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Tataranu LG. A Brief Overview of Molecular Biology in Pituitary Adenomas with a Focus on Aggressive Lesions. Int J Mol Sci 2025; 26:3717. [PMID: 40332351 PMCID: PMC12027641 DOI: 10.3390/ijms26083717] [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: 11/15/2024] [Revised: 12/16/2024] [Accepted: 12/18/2024] [Indexed: 05/08/2025] Open
Abstract
Arising from the anterior lobe of the hypophysis, pituitary neuroendocrine tumors (PitNETs), previously known as pituitary adenomas, constitute an intricate and heterogeneous entity. Although they are defined as benign pathology, these tumors can often invade neighboring structures and demonstrate aggressive behavior. The continuous advancement of molecular biology has begun to shed light on the genetic mutations behind the development and evolution of this pathology, providing a better understanding. Notwithstanding, the rising occurrence in recent decades can mainly be attributed to advanced diagnostic techniques; however, these tumors continue to increase in prevalence and incidence, creating a heavy burden on healthcare systems. Consequently, the need for further studies is dire, primarily due to a lack of tailored therapeutic approaches. Thus, this article aims to offer a brief overview of the molecular biology behind these complex tumors to contribute, even on a small scale, to more comprehensive care.
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Affiliation(s)
- Ligia Gabriela Tataranu
- Department of Neurosurgery, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania;
- Department of Neurosurgery, Bagdasar-Arseni Emergency Clinical Hospital, 041915 Bucharest, Romania
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Cela E, De Alcubierre D, Sbardella E. Polycystic Ovary Syndrome in the Context of Pituitary Adenomas: Prevalence, Pathophysiology and Clinical Management. Clin Endocrinol (Oxf) 2025; 102:462-481. [PMID: 39718187 DOI: 10.1111/cen.15182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 11/07/2024] [Accepted: 12/07/2024] [Indexed: 12/25/2024]
Abstract
OBJECTIVE Many review articles have explored data regarding the coexistence of specific types of pituitary adenomas (PAs) and polycystic ovary syndrome (PCOS), particularly focusing on the potential pathogenesis of this intersection and overlapping features. However, a comprehensive evaluation encompassing the full spectrum of PAs and their association with PCOS remains lacking. This review aims to provide a broad assessment of the interactions between these entities, emphasizing pathophysiological mechanisms, clinical presentations, diagnostic challenges and therapeutic implications. METHODS A comprehensive literature search was conducted in the PubMed/MEDLINE database, focusing primarily on publications from the years 2000 to 2024, while also including seminal papers from the 1950s. The reference lists of selected articles were also manually searched. Inclusion criteria encompassed review articles, retrospective studies, clinical trials, case reports and meta-analyses providing data on the pathogenesis, clinical features, diagnostic challenges and therapeutic approaches related to PCOS and different PAs. RESULTS PCOS and functioning PAs often exhibit overlapping clinical features, complicating diagnosis and management. PCOS may precede and delay the diagnosis of growth hormone (GH)-secreting adenomas. The prevalence of PCOS or its features in acromegaly is influenced by disease activity, while approximating 13% in cases with controlled disease. Excess GH and insulin-like growth factor 1 (IGF-1) adversely affect ovarian function through direct pathways and by inducing insulin resistance, contributing to acromegaly-associated PCOS. In Cushing's syndrome (CS), findings consistent with PCOS may be present in 46% of patients, with cortisol excess contributing to menstrual dysfunction, hyperandrogenism and insulin resistance. While the prevalence of PCOS in patients with prolactinomas remains under-researched, recent studies indicate a 2.8%-10% prevalence of prolactinomas in PCOS. Elevated prolactin (PRL) levels in these patients may promote insulin resistance, further contributing to PCOS pathogenesis. Moreover, increased androgen bioavailability may be observed in all three aforementioned adenomas. To date, no studies have provided prevalence data for PCOS in other types of PAs. CONCLUSIONS Distinct clinical features, along with biochemical evaluations and imaging, can help differentiate the presence of both PAs and PCOS. Moreover, excluding other mimicking disorders is essential for an accurate diagnosis of PCOS. The persistence or recurrence of menstrual dysfunction, hyperandrogenism and metabolic disturbances in patients with controlled functioning adenomas may indicate a coexisting PCOS diagnosis. Timely diagnosis may optimize management and improve long-term outcomes for both conditions. Future studies should focus on investigating the clinical differences between patients with co-occurring PCOS and PAs compared to those with PCOS alone, ideally in larger cohorts, to better understand unique diagnostic and therapeutic considerations.
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Affiliation(s)
- Esmeralda Cela
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Dario De Alcubierre
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Emilia Sbardella
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
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Bonomi M, Cangiano B, Cianfarani S, Garolla A, Gianfrilli D, Lanfranco F, Rastrelli G, Sbardella E, Corona G, Isidori AM, Rochira V. "Management of andrological disorders from childhood and adolescence to transition age: guidelines from the Italian Society of Andrology and Sexual Medicine (SIAMS) in collaboration with the Italian Society for Pediatric Endocrinology and Diabetology (SIEDP)-Part-1". J Endocrinol Invest 2025; 48:1-22. [PMID: 39126560 PMCID: PMC11729124 DOI: 10.1007/s40618-024-02435-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 07/23/2024] [Indexed: 08/12/2024]
Abstract
PURPOSE Andrological pathologies in the adulthood are often the results of conditions that originate during childhood and adolescence and sometimes even during gestation and neonatal period. Unfortunately, the reports in the literature concerning pediatric andrological diseases are scares and mainly concerning single issues. Furthermore, no shared position statement are so far available. METHODS The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP) to provide an updated guideline on the diagnosis and management of andrological disorders from childhood and adolescence to transition age. Derived recommendations were based on the grading of recommendations, assessment, development, and evaluation (GRADE) system. RESULTS A literature search of articles in English for the term "varicoceles", "gynecomastia", "fertility preservation", "macroorchidism", "precocious puberty" and "pubertal delay" has been performed. Three major aspects for each considered disorder were assessed including diagnosis, clinical management, and treatment. Recommendations and suggestions have been provided for each of the mentioned andrological disorders. CONCLUSIONS These are the first guidelines based on a multidisciplinary approach that involves important societies related to the field of andrological medicine from pediatric to transition and adult ages. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving andrological and general health of the transitional age.
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Affiliation(s)
- M Bonomi
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
- Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149, Milan, Italy.
| | - B Cangiano
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
- Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149, Milan, Italy
| | - S Cianfarani
- Endocrinology and Diabetes Unit, Bambino Gesù Children's Hospital, Rome, Italy
- Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy
- Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden
| | - A Garolla
- Unit of Andrology and Reproductive Medicine, Department of Medicine, University of Padova, Padua, Italy
| | - D Gianfrilli
- Section of Medical Pathophysiology and Endocrinology, Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy
- Centre for Rare Diseases (Endo-ERN Accredited), Policlinico Umberto I, Rome, Italy
| | - F Lanfranco
- Division of Endocrinology, Andrology and Metabolism, Department of Medical Sciences, Humanitas Gradenigo, University of Turin, Turin, Italy
| | - G Rastrelli
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Careggi Hospital, University of Florence, Florence, Italy
| | - E Sbardella
- Section of Medical Pathophysiology and Endocrinology, Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy
- Centre for Rare Diseases (Endo-ERN Accredited), Policlinico Umberto I, Rome, Italy
| | - G Corona
- Endocrinology Unit, Medical Department, Maggiore-Bellaria Hospital, Azienda Usl, Bologna, Italy
| | - A M Isidori
- Section of Medical Pathophysiology and Endocrinology, Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy
- Centre for Rare Diseases (Endo-ERN Accredited), Policlinico Umberto I, Rome, Italy
| | - V Rochira
- Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
- Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria Di Modena Policlinico Di Modena, Ospedale Civile Di Baggiovara, Via Giardini 1355, 41126, Modena, Italy.
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Feng JJ, Cannon SM, Cheok SK, Shiroishi MS, Hurth KM, Mathew AJ, Zada G, Carmichael JD. Successful Multimodal Management of an Aggressive Functional Gonadotropic Pituitary Macroadenoma. AACE Clin Case Rep 2025; 11:14-17. [PMID: 39896951 PMCID: PMC11784608 DOI: 10.1016/j.aace.2024.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 08/28/2024] [Accepted: 09/06/2024] [Indexed: 02/04/2025] Open
Abstract
Background/Objective Although most gonadotroph cell-derived pituitary adenomas (PAs) give rise to nonfunctional PAs, hormonally active functional gonadotroph adenomas (FGAs) are exceedingly rare. We present a case of a giant and invasive functional gonadotropic pituitary macroadenoma treated with endoscopic transsphenoidal surgery and subsequent postoperative radiotherapy. Case Report A 54-year-old man presented with gradually worsening vision over 1 year. Magnetic resonance imaging demonstrated a 5.2-cm sellar and suprasellar mass with cavernous sinus invasion, mass effect on the optic chiasm, and extension into the sphenoid sinus, nasal cavity, and clivus. Preoperative workup was remarkable for erythrocytosis without sleep apnea and increased levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and testosterone. Immunohistochemistry results following endoscopic transsphenoidal resection confirmed dominant staining for steroidogenic factor-1, FSH, and LH. Postoperatively, the patient's FSH level decreased, whereas the LH level normalized within 1 week. The free testosterone level normalized at 9 months. The patient underwent radiotherapy for a small amount of residual tumor in the right cavernous sinus and has demonstrated no evidence of disease or hormonal progression. Discussion There is no consensus on FGA-specific management that differs from the management of nonfunctional PAs; surgery is recommended when vision is impacted. The invasive nature of the tumor presented in this case is rare and limited safe gross total resection, requiring adjuvant radiotherapy. Conclusion FGAs are rare, and those of similar size and extent of invasion as in our case are even more so. In addition to surgical resection, consideration of adjunct therapies including radiation and multidisciplinary physician involvement are vital in achieving clinical improvement and remission while preventing possible progression and recurrence.
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Affiliation(s)
- Jeffrey J. Feng
- Department of Neurological Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California
- Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan
| | - Sophie M. Cannon
- Department of Neurological Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, David Geffen University of California, Los Angeles School of Medicine, Los Angeles, California
| | - Stephanie K. Cheok
- Department of Neurological Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California
- Department of Neurological Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Mark S. Shiroishi
- Department of Radiology, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Kyle M. Hurth
- Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Anna J. Mathew
- Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Gabriel Zada
- Department of Neurological Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - John D. Carmichael
- Department of Neurological Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California
- Division of Endocrinology and Diabetes, Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California
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Ishii R, Harai N, Hosokawa T, Tahara I, Ogiwara M, Tsuchiya K. Reduction of Ovarian Cysts After Endoscopic Surgery for Follicle-Stimulating Hormone-Producing Pituitary Adenoma. JCEM CASE REPORTS 2024; 2:luae231. [PMID: 39659387 PMCID: PMC11630798 DOI: 10.1210/jcemcr/luae231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Indexed: 12/12/2024]
Abstract
A 49-year-old woman presented with irregular menstrual bleeding, elevated estradiol (E2) (665 pg/mL [2441.21 pmol/L]) (reference range [RR]: menstrual period [MP] 20-50 pg/mL; 73.42-183.55 pmol/L), unsuppressed follicle-stimulating hormone (FSH) (19.3 mIU/mL [19.3 IU/L]) (RR: MP 3.5-10.0 mIU/mL; 3.5-10.0 IU/L), and cystic ovarian enlargement (right ovary, 109 mL; left ovary, 146 mL). A 7-mm pituitary microadenoma was also observed, and 6 months after referral, endoscopic transsphenoidal surgery was performed, resulting in a diagnosis of FSH-producing pituitary adenoma. Nine months postoperatively, the ovarian cysts had markedly shrunk. Although FSH-producing pituitary adenomas are rare, approximately 64% of nonfunctioning pituitary adenomas are positive for gonadotropin immunostaining. FSH-producing pituitary adenomas are often endocrinologically silent, with symptoms typically triggered by pituitary tumor enlargement. Early diagnosis can be facilitated by measuring FSH and E2 levels in cases of irregular vaginal bleeding, abnormal menstruation, ovarian enlargement, ovarian hyperstimulation syndrome, or infertility. If E2 is elevated but FSH is not suppressed, pituitary magnetic resonance imaging should be performed to identify FSH-producing pituitary adenomas. In cases of FSH-producing pituitary adenomas, including microadenomas, symptoms may improve after tumor resection, making surgery the preferred treatment option.
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Affiliation(s)
- Reo Ishii
- Department of Diabetes and Endocrinology, University of Yamanashi Hospital, Yamanashi 4093898, Japan
| | - Nozomi Harai
- Department of Diabetes and Endocrinology, University of Yamanashi Hospital, Yamanashi 4093898, Japan
| | - Tadatsugu Hosokawa
- Department of Diabetes and Endocrinology, University of Yamanashi Hospital, Yamanashi 4093898, Japan
| | - Ippei Tahara
- Department of Pathology, University of Yamanashi Hospital, Yamanashi 4093898, Japan
| | - Masakazu Ogiwara
- Department of Neurosurgery, Tokyo Metropolitan Tama Medical Center, Tokyo 1838524, Japan
| | - Kyoichiro Tsuchiya
- Department of Diabetes and Endocrinology, University of Yamanashi Hospital, Yamanashi 4093898, Japan
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Maiter D, Chanson P, Constantinescu SM, Linglart A. Diagnosis and management of pituitary adenomas in children and adolescents. Eur J Endocrinol 2024; 191:R55-R69. [PMID: 39374844 DOI: 10.1093/ejendo/lvae120] [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: 04/24/2024] [Revised: 07/11/2024] [Accepted: 09/27/2024] [Indexed: 10/09/2024]
Abstract
BACKGROUND Pituitary adenomas (PAs)-also now called pituitary neuroendocrine tumours or Pit-NETS-are rare in children and adolescents and exceptional below the age of 10. Most evidence-based high-quality data are derived from larger studies in adult patients. AIMS We will review recent knowledge on the epidemiology, clinical features, diagnosis, and treatment modalities of the different types of pituitary adenomas diagnosed in children and adolescents, emphasizing the many reasons why these cases should be discussed within pituitary-specific multidisciplinary teams with experts from both paediatric and adult practice. CONCLUSIONS Paediatric PA presents multiple peculiarities that may challenge their adequate management. They are overall proportionally larger and more aggressive than in adults, with potential mass effects including hypopituitarism. Hormonal hypersecretion is frequent, resulting in clinical syndromes affecting normal growth and pubertal development. Prolactinomas represent the most frequent subtype of PA found during childhood, followed by adrenocorticotropin (ACTH) and growth hormone (GH)-secreting adenomas, while clinically non-functioning adenomas are exceptionally diagnosed before the age of 16. The occurrence of a pituitary tumour in a young individual should also prompt genetic testing in each case, searching for either germline mutations in one of the known genes that may drive inherited/familial PA (such as the multiple endocrine neoplasia type 1 or MEN1 gene, or the aryl hydrocarbon receptor interacting protein or AIP gene), or for a mosaic activating mutation of GNAS as found in the McCune-Albright syndrome.
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Affiliation(s)
- Dominique Maiter
- Department of Endocrinology and Nutrition, UCLouvain Cliniques universitaires Saint Luc, 1200 Brussels, Belgium
| | - Philippe Chanson
- Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction et Centre de Référence des Maladies Rares de l'Hypophyse HYPO, 94270 Le Kremlin-Bicêtre, France
| | - Stefan Matei Constantinescu
- Department of Endocrinology and Nutrition, UCLouvain Cliniques universitaires Saint Luc, 1200 Brussels, Belgium
| | - Agnès Linglart
- INSERM-U1185, Paris Sud Paris-Saclay University and AP-HP Division of Endocrinology and Diabetes for Children, Bicêtre Paris Sud Hospital, 64 Gabriel Péri Street, 94270 Le Kremlin Bicêtre, France
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7
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Owolabi M, Malone M, Merritt A. Pituitary Disorders. Prim Care 2024; 51:467-481. [PMID: 39067972 DOI: 10.1016/j.pop.2024.04.004] [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] [Indexed: 07/30/2024]
Abstract
In this article, we will review common pituitary disorders. There are 6 hormones secreted by the anterior pituitary gland: thyroid-stimulating hormone, adrenocorticotropic hormone, follicle-stimulating hormone, luteinizing hormone, growth hormone, and prolactin. The posterior pituitary gland stores and releases the hormones made in the hypothalamus, oxytocin and antidiuretic hormone, based on the body's needs. This article will discuss the role of these hormones, conditions and symptoms that occur with elevated or reduced hormone levels, as well as the evaluation and treatment of these pituitary disorders.
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Affiliation(s)
- Mark Owolabi
- Department of Family Medicine, Medstar Health/Georgetown-Washington Hospital Center, 4151 Bladensburg Road, Colmar Manor, MD 20722, USA.
| | - Michael Malone
- Department of Family Medicine, Tidelands Health Family Medicine Residency Program, 4320 Holmestown Road, Myrtle Beach, SC 29588, USA
| | - Andrew Merritt
- Department of Family Medicine, Tidelands Health Family Medicine Residency Program, 4320 Holmestown Road, Myrtle Beach, SC 29588, USA
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Shah H, Slavin A, Botvinov J, O'Malley GR, Sarwar S, Patel NV. Endoscopic Endonasal Transsphenoidal Surgery for the Resection of Pituitary Adenomas: A Prime Candidate for a Shortened Length of Stay Enhanced Recovery after Surgery Protocol? A Systematic Review. World Neurosurg 2024; 186:145-154. [PMID: 38552787 DOI: 10.1016/j.wneu.2024.03.135] [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: 03/17/2024] [Revised: 03/22/2024] [Accepted: 03/23/2024] [Indexed: 04/25/2024]
Abstract
BACKGROUND Enhanced Recovery After Surgery (ERAS) is a perioperative model of care aimed at optimizing postoperative rehabilitation and reducing hospital length of stay (LOS). Decreasing LOS avoids hospital-acquired complications, reduces cost of care, and improves patient satisfaction. Given the lack of ERAS protocols for endoscopic endonasal transsphenoidal surgery (EETS) resection of pituitary adenomas, a systematic review of EETS was performed to compile patient outcomes and analyze factors that may lead to increased LOS, reoperation, and readmission rates with the intention to contribute to the development of a successful ERAS protocol for EETS. METHODS The authors performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines-based systematic review of the literature. Information was extracted regarding patient LOS, surgery complications, and readmission/reoperation rates. Pearson's correlations to LOS and reoperation/readmission rates were performed with variables normalized to the number of participants. Statistical significance was set at P value <0.05. RESULTS Fourteen studies were included, consisting of 2083 patients. The most common complications were cerebrospinal fluid leaks (37%) and postoperative diabetes insipidus (DI) (9%). Transient DI was significantly correlated with shorter LOS. Functional pituitary adenomas were significantly correlated with lower readmission rates while nonfunctional pituitary adenomas were correlated with higher readmission rates. No other factor was found to be significantly correlated with a change in LOS or reoperation rate. CONCLUSIONS EETS may be an ideal candidate for the development of ERAS cranial protocols. While our data largely supports the safe implementation of shortened LOS protocols in EETS, our findings highlight the importance of transient DI and nonfunctional pituitary adenomas management when formulating ERAS protocols.
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Affiliation(s)
- Harshal Shah
- Department of Neurosurgery, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA.
| | - Avi Slavin
- Department of Neurosurgery, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA
| | - Julia Botvinov
- Department of Neurosurgery, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA
| | - Geoffrey R O'Malley
- Department of Neurosurgery, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA
| | - Syed Sarwar
- Department of Neurosurgery, HMH-Jersey Shore University Medical Center, Neptune, New Jersey, USA
| | - Nitesh V Patel
- Department of Neurosurgery, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA; Department of Neurosurgery, HMH-Jersey Shore University Medical Center, Neptune, New Jersey, USA
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Balen AH, Tamblyn J, Skorupskaite K, Munro MG. A comprehensive review of the new FIGO classification of ovulatory disorders. Hum Reprod Update 2024; 30:355-382. [PMID: 38412452 DOI: 10.1093/humupd/dmae003] [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: 06/12/2023] [Revised: 01/23/2024] [Indexed: 02/29/2024] Open
Abstract
BACKGROUND The World Health Organization (WHO) system for the classification of disorders of ovulation was produced 50 years ago and, by international consensus, has been updated by the International Federation of Gynecology and Obstetrics (FIGO). OBJECTIVE AND RATIONALE This review outlines in detail each component of the FIGO HyPO-P (hypothalamic, pituitary, ovarian, PCOS) classification with a concise description of each cause, and thereby provides a systematic method for diagnosis and management. SEARCH METHODS We searched the published articles in the PubMed database in the English-language literature until October 2022, containing the keywords ovulatory disorders; ovulatory dysfunction; anovulation, and each subheading in the FIGO HyPO-P classification. We did not include abstracts or conference proceedings because the data are usually difficult to assess. OUTCOMES We present the most comprehensive review of all disorders of ovulation, published systematically according to the logical FIGO classification. WIDER IMPLICATIONS Improving the diagnosis of an individual's ovulatory dysfunction will significantly impact clinical practice by enabling healthcare practitioners to make a precise diagnosis and plan appropriate management.
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Affiliation(s)
- Adam H Balen
- Leeds Centre for Reproductive Medicine, The University of Leeds, Leeds, UK
| | - Jennifer Tamblyn
- Leeds Centre for Reproductive Medicine, The University of Leeds, Leeds, UK
| | | | - Malcolm G Munro
- Department of Obstetrics and Gynecology, The University of California, Los Angeles, Los Angeles, CA, USA
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Korbonits M, Blair JC, Boguslawska A, Ayuk J, Davies JH, Druce MR, Evanson J, Flanagan D, Glynn N, Higham CE, Jacques TS, Sinha S, Simmons I, Thorp N, Swords FM, Storr HL, Spoudeas HA. Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 2, specific diseases. Nat Rev Endocrinol 2024; 20:290-309. [PMID: 38336898 DOI: 10.1038/s41574-023-00949-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/19/2023] [Indexed: 02/12/2024]
Abstract
Pituitary adenomas are rare in children and young people under the age of 19 (hereafter referred to as CYP) but they pose some different diagnostic and management challenges in this age group than in adults. These rare neoplasms can disrupt maturational, visual, intellectual and developmental processes and, in CYP, they tend to have more occult presentation, aggressive behaviour and are more likely to have a genetic basis than in adults. Through standardized AGREE II methodology, literature review and Delphi consensus, a multidisciplinary expert group developed 74 pragmatic management recommendations aimed at optimizing care for CYP in the first-ever comprehensive consensus guideline to cover the care of CYP with pituitary adenoma. Part 2 of this consensus guideline details 57 recommendations for paediatric patients with prolactinomas, Cushing disease, growth hormone excess causing gigantism and acromegaly, clinically non-functioning adenomas, and the rare TSHomas. Compared with adult patients with pituitary adenomas, we highlight that, in the CYP group, there is a greater proportion of functioning tumours, including macroprolactinomas, greater likelihood of underlying genetic disease, more corticotrophinomas in boys aged under 10 years than in girls and difficulty of peri-pubertal diagnosis of growth hormone excess. Collaboration with pituitary specialists caring for adult patients, as part of commissioned and centralized multidisciplinary teams, is key for optimizing management, transition and lifelong care and facilitates the collection of health-related quality of survival outcomes of novel medical, surgical and radiotherapeutic treatments, which are currently largely missing.
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Affiliation(s)
- Márta Korbonits
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
| | | | - Anna Boguslawska
- Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland
| | - John Ayuk
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Justin H Davies
- University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Maralyn R Druce
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Jane Evanson
- Neuroradiology, Barts Health NHS Trust, London, UK
| | | | - Nigel Glynn
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | | | - Thomas S Jacques
- Great Ormond Street Institute of Child Health, University College London, London, UK
- Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
| | - Saurabh Sinha
- Sheffield Children's and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Ian Simmons
- The Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Nicky Thorp
- The Christie NHS Foundation Trust, Manchester, UK
| | | | - Helen L Storr
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Helen A Spoudeas
- Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
- University College London Hospitals NHS Foundation Trust, London, UK
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11
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Carbonara F, Feola T, Gianno F, Polidoro MA, Di Crescenzo RM, Arcella A, De Angelis M, Morace R, de Alcubierre D, Esposito V, Giangaspero F, Jaffrain-Rea ML. Clinical and Molecular Characteristics of Gonadotroph Pituitary Tumors According to the WHO Classification. Endocr Pathol 2024; 35:1-13. [PMID: 38095839 PMCID: PMC10944444 DOI: 10.1007/s12022-023-09794-w] [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: 11/20/2023] [Indexed: 03/17/2024]
Abstract
Since 2017, hormone-negative pituitary neuroendocrine tumors expressing the steroidogenic factor SF1 have been recognized as gonadotroph tumors (GnPT) but have been poorly studied. To further characterize their bio-clinical spectrum, 54 GnPT defined by immunostaining for FSH and/or LH (group 1, n = 41) or SF1 only (group 2, n = 13) were compared and studied for SF1, βFSH, βLH, CCNA2, CCNB1, CCND1, caspase 3, D2R, and AIP gene expression by qRT-PCR. Immunohistochemistry for AIP and/or D2R was performed in representative cases. Overall, patients were significantly younger in group 1 (P = 0.040 vs group 2), with a similar trend excluding recurrent cases (P = 0.078), and no significant difference in gender, tumor size, invasion or Ki67. SF1 expression was similar in both groups but negatively correlated with the patient's age (P = 0.013) and positively correlated with βLH (P < 0.001) expression. Beta-FSH and AIP were significantly higher in group 1 (P = 0.042 and P = 0.024, respectively). Ki67 was unrelated to gonadotroph markers but positively correlated with CCNB1 (P = 0.001) and negatively correlated with CCND1 (P = 0.008). D2R and AIP were strongly correlated with each other (P < 0.001), and both positively correlated with SF1, βFSH, βLH, and CCND1. AIP immunopositivity was frequently observed in both groups, with a similar median score, and unrelated to Ki67. D2R immunostaining was best detected with a polyclonal antibody and mostly cytoplasmic. This study indicates that hormone-negative GnPT tend to occur in older patients but do not significantly differ from other GnPT in terms of invasion or proliferation. It also points out the current limits of D2R immunostaining in such tumors.
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Affiliation(s)
- Francesca Carbonara
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Tiziana Feola
- Neuromed IRCCS, Pozzilli, Italy
- Department of Experimental Medicine, La Sapienza University of Rome (RM), Rome, Italy
| | - Francesca Gianno
- Neuromed IRCCS, Pozzilli, Italy
- Department of Radiological, Oncological and Pathological Sciences, La Sapienza University of Rome (RM), Rome, Italy
| | - Michela Anna Polidoro
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
- Hepatobiliary Immunopathology, Humanitas Clinical and Research Center IRCCS, Rozzano, Italy
| | - Rosa Maria Di Crescenzo
- Neuromed IRCCS, Pozzilli, Italy
- Department of Advanced Biomedical Sciences, Pathology Section, University of Naples Federico II, Naples, Italy
| | | | | | | | - Dario de Alcubierre
- Department of Experimental Medicine, La Sapienza University of Rome (RM), Rome, Italy
| | - Vincenzo Esposito
- Neuromed IRCCS, Pozzilli, Italy
- Department of Neurology and Psychiatry, La Sapienza University of Rome (RM), Rome, Italy
| | - Felice Giangaspero
- Neuromed IRCCS, Pozzilli, Italy
- Department of Radiological, Oncological and Pathological Sciences, La Sapienza University of Rome (RM), Rome, Italy
| | - Marie-Lise Jaffrain-Rea
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
- Neuromed IRCCS, Pozzilli, Italy.
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12
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Karlekar M, Diwaker C, Sarathi V, Lila A, Sharma A, Memon SS, Patil V, Bandgar T. Gonadotropin-secreting and thyrotropin-secreting pituitary adenomas: A single-center experience. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2023; 68:e230072. [PMID: 37988667 PMCID: PMC10916838 DOI: 10.20945/2359-4292-2023-0072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 05/23/2023] [Indexed: 11/23/2023]
Abstract
Objective Data regarding rare FPAs from India, a resource limited setting, are limited. We describe a case series of rare FPAs from a single center in western India. Materials and methods This was a retrospective case record review of patients diagnosed between January 2010 and July 2022. The diagnosis was based on biochemical(inappropriately elevated serum FSH/LH) and pathologic (positive immunostaining for FSH/LH) features in patients with FGA, and elevated serum thyroid hormones and normal/elevated TSH in patients with TSHomas. Results We identified 11 patients with a total of six FGAs (median age 43.5 years, five men, one FGA cosecreting TSH, median largest dimension 40 mm, range 33-60 mm) and six TSHomas (median age 34.5 years, four women, two TSHomas cosecreting GH, median largest dimension 42.5 mm, range 13-60 mm). Symptoms of sellar mass effects led to pituitary imaging in most patients with FGA. Patients with TSHomas had symptoms of excess hormone secretion (GH/TSH) or sellar mass effects. The TSHomas that cosecreted GH/FSH were larger than those secreting only TSH. Transsphenoidal resection was the most common first-line therapy but significant residual disease was frequent (3 out of 6 FGAs and 4 out of 5 TSHomas). Conclusion This is the first and second case series of FGAs and TSHomas, respectively, from India. In this study, TSHomas presented at younger age, were larger andhad low surgical cure rates.
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Affiliation(s)
- Manjiri Karlekar
- Department of Endocrinology, Seth G.S. Medical College and KEM Hospital, Mumbai, India
- Manjiri Karlekar and Chakra Diwaker have contributed equally as first authors
| | - Chakra Diwaker
- Department of Endocrinology, Seth G.S. Medical College and KEM Hospital, Mumbai, India
- Manjiri Karlekar and Chakra Diwaker have contributed equally as first authors
| | - Vijaya Sarathi
- Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, India
| | - Anurag Lila
- Department of Endocrinology, Seth G.S. Medical College and KEM Hospital, Mumbai, India,
| | - Anima Sharma
- Department of Endocrinology, Seth G.S. Medical College and KEM Hospital, Mumbai, India
| | - Saba Samad Memon
- Department of Endocrinology, Seth G.S. Medical College and KEM Hospital, Mumbai, India
| | - Virendra Patil
- Department of Endocrinology, Seth G.S. Medical College and KEM Hospital, Mumbai, India
| | - Tushar Bandgar
- Department of Endocrinology, Seth G.S. Medical College and KEM Hospital, Mumbai, India
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13
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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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Tsukaguchi R, Hasebe M, Honjo S, Hamasaki A. Ovarian Hyperstimulation Syndrome Caused by Functional Gonadotroph Pituitary Adenoma. JCEM CASE REPORTS 2023; 1:luad087. [PMID: 37908987 PMCID: PMC10580461 DOI: 10.1210/jcemcr/luad087] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Indexed: 11/02/2023]
Abstract
Functional gonadotroph adenomas (FGAs) are rare, manifesting symptoms like menstrual irregularities or ovarian hyperstimulation syndrome (OHSS). We present a case of OHSS caused by an FGA during the follow-up of a pituitary tumor initially considered nonfunctioning. The patient presented with lower abdominal pain, abdominal swelling, and dyspnea. Magnetic resonance imaging (MRI) revealed 15 cm enlarged ovarian cysts and pleural effusion. Laboratory examination showed an elevated serum estradiol (E2) level (5741.4 pmol/L [1564.0 pg/mL]), suppressed luteinizing hormone, and nonsuppressed follicular-stimulating hormone (FSH). However, no pituitary hormone disorders were observed when a 19 mm pituitary tumor was discovered 11 months prior. Given the absence of human chorionic gonadotropin (hCG) administration, OHSS due to the FGA was suspected. Cabergoline, known for alleviating the severity of OHSS, was administered, but the ovarian cysts continued to enlarge. Subsequently, endoscopic transsphenoidal surgery was performed, and immunohistochemical analysis confirmed the diagnosis of the FSH-producing adenoma. Follow-up MRI scans showed reduced ovarian cysts and successful pituitary tumor resection with a reduced E2 level. This case highlights the importance of considering FGAs when encountering OHSS without hCG administration or following up on pituitary tumors in premenopausal female patients to take appropriate measures for accurate diagnosis and management.
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Affiliation(s)
- Ryo Tsukaguchi
- Department of Diabetes and Endocrinology, Medical Research Institute Kitano Hospital, Osaka, 530-8480, Japan
| | - Masashi Hasebe
- Department of Diabetes and Endocrinology, Medical Research Institute Kitano Hospital, Osaka, 530-8480, Japan
| | - Sachiko Honjo
- Department of Diabetes and Endocrinology, Medical Research Institute Kitano Hospital, Osaka, 530-8480, Japan
| | - Akihiro Hamasaki
- Department of Diabetes and Endocrinology, Medical Research Institute Kitano Hospital, Osaka, 530-8480, Japan
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15
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Kolnes AJ, Øystese KAB, Sjöstedt E, Olarescu NC, Heck A, Pahnke J, Dahlberg D, Berg-Johnsen J, Ringstad G, Casar-Borota O, Bollerslev J, Jørgensen AP. TGFBR3L is associated with gonadotropin production in non-functioning gonadotroph pituitary neuroendocrine tumours. Pituitary 2023:10.1007/s11102-023-01310-x. [PMID: 36952069 DOI: 10.1007/s11102-023-01310-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/06/2023] [Indexed: 03/24/2023]
Abstract
PURPOSE Transforming growth factor-beta receptor 3-like (TGFBR3L) is a pituitary enriched membrane protein selectively detected in gonadotroph cells. TGFBR3L is named after transforming growth factor-beta receptor 3 (TGFBR3), an inhibin A co-receptor in mice, due to sequence identity to the C-terminal region. We aimed to characterize TGFBR3L detection in a well-characterized, prospectively collected cohort of non-functioning pituitary neuroendocrine tumours (NF-PitNETs) and correlate it to clinical data. METHODS 144 patients operated for clinically NF-PitNETs were included. Clinical, radiological and biochemical data were recorded. Immunohistochemical (IHC) staining for FSHβ and LHβ was scored using the immunoreactive score (IRS), TGFBR3L and TGFBR3 were scored by the percentage of positive stained cells. RESULTS TGFBR3L staining was selectively present in 52% of gonadotroph tumours. TGFBR3L was associated to IRS of LHβ (median 2 [IQR 0-3] in TGFBR3L negative and median 6 [IQR 3-9] in TGFBR3L positive tumours, p < 0.001), but not to the IRS of FSHβ (p = 0.32). The presence of TGFBR3L was negatively associated with plasma gonadotropin concentrations in males (P-FSH median 5.5 IU/L [IQR 2.9-9.6] and median 3.0 [IQR 1.8-5.6] in TGFBR3L negative and positive tumours respectively, p = 0.008) and P-LH (median 2.8 IU/L [IQR 1.9-3.7] and median 1.8 [IQR 1.1-3.0] in TGFBR3L negative and positive tumours respectively, p = 0.03). TGFBR3 stained positive in 22% (n = 25) of gonadotroph tumours with no correlation to TGFBR3L. CONCLUSION TGFBR3L was selectively detected in half (52%) of gonadotroph NF-PitNETs. The association to LHβ staining and plasma gonadotropins suggests that TGFBR3L may be involved in hormone production in gonadotroph NF-PitNETs.
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Affiliation(s)
- Anders Jensen Kolnes
- Department of Medical Biochemistry, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Sognsvannsveien 20, 0372, Oslo, Norway
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway
| | - Kristin Astrid Berland Øystese
- Department of Medical Biochemistry, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Sognsvannsveien 20, 0372, Oslo, Norway.
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway.
| | - Evelina Sjöstedt
- Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
| | - Nicoleta Cristina Olarescu
- Department of Medical Biochemistry, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Sognsvannsveien 20, 0372, Oslo, Norway
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway
| | - Ansgar Heck
- Department of Medical Biochemistry, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Sognsvannsveien 20, 0372, Oslo, Norway
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway
| | - Jens Pahnke
- Department of Pathology, Section of Neuropathology, University of Oslo and Oslo University Hospital, Oslo, Norway
- Pahnke lab (Drug Discovery and Chemical Biology), Lübeck Institute of Dermatology, LIED, University of Lübeck, Lübeck, Germany
- Department of Pharmacology, Faculty of Medicine, University of Latvia, Rīga, Latvia
| | - Daniel Dahlberg
- Department of Neurosurgery, Oslo University Hospital, Oslo, Norway
| | - Jon Berg-Johnsen
- Department of Medical Biochemistry, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Sognsvannsveien 20, 0372, Oslo, Norway
- Department of Neurosurgery, Oslo University Hospital, Oslo, Norway
| | - Geir Ringstad
- Department of Radiology, Oslo University Hospital, Oslo, Norway
| | - Olivera Casar-Borota
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
- Department of Clinical Pathology, Uppsala University Hospital, Uppsala, Sweden
| | - Jens Bollerslev
- Department of Medical Biochemistry, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Sognsvannsveien 20, 0372, Oslo, Norway
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway
| | - Anders Palmstrøm Jørgensen
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway
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16
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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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17
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Caroppo E, Niederberger CS. Follicle-stimulating hormone treatment for male factor infertility. Fertil Steril 2023; 119:173-179. [PMID: 36470702 DOI: 10.1016/j.fertnstert.2022.09.362] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 09/29/2022] [Indexed: 12/11/2022]
Abstract
Follicle-stimulating hormone (FSH) treatment has been proven effective in stimulating spermatogenesis and improving the reproductive ability of men with hypogonadotropic hypogonadism, while the usefulness of such a treatment in infertile patients with normal pituitary function is restricted to a subgroup of responders that, however, cannot be identified by the current diagnostic tools before treatment. In this review we summarize the role played by FSH in the modulation of spermatogenesis, the effect of FSH treatment at a standard replacement dose and at higher dose on sperm parameters, spontaneous and in vitro fertilization pregnancy rates, and the efforts made to identify possible responders to FSH treatment.
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Affiliation(s)
- Ettore Caroppo
- Asl Bari, Reproductive Unit, Andrology Outpatients Clinics, Conversano, Italy.
| | - Craig S Niederberger
- Department of Urology, University of Illinois at Chicago, Chicago, Illinois; Department of Bioengineering, University of Illinois at Chicago College of Engineering, Chicago, Illinois
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18
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Li M, Zhang J, Yang G, Zhang J, Han M, Zhang Y, Liu Y. Effects of Anterior Pituitary Adenomas' Hormones on Glucose Metabolism and Its Clinical Implications. Diabetes Metab Syndr Obes 2023; 16:409-424. [PMID: 36816815 PMCID: PMC9937076 DOI: 10.2147/dmso.s397445] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 02/02/2023] [Indexed: 02/17/2023] Open
Abstract
Pituitary adenomas have recently become more common and their incidence is increasing yearly. Functional pituitary tumors commonly secrete prolactin, growth hormones, and adrenocorticotropic hormones, which cause diseases such as prolactinoma, acromegaly, and Cushing's disease, but rarely secrete luteinizing, follicle-stimulating, thyroid-stimulating, and melanocyte-stimulating hormones. In addition to the typical clinical manifestations of functional pituitary tumors caused by excessive hormone levels, some pituitary tumors are also accompanied by abnormal glucose metabolism. The effects of these seven hormones on glucose metabolism are important for the treatment of diabetes secondary to pituitary tumors. This review focuses on the effects of hormones on glucose metabolism, providing important clues for the diagnosis and treatment of related diseases.
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Affiliation(s)
- Mengnan Li
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China
- First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China
| | - Jian Zhang
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China
- First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China
| | - Guimei Yang
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China
- First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China
| | - Jiaxin Zhang
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China
- First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China
| | - Minmin Han
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China
- First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China
| | - Yi Zhang
- Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China
- Correspondence: Yi Zhang, Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China, Email
| | - Yunfeng Liu
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China
- Yunfeng Liu, Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Tel +86 18703416196, Email
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19
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Abstract
Gonadotroph cell adenoma is the most common clinically nonfunctioning pituitary adenoma; and is pathologically defined by immunopositivity for SF-1, GATA2 and ER-α. Most tumors also stain for follicle stimulating hormone and luteinizing hormone β-subunits, but are usually hormonally silent and discovered incidentally or due to local mass effects. Complete transsphenoidal resection should be attempted when surgery is indicated. Post-surgical treatment can include radiation of the tumor remnant and medical treatment. Among medical treatments, dopamine agonists show the best evidence for preventing the need for recurrent surgery or radiation, and should be considered in patients with relatively bulky remnants or who have high risk features associated with tumor progression. Temozolomide is indicated for aggressive adenomas and carcinomas. Less well-established treatments include somatostatin receptor ligands, peptide receptor radionucleotide therapy and immunomodulatory agents.
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Affiliation(s)
- Naomi Even-Zohar
- Institute of Endocrinology, Diabetes, Metabolism, and Hypertension, Tel Aviv-Sourasky Medical Center, Israel.
| | - Yona Greenman
- Institute of Endocrinology, Diabetes, Metabolism, and Hypertension, Tel Aviv-Sourasky Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.
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20
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Zhang F, Zhang Q, Zhu J, Yao B, Ma C, Qiao N, He S, Ye Z, Wang Y, Han R, Feng J, Wang Y, Qin Z, Ma Z, Li K, Zhang Y, Tian S, Chen Z, Tan S, Wu Y, Ran P, Wang Y, Ding C, Zhao Y. Integrated proteogenomic characterization across major histological types of pituitary neuroendocrine tumors. Cell Res 2022; 32:1047-1067. [PMID: 36307579 PMCID: PMC9715725 DOI: 10.1038/s41422-022-00736-5] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 09/30/2022] [Indexed: 02/07/2023] Open
Abstract
Pituitary neuroendocrine tumor (PitNET) is one of the most common intracranial tumors. Due to its extensive tumor heterogeneity and the lack of high-quality tissues for biomarker discovery, the causative molecular mechanisms are far from being fully defined. Therefore, more studies are needed to improve the current clinicopathological classification system, and advanced treatment strategies such as targeted therapy and immunotherapy are yet to be explored. Here, we performed the largest integrative genomics, transcriptomics, proteomics, and phosphoproteomics analysis reported to date for a cohort of 200 PitNET patients. Genomics data indicate that GNAS copy number gain can serve as a reliable diagnostic marker for hyperproliferation of the PIT1 lineage. Proteomics-based classification of PitNETs identified 7 clusters, among which, tumors overexpressing epithelial-mesenchymal transition (EMT) markers clustered into a more invasive subgroup. Further analysis identified potential therapeutic targets, including CDK6, TWIST1, EGFR, and VEGFR2, for different clusters. Immune subtyping to explore the potential for application of immunotherapy in PitNET identified an association between alterations in the JAK1-STAT1-PDL1 axis and immune exhaustion, and between changes in the JAK3-STAT6-FOS/JUN axis and immune infiltration. These identified molecular markers and alternations in various clusters/subtypes were further confirmed in an independent cohort of 750 PitNET patients. This proteogenomic analysis across traditional histological boundaries improves our current understanding of PitNET pathophysiology and suggests novel therapeutic targets and strategies.
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Affiliation(s)
- Fan Zhang
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qilin Zhang
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. .,National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Jiajun Zhu
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Boyuan Yao
- grid.8547.e0000 0001 0125 2443Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China ,grid.8547.e0000 0001 0125 2443National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Chi Ma
- grid.462338.80000 0004 0605 6769State Key Laboratory of Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan center for outstanding overseas scientists of pulmonary fibrosis, College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, Henan China
| | - Nidan Qiao
- grid.8547.e0000 0001 0125 2443Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China ,grid.8547.e0000 0001 0125 2443National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shiman He
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhao Ye
- grid.8547.e0000 0001 0125 2443Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China ,grid.8547.e0000 0001 0125 2443National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yunzhi Wang
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Rui Han
- grid.8547.e0000 0001 0125 2443Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China ,grid.8547.e0000 0001 0125 2443National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jinwen Feng
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yongfei Wang
- grid.8547.e0000 0001 0125 2443Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China ,grid.8547.e0000 0001 0125 2443National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhaoyu Qin
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zengyi Ma
- grid.8547.e0000 0001 0125 2443Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China ,grid.8547.e0000 0001 0125 2443National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Kai Li
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yichao Zhang
- grid.8547.e0000 0001 0125 2443Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China ,grid.8547.e0000 0001 0125 2443National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Sha Tian
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhengyuan Chen
- grid.8547.e0000 0001 0125 2443Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China ,grid.8547.e0000 0001 0125 2443National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Subei Tan
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yue Wu
- grid.8547.e0000 0001 0125 2443National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China ,grid.8547.e0000 0001 0125 2443Department of Radiology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Peng Ran
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ye Wang
- grid.8547.e0000 0001 0125 2443Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China ,grid.8547.e0000 0001 0125 2443National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Chen Ding
- State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
| | - Yao Zhao
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. .,National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. .,State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China. .,Shanghai Key laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China. .,Neurosurgical Institute of Fudan University, Shanghai, China. .,National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
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21
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Ibrahim B, Mandel M, Ali A, Najera E, Obrzut M, Adada B, Borghei-Razavi H. Pituitary Adenomas: Classification, Clinical Evaluation and Management. Skull Base Surg 2022. [DOI: 10.5772/intechopen.103778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Pituitary adenomas are one of the most common brain tumors. They represent approximately 18% of all intracranial, and around 95% of sellar neoplasms. In recent years, our understanding of the pathophysiology and the behavior of these lesions has led to better control and higher curative rates. The treatment decision is largely dependent on type of the adenoma, clinical presentation, and the size of the lesion. In addition, incidental pituitary lesions add uncertainty in the decision-making process, especially for pituitary adenomas that can be medically managed. When surgery is indicated, the endoscopic endonasal transsphenoidal approach is the technique of choice, but open standard craniotomy approaches can also be the option in selected cases. The following chapter will review the classification, clinical presentation, pathophysiology, diagnostic work-up, selection of surgical approach, and treatment complications in pituitary adenomas.
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22
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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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23
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Wang L, Liang H, Deng C, Yu Q, Gong F, Feng F, You H, Liang Z, Chen B, Deng K, Ma J, Wang R, Yao Y, Zhu H. Functioning gonadotroph adenomas in premenopausal women: clinical and molecular characterization and review of the literature. Pituitary 2022; 25:454-467. [PMID: 35138520 DOI: 10.1007/s11102-021-01205-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/27/2021] [Indexed: 12/26/2022]
Abstract
PURPOSE To summary the clinical features of premenopausal women with functioning gonadotroph adenomas (FGAs) and preliminarily explore their molecular characterization. METHODS 12 premenopausal females with FGAs in our center were retrospectively analyzed. Previously reported cases were also summarized. The patients were clinically divided into FSH- or LH-predominant types according to their preoperative serum FSH/LH ratio. The expressions of related genes in the tumor tissues of female FGAs, non-functioning gonadotroph adenomas (NFGAs), and silent corticotropin adenomas were evaluated by RT-qPCR. RESULTS Of all the 12 patients with FGAs from our center, 11 (91.7%) were diagnosed as FSH-predominant type, and they all had menstrual disorders, including 9 with spontaneous ovarian hyperstimulation syndrome (sOHSS). Their hormonal profiles showed non-suppressed FSH (12.45 ± 7.34 IU/L) with hyperestrogenemia [median estradiol level 1353.0 pg/mL (636.0, 3535.0)]. The other patient (8.3%) with LH-predominant type mainly manifested with infertility and sustained elevated serum LH without FSH or estradiol increasing. 65 premenopausal FGAs patients were systematic reviewed. 60 patients (92.3%) were FSH-predominant type, including 86.7% presented with menstrual disorders, 16.7% reported infertility, and 98.2% (55/56) showed sOHSS. No sOHSS or hyperestrogenemia were found in the 5 patients (7.7%) with LH-predominant type. Pituitary imaging data revealed macroadenomas and microadenomas accounted for 89.2% and 10.8%, respectively. Of 63 patients (96.9%) who underwent pituitary adenoma resection, 77.8% had complete tumor resection and no recurrence at the last follow-up. The relative expressions of KISS1 mRNA were significantly higher in FGA group than in NFGA group (p = 0.018), and significantly positively correlated with the preoperative serum estradiol levels (p = 0.004). CONCLUSIONS Different clinical features were observed in premenopausal women with FGAs of FSH- or LH-predominant types. The elevated KISS1 expression in tumor tissues might involve in the secretion function of FGAs.
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Affiliation(s)
- Linjie Wang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1# Shuai Fu Yuan, Dong Dan, Beijing, 100730, China
| | - Hanting Liang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1# Shuai Fu Yuan, Dong Dan, Beijing, 100730, China
| | - Chengyan Deng
- Reproductive Center, Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Qi Yu
- Reproductive Center, Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Fengying Gong
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1# Shuai Fu Yuan, Dong Dan, Beijing, 100730, China
| | - Feng Feng
- Department of Radiology, Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, PekingBeijing, China
| | - Hui You
- Department of Radiology, Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, PekingBeijing, China
| | - Zhiyong Liang
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Bo Chen
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Kan Deng
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Jin Ma
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 1# Shuai Fu Yuan, Dong Dan, Beijing, 100730, China
| | - Renzhi Wang
- 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.
| | - Huijuan Zhu
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1# Shuai Fu Yuan, Dong Dan, Beijing, 100730, China.
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24
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Zhao K, Nimchinsky E, Agarwalla PK. Differential Diagnosis and Radiographic Imaging of Pituitary Lesions. Otolaryngol Clin North Am 2022; 55:247-264. [DOI: 10.1016/j.otc.2021.12.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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25
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Abstract
This review summarizes the changes in the 5th Edition of the WHO Classification of Endocrine and Neuroendocrine Tumors that relate to the pituitary gland. The new classification clearly distinguishes anterior lobe (adenohypophyseal) from posterior lobe (neurohypophyseal) and hypothalamic tumors. Other tumors arising in the sellar region are also discussed. Anterior lobe tumors include (i) well-differentiated adenohypophyseal tumors that are now classified as pituitary neuroendocrine tumors (PitNETs; formerly known as pituitary adenomas), (ii) pituitary blastoma, and (iii) the two types of craniopharyngioma. The new WHO classification provides detailed histological subtyping of a PitNET based on the tumor cell lineage, cell type, and related characteristics. The routine use of immunohistochemistry for pituitary transcription factors (PIT1, TPIT, SF1, GATA3, and ERα) is endorsed in this classification. The major PIT1, TPIT, and SF1 lineage-defined PitNET types and subtypes feature distinct morphologic, molecular, and clinical differences. The "null cell" tumor, which is a diagnosis of exclusion, is reserved for PitNETs with no evidence of adenohypophyseal lineage differentiation. Unlike the 2017 WHO classification, mammosomatotroph and acidophil stem cell tumors represent distinct PIT1-lineage PitNETs. The diagnostic category of PIT1-positive plurihormonal tumor that was introduced in the 2017 WHO classification is replaced by two clinicopathologically distinct PitNETs: the immature PIT1-lineage tumor (formerly known as silent subtype 3 tumor) and the mature plurihormonal PIT1-lineage tumor. Rare unusual plurihormonal tumors feature multi-lineage differentiation. The importance of recognizing multiple synchronous PitNETs is emphasized to avoid misclassification. The term "metastatic PitNET" is advocated to replace the previous terminology "pituitary carcinoma" in order to avoid confusion with neuroendocrine carcinoma (a poorly differentiated epithelial neuroendocrine neoplasm). Subtypes of PitNETs that are associated with a high risk of adverse biology are emphasized within their cell lineage and cell type as well as based on clinical variables. Posterior lobe tumors, the family of pituicyte tumors, include the traditional pituicytoma, the oncocytic form (spindle cell oncocytoma), the granular cell form (granular cell tumor), and the ependymal type (sellar ependymoma). Although these historical terms are entrenched in the literature, they are nonspecific and confusing, such that oncocytic pituicytoma, granular cell pituicytoma, and ependymal pituicytoma are now proposed as more accurate. Tumors with hypothalamic neuronal differentiation are classified as gangliocytomas or neurocytomas based on large and small cell size, respectively. This classification sets the standard for a high degree of sophistication to allow individualized patient management approaches.
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Affiliation(s)
- Sylvia L Asa
- Department of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA.
| | - Ozgur Mete
- Department of Pathology, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Arie Perry
- Departments of Pathology and Neurological Surgery, University of California San Francisco, San Francisco, CA, USA
| | - Robert Y Osamura
- Department of Pathology, Nippon Koukan Hospital, Kawasaki and Keio University School of Medicine, Tokyo, Japan
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26
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An extremely rare case of pituitary functioning gonadotroph microadenoma accompanied by ovarian hyperstimulation syndrome in a reproductive-aged woman. F S Rep 2022; 3:79-83. [PMID: 35386509 PMCID: PMC8978087 DOI: 10.1016/j.xfre.2022.01.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 01/21/2022] [Accepted: 01/21/2022] [Indexed: 11/23/2022] Open
Abstract
Objective Design Setting Patients Interventions Main Outcome Measures Results Conclusions
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27
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Chanson P, Wolf P. Clinically non-functioning pituitary adenomas. Presse Med 2021; 50:104086. [PMID: 34718111 DOI: 10.1016/j.lpm.2021.104086] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Accepted: 10/20/2021] [Indexed: 12/30/2022] Open
Abstract
Clinically non functioning pituitary adenomas (NFPAs) include all pituitary adenomas that are not hormonally active. They are not associated with clinical syndromes such as amenorrhea-galactorrhea (prolactinomas), acromegaly, Cushing's disease or hyperthyroidism (TSH-secreting adenomas) and are therefore usually diagnosed by signs and symptoms related to a mass effect (headache, visual impairment, sometimes pituitary apoplexy), but also incidentally. Biochemical work up often documents several pituitary insufficiencies. In histopathology, the majority of NFPAs are gonadotroph. In the absence of an established medical therapy, surgery is the mainstay of treatment, unless contraindicated or in particular situations (e.g. small incidentalomas, distance from optic pathways). Resection, generally via a trans-sphenoidal approach (with the help of an endoscope), should be performed by a neurosurgeon with extensive experience in pituitary surgery, in order to maximize the chances of complete resection and to minimize complications. If a tumor remnant persists, watchful waiting is preferred to routine radiotherapy, as long as the tumor residue does not grow and is distant from the optic pathways. NFPA can sometimes recur even after complete resection, but predicting the individual risk of tumor remnant progression is difficult. Postoperative irradiation is only considered in case of residual tumor growth or relapse, due to its potential side effects.
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Affiliation(s)
- Philippe Chanson
- Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, 94275 Le Kremlin-Bicêtre, France.
| | - Peter Wolf
- Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, 94275 Le Kremlin-Bicêtre, France; Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, 1090 Vienna, Austria
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28
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Picó A, Aranda-López I, Sesmilo G, Toldos-González Ó, Japón MA, Luque RM, Puig-Domingo M. [Recommendations on the pathological report of pituitary tumors. A consensus of experts of the Spanish Society of Endocrinology and Nutrition and the Spanish Society of Pathology]. REVISTA ESPAÑOLA DE PATOLOGÍA : PUBLICACIÓN OFICIAL DE LA SOCIEDAD ESPAÑOLA DE ANATOMÍA PATOLÓGICA Y DE LA SOCIEDAD ESPAÑOLA DE CITOLOGÍA 2021; 54:263-274. [PMID: 34544556 DOI: 10.1016/j.patol.2020.11.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/09/2020] [Accepted: 11/14/2020] [Indexed: 01/24/2023]
Abstract
Pituitary neuroendocrine tumors (PitNETs) constitute, together with other tumors of the sellar region, 15-25% of intracranial neoplasms. In 2017, the World Health Organization proposed a new classification of PitNETs. The main innovation with respect to the 2004 classification was the recommendation to include in the immunohistochemical evaluation of PitNETs the determination of the transcription factors of the 3 pituitary cell lineages: Pit-1, Tpit and SF-1. Additionally, other clinicopathological classifications with a predictive capacity of tumor behavior during follow-up were proposed. Given these changes, it is appropriate to adapt the knowledge generated during the last 15 years to the daily practice of the treatment and monitoring of PitNETs at the Centers of Excellence in Pituitary Pathology. This document includes the positioning of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Society of Pathology (SEAP) on the classification and denomination of the PitNETs and the information that the pathologist should provide to the clinician to facilitate the treatment and monitoring of these tumors.
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Affiliation(s)
- Antonio Picó
- Servicio de Endocrinología y Nutrición, Instituto de Investigación Sanitaria y Biomédica de Alicante-Hospital General Universitario de Alicante, Universidad Miguel Hernández, Alicante, España.
| | - Ignacio Aranda-López
- Servicio de Anatomía Patológica, Hospital General Universitario de Alicante/ISABIAL, Alicante, España
| | - Gemma Sesmilo
- Servicio de Endocrinología y Nutrición, Hospital Universitari Dexeus, Barcelona, España
| | - Óscar Toldos-González
- Sección de Neuropatología, Servicio de Anatomía Patológica, Hospital Universitario 12 de Octubre, Madrid, España
| | - Miguel A Japón
- Servicio de Anatomía Patológica, Hospital Universitario Virgen del Rocío, Sevilla, España
| | - Raúl M Luque
- Grupo Obesidad y Metabolismo, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC); Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba; Hospital Universitario Reina Sofía de Córdoba; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, España
| | - Manel Puig-Domingo
- Servicio de Endocrinología y Nutrición, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona (Barcelona), España
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Alvarez-Payares JC, Bello-Simanca JD, De La Peña-Arrieta EDJ, Agamez-Gomez JE, Garcia-Rueda JE, Rodriguez-Arrieta A, Rodriguez-Arrieta LA. Common Pitfalls in the Interpretation of Endocrine Tests. Front Endocrinol (Lausanne) 2021; 12:727628. [PMID: 34557164 PMCID: PMC8453144 DOI: 10.3389/fendo.2021.727628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 08/23/2021] [Indexed: 11/15/2022] Open
Abstract
Endocrine tests are the cornerstone of diagnosing multiple diseases that primary care physicians are frequently faced with. Some of these tests can be affected by situations that affect the proper interpretation, leading to incorrect diagnoses and unnecessary treatment, such as the interference of biotin with thyroid function test, falsely elevated prolactin values in presence of macroprolactinemia or falsely normal due to the "hook effect" in macroprolactinomas. Recognizing these situations is essential for the clinician to make an adequate interpretation of these tests as well as an accurate diagnosis that guarantees the best outcomes for the patient.
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Affiliation(s)
- Jose C. Alvarez-Payares
- Internal Medicine Department, Faculty of Medicine, University of Antioquia, Medellin, Colombia
- Internal Medicine Service, Institución Prestadora de Servicios (IPS) Universitaria - Clínica León XIII, Medellin, Colombia
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30
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Maheshwari A, Nippoldt T, Davidge-Pitts C. An Approach to Nonsuppressed Testosterone in Transgender Women Receiving Gender-Affirming Feminizing Hormonal Therapy. J Endocr Soc 2021; 5:bvab068. [PMID: 34278180 PMCID: PMC8279075 DOI: 10.1210/jendso/bvab068] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Indexed: 12/14/2022] Open
Abstract
Nonsuppressed levels of testosterone are seen in up to a quarter of transgender women on gender-affirming feminizing hormonal treatment. Multiple factors contribute to this situation, including patient, medication, laboratory, and organ-specific concerns. We propose a stepwise approach to determine the etiology of nonsuppressed levels of testosterone in transgender women. This may lead to an appropriate feminizing hormonal therapy regimen and diagnosis of manageable medical conditions.
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Affiliation(s)
- Arvind Maheshwari
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN 55905, USA
| | - Todd Nippoldt
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN 55905, USA
| | - Caroline Davidge-Pitts
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN 55905, USA
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31
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Kim KC, Park MH, Yun JI, Lim JM, Lee ST. The native form of follicle-stimulating hormone is essential for the growth of mouse preantral follicles in vitro. Reprod Biol 2021; 21:100469. [PMID: 34144372 DOI: 10.1016/j.repbio.2020.100469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 11/23/2020] [Accepted: 11/25/2020] [Indexed: 11/28/2022]
Abstract
To assess whether the follicle-stimulating hormone (FSH) subunits observed in patients with gonadotroph adenomas (GA) can cause infertility, the effects of subunits and heterodimeric FSH on the in vitro follicle development were evaluated in mice. The partial forms of FSH in follicle culture did not induce development into pseudoantral follicles, whereas follicles cultured with native FSH developed into pseudoantral follicles and produced mature metaphase II oocyte. Therefore, intact FSH is needed for folliculogenesis, implying that production of FSH with a partial structure in GA may result in infertility.
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Affiliation(s)
- Keun Cheon Kim
- Department of Agricultural Biotechnology, Seoul National University, Seoul, 151-921, Republic of Korea; Research Institutes of Agriculture and Life Sciences, Seoul National University, Seoul, 151-921, Republic of Korea
| | - Min Hee Park
- Department of Animal Life Science, Kangwon National University, Chuncheon, 24341, Republic of Korea
| | - Jung Im Yun
- Kustogen, Chuncheon, 24341, Republic of Korea
| | - Jeong Mook Lim
- Department of Agricultural Biotechnology, Seoul National University, Seoul, 151-921, Republic of Korea; Research Institutes of Agriculture and Life Sciences, Seoul National University, Seoul, 151-921, Republic of Korea.
| | - Seung Tae Lee
- Department of Animal Life Science, Kangwon National University, Chuncheon, 24341, Republic of Korea; Kustogen, Chuncheon, 24341, Republic of Korea; Department of Applied Animal Science, Kangwon National University, Chuncheon, 24341, Republic of Korea.
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Mamedova EO, Selivanova LS, Potapova KA, Buryakina SA, Azizyan VN, Grigoriev AY, Belaya ZE. [A rare case of a functioning gonadotroph tumor accompanied by erythrocytosis in an elderly man]. ACTA ACUST UNITED AC 2021; 67:37-44. [PMID: 34297500 DOI: 10.14341/probl12758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 06/21/2021] [Accepted: 06/13/2021] [Indexed: 11/06/2022]
Abstract
Functioning gonadotroph adenomas are rare pituitary tumors secreting one or two gonadotropins (follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH)), which are hormonally active. In the majority of cases, gonadotroph tumors are endocrinologically "silent" and make up more than a half of non-functioning pituitary adenomas. In this article we describe a rare clinical case of LH/FSH-secreting pituitary macroadenoma with bitemporal hemianopsia in a 62-year-old man. The patient underwent transnasal transsphenoidal adenomectomy, leading to remission. The distinctive feature of this case is the presence of secondary erythrocytosis due to endogenous hyperandrogenism, which required several blood exfusions to normaliza the level of hematocrit before surgery. It is noteworthy that clinical signs of erythrocytosis were present long before visual impairment. This clinical case demonstrates difficulties in the early diagnosis of functioning gonadotroph adenomas.
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Recommendations on the pathological report of pituitary tumors. A consensus of experts of the Spanish Society of Endocrinology and Nutrition and the Spanish Society of Pathology. ENDOCRINOL DIAB NUTR 2021; 68:196-207. [PMID: 34167699 DOI: 10.1016/j.endien.2020.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 10/17/2020] [Indexed: 11/23/2022]
Abstract
Pituitary neuroendocrine tumors (PitNETs) constitute, together with other tumors of the sellar region, 15-25% of intracranial neoplasms. In 2017, the World Health Organization proposed a new classification of PitNETs. The main innovation with respect to the 2004 classification was the recommendation to include in the immunohistochemical evaluation of PitNETs the determination of the transcription factors of the 3 pituitary cell lineages: Pit-1, Tpit and SF-1. Additionally, other clinicopathological classifications with a predictive capacity of tumor behavior during follow-up were proposed. Given these changes, it is appropriate to adapt the knowledge generated during the last 15 years to the daily practice of the treatment and monitoring of PitNETs at the Centers of Excellence in Pituitary Pathology. This document includes the positioning of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Society of Pathology (SEAP) on the classification and denomination of the PitNETs and the information that the pathologist should provide to the clinician to facilitate the treatment and monitoring of these tumors.
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Lakomkin N, Van Gompel JJ, Post KD, Cho SS, Lee JYK, Hadjipanayis CG. Fluorescence guided surgery for pituitary adenomas. J Neurooncol 2021; 151:403-413. [PMID: 33611707 DOI: 10.1007/s11060-020-03420-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Accepted: 01/31/2020] [Indexed: 12/28/2022]
Abstract
PURPOSE Resection of pituitary adenomas presents a number of unique challenges in neuro-oncology. The proximity of these lesions to key vascular and endocrine structures as well as the need to interpret neuronavigation in the context of shifting tumor position increases the complexity of the operation. More recently, substantial advances in fluorescence-guided surgery have been demonstrated to facilitate the identification of numerous tumor types and result in increased rates of complete resection and overall survival. METHODS A review of the literature was performed, and data regarding the mechanism of the fluorescence agents, their administration, and intraoperative tumor visualization were extracted. Both in vitro and in vivo studies were assessed. The application of these agents to pituitary tumors, their advantages and limitations, as well as future directions are presented here. RESULTS Numerous laboratory and clinical studies have described the use of 5-ALA, fluorescein, indocyanine green, and OTL38 in pituitary lesions. All of these drugs have been demonstrated to accumulate in tumor cells. Several studies have reported the successful use of the majority of the agents in inducing intraoperative tumor fluorescence. However, their sensitivity and specificity varies across the literature and between functioning and non-functioning adenomas. CONCLUSIONS At present, numerous studies have shown the feasibility and safety of these agents for pituitary adenomas. However, further research is needed to assess the applicability of fluorescence-guided surgery across different tumor subtypes as well as explore the relationship between their use and postoperative clinical outcomes.
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Affiliation(s)
- Nikita Lakomkin
- Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, Mount Sinai Downtown Union Square, 10 Union Square East, Suite 5E, New York, NY, 10003, USA.,Department of Neurosurgery, Icahn School of Medicine, Mount Sinai Beth Israel, Mount Sinai Health System, New York, USA
| | | | - Kalmon D Post
- Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, Mount Sinai Downtown Union Square, 10 Union Square East, Suite 5E, New York, NY, 10003, USA
| | - Steve S Cho
- Department of Neurosurgery, University of Pennsylvania, Philadelphia, USA
| | - John Y K Lee
- Department of Neurosurgery, University of Pennsylvania, Philadelphia, USA
| | - Constantinos G Hadjipanayis
- Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, Mount Sinai Downtown Union Square, 10 Union Square East, Suite 5E, New York, NY, 10003, USA. .,Department of Neurosurgery, Icahn School of Medicine, Mount Sinai Beth Israel, Mount Sinai Health System, New York, USA.
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Picó A, Aranda-López I, Sesmilo G, Toldos-González Ó, Japón MA, Luque RM, Puig-Domingo M. Recommendations on the pathological report of pituitary tumors. A consensus of experts of the Spanish Society of Endocrinology and Nutrition and the Spanish Society of Pathology. ACTA ACUST UNITED AC 2021; 68:196-207. [PMID: 33549511 DOI: 10.1016/j.endinu.2020.10.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 10/13/2020] [Accepted: 10/17/2020] [Indexed: 01/15/2023]
Abstract
Pituitary neuroendocrine tumors (PitNETs) constitute, together with other tumors of the sellar region, 15-25% of intracranial neoplasms. In 2017, the World Health Organization proposed a new classification of PitNETs. The main innovation with respect to the 2004 classification was the recommendation to include in the immunohistochemical evaluation of PitNETs the determination of the transcription factors of the 3 pituitary cell lineages: Pit-1, Tpit and SF-1. Additionally, other clinicopathological classifications with a predictive capacity of tumor behavior during follow-up were proposed. Given these changes, it is appropriate to adapt the knowledge generated during the last 15 years to the daily practice of the treatment and monitoring of PitNETs at the Centers of Excellence in Pituitary Pathology. This document includes the positioning of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Society of Pathology (SEAP) on the classification and denomination of the PitNETs and the information that the pathologist should provide to the clinician to facilitate the treatment and monitoring of these tumors.
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Affiliation(s)
- Antonio Picó
- Servicio de Endocrinología y Nutrición, Instituto de Investigación Sanitaria y Biomédica de Alicante-Hospital General Universitario de Alicante, Universidad Miguel Hernández, Alicante, España.
| | - Ignacio Aranda-López
- Servicio de Anatomía Patológica, Hospital General Universitario de Alicante/ISABIAL, Alicante, España
| | - Gemma Sesmilo
- Servicio de Endocrinología y Nutrición, Hospital Universitari Dexeus, Barcelona, España
| | - Óscar Toldos-González
- Sección de Neuropatología, Servicio de Anatomía Patológica, Hospital Universitario 12 de Octubre, Madrid, España
| | - Miguel A Japón
- Servicio de Anatomía Patológica, Hospital Universitario Virgen del Rocío, Sevilla, España
| | - Raúl M Luque
- Grupo Obesidad y Metabolismo, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC); Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba; Hospital Universitario Reina Sofía de Córdoba; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, España
| | - Manel Puig-Domingo
- Servicio de Endocrinología y Nutrición, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona (Barcelona), España
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Zhang Y, Chen C, Lin M, Deng K, Zhu H, Ma W, Pan H, Wang R, Yao Y. Successful pregnancy after operation in an infertile woman caused by luteinizing hormone-secreting pituitary adenoma: case report and literature review. BMC Endocr Disord 2021; 21:15. [PMID: 33435923 PMCID: PMC7802169 DOI: 10.1186/s12902-020-00677-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 12/30/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Functional gonadotroph adenomas (FGAs) are rare adenomas that most commonly secrete FSH. However, solitary LH-secreting pituitary adenomas are unusual. CASE PRESENTATION A 30-year-old woman with elevated LH and normal FSH presented with inability to conceive. An MRI revealed an enlarged sella turcica and an intrasellar mass. Treatment with transsphenoidal resection led to normalization of LH and estradiol, as well as successful pregnancy. And we reviewed 6 cases of LH-secreting pituitary adenomas from 1981 to 2020. CONCLUSIONS Our case is unique because of the LH-secreting pituitary adenoma without FSH hypersecretion. This case indicates that pituitary adenoma should be considered when other diseases causing infertility have been excluded.
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Affiliation(s)
- Yi Zhang
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Cheng Chen
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Min Lin
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Kan Deng
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Huijuan Zhu
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenbin Ma
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Hui Pan
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Renzhi Wang
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Yong Yao
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.
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Du X, Zhang W, Wang X, Yu X, Li Z, Guan Y. Follicle-Stimulating Hormone-Secreting Pituitary Adenoma Inducing Spontaneous Ovarian Hyperstimulation Syndrome, Treatment Using In Vitro Fertilization and Embryo Transfer: A Case Report. Front Endocrinol (Lausanne) 2021; 12:621456. [PMID: 34248835 PMCID: PMC8264655 DOI: 10.3389/fendo.2021.621456] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 05/18/2021] [Indexed: 12/04/2022] Open
Abstract
OBJECTIVE To describe the management of a patient with a pituitary adenoma secreting follicle-stimulating hormone (FSH) associated with spontaneous ovarian hyperstimulation syndrome (sOHSS) who was treated with in vitro fertilization and embryo transfer (IVF-ET). METHODS We report a clinical case of a woman of reproductive age with menstrual irregularity, infertility and ovarian hyperstimulation due to recurrent pituitary adenoma secreting FSH, which persisted after transsphenoidal surgery.She underwent the diagnosis by magnetic resonance imaging (MRI) and laboratory tests,and finally she was treated with IVF-ET. RESULTS The patient was plagued by a recurrent pituitary adenoma for many years and tried various treatments. After complete transsphenoidal surgery, sOHSS decreased, as shown by a reduction in oestradiol levels and an improvement in the ultrasonography parameters; however, secondary amenorrhea occurred. Finally, pregnancy was achieved through IVF-ET and the symptoms of ovarian hyperstimulation were relieved. CONCLUSIONS IVF-ET was found to be effective for the treatment of recurrent pituitary adenoma, thus representing a therapeutic option that should be taken into consideration in such cases.
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Bao X, Wang G, Yu S, Sun J, He L, Zhao H, Ma Y, Wang F, Wang X, Wang R, Yu J. Transcriptomic analysis identifies a tumor subtype mRNA classifier for invasive non-functioning pituitary neuroendocrine tumor diagnostics. Am J Cancer Res 2021; 11:132-146. [PMID: 33391466 PMCID: PMC7681103 DOI: 10.7150/thno.47525] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 09/01/2020] [Indexed: 02/07/2023] Open
Abstract
Rationale: The invasive behavior of non-functioning pituitary neuroendocrine tumors (NF-PitNEts) presents obstacles for complete surgical resection and is indicative of poor prognosis. Therefore, developing reliable diagnostic tools for identifying invasive PitNEts would be helpful in guiding surgical decisions and, in particular, the follow-up treatment. Methods: We analyzed differential gene expression profiles between 39 non-invasive and 22 invasive NF-PitNEts by high-throughput sequencing, gene co-expression, and functional annotation. Twenty-one transcripts were further validated by Taqman-qPCR in another 143 NF-PitNEt samples. The histological expression and serum-exosomal mRNA of three candidate genes were examined by tissue microarray and droplet digital PCR. Results: Non-invasive and invasive NF-PitNEts were clustered into distinct groups with a few outliers because of their gonadotroph, corticotroph, or null cell lineages. The gene signature with strong invasive potential was enriched in 'Pathways in cancers' and 'MAPK pathway', with significantly higher in situ INSM1 and HSPA2 protein expression in invasive NF-PitNEts. Further integration of the 20 qPCR-validated differentially expressed genes and pituitary cell lineages provided a gene-subtype panel that performed 80.00-90.24% diagnostic accuracy for the invasiveness of NF-PitNEts. Conclusion: Our approach defined new characteristics in the core molecular network for patients at risk for invasive NF-PitNEt, representing a significant clinical advance in invasive PitNEt diagnostics.
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Hyperreactio Luteinalis (Multiple Luteinized Follicle Cysts): A Report of 10 Cases. Int J Gynecol Pathol 2020; 40:427-434. [PMID: 33323862 DOI: 10.1097/pgp.0000000000000746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Hyperreactio luteinalis is a rare entity arising in pregnancy and in the setting of gestational trophoblastic diseases (ie choriocarcinoma, molar pregnancy) that presents with, typically, bilateral ovarian enlargement due to numerous follicle cysts. While the phenomenon is benign and spontaneously regresses following delivery or treatment, a specimen may be seen in pathology when oophorectomy or cystectomy is performed to exclude malignancy or to manage acute complications such as torsion. Such resections may exhibit overlapping microscopic features with cystic granulosa cell tumors. We thus reviewed 10 cases of hyperreactio luteinalis in the setting of pregnancy, the largest pathologic cohort to date, to highlight notable features of this disorder. Patients ranged from 22 to 30 yr old. Most patients (n=6) presented at time of cesarean section with incidentally discovered ovarian masses. Three patients presented in the postpartum period, and 1 underwent surgery at 28 wk gestation due to the finding of a unilateral ovarian mass. The ovaries ranged from 8.5 to 29 cm and were multicystic and bilateral in 8 of the cases. Histologic examination demonstrated multiple, variably sized cystic follicles lined by a granulosa cell layer of varying thickness and theca cells with marked eosinophilic cytoplasm. Stromal edema was often prominent, with theca cells occasionally noted in nests, cords, and as single cells in foci of edema. Mitoses were generally seen more often in the granulosa cell layer (mean=2.6 per high power fields) compared with the theca cell layer (mean=1 per 10 high power fields). This series documents the key features of hyperreactio luteinalis that differentiate it from the other benign mass forming lesions encountered in pregnancy, most notably large solitary follicle cyst of pregnancy and puerperium, as well as cystic granulosa cell tumors, especially the juvenile variant, which may also present during pregnancy. Of particular use in differentiating them from juvenile granulosa cell tumor is the absence of pale or vacuolated cytoplasm and solid growth of granulosa cells in cases of hyperreactio luteinalis.
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Araujo-Castro M, Pascual-Corrales E, Martínez San Millan J, Rebolleda G, Pian H, Ruz-Caracuel I, De Los Santos Granados G, Ley Urzaiz L, Escobar-Morreale HF, Rodríguez Berrocal V. Multidisciplinary protocol of preoperative and surgical management of patients with pituitary tumors candidates to pituitary surgery. ANNALES D'ENDOCRINOLOGIE 2020; 82:20-29. [PMID: 33278380 DOI: 10.1016/j.ando.2020.11.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 10/05/2020] [Accepted: 11/22/2020] [Indexed: 12/11/2022]
Abstract
The optimal planning of preoperative diagnosis, management and treatment of pituitary tumors (PT) candidates to pituitary surgery (PS) requires a multidisciplinary approach involving a team of endocrinologists, neurosurgeons, ENT, neuro-ophthalmologists and neuroradiologists with experience in pituitary diseases. Such teams improve surgical results, minimize complications and facilitate their correct treatment if occurring, and optimize the hormonal, ophthalmological and radiological preoperative and follow-up evaluation. We have developed a clinical practice protocol for patients with PT who are candidates to PS based on the most recent national and international guidelines and the relevant literature regarding PT published in the last years. The protocol has been elaborated by a multidisciplinary team of a Spanish Pituitary Tumor Center of Excellence (PTCE) that includes at least one neurosurgeon, ENT, neuroradiologist, neuro-ophthalmologist, endocrine pathologist and endocrinologist specialized in pituitary diseases. We elaborated this guideline with the aim of sharing our experience with other centers involved in the perioperative and surgical management of PT thereby facilitating the management of patients undergoing PS.
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Affiliation(s)
- Marta Araujo-Castro
- Neuroendocrinology unit, department of endocrinology and nutrition, hospital universitario Ramón y Cajal, M-607, km. 9, 100, 28034 Madrid, Spain; Instituto de investigación Sanitaria Ramón y Cajal (IRYCIS), Madrid, Spain.
| | - Eider Pascual-Corrales
- Neuroendocrinology unit, department of endocrinology and nutrition, hospital universitario Ramón y Cajal, M-607, km. 9, 100, 28034 Madrid, Spain
| | - Juan Martínez San Millan
- Neuroradiology unit, department of diagnostic imaging, hospital universitario Ramón y Cajal, Madrid, Spain
| | - Gema Rebolleda
- Neuro-ophthalmology unit, department of ophthalmology, hospital universitario Ramón y Cajal, Madrid, Spain; Universidad de Alcalá, Madrid, Spain
| | - Héctor Pian
- Endocrinology unit, department of pathology, hospital universitario Ramón y Cajal, Madrid, Spain
| | - Ignacio Ruz-Caracuel
- Endocrinology unit, department of pathology, hospital universitario Ramón y Cajal, Madrid, Spain
| | - Gonzalo De Los Santos Granados
- Rinology unit, department of otorhinolaryngology (ENT), hospital universitario Ramón y Cajal, Madrid, Spain; Universidad de Alcalá, Madrid, Spain; Instituto de investigación Sanitaria Ramón y Cajal (IRYCIS), Madrid, Spain
| | - Luis Ley Urzaiz
- Pituitary surgery unit, department of neurosurgery, hospital universitario Ramón y Cajal, Madrid, Spain
| | - Héctor Francisco Escobar-Morreale
- Neuroendocrinology unit, department of endocrinology and nutrition, hospital universitario Ramón y Cajal, M-607, km. 9, 100, 28034 Madrid, Spain; Universidad de Alcalá, Madrid, Spain; Instituto de investigación Sanitaria Ramón y Cajal (IRYCIS), Madrid, Spain; Centro de investigación biomédica en red diabetes y enfermedades metabólicas asociadas (CIBERDEM), Madrid, Spain
| | - Victor Rodríguez Berrocal
- Pituitary surgery unit, department of neurosurgery, hospital universitario Ramón y Cajal, Madrid, Spain
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Follicle Cysts of the Ovary: A Report of 30 Cases of a Common Benign Lesion Emphasizing its Unusual Clinical and Pathologic Aspects. Int J Gynecol Pathol 2020; 40:359-368. [PMID: 33075022 DOI: 10.1097/pgp.0000000000000720] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The common ovarian follicle cyst is typically straightforward from both clinical and pathologic perspectives, but may have a variety of unusual features from both aspects at various stages of life. Lack of familiarity with these may lead to diagnostic quandaries, the most common of which is distinguishing between a follicle cyst and cystic granulosa cell tumor of either adult or juvenile type. We reviewed 30 cases of follicle cysts, all sent in consultation, to highlight unusual aspects of a common lesion. Patients ranged from 3 d to 47 yr old. Clinical presentations included precocious puberty, pelvic pain, or an incidentally discovered pelvic mass, including those occurring in neonates and in 2 adults with pituitary adenomas, one of which was diagnosed 3 yr after presentation with the ovarian cyst. Size ranged from 0.5 cm (deflated) to 18.5 cm, with 7 exceeding 8 cm in greatest dimension. Twelve cases demonstrated small satellite cystic follicles in the wall of the dominant cyst. The granulosa cell layer varied in thickness and mitotic activity (which ranged from 1 to 36 per 10 HPF), but uniformly displayed round nuclei that lacked nuclear grooves. Luteinization of the granulosa cell layer, theca layer, or both was seen across all clinical scenarios, with unluteinized cysts being most common in precocious puberty patients. This series documents that although typically smaller, a subset of follicle cysts are the same size as cystic granulosa cell tumors and the 2 entities may be grossly indistinguishable. Helpful clues to the diagnosis of follicle cyst are the lack of nuclear grooves (vs. adult granulosa cell tumor) and lack of invagination of granulosa cells into the cyst wall (vs. both forms of granulosa cell tumor). Mitoses in the granulosa cells are of no aid in the differential with either form of granulosa cell tumor as follicle cysts may exhibit brisk mitotic activity. Our series highlights some of the unusual clinical aspects, one relatively well known-an association with isosexual precocity, but 2 not as widely known, those occurring in neonates and those due to a pituitary adenoma, the latter sometimes not being discovered until a few years after presentation with a follicle cyst.
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Management of infertility and long-term follow-up in women with follicle-stimulating hormone-secreting adenoma. Chin Med J (Engl) 2020; 134:101-103. [PMID: 32858594 PMCID: PMC7862812 DOI: 10.1097/cm9.0000000000001059] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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A Case of Recurrent Hemorrhagic Corpus Luteum with Elevated Follicle-Stimulating Hormone, Controlled by Estrogen/Gestagen Therapy. Case Rep Obstet Gynecol 2020; 2020:4098085. [PMID: 32774957 PMCID: PMC7399774 DOI: 10.1155/2020/4098085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2019] [Revised: 04/21/2020] [Accepted: 07/16/2020] [Indexed: 11/17/2022] Open
Abstract
A high secretion of follicle-stimulating hormone (FSH) in reproductive-aged women is unusual. We report a case of recurrent corpus luteum hemorrhage and subsequent ovarian torsion with markedly elevated FSH levels in a reproductive-aged woman in the absence of functional gonadotroph adenoma (FGA) or premature ovarian failure (POF). A 22-year-old nulligravid woman with a history of bilateral hemorrhagic corpus luteum and subsequent ovarian torsion presented with acute abdominal pain. An emergency salpingo-oophorectomy of the right side was performed, and the right ovarian torsion due to hemorrhagic corpus luteum was diagnosed. Laboratory tests revealed markedly elevated FSH levels (77.6 mIU/mL). FGA was suspected, but no evidence of tumor was identified. The left ovary enlarged again at one-month follow-up. Estrogen/gestagen therapy (EGT) was started, which reduced the enlarged ovary to normal size. Two years later, her pituitary hormonal status was evaluated in detail. Besides markedly elevated FSH level, slightly elevated LH (31.2 mIU/mL), normal total inhibin B (35.3 pg/ml), abnormally low anti-Müllerian hormone (AMH) (<0.03 ng/mL), and poor FSH response to gonadotropin-releasing hormone stimulation test were found. In the absence of FGA, we conclude that certain disorders of inhibitory factors for FSH function, including inhibin and AMH may exist, which could attribute to the patient's symptoms. EGT was very effective in suppressing the ovarian hyperactivity.
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Kolnes AJ, Øystese KAB, Olarescu NC, Ringstad G, Berg-Johnsen J, Casar-Borota O, Bollerslev J, Jørgensen AP. FSH Levels Are Related to E-cadherin Expression and Subcellular Location in Nonfunctioning Pituitary Tumors. J Clin Endocrinol Metab 2020; 105:5839824. [PMID: 32421791 PMCID: PMC7758833 DOI: 10.1210/clinem/dgaa281] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 05/14/2020] [Indexed: 12/11/2022]
Abstract
CONTEXT Gonadotroph pituitary neuroendocrine tumors (PitNETs) can express follicle-stimulating hormone (FSH) and luteinizing hormone (LH) or be hormone negative, but they rarely secrete hormones. During tumor development, epithelial cells develop a mesenchymal phenotype. This process is characterized by decreased membranous E-cadherin and translocation of E-cadherin to the nucleus. Estrogen receptors (ERs) regulate both E-cadherin and FSH expression and secretion. Whether the hormone status of patients with gonadotroph PitNETs is regulated by epithelial-to-mesenchymal transition (EMT) and ERs is unknown. OBJECTIVES To study the effect of EMT on hormone expression in gonadotroph nonfunctioning (NF)-PitNETs. DESIGN Molecular and clinical analyses of 105 gonadotroph PitNETs. Immunohistochemical studies and real-time quantitative polymerase chain reaction were performed for FSH, LH, E-cadherin, and ERα. Further analyses included blood samples, clinical data, and radiological images. SETTING All patients were operated on in the same tertiary referral center. RESULTS NF-PitNET with high FSH expression had decreased immunohistochemical staining for membranous E-cadherin (P < .0001) and increased staining for nuclear E-cadherin (P < .0001). Furthermore, high FSH expression was associated with increased ERα staining (P = .0002) and ERα mRNA (P = .0039). Circulating levels of plasma-FSH (P-FSH) correlated with FSH staining in gonadotroph NF-PitNET (P = .0025). Tumor size and invasiveness was not related to FSH staining, E-cadherin, or ERα. LH expression was not associated with E-cadherin or ERα. CONCLUSION In gonadotroph PitNETs, FSH staining is related to E-cadherin, ERα expression, and circulating levels of P-FSH. There was no association between FSH staining and invasiveness. The clinical significance of these findings will be investigated in ongoing prospective studies.
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Affiliation(s)
- Anders J Kolnes
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway
- Faculty of Medicine, University of Oslo, Oslo, Norway
- Correspondence and Reprint Requests: Anders Jensen Kolnes, Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Rikshospitalet, Pb. 4950 Nydalen, 0424 Oslo, Norway, E-mail:
| | - Kristin A B Øystese
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway
- Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Nicoleta C Olarescu
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway
- Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Geir Ringstad
- Department of Radiology, Oslo University Hospital, Oslo, Norway
| | - Jon Berg-Johnsen
- Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Neurosurgery, Rikshospitalet, Oslo University Hospital, Oslo, Norway
| | - Olivera Casar-Borota
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
- Department of Clinical Pathology, Uppsala University Hospital, Uppsala, Sweden
| | - Jens Bollerslev
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway
- Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Anders P Jørgensen
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway
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Araujo-Castro M, Berrocal VR, Pascual-Corrales E. Pituitary tumors: epidemiology and clinical presentation spectrum. Hormones (Athens) 2020; 19:145-155. [PMID: 31933100 DOI: 10.1007/s42000-019-00168-8] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 12/16/2019] [Indexed: 02/07/2023]
Abstract
Pituitary tumors (PTs) are a heterogeneous group of lesions of the central nervous system that are usually benign. Most of them occur sporadically, but 5% can do so within family syndromes, usually at a young age. There are differences by sex, age, race, and genetic factors in the prevalence of different tumor cell types and clinical presentation. Functioning-PTs (FPTs) are usually diagnosed earlier than non-functioning PTs (NFPTs). However, this depends on the PT type. Headaches and visual disturbances are the most frequent mass-effect symptoms, but seizures or hydrocephalus may also occur. Pituitary apoplexy is another possible mode of presentation, and it requires special attention because of its potential severity. PTs in pregnancy, childhood, and old age present a series of clinical peculiarities that must be taken into account when evaluating these patients. Ectopic PTs (EPTs) are uncommon and share the same clinical-epidemiological data as eutopic PTs, but, depending on their location, other types of clinical manifestations may appear. Silent PTs are often detected as an incidentaloma or due to neurologic symptoms related to mass-effect. Aggressive PTs and pituitary carcinomas (PCs), which are very rare, are characterized by multiple local recurrences and metastases, respectively. This review addresses the epidemiology and clinical presentation of PTs, from the classical hormonal and mass-effect symptoms to the different rare presentations, such as pituitary apoplexy, hydrocephalus, or diabetes insipidus. Moreover, special situations of the presentation of PTs are discussed, namely, PTs in pregnancy, childhood, and the elderly, EPTs, silent and aggressive PTs, and PCs.
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Affiliation(s)
- Marta Araujo-Castro
- Neuroendocrinology Unit, Endocrinology Department, Ramón y Cajal University Hospital, Madrid, Spain.
| | | | - Eider Pascual-Corrales
- Neuroendocrinology Unit, Endocrinology Department, Ramón y Cajal University Hospital, Madrid, Spain
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Gorbacheva AM, Przhiyalkovskaya EG, Azizyan VN, Stanoevich IV, Grigoriev AY, Sazonova AI, Lapshina AM, Belaya ZE. [An ovarian hyperstimulation syndrome caused by gonadotropinoma in a young woman]. ACTA ACUST UNITED AC 2019; 65:278-288. [PMID: 32202731 DOI: 10.14341/probl10178] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 08/21/2019] [Accepted: 07/30/2019] [Indexed: 01/05/2023]
Abstract
From 14 to 54% of all pituitary adenomas are nonfunctioning pituitary adenomas (NPAs), their prevalence is estimated as 7.041.3 cases per 100 000 population. The most common type of NPAs (73% of cases) are gonadotropinomas. In most cases, gonadotropinoma is characterized by secretion of biologically inactive hormones, so the release of gonadotropins does not lead to the development of any clinical symptoms. For this reason the diagnosis of gonadotropinomas is most often performed on the basis of immunohistochemical analysis. However, in rare cases, gonadotropinomas secrete biologically active hormones, most often follicle-stimulating (FSH). Ovarian hyperstimulation syndrome due to gonadotropin-secreting pituitary tumors occurs in about 3% of women with hormonally inactive pituitary adenomas at reproductive age and in 8% of patients with verified gonadotropinomas. This clinical case describes a young patient with a rare pathology: FSH/LH-secreting macroadenoma of the pituitary, which led to the development of ovary hyperstymulation symdrome. The diagnosis of pituitary adenoma was performed due to the identified hyperprolactinemia one month before the development of visual impairment, which can be considered a late diagnosis. Surgical treatment of gonadotropinomy was carried out successfully and without complications, remission of the disease was achieved, visual function was restored, the patient successfully became pregnant.
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Affiliation(s)
| | | | | | | | | | - A I Sazonova
- Research Center for Obstetrics, Gynecology and Perinatology
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Triviño V, Fidalgo O, Juane A, Pombo J, Cordido F. Gonadotrophin-releasing hormone agonist-induced pituitary adenoma apoplexy and casual finding of a parathyroid carcinoma: A case report and review of literature. World J Clin Cases 2019; 7:3259-3265. [PMID: 31667176 PMCID: PMC6819301 DOI: 10.12998/wjcc.v7.i20.3259] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Revised: 09/24/2019] [Accepted: 10/05/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Pituitary apoplexy represents one of the most serious, life threatening endocrine emergencies that requires immediate management. Gonadotropin-releasing hormone agonist (GnRHa) can induce pituitary apoplexy in those patients who have insidious pituitary adenoma coincidentally. CASE SUMMARY A 46-year-old woman, with a history of hypertension and menorrhagia was transferred to our hospital from a secondary care hospital after complaints of headache and vomiting, with loss of consciousness 5 min after an injection of GnRHa. The drug was prescribed by her gynecologist due to the presence of uterine myomas. The clinical neurological examination revealed right cranial nerve III palsy, ptosis and movement limitation of the right eye. Our first clinical consideration was a pituitary apoplexy. Blood hormonal analysis revealed mild hyperprolactinemia and high follicle stimulating hormone level; PTH and calcium was high with glomerular filtration rate mildly to moderately decrease. A computed tomography scan, revealed an enlarged pituitary gland (3.5 cm) impinging upon the optic chiasm with bone involvement of the sella. Following contrast media administration, the lesion showed homogeneous enhancement with high-density focus that suggests hemorrhagic infarction of the tumor. Transsphenoidal endoscopic surgery was perfomed and adenomatous tissue was removed. Immunohistochemistry was positive for luteinizing hormone (LH) and follicular-stimulating hormone (FSH). A solid hypoechoic nodule (14 mm x 13 mm x 16 mm) was found in the caudal portion of the right thyroid lobe after a parathyroid ultrasound. A genetic test of Multiple Endocrine Neoplasia type 1 (MEN1) was negative. A right lower parathyroidectomy was performed and the pathologic study showed the presence of an encapsulated parathyroid carcinoma of 1.5 cm. A MEN type 4 genetic test was performed result was negative. CONCLUSION This case demonstrates an uncommon complication of GnRH agonist therapy in the setting of a pituitary macroadenoma and the casual finding of parathyroid carcinoma. It also highlights the importance of suspecting the presence of a multiple endocrine neoplasia syndrome and to carry out relevant genetic studies.
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Affiliation(s)
- Vanessa Triviño
- Department of Endocrinology, Complejo Hospitalario Universitario A Coruña, A Coruña 15006, Spain
| | - Olga Fidalgo
- Department of Endocrinology, Complejo Hospitalario Universitario A Coruña, A Coruña 15006, Spain
| | - Antía Juane
- Department of Endocrinology, Complejo Hospitalario Universitario A Coruña, A Coruña 15006, Spain
| | - Jorge Pombo
- Department of pathological anatomy, Complejo Hospitalario Universitario A Coruña, A Coruña 15006, Spain
| | - Fernando Cordido
- Department of Endocrinology, Complejo Hospitalario Universitario A Coruña, A Coruña 15006, Spain
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49
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Hirano M, Wada-Hiraike O, Miyamamoto Y, Yamada S, Fujii T, Osuga Y. A case of functioning gonadotroph adenoma in a reproductive aged woman. Endocr J 2019; 66:653-656. [PMID: 31006723 DOI: 10.1507/endocrj.ej19-0066] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
A 34-year-old woman presented our hospital with complaint of irregular menstruation and abnormal uterine bleeding lasting for a month. After her second parturition at the age of 27, her menstrual cycle had been regular, but it suddenly became irregular at the age of 30. Transvaginal ultrasound revealed the presence of ovarian mass, and the patient underwent diagnostic laparoscopic surgery. Bilateral ovaries temporally shrink after puncture but the size soon resumed. Gonadotropins were almost normal, but estradiol and PRL levels turned out to be elevated, and cabergoline treatment was initiated. After referral to our hospital, we found that the ovaries showed multifollicular appearance. Brain magnetic resonance imaging showed an 18-mm macroadenoma in the suprasellar area. To suppress the secretion of endogenous gonadotropins and estrogen, low-dose estrogen-progestin was prescribed. Surprisingly, the treatment temporarily reduced the size of the ovaries. The patient was referred to a neurosurgeon, and a functioning gonadotroph adenoma was suspected. After the resection of the pituitary tumor, her menstrual cycle became regular, and the size of bilateral ovaries became normal. We also noticed that her ovarian reserve judged by anti-Müllerian hormone had been almost diminished after the surgical treatment, probably reflecting the exhaustion of follicular pool. Women with multifollicular ovaries and elevated estradiol levels may have functioning gonadotroph adenomas, although the level of FSH is relatively normal, and ovarian reserve can be followed by measuring anti-Müllerian hormone.
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Affiliation(s)
- Mana Hirano
- Department of Obstetrics and Gynecology, The University of Tokyo Hospital, Tokyo 1138655, Japan
| | - Osamu Wada-Hiraike
- Department of Obstetrics and Gynecology, The University of Tokyo Hospital, Tokyo 1138655, Japan
| | - Yuichiro Miyamamoto
- Department of Obstetrics and Gynecology, The University of Tokyo Hospital, Tokyo 1138655, Japan
| | - Shozo Yamada
- Department of Pituitary and Hypothalamic Surgery, Toranomon Hospital, Tokyo 1058470, Japan
| | - Tomoyuki Fujii
- Department of Obstetrics and Gynecology, The University of Tokyo Hospital, Tokyo 1138655, Japan
| | - Yutaka Osuga
- Department of Obstetrics and Gynecology, The University of Tokyo Hospital, Tokyo 1138655, Japan
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Patel S, Pacione D, Fischer I, Maloku E, Agrawal N. FOLLICLE-STIMULATING HORMONE-PRODUCING PITUITARY ADENOMA: A CASE REPORT AND REVIEW OF THE LITERATURE. AACE Clin Case Rep 2019; 5:e175-e180. [PMID: 31967028 DOI: 10.4158/accr-2018-0454] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Accepted: 10/22/2018] [Indexed: 01/19/2023] Open
Abstract
Objective To describe an unusual presentation of a follicle-stimulating hormone-secreting pituitary adenoma leading to ovarian hyperstimulation syndrome. We also discuss the pathophysiology and subsequent management of these tumors. Methods This is a case report and review of the literature. A 37-year-old female with menorrhagia was found to have bilateral multilocular adnexal cysts with concern for ovarian hyperstimulation syndrome. Results Labs revealed elevated follicle-stimulating hormone, and an eminent estradiol level. Pituitary magnetic resonance imaging revealed a macroadenoma with cavernous sinus invasion. The patient went on to have a successful transsphenoidal resection with normalization of hormones and subsequent resumption of menstrual cycles. Conclusion With the help of this case report, we illustrate the pathogenesis of functioning gonadotroph adenomas as well as the management challenges associated with these tumors. Our case is unique in its presentation with severe hyperestrogenemia and cavernous sinus invasion pointing towards a clinically aggressive adenoma. It is important to increase awareness of these tumors to ensure timely and effective management of their complications.
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