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Papanikolaou N, Millar O, Coulden A, Parker N, Sit L, Kelly C, Cox J, Dhillo WS, Meeran K, Al Memar M, Anderson R, Rees DA, Karavitaki N, Jayasena CN. Clinical characteristics of functioning gonadotroph adenoma in women presenting with ovarian hyperstimulation: Audit of UK pituitary centres. Clin Endocrinol (Oxf) 2023; 99:386-395. [PMID: 37430451 DOI: 10.1111/cen.14949] [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: 02/13/2023] [Revised: 05/17/2023] [Accepted: 07/03/2023] [Indexed: 07/12/2023]
Abstract
OBJECTIVE Functioning gonadotroph adenomas (FGAs) are rare pituitary tumours stimulating ovarian function with potential life-threatening consequences in women. However, a lack of aggregated clinical experience of FGAs impairs management in affected women. The aim of this study is to present the clinical course of FGA-induced ovarian hyperstimulation syndrome (OHSS) cases as identified by some of the largest UK pituitary endocrine tertiary centres with a view to increasing awareness and improving diagnosis and management of women with FGA. DESIGN A retrospective observational study; audit of eight UK regional pituitary centres for cases of FGAs. SETTING Specialist neuroendocrine centres in the United Kingdom. PATIENTS AND MEASUREMENTS Women diagnosed with FGA-induced OHSS. Description of their clinical course. RESULTS Seven cases of FGA were identified in women, all causing OHSS. Mean age was 33.4 years at diagnosis. Abdominal pain, irregular periods, headache, and visual disturbances were reported at presentation by 100%, 71%, 57% and 43% of women, respectively. Three of seven women underwent ovarian surgery before FGA diagnosis. Six women underwent transsphenoidal surgery (TSS) with incomplete tumour resection in five of those, but all showed improvement or resolution in symptoms and biochemistry postoperatively. CONCLUSION FGA is a rare cause of spontaneous OHSS. TSS improves clinical and biochemical features of ovarian hyperstimulation in FGAs. Improved awareness of FGA will prevent inappropriate emergency ovarian surgery.
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Affiliation(s)
| | - Ophelia Millar
- Department of Metabolism, Digestion and Reproduction, Imperial College, London, UK
| | - Amy Coulden
- Institute of Metabolism and Systems Research (IMSR), College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Edgbaston, Birmingham, UK
| | - Nina Parker
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Lee Sit
- The Royal Infirmary of Edinburgh Hospital, Edinburgh, UK
| | - Chris Kelly
- Department of Endocrinology, Forth Valley Royal Hospital, Larbert, UK
| | - Jeremy Cox
- Department of Metabolism, Digestion and Reproduction, Imperial College, London, UK
| | - Waljit S Dhillo
- Department of Metabolism, Digestion and Reproduction, Imperial College, London, UK
| | - Karim Meeran
- Department of Metabolism, Digestion and Reproduction, Imperial College, London, UK
| | - Maya Al Memar
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Richard Anderson
- MRC Centre for Reproductive Health, Institute of Regeneration and Repair, University of Edinburgh, Edinburgh, UK
| | - D Aled Rees
- Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
| | - Niki Karavitaki
- Institute of Metabolism and Systems Research (IMSR), College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Edgbaston, Birmingham, UK
| | - Channa N Jayasena
- Department of Metabolism, Digestion and Reproduction, Imperial College, London, UK
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He Y, Gao YT, Sun L. Functioning gonadotroph adenoma with hyperestrogenemia and ovarian hyperstimulation in a reproductive-aged woman: A case report and review of literature. World J Clin Cases 2023; 11:1341-1348. [PMID: 36926127 PMCID: PMC10013118 DOI: 10.12998/wjcc.v11.i6.1341] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Revised: 12/28/2022] [Accepted: 02/02/2023] [Indexed: 02/23/2023] Open
Abstract
BACKGROUND Functioning gonadotroph adenomas are extremely rare pituitary tumors that secrete gonadotropins and exhibit distinct clinical manifestations. Here, we report a case of functioning gonadotroph adenoma in a reproductive-aged woman and discuss its diagnosis and management.
CASE SUMMARY A 21-year-old female patient with abdominal pain, irregular menstruation, hyperestrogenemia, and an ovarian mass was included. Brain magnetic resonance imaging (MRI) revealed a pituitary macroadenoma, and transsphenoidal surgery relieved her clinical symptoms. Before transsphenoidal surgery, plasma CA125, estradiol levels were elevated, while prolactin, luteinizing hormone, follicle-stimulating hormone, PROG, cortisol, FT4, thyroid-stimulating hormone, parathyroid hormone, and GH levels were maintained at normal levels. After transsphenoidal surgery, the patient was diagnosed with a functioning gonadotroph adenoma. During follow-up, pelvic ultrasound confirmed normal-sized ovaries in the patient, the menstrual cycle returned to regular, and her hormones were maintained within a normal range. There was no evidence of tumor recurrence after two years of follow-up.
CONCLUSION Early diagnosis of functioning gonadotroph adenomas should be considered in patients with hyperestrogenism, irregular menstruation, large or recurrent ovarian cysts, and visual field defects. Pituitary MRI should be performed, and transsphenoidal surgery is recommended for the management of this disease.
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Affiliation(s)
- Ying He
- Department of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Yu-Tao Gao
- Department of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Li Sun
- Department of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Department of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
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Ntali G, Capatina C. Updating the Landscape for Functioning Gonadotroph Tumors. Medicina (B Aires) 2022; 58:medicina58081071. [PMID: 36013538 PMCID: PMC9414558 DOI: 10.3390/medicina58081071] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 08/03/2022] [Accepted: 08/04/2022] [Indexed: 11/16/2022] Open
Abstract
Functioning gonadotroph adenomas (FGAs) are rare tumors, as the overwhelming majority of gonadotroph tumors are clinically silent. Literature is based on case reports and small case series. Gonadotroph tumors are poorly differentiated and produce and secrete hormones inefficiently, but in exceptional cases, they cause clinical syndromes due to hypersecretion of intact gonadotropins. The clinical spectrum of endocrine dysfunction includes an exaggerated response of ovaries characterized as ovarian hyperstimulation syndrome (OHSS) in premenopausal females and adolescent girls, testicular enlargement in males, and isosexual precocious puberty in children. Transsphenoidal surgery and removal of tumor reduces hormonal hypersecretion, improves endocrine dysfunction, and provides tissue for further analysis. Medical therapies (somatostatin analogues, dopamine agonists, GnRH agonists/antagonists) are partially or totally ineffective in many cases, especially with respect to antitumor effect. This review aims to update recent literature on these rare functioning tumors and highlight their therapeutic management.
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Affiliation(s)
- Georgia Ntali
- Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital, 10676 Athens, Greece
- Correspondence:
| | - Cristina Capatina
- Department of Endocrinology, Carol Davila UMPh, 011863 Bucharest, Romania
- Department of Pituitary and Neuroendocrine diseases, CI Parhon National Institute of Endocrinology, 011863 Bucharest, Romania
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Gonadotroph Pituitary Adenoma Causing Treatable Infertility and Ovarian Hyperstimulation Syndrome in Female Patients: Neurosurgical, Endocrinologic, Gynecologic, and Reproductive Outcomes. World Neurosurg 2021; 150:e162-e175. [PMID: 33684575 DOI: 10.1016/j.wneu.2021.02.115] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 02/22/2021] [Accepted: 02/26/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND Gonadotroph pituitary adenoma (Gn-PA) may rarely cause ovarian hyperstimulation syndrome, leading to infertility in women, although this remains poorly described. METHODS We present a quantitative systematic review including 2 patients from our institutional and 48 from the literature with Gn-PA causing ovarian hyperstimulation syndrome to thoroughly describe the clinical features and therapeutic outcomes from multidisciplinary aspects. RESULTS The patients had a mean age of 31.5 years and a mean follicle-stimulating hormone level of 14.4 IU/L. Estradiol level was high in 82% of patients, at >350 pg/mL. The mean maximal adenoma diameter was 22 mm, with a Knosp grade ≥3 in 10 patients. Abdominal surgery preceded adenoma resection in 24 patients (48%). Among 25 patients for whom extent of resection was recorded, total adenoma resection was achieved in 12. Through a mean follow-up of 25 months, adenoma recurrence was observed in 5 patients, who were treated with re-resection (n = 2), radiation (n = 2), and medical therapy followed by bilateral oophorectomy (n = 1). Medical therapies were partially effective or ineffective, and adenoma shrinkage did not follow; gonadotropin-releasing hormone agonists/antagonists were partially effective in 20% of patients (2/10), dopamine agonists in 44% (8/18), and somatostatin analogues in 50% (1/2). Four experienced swelling of tumor/ovaries after gonadotropin-releasing hormone agonists/antagonists administration. Overall, chemical remission was obtained in 26 of 28 patients, normalization of ovaries in 25 of 27, and successful pregnancy in 12 of 14. CONCLUSIONS Adenoma resection is the main treatment, leading to reduction in ovarian size and biochemical remission, with a high likelihood of subsequent spontaneous pregnancy. Increased awareness of this rare condition may help avoid unnecessary abdominal procedures.
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Multiple Luteinized Follicle Cysts of the Ovary in a Patient With a Pituitary Adenoma. Int J Gynecol Pathol 2019; 38:562-567. [DOI: 10.1097/pgp.0000000000000555] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Graillon T, Castinetti F, Chabert-Orsini V, Morange I, Cuny T, Albarel F, Brue T, Dufour H. Functioning gonadotroph adenoma with severe ovarian hyperstimulation syndrome: A new emergency in pituitary adenoma surgery? Surgical considerations and literature review. ANNALES D'ENDOCRINOLOGIE 2019; 80:122-127. [DOI: 10.1016/j.ando.2018.11.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 10/27/2018] [Accepted: 11/10/2018] [Indexed: 10/27/2022]
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Vargas G, Balcazar-Hernandez LJ, Melgar V, Magriña-Mercado RM, Gonzalez B, Baquera J, Mercado M. An FSH and TSH pituitary adenoma, presenting with precocious puberty and central hyperthyroidism. Endocrinol Diabetes Metab Case Rep 2017; 2017:EDM170057. [PMID: 28721217 PMCID: PMC5510394 DOI: 10.1530/edm-17-0057] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2017] [Accepted: 06/06/2017] [Indexed: 11/20/2022] Open
Abstract
A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH.
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Affiliation(s)
- Guadalupe Vargas
- Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico CityMexico
| | - Lourdes-Josefina Balcazar-Hernandez
- Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico CityMexico
| | | | - Roser-Montserrat Magriña-Mercado
- Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico CityMexico
| | - Baldomero Gonzalez
- Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico CityMexico
| | - Javier Baquera
- Pathology Department, American British Cowdray Hospital, Mexico CityMexico
| | - Moisés Mercado
- Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico CityMexico.,Neurological Center
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Ceccato F, Occhi G, Regazzo D, Randi ML, Cecchin D, Gardiman MP, Manara R, Lombardi G, Denaro L, Mantero F, Scaroni C. Gonadotropin secreting pituitary adenoma associated with erythrocytosis: case report and literature review. Hormones (Athens) 2014; 13:131-9. [PMID: 24722134 DOI: 10.1007/bf03401328] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Most pituitary adenomas with FSH- or LH-positive immunohistochemistry are endocrinologically silent, and neurological symptoms due to their large volume are the first clinical signs; they are rarely reported to be secreting gonadotropins, this usually occurring in cases with clinical endocrine findings. Gonadotropinomas are often treated surgically because they are unresponsive to conventional medical therapies. Temozolomide was recently recommended for non-responder aggressive pituitary adenoma management. CASE REPORT A 43-year-old male with a history of 5 years of erythrocytosis presented with severe headache, orthostatic dizziness, and difficulty walking. MRI documented a giant pituitary adenoma and high uptake of 111In-pentetreotide indicated somatostatin receptor (SSR) expression. Biochemical tests revealed a secreting gonadotropinoma. Therapy with somatostatin analogs and dopamine agonists improved the patient's headache, achieved partial hormone control, slightly reduced the size of the adenoma, and controlled erythrocytosis. Six months after the diagnosis, hormone escape occurred despite therapy, thus neurosurgery was performed. After the procedure the patient died of untreatable intracranial hypertension. The surgical specimen revealed SSR 2 and 3 expression, and temozolomide did not induce apoptosis in primary cell culture. REVIEW OF LITERATURE Among gonadotropinomas, female gender (77%), macroadenoma (84%), young age at diagnosis (28 ± 12 years), delay from first symptoms to diagnosis (up to 15 years), and ovarian cysts/menstrual disorders in females or macro-orchidism in males were the foremost clinical and neuroimaging features. CONCLUSIONS Male gonadotropin-secreting pituitary adenomas may have a variable clinical expression secondary to testosterone excess. Somatostatin analogs, dopamine agonists or temozolomide may have a role that needs to be assessed case by case.
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Affiliation(s)
- Filippo Ceccato
- Endocrinology Unit, Department of Medicine DIMED; University of Padua Medical School, Padua, Italy
| | - Gianluca Occhi
- Endocrinology Unit, Department of Medicine DIMED; University of Padua Medical School, Padua, Italy
| | - Daniela Regazzo
- Endocrinology Unit, Department of Medicine DIMED; University of Padua Medical School, Padua, Italy
| | - Maria Luigia Randi
- Internal Medicine, Department of Medicine DIMED; University of Padua Medical School, Padua, Italy
| | - Diego Cecchin
- Nuclear Medicine Unit, Department of Medicine DIMED; University of Padua Medical School, Padua, Italy
| | - Marina Paola Gardiman
- Surgical Pathology and Cytopathology Unit, Department of Medicine DIMED; University of Padua Medical School, Padua, Italy
| | - Renzo Manara
- Neuroradiologic Unit, University Hospital of Padua, Padua, Italy
| | - Giuseppe Lombardi
- Medical Oncology 1, Venetian Oncology Institute - IRCCS, Padua, Italy
| | - Luca Denaro
- Neurosurgery Division, University Hospital of Padua; Padua, Italy
| | - Franco Mantero
- Endocrinology Unit, Department of Medicine DIMED; University of Padua Medical School, Padua, Italy
| | - Carla Scaroni
- Endocrinology Unit, Department of Medicine DIMED; University of Padua Medical School, Padua, Italy
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Uchida S, Uchida H, Maruyama T, Kajitani T, Oda H, Miyazaki K, Kagami M, Yoshimura Y. Molecular analysis of a mutated FSH receptor detected in a patient with spontaneous ovarian hyperstimulation syndrome. PLoS One 2013; 8:e75478. [PMID: 24058690 PMCID: PMC3772932 DOI: 10.1371/journal.pone.0075478] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Accepted: 08/20/2013] [Indexed: 11/18/2022] Open
Abstract
Spontaneous ovarian hyperstimulation syndrome (sOHSS) is a rare event that may result from a FSH-producing pituitary adenoma (FSHoma), activating mutations of the FSH receptor (FSHR), and cross-reactivity of the FSHR to elevated hCG and TSH in the setting of pregnancy or hypothyroidism. The objective of this study was to investigate whether an aberrant FSHR was present in a woman with sOHSS and a non-surgically diagnosed FSHoma whose serum FSH levels and FSH bioactivity were nearly normal. Sequencing of the patient's FSHR gene revealed a heterozygous novel missense mutation c. 1536G>A resulting in an amino acid substitution M512I. We asked whether this mutant FSHR affected FSHR-mediated signaling pathways involving cAMP/protein kinase A (PKA), phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) and v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog kinase (SRC)/ p42/p44 extracellular signal-regulated protein kinases (ERK1/2). Thus, 293T cells expressing wild-type (FSHRwt), the mutant FSHR (FSHRmt), or both (FSHRwt/mt) were treated with FSH and subjected to measurements of intracellular cAMP, cAMP-induced CRE (cAMP response element)-mediated luciferase assays and immunoblot analyses of phosphorylated PI3K and ERK1/2. There were no differences in luciferase activities or phosphorylation levels of ERK1/2 among FSHRwt, FSHRmt cells and FSHwt/mt cells. However, FSHRmt cells showed a significant reduction in both cAMP production and PI3K phosphorylation levels with unchanged phosphorylation of ERK1/2 upon FSH stimulation in comparison to FSHwt cells. Also, FSH treatment did not provoke PI3K phosphorylation in FSHwt/mt cells. These results indicate that the novel missense M512I FSHR mutation identified herein did not participate in hyperactivation of FSHR-mediated signaling pathways but rather in hypoactivation of the FSH-mediated PI3K/AKT pathway. Thus, this study demonstrates a new functional property of this novel mutatnt FSHR, which, however, might not be involved in the pathogenesis of sOHSS in this FSHoma patient.
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Affiliation(s)
- Sayaka Uchida
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
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Tamiya H, Fukuhara N, Yoshida N, Suzuki H, Takeshita A, Inoshita N, Nishioka H, Takeuchi Y, Sano T, Yamada S. A silent follicle-stimulating hormone-producing pituitary adenoma in a teenage male. Endocr Pathol 2011; 22:212-7. [PMID: 21853289 DOI: 10.1007/s12022-011-9173-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
An 18-year-old male was referred to Toranomon Hospital seeking reoperation for recurrent clinically nonfunctioning pituitary adenoma. A pituitary macroadenoma was first suspected at age 15 due to intractable headaches. Endocrine data were unremarkable except slightly elevated serum follicle-stimulating hormone (FSH). Transsphenoidal surgery done at another hospital achieved partial tumor removal but the remaining tumor regrew 2 years after surgery. The recurrent tumor was completely and selectively removed on repeat surgery at Toranomon Hospital. Pathological examination confirmed a silent FSH-producing pituitary adenoma. Forty-five patients less than 20 years old underwent transsphenoidal surgery for pituitary adenoma at Toranomon Hospital between 1993 and 2010. Of the 45 patients, 36 (80.0%) had clinically functioning adenomas and the other 9 (20.0%) had clinically non-functioning adenomas. No patients, other than the present case, had a silent gonadotroph adenoma. In contrast, among 579 patients over 20 years old undergoing surgery for nonfunctioning pituitary adenomas between 2006 and 2010 at Toranomon Hospital, 304 (52.3%) had silent gonadotroph adenomas. Gonadotroph adenomas are more common with aging: for example, 37 (61.7%) of 60 patients more than 70 years old at the time of operation had gonadotroph adenomas. In conclusion, gonadotroph adenomas, especially silent gonadotroph adenomas, are extremely rare in childhood and adolescence.
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Affiliation(s)
- Hiroyuki Tamiya
- Department of Endocrinology, Toranomon Hospital, Toranomon 2-2-2, Minato, Tokyo, 105-8470, Japan.
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Burgos J, Cobos P, Vidaurrazaga N, Prieto B, Ocerin I, Matorras R. Ovarian hyperstimulation secondary to ectopic secretion of follicle-stimulating hormone. Literature review prompted by a case. Fertil Steril 2009; 92:1168.e5-1168.e8. [PMID: 19608176 DOI: 10.1016/j.fertnstert.2009.06.023] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2009] [Revised: 06/07/2009] [Accepted: 06/08/2009] [Indexed: 10/20/2022]
Abstract
OBJECTIVE To present an exceptional clinical case of functional follicle-stimulating gonadotropin secretion by a thorax neuroendocrine carcinoid tumor. DESIGN Case report. SETTING Department of Obstetrics and Gynecology, Cruces University Hospital, Vizcaya, Spain. PATIENT(S) A 26-year-old woman with ovarian hyperstimulation. INTERVENTION(S) Diagnosis algorithm. MAIN OUTCOME MEASURE(S) Successful management of ovarian hyperstimulation. RESULT(S) A 26-year-old woman seen with abdominal pain and swelling had bilateral multicystic ovaries. The diagnosis algorithm revealed the presence of ovarian hyperstimulation but with no due etiology. On the basis of the persistence of high levels of FSH a computed tomographic scan was taken looking for an FSH-producing neuroendocrine tumor. CONCLUSION(S) In idiopathic ovarian hyperstimulation secondary to supraphysiologic secretion of FSH, the presence of an FSH-producing neuroendocrine tumor should be considered. As far as we know, there are no similar cases with a confirmed diagnosis published in the literature.
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Affiliation(s)
- Jorge Burgos
- Human Reproduction Unit, Department of Obstetrics and Gynecology, Hospital de Cruces, Vizcaya, Spain; School of Medicine, Universidad del País Vasco, Vizcaya, Spain.
| | - Patricia Cobos
- Human Reproduction Unit, Department of Obstetrics and Gynecology, Hospital de Cruces, Vizcaya, Spain
| | - Nerea Vidaurrazaga
- School of Medicine, Universidad del País Vasco, Vizcaya, Spain; Department of Anatomopathology, Hospital de Cruces, Vizcaya, Spain
| | - Begoña Prieto
- Human Reproduction Unit, Department of Obstetrics and Gynecology, Hospital de Cruces, Vizcaya, Spain
| | - Iratxe Ocerin
- School of Medicine, Universidad del País Vasco, Vizcaya, Spain; Endoscopy Unit, Department of Obstetrics and Gynecology, Hospital de Cruces, Vizcaya, Spain
| | - Roberto Matorras
- Human Reproduction Unit, Department of Obstetrics and Gynecology, Hospital de Cruces, Vizcaya, Spain; School of Medicine, Universidad del País Vasco, Vizcaya, Spain
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Castelo-Branco C, del Pino M, Valladares E. Ovarian hyperstimulation, hyperprolactinaemia and LH gonadotroph adenoma. Reprod Biomed Online 2009; 19:153-5. [DOI: 10.1016/s1472-6483(10)60065-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Knoepfelmacher M, Danilovic DLS, Rosa Nasser RHR, Mendonça BB. Effectiveness of treating ovarian hyperstimulation syndrome with cabergoline in two patients with gonadotropin-producing pituitary adenomas. Fertil Steril 2006; 86:719.e15-8. [PMID: 16952513 DOI: 10.1016/j.fertnstert.2006.01.055] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2005] [Revised: 01/08/2006] [Accepted: 01/08/2006] [Indexed: 11/28/2022]
Abstract
OBJECTIVE To report the effect of cabergoline on ovarian hyperstimulation syndrome associated with gonadotropin-secreting pituitary adenomas. DESIGN Case report. SETTING Outpatient practice. PATIENT(S) Two women with menstrual irregularity, enlarged ovaries, high E(2), and normal gonadotropin levels. INTERVENTION(S) Cabergoline treatment and transsphenoidal surgery. MAIN OUTCOME MEASURE(S) Estradiol levels, transvaginal ultrasonography, and pituitary magnetic resonance imaging. Transsphenoidal surgery showed pituitary adenoma staining for LH in both patients. RESULT(S) Cabergoline was effective in reducing E(2) levels and decreasing ovarian size but ineffective in shrinking the pituitary adenomas. CONCLUSION(S) This is the first description of the effectiveness of cabergoline as the primary treatment of spontaneous ovarian hyperstimulation syndrome in patients with gonadotropin-producing pituitary adenomas.
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Affiliation(s)
- Mirta Knoepfelmacher
- Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM/42, Disciplina de Endocrinologia e Metabologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
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Sicilia V, Earle J, Mezitis SGE. Multiple Ovarian Cysts and Oligomenorrhea as The Initial Manifestations of A Gonadotropin-Secreting Pituitary Macroadenoma. Endocr Pract 2006; 12:417-21. [PMID: 16901798 DOI: 10.4158/ep.12.4.417] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE To report a case of a follicle-stimulating hormone (FSH)-secreting pituitary adenoma, which manifested with oligomenorrhea, dysmenorrhea, and multiple bilateral ovarian cysts. METHODS We present a case report of a 29-year-old woman, including detailed laboratory, radiologic, and pathologic findings, who was diagnosed as having an FSH-secreting pituitary tumor. The pertinent literature is also reviewed. RESULTS A 29-year-old woman, after experiencing oligomenorrhea and increasing abdominal girth for >1 year, presented with an acute abdomen. Ultrasonography revealed multicystic ovaries >15 cm in maximal diameter, causing bilateral adnexal torsion. After bilateral ovarian cystectomies, ultrasound study showed recurrence of the cysts. Relevant laboratory data were as follows: serum FSH 6.8 mIU/mL, luteinizing hormone 0.1 mIU/mL, prolactin 67 ng/mL, human chorionic gonadotropin <2 mIU/mL, progesterone 3.5 ng/dL, estradiol 237 pg/mL, thyrotropin 1.8 microIU/mL, testosterone <4 ng/dL, insulin 8.0 microIU/mL, and fasting plasma glucose 87 mg/dL. Magnetic resonance imaging (MRI) of the brain revealed a 2.5-cm pituitary mass, although the patient had no symptoms of pituitary dysfunction. Transsphenoidal removal of the mass was performed, and pathology studies were positive for FSH-secreting adenoma. Repeated MRI at 3 months showed an 0.8-cm residual tumor. The patient refused adjuvant radiotherapy. Regular menses resumed within 2 months postoperatively, and she later successfully became pregnant. Almost 3 years after treatment, the patient remained asymptomatic, results of pituitary function tests were normal, and follow-up MRI showed no signs of tumor regrowth. CONCLUSION Although very uncommon, gonadotropin-secreting pituitary adenomas should be considered in the differential diagnosis of new-onset oligomenorrhea and dysmenorrhea, especially if associated with multicystic ovaries on ultrasound study, even in the absence of elevated levels of serum gonadotropins. Furthermore, we propose that it may be acceptable to withhold adjuvant radiotherapy in patients who are asymptomatic after transsphenoidal surgical excision of these tumors.
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Affiliation(s)
- Vitaliano Sicilia
- Department of Internal Medicine, Lenox Hill Hospital, New York, New York, USA
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Kihara M, Sugita T, Nagai Y, Saeki N, Tatsuno I, Seki K. Ovarian hyperstimulation caused by gonadotroph cell adenoma: a case report and review of the literature. Gynecol Endocrinol 2006; 22:110-3. [PMID: 16603438 DOI: 10.1080/09513590600581665] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
Abstract
OBJECTIVE We present a case of spontaneous ovarian hyperstimulation caused by pituitary gonadotroph macroadenoma, and include a review of the literature. CASE REPORT A 27-year-old woman presented with irregular menstruation and bilateral multicystic enlargement of the ovaries. Serum estradiol (E(2)) levels were marginally elevated for the follicular phase but within the physiological range. Serum luteinizing hormone (LH) was extremely low, follicle-stimulating hormone (FSH) was normal, and prolactin (PRL) was high. Magnetic resonance imaging disclosed a pituitary macroadenoma. Immunohistochemical examination of the surgically removed adenoma showed intense reactivity for FSH and LH. After the operation, E(2), LH and PRL levels were normalized, the ovaries returned to a normal morphology, and regular menstrual cycles were resumed. CONCLUSION A review of the literature showed that ovarian hyperstimulation caused by pituitary gonadotroph adenoma is not always accompanied by elevated FSH levels. High PRL and E(2) and low LH were reported in the majority of the cases, but E(2) may stay within the range observed in normal menstrual cycles.
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Affiliation(s)
- Maki Kihara
- Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
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Maruyama T, Masuda H, Uchida H, Nagashima T, Yoshimura Y. Follicle stimulating hormone-secreting pituitary microadenoma with fluctuating levels of ovarian hyperstimulation. Obstet Gynecol 2005; 105:1215-8. [PMID: 15863587 DOI: 10.1097/01.aog.0000141554.50747.16] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Enlarged multicystic ovaries and an elevated estradiol (E2) concentration have been reported as characteristics of follicle stimulating hormone (FSH)-secreting adenomas in reproductive-aged women. The natural course of the hormone in relationship to the microadenoma and ovarian findings, however, remains largely unknown. CASE A 40-year-old woman with enlarged multicystic ovaries was nonsurgically diagnosed with an FSH-producing pituitary microadenoma. During her subsequent 12-month follow-up, the serum concentration of E2, but not FSH, and the size of the multicystic ovaries fluctuated dramatically. Both the E2 level and ovarian size were transiently normalized. CONCLUSION Because of disease-related fluctuations, a reproductive-aged woman with an FSH-producing adenoma did not always present with laboratory values characteristic of ovarian hyperstimulation. This finding points out a possible pitfall in diagnosis and clinical management.
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Affiliation(s)
- Tetsuo Maruyama
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
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Murakami T, Higashitsuji H, Yoshinaga K, Terada Y, Ito K, Ikeda H. CASE REPORT: Management of ovarian hyperstimulation due to follicle-stimulating hormone-secreting gonadotroph adenoma. BJOG 2004; 111:1297-300. [PMID: 15521879 DOI: 10.1111/j.1471-0528.2004.00409.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Takashi Murakami
- Department of Obstetrics and Gynaecology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
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Saito T, Tojo K, Kuriyama G, Murakawa Y, Fujimoto K, Taniguchi K, Tanii K, Katakami H, Hashimoto K, Tajima N. A case of acquired deficiency of pituitary GH, PRL and TSH, associated with type 1 diabetes mellitus. Endocr J 2004; 51:287-93. [PMID: 15256773 DOI: 10.1507/endocrj.51.287] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
A 75-year-old male showed combined anterior pituitary hormone deficiency (CPHD). Basal and TRH-stimulated PRL levels were undetectable. Basal and GRH-stimulated GH levels were very low, and could barely be measured by means of an ultrasensitive enzyme immunoassay. In addition, basal TSH levels were under the normal limit, and TRH-stimulated TSH secretions were impaired. On the other hand, the secretions of ACTH, LH and FSH remained intact. There was no mutation of Pit-1 gene in this patient, and immunohistochemical studies using human pituitary and the patient's serum showed no positive staining. The HLA types frequently detected in lymphocytic hypophysitis were recognized, supporting the view that the CPHD in this case may be caused by lymphocytic hypophysitis, although magnetic resonance imaging of the pituitary gland showed no specific findings. Interestingly, a high titer of anti-glutamic acid decarboxylase antibody, suggested that the patient suffered from type 1 diabetes mellitus (DM). Five years ago, his thyroid function was normal and the treatment of DM with oral hypoglycemic agent was effective, indicating that the onset of both diseases at least occurred within the last half decade. We report here a rare case of SPIDDM with CPHD which might be caused by lymphocytic hypophysitis.
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Affiliation(s)
- Takatoshi Saito
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
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Castelbaum AJ, Bigdeli H, Post KD, Freedman MF, Snyder PJ. Exacerbation of ovarian hyperstimulation by leuprolide reveals a gonadotroph adenoma. Fertil Steril 2002; 78:1311-3. [PMID: 12477530 DOI: 10.1016/s0015-0282(02)04342-x] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To report a case of a gonadotroph adenoma diagnosed after a dramatic increase in estradiol level and ovarian hyperstimulation in response to a gonadotropin-releasing hormone agonist. DESIGN Case report. SETTING Outpatient practice and university hospital. PATIENT(S) A 35-year-old woman who presented with infertility, amenorrhea, and an elevated basal estradiol concentration. INTERVENTION(S) Ultrasonography, laparoscopy, endocrinologic assays, magnetic resonance imaging, transsphenoidal surgery, and immunocytochemical staining. MAIN OUTCOME MEASURE(S) Ultrasonography and laparoscopy demonstrated bilaterally enlarged ovaries containing multiple preovulatory follicles, similar in appearance in those women undergoing controlled ovarian hyperstimulation with exogenous FSH. The serum estradiol level was moderately elevated, the FSH level was within the normal range, and LH was suppressed. Administration of leuprolide acetate resulted in very elevated estradiol concentrations and even larger ovarian cysts. Magnetic resonance imaging demonstrated a sellar mass. Examination of the tissue excised by transsphenoidal excision of the mass showed a pituitary adenoma that stained strongly for FSH. RESULT(S) Regular menses resumed soon after excision of the gonadotroph adenoma, followed by a spontaneous pregnancy. CONCLUSIONS Gonadotroph adenoma should be suspected in a reproductive age woman with oligomenorrhea or amenorrhea, infertility, multiple preovulatory follicles, and a persistently elevated serum estradiol concentration. Exacerbation of the ovarian hyperstimulation in response to a gonadotropin-releasing hormone agonist in this setting also strongly suggests a gonadotroph adenoma but can be avoided by recognizing the presenting features of this condition.
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Affiliation(s)
- Arthur J Castelbaum
- University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6149, USA
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Shimon I, Rubinek T, Bar-Hava I, Nass D, Hadani M, Amsterdam A, Harel G. Ovarian hyperstimulation without elevated serum estradiol associated with pure follicle-stimulating hormone-secreting pituitary adenoma. J Clin Endocrinol Metab 2001; 86:3635-40. [PMID: 11502789 DOI: 10.1210/jcem.86.8.7766] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
We report a unique case of a 28-yr-old woman with a gonadotroph adenoma secreting FSH, presented with ovarian hyperstimulation, without elevation of serum estradiol. She presented with abdominal pain and large ovaries (both 10 cm in diameter) with multiple follicular cysts shortly after discontinuing oral contraceptive pills. She had a supranormal PRL level of 71 microg/liter (normal, <20), FSH of 8.4-9.2 IU/liter (normal for follicular phase, 2.4-10), LH of 0.01 IU/liter (normal, 1.6-9.3), estradiol of 108 pmol/liter (normal for follicular phase, 80-790), and free alpha-subunit level of 0.11 microg/liter (normal, <1.8). A nuclear magnetic resonance study revealed invasive pituitary macroadenoma, 30 mm in diameter. Dopamine agonist (cabergoline) treatment normalized serum PRL but had no affect on FSH levels. A transsphenoidal surgery was performed, and most of the adenoma was resected. One month after surgery the patient resumed menstruation, and the hormonal profile included serum FSH of 6.3 IU/liter, LH of 2.1 IU/liter, estradiol of 156 pmol/liter, and PRL of 10 microg/liter. The excised adenoma tissue exhibited intense immunostaining for FSH and secreted this hormone to culture medium. Stimulation with TRH (both in vivo preoperatively and in vitro study of the excised tumor) had no effect on FSH secretion from the adenoma. Estradiol did not suppress FSH release from cultured adenoma cells. Patient serum samples showed significant FSH bioactivity when tested in a human granulosa cell line. This case is remarkable because the ovarian hyperstimulation related to the FSH-secreting adenoma was not associated with high levels of serum estradiol, probably due to insufficient LH production by the normal pituitary. Thus, it supports the two-cell, two-gonadotropin theory, that both FSH and LH are necessary for normal ovarian estrogen production.
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Affiliation(s)
- I Shimon
- Institutes of Endocrinology, Sheba Medical Center, Tel-Hashomer 52621, Israel.
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