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      Functioning gonadotroph adenoma with hyperestrogenemia and ovarian hyperstimulation in a reproductive-aged woman: A case report and review of literature

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          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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          Most cited references35

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          The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited.

          Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired obesity is a major postnatal factor. The variety of pathways involved and lack of a common thread attests to the multifactorial nature and heterogeneity of the syndrome. Further research into the fundamental basis of the disorder will be necessary to optimally correct androgen levels, ovulation, and metabolic homeostasis.
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            Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART).

            In women, anti-Müllerian hormone (AMH) levels may represent the ovarian follicular pool and could be a useful marker of ovarian reserve. The clinical application of AMH measurement has been proposed in the prediction of quantitative and qualitative aspects in assisted reproductive technologies (ART). In men AMH is secreted in both the serum and seminal fluid. Its measurement may be useful in clinical evaluation of the infertile male. The PubMed database was systematically searched for studies published until the end of January 2009, search criteria relevant to AMH, ovarian reserve, ovarian response to gonadotrophin stimulation, spermatogenesis and azoospermia were used. AMH seems to be a better marker in predicting ovarian response to controlled ovarian stimulation than age of the patient, FSH, estradiol and inhibin B. A similar performance for AMH and antral follicular count has been reported. In clinical practice, AMH measurement may be useful in the prediction of poor response and cycle cancellation and also of hyper-response and ovarian hyperstimulation syndrome. In the male, the wide overlap of AMH values between controls and infertile men precludes this hormone from being a useful marker of spermatogenesis. As AMH may permit the identification of both the extremes of ovarian stimulation, a possible role for its measurement may be in the individualization of treatment strategies in order to reduce the clinical risk of ART along with optimized treatment burden. It is fundamental to clarify the cost/benefit of its use in ovarian reserve testing. Regarding the role of AMH in the evaluation of infertile men, AMH as single marker of spermatogenesis does not seem to reach a satisfactory clinical utility.
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              Epidemiology and etiopathogenesis of pituitary adenomas.

              Pituitary adenomas are usually benign monoclonal tumours presenting either due to hypersecretion of pituitary hormones, and/or due to local space occupying effects and hyposecretion of some or all of the pituitary hormones. Some pituitary adenomas cause prominent symptoms, while others may result in slowly developing, insidious, non-specific complains delaying accurate diagnosis, with a third group remaining symptomless and recognised only incidentally. Therefore, it is a challenge to accurately determine the prevalence and incidence of pituitary adenomas in the general population. The vast majority of pituitary adenomas occur sporadically, but familial cases are now increasingly recognised. Hereditary predisposition, somatic mutations and endocrine factors were shown to have a pathophysiologic role in the initiation and progression of pituitary adenomas, which interestingly almost always remain benign. Here, we summarize the available epidemiological data and the known pathogenesis of the pituitary adenomas.
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                Author and article information

                Contributors
                Journal
                World J Clin Cases
                WJCC
                World Journal of Clinical Cases
                Baishideng Publishing Group Inc
                2307-8960
                26 February 2023
                26 February 2023
                : 11
                : 6
                : 1341-1348
                Affiliations
                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
                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
                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. xjsunli@ 123456sina.com
                Author notes

                Author contributions: He Y contributed to manuscript writing, editing, and data collection; Gao YT contributed to manuscript editing; Sun L contributed to supervision; all authors have read and approved the final manuscript.

                Supported by Shenzhen High-level Hospital Construction Fund and Sanming Project of Medicine in Shenzhen , No. SZSM201812075.

                Corresponding author: Li Sun, MD, Chief Doctor, 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, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China. xjsunli@ 123456sina.com

                Article
                jWJCC.v11.i6.pg1341
                10.12998/wjcc.v11.i6.1341
                10013118
                36926127
                afee76a3-e5c7-4eb5-8d4d-283d2ddaed86
                ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

                History
                : 26 November 2022
                : 28 December 2022
                : 2 February 2023
                Categories
                Case Report

                functional gonadotroph adenoma,ovarian hyperstimulation,hyperestrogenemia,transsphenoidal surgery,case report

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