexed: 11/06/2022]
Abstract
Tumors involving the sella are commonly craniopharyngiomas, optic pathway gliomas, or pituitary adenomas. Functioning adenomas are expected, with prolactinomas topping the differential. The authors present the case of a silent corticotroph adenoma, which has not been described in the pediatric population, and they detail the use of proton therapy, which is also novel.
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Affiliation(s)
- Nicole Prendergast
- 1Frank H. Netter MD School of Medicine, Quinnipiac University, North Haven, Connecticut
| | | | - Ronny L Rotondo
- 3Department of Radiation Oncology, University of Florida, Gainesville; and
| | - Lournaris Torres-Santiago
- 4Division of Pediatric Endocrinology, Diabetes and Metabolism, Nemours Children's Health System, Jacksonville, Florida
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17
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Eremkina AK, Dzeranova LK, Pigarova EK, Mokrysheva NG, Dedov II. [Morphofunctional features of non-functioning pituitary adenomas]. Arkh Patol 2019; 81:71-78. [PMID: 30830109 DOI: 10.17116/patol20198101171] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Non-functioning pituitary adenomas (NFPAs) account for about 30% of all pituitary tumors. NFPAs are characterized by the lack of secretory potential or its weak expression insufficient for determination of the blood level of adenohypophyseal tropic hormones and for development of a specific clinical picture. Morphologically, NFPAs are a heterogeneous group of tumors, the classification of which was previously based only on immunoreactivity for pituitary tropic hormones. The WHO revised its Classification of Tumors of Endocrine Organs (4th edition) in 2017. The main changes relate to adenohypophysial-cell lineage for the designation of adenomas into subtypes. The introduction of transcription factor antibodies has become a fundamentally new approach to the classification of NFPAs, which is necessary to recognize less differentiated tumor types. This paper provides information on the new histopathological classification of pituitary adenomas, on the theories of silent adenomas, and on the proliferative and prognostic markers of NFPAs.
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Affiliation(s)
- A K Eremkina
- National Medical Research Center for Endocrinology, Ministry of Health of Russia, Moscow, Russia
| | - L K Dzeranova
- National Medical Research Center for Endocrinology, Ministry of Health of Russia, Moscow, Russia
| | - E K Pigarova
- National Medical Research Center for Endocrinology, Ministry of Health of Russia, Moscow, Russia
| | - N G Mokrysheva
- National Medical Research Center for Endocrinology, Ministry of Health of Russia, Moscow, Russia
| | - I I Dedov
- National Medical Research Center for Endocrinology, Ministry of Health of Russia, Moscow, Russia
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18
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Delgado-López PD, Pi-Barrio J, Dueñas-Polo MT, Pascual-Llorente M, Gordón-Bolaños MC. Recurrent non-functioning pituitary adenomas: a review on the new pathological classification, management guidelines and treatment options. Clin Transl Oncol 2018; 20:1233-1245. [PMID: 29623588 DOI: 10.1007/s12094-018-1868-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 03/26/2018] [Indexed: 11/25/2022]
Abstract
At least 50% of surgically resected non-functioning pituitary adenomas (NFPA) recur. Either early or late adjuvant radiotherapy is highly efficacious in controlling recurrent NFPA but associates potentially burdensome complications like hypopituitarism, vascular complications or secondary neoplasm. Reoperation is indicated in bulky tumor rests compressing the optic pathway. To date, no standardized medical therapy is available for recurrent NFPA although cabergoline and temozolomide show promising results. Guidelines on the management of recurrent NFPAs are now available. The new 2017 WHO pituitary tumor classification, based on immunohistochemistry and transcription factor assessment, identifies a group of aggressive NFPA variants that may benefit from earlier adjuvant therapy. Nevertheless, NFPA patients exhibit a reduced overall life expectancy largely due to hypopituitarism and treatment-related morbidity. The management of recurrent NFPA benefits from a multidisciplinary teamwork of surgeons, endocrinologists, radiation oncologists, ophthalmologists, pathologists and neuro-radiologists in order to provide individualized therapy and anticipate deterioration.
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Affiliation(s)
- P D Delgado-López
- Servicio de Neurocirugía, Hospital Universitario de Burgos, Avda Islas Baleares 3, 09006, Burgos, Spain.
| | - J Pi-Barrio
- Servicio de Endocrinología Y Nutrición, Hospital Universitario de Burgos, Burgos, Spain
| | - M T Dueñas-Polo
- Servicio de Oncología Radioterápica, Hospital Universitario de Burgos, Burgos, Spain
| | - M Pascual-Llorente
- Servicio de Anatomía Patológica, Hospital Universitario de Burgos, Burgos, Spain
| | - M C Gordón-Bolaños
- Servicio de Oftalmología, Hospital Universitario de Burgos, Burgos, Spain
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19
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Abstract
Non-functioning pituitary neuroendocrine tumors do not cause endocrine symptoms related to hypersecretion of adenohypophyseal hormones and are clinically characterized by symptoms due to growing sellar tumor mass. Histopathological classification of this tumor group has always been challenging due to their heterogeneity, limited knowledge on their biology, and diverse methodological problems. We have searched PubMed database for data related to the histopathological classification of non-functioning pituitary tumors and methods for its application. Principles of the classification and grading presented in the recently released 4th edition of the World Health Organization classification of endocrine tumors have been summarized. Based on the expression of anterior pituitary hormones and pituitary specific transcription factors, gonadotroph tumors dominate within the group of clinically non-functioning tumors, followed by corticotroph type; however, other less common types of the non-functioning tumors can be identified. Assessment of tumor cell proliferation is important to identify "high-risk adenomas." A few subtypes of non-functioning tumors belong to the category of potentially aggressive tumors, independent of the cell proliferation rate. Here, we present up to date criteria for the classification of clinically non-functioning pituitary tumors, offer a diagnostic approach for the routine clinical use, and emphasize a need for inclusion of prognostic and predictive markers in the classification.
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Affiliation(s)
| | - Britt Edén Engström
- Department of Medical Sciences, Endocrinology and Metabolism, Uppsala University Hospital, Uppsala, Sweden
| | - Olivera Casar-Borota
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
- Department of Clinical Pathology, Uppsala University Hospital, Uppsala, Sweden.
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20
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Abstract
PURPOSE Silent corticotroph adenomas (SCAs) present clinically as non-functioning adenomas (NFAs) but are immunopositive for adrenocorticotrophic hormone (ACTH) without biochemical and clinical manifestation of hypercortisolism. Pathologic examination of resected NFAs that demonstrate positive ACTH and/or TPIT expression confirms its corticotroph lineage. SCAs comprise up to 20% of NFAs and exhibit a higher rate of recurrence. Studies of molecular mechanisms have generated multiple hypotheses on SCA tumorigenesis, pathophysiology, and growth that as yet remain to be proven. An improved understanding of their pathologic and clinical characteristics is needed. METHODS A literature review was performed using PubMed to identify research reports and clinical case series on SCAs. RESULTS Up to date findings regarding epidemiology, mechanisms of pathogenesis, differentiation, progression, and growth, as well as clinical presentation, postoperative course, and treatment options for patients with SCAs are presented. Pooled results demonstrate that 25-40% of cases show cavernous sinus invasion, preoperative hypopituitarism, new-onset hypopituitarism, and recurrence. CONCLUSION This article reviews the incidence, molecular pathology, and clinical behavior of these unique non-functioning pituitary corticotroph adenomas, and highlights the need for rigorous monitoring for recurrences and hypopituitarism in patients with SCAs.
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Affiliation(s)
- Anat Ben-Shlomo
- Pituitary Center, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd, A6600, Los Angeles, CA, 90048, USA
| | - Odelia Cooper
- Pituitary Center, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd, A6600, Los Angeles, CA, 90048, USA.
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21
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Langlois F, Lim DST, Yedinak CG, Cetas I, McCartney S, Cetas J, Dogan A, Fleseriu M. Predictors of silent corticotroph adenoma recurrence; a large retrospective single center study and systematic literature review. Pituitary 2018; 21:32-40. [PMID: 29032459 DOI: 10.1007/s11102-017-0844-4] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
PURPOSE Silent corticotroph adenomas (SCAs) are clinically silent and non-secreting, but exhibit positive adrenocorticotropic hormone (ACTH) immunostaining. We characterized a single center cohort of SCA patients, compared the SCAs to silent gonadotroph adenomas (SGAs), identified predictors of recurrence, and reviewed and compared the cohort to previously published SCAs cases. METHODS Retrospective review of SCA and SGA surgically resected patients over 10 years and 6 years, respectively. Definitions; SCA-no clinical or biochemical evidence of Cushing's syndrome and ACTH positive immunostaining, and SGA-steroidogenic factor (SF-1) positive immunostaining. A systematic literature search was undertaken using Pubmed and Scopus. RESULTS Review revealed 814 pituitary surgeries, 39 (4.8%) were SCAs. Mean follow-up was 6.4 years (range 0.5-23.8 years). Pre-operative magnetic resonance imaging demonstrated sphenoid and/or cavernous sinus invasion in 44%, 33% were > 50% cystic, and 28% had high ACTH levels pre-operatively. Compared to SGAs (n = 70), SCAs were of similar size and invasiveness (2.5 vs. 2.9 cm, p = 0.2; 44 vs. 41%, p = 0.8, respectively), but recurrence rate was higher (36 vs. 10%, p = 0.001) and more patients received radiation therapy (18 vs. 3%, p = 0.006). Less cystic tumors (0 vs. 50%, p < 0.001) and higher pre-operative ACTH levels (54 vs. 28 pg/ml, p = 0.04) were predictors of recurrence for SCAs. CONCLUSION This review is unique; a strict definition of SCA was used, and single center SCAs were compared with SGAs and with SCAs literature reviewed cases. We show that SCAs are aggressive and identify predictors of recurrence. Accurate initial diagnosis, close imaging and biochemical follow up are warranted.
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Affiliation(s)
- Fabienne Langlois
- Department of Medicine, Oregon Health & Science University, Portland, OR, USA
- Department of Medicine Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Dawn Shao Ting Lim
- Department of Medicine, Oregon Health & Science University, Portland, OR, USA
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - Chris G Yedinak
- Department of Neurological Surgery, Oregon Health & Science University, Mail Code CH8N, 3303 SW Bond Avenue, Portland, OR, 97239, USA
- Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA
| | - Isabelle Cetas
- Department of Neurological Surgery, Oregon Health & Science University, Mail Code CH8N, 3303 SW Bond Avenue, Portland, OR, 97239, USA
| | - Shirley McCartney
- Department of Neurological Surgery, Oregon Health & Science University, Mail Code CH8N, 3303 SW Bond Avenue, Portland, OR, 97239, USA
- Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA
| | - Justin Cetas
- Department of Neurological Surgery, Oregon Health & Science University, Mail Code CH8N, 3303 SW Bond Avenue, Portland, OR, 97239, USA
- Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA
| | - Aclan Dogan
- Department of Neurological Surgery, Oregon Health & Science University, Mail Code CH8N, 3303 SW Bond Avenue, Portland, OR, 97239, USA
- Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA
| | - Maria Fleseriu
- Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
- Department of Neurological Surgery, Oregon Health & Science University, Mail Code CH8N, 3303 SW Bond Avenue, Portland, OR, 97239, USA.
- Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA.
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22
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Langlois F, Lim DST, Varlamov E, Yedinak CG, Cetas JS, McCartney S, Dogan A, Fleseriu M. Clinical profile of silent growth hormone pituitary adenomas; higher recurrence rate compared to silent gonadotroph pituitary tumors, a large single center experience. Endocrine 2017; 58:528-534. [PMID: 29043561 DOI: 10.1007/s12020-017-1447-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Accepted: 09/30/2017] [Indexed: 12/12/2022]
Abstract
PURPOSE Study and comparison of characteristics of silent growth hormone adenomas (SGHA), silent corticotroph adenomas (SCA), and silent gonadotroph adenomas (SGA) in a single institution cohort of surgically treated pituitary adenomas. METHODS Retrospective analysis of SGHA surgically resected over 10 years: SGHA was defined as no clinical or biochemical evidence of acromegaly and positive GH immunostaining. RESULTS Of 814 pituitary surgeries; 2.1% (n = 17) were SGHA, 4.5% (n = 37) SCA, and 18.9% (n = 70/371; 2011-2016) SGA. Mean age at SGHA diagnosis was 43 years, with a large female predominance (82%). Mean tumor size and cavernous/sphenoid sinus invasiveness for SGHA, SCA, and SGA were 1.5 ± 1.0 cm and 25%, 2.5 ± 1.2 cm and 43%, 2.9 ± 2.0 cm and 41%, respectively (tumor size p = 0.009, SGHA vs. SGA, and invasion p; not-significant). During mean follow-up of 3.9 years, two patients (11%) developed elevated insulin-like growth factor-1 and five patients (29%) required a second surgery for tumor recurrence. Rate of surgical reintervention was similar to SCA (31%), but higher than SGA (10%) (p = 0.035, SGHA vs. SGA), and 18% underwent radiation therapy, similar to SCA (19%, p; not-significant) but higher than SGA (2.9%, p = 0.018). CONCLUSION This is the largest single center study characterizing SGHA behavior with SGA and SCA control groups in a cohort of surgically resected pituitary adenomas. SGHA present mostly in young females, and should be closely followed due to their higher likelihood of recurrence and potential of progression to clinical acromegaly. We propose that a complete hormonal staining panel be routinely performed for all pituitary adenomas.
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Affiliation(s)
- Fabienne Langlois
- Department of Medicine, Oregon Health & Science University, Portland, OR, USA
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
- Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA
- Department of Endocrinology, Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Canada
| | - Dawn Shao Ting Lim
- Department of Medicine, Oregon Health & Science University, Portland, OR, USA
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
- Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - Elena Varlamov
- Department of Medicine, Oregon Health & Science University, Portland, OR, USA
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
- Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA
| | - Chris G Yedinak
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
- Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA
| | - Justin S Cetas
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
- Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA
| | - Shirley McCartney
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
- Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA
| | - Aclan Dogan
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
- Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA
| | - Maria Fleseriu
- Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA.
- Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA.
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23
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Pojskić M, Zbytek B, Beckford NS, Boop FA, Arnautović KI. First Report of Coexistence of Two Ectopic Pituitary Tumors: Rathke Cleft Cyst and Silent Adrenocorticotropic Hormone Adenoma. World Neurosurg 2017; 104:1048.e1-1048.e7. [PMID: 28532906 DOI: 10.1016/j.wneu.2017.05.070] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Revised: 05/09/2017] [Accepted: 05/11/2017] [Indexed: 11/26/2022]
Abstract
BACKGROUND Rathke cleft cysts (RCCs) and pituitary adenomas (PAs) are thought to have a common embryonic ancestry; however, PAs with a concomitant RCC inside the sella turcica are rarely observed. Ectopic pituitary tumors are also rare. CASE DESCRIPTION We present the case of a 65-year-old woman with an ectopic RCC in the sphenoid sinus and outside the sella turcica concomitant with an adrenocorticotropic hormone (ACTH)-staining, clinically silent PA. The patient had headache but no endocrine or visual disturbances. Preoperative magnetic resonance imaging revealed infrasellar cystic lesion in the sphenoid sinus with erosion of the clivus and intact sellar floor. The patient underwent gross total microsurgical resection through the transnasal route with an uneventful postoperative course. CONCLUSIONS To our knowledge, this is the first reported ectopic RCC located outside the sella turcica with a concomitant ACTH-staining PA. This also appears to be the first ACTH-staining adenoma concomitant with RCC reported in the literature, regardless of location, not presenting with Cushing disease. This case shows that we can now include pituitary adenoma with or without a concomitant RCC in the differential diagnosis of processes in the sphenoid sinus. As both PAs and RCCs are benign sellar lesions, surgical management of a concomitant occurrence of these tumors mainly depends on the size of the lesions and their clinical manifestations. For patients with PA and concomitant RCC, surgical resection should be considered, as there is an approximatrely 20% recurrence rate of the cyst after resection and the possibility of future clival erosion, if left untreated.
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Affiliation(s)
- Mirza Pojskić
- Department of Neurosurgery, University of Marburg, Marburg, Germany
| | - Blazej Zbytek
- Department of Pathology and Laboratory Medicine; Center for Adult Cancer Research; University of Tennessee Health Science Center, Memphis, Tennessee
| | - Neal S Beckford
- Department of Otolaryngology-Head-Neck Surgery, University of Tennessee-Memphis, Memphis, Tennessee
| | - Frederick A Boop
- Semmes Murphey Neurologic and Spine Institute and Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Kenan I Arnautović
- Semmes Murphey Neurologic and Spine Institute and Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
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Righi A, Faustini-Fustini M, Morandi L, Monti V, Asioli S, Mazzatenta D, Bacci A, Foschini MP. The changing faces of corticotroph cell adenomas: the role of prohormone convertase 1/3. Endocrine 2017; 56:286-297. [PMID: 27491554 DOI: 10.1007/s12020-016-1028-0] [Citation(s) in RCA: 24] [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] [Received: 03/09/2016] [Accepted: 06/18/2016] [Indexed: 10/21/2022]
Abstract
The spectrum of corticotroph cell adenomas is very wide. Though rarely, silent corticotroph cell adenomas (SCA) may transform into corticotroph cell adenomas associated with Cushing's disease (CD). The aim of the study was to investigate the role of prohormone convertase 1/3 (PC1/3) in the transformation of SCA into CD. We reviewed the records of 1259 consecutive endoscopic endonasal procedures for pituitary adenomas from 1998 to 2013. Of these, 132 were CD and 44 were SCA. During the follow-up, three patients with SCA showed a clear transformation from SCA into CD and underwent surgery once again to remove the recurrent tumour. The PC1/3 expression was analysed by both immunohistochemistry and quantitative real time-polymerase chain reaction (qRT-PCR) in primary and recurrent tumours. The immunohistochemical PC1/3 expression was negative or weak in the three patients in the initial phase of SCA, while a strong expression was observed in the majority of neoplastic cells in tissue specimens obtained from the same three patients at the time of recurrence as CD. The immunohistochemical PC1/3 expression showed a strict correlation with the PC1/3 levels obtained by qRT-PCR. In 14 cases of SCA with no change of phenotype during the follow-up, the immunohistochemical PC1/3 expression was low and strictly associated with the level of PC1/3 obtained by qRT-PCR both in primary (14/14 cases) and in recurrent tumours (4/4 cases). Our study provides insight into the crucial role of the PC1/3 protein in the transformation of phenotype from SCA to CD.
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Affiliation(s)
- Alberto Righi
- Department of Pathology, Rizzoli Institute, Bologna, Italy
| | - Marco Faustini-Fustini
- IRCCS Institute of Neurological Sciences of Bologna (ISNB), Bellaria Hospital, Via Altura, 3, Bologna, 40139, Italy.
| | - Luca Morandi
- Department of Biomedical and Neuro-Muscular Sciences, Section of Anatomic Pathology 'M.Malpighi' at Bellaria Hospital, University of Bologna, Bologna, Italy
| | - Valentina Monti
- Department of Biomedical and Neuro-Muscular Sciences, Section of Anatomic Pathology 'M.Malpighi' at Bellaria Hospital, University of Bologna, Bologna, Italy
| | - Sofia Asioli
- Department of Biomedical and Neuro-Muscular Sciences, Section of Anatomic Pathology 'M.Malpighi' at Bellaria Hospital, University of Bologna, Bologna, Italy
| | - Diego Mazzatenta
- Department of Neurosurgery, Center of Pituitary Tumors and Endoscopic Skull Base Surgery, IRCCS Institute of Neurological Sciences of Bologna (ISNB), Bellaria Hospital, Bologna, Italy
| | - Antonella Bacci
- Department of Neuroradiology, IRCCS Institute of Neurological Sciences of Bologna (ISNB), Bologna, Italy
| | - Maria Pia Foschini
- Department of Biomedical and Neuro-Muscular Sciences, Section of Anatomic Pathology 'M.Malpighi' at Bellaria Hospital, University of Bologna, Bologna, Italy
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Kulubya ES, Donoho DA, Carmichael JD, Zada G. Surgical management of adrenocorticotropic hormone-secreting pituitary adenomas. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2016. [DOI: 10.2217/ije.15.26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Cushing's disease is defined as hypercortisolemia caused by secretion of adrenocorticotropic hormone from a pituitary adenoma. The diagnosis of Cushing's disease is based on clinical symptoms, laboratory and imaging findings. Once an adrenocorticotropic-hormone-secreting adenoma is found, the standard of care is transsphenoidal adenomectomy. MRI negative microadenomas and large, invasive macroadenomas provide a surgical and clinical challenge and are best handled at high volume centers. Multiple options exist for refractory disease or recurrence, including repeat surgery, radiosurgery and radiotherapy, medical management and bilateral adrenalectomy.
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Affiliation(s)
- Edwin S Kulubya
- Department of Neurosurgery, Keck School of Medicine of USC, 1200 North State Street, Suite 5046, Los Angeles, CA 90089, USA
| | - Daniel A Donoho
- Department of Neurosurgery, Keck School of Medicine of USC, 1200 North State Street, Suite 5046, Los Angeles, CA 90089, USA
| | - John D Carmichael
- USC Pituitary Center, Keck School of Medicine of USC, Los Angeles, CA 90089, USA
| | - Gabriel Zada
- Department of Neurosurgery, Keck School of Medicine of USC, 1200 North State Street, Suite 5046, Los Angeles, CA 90089, USA
- USC Pituitary Center, Keck School of Medicine of USC, Los Angeles, CA 90089, USA
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