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Functioning gonadotroph adenomas in premenopausal women: clinical and molecular characterization and review of the literature

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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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Data availability

All data generated or analysed during this study are included in this article and its supplementary material file. Further enquiries can be directed to the corresponding authors.

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Acknowledgements

We thank Dr. Yuelun Zhang for his help in statistical analysis.

Funding

This work was supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Science (CAMS-2016-I2M-1-002, 2017-I2M-1-011).

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  1. Linjie Wang and Hanting Liang have contributed equally to this work.

Authors and Affiliations

  1. 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

    Linjie Wang, Hanting Liang, Fengying Gong & Huijuan Zhu

  2. Reproductive Center, Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

    Chengyan Deng & Qi Yu

  3. Department of Radiology, Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, PekingBeijing, China

    Feng Feng & Hui You

  4. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

    Zhiyong Liang & Bo Chen

  5. Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

    Kan Deng, Renzhi Wang & Yong Yao

  6. 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

    Jin Ma

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Contributions

Conception and design: All authors. Administrative support: HZ and YY. Collection and assembly of data: LW. RT-qPCR: HL. Data analysis and interpretation: All authors. Manuscript writing: LW. Final approval of manuscript: All authors. Accountable for all aspects of the work: All authors.

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Correspondence to Yong Yao or Huijuan Zhu.

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Wang, L., Liang, H., Deng, C. et al. Functioning gonadotroph adenomas in premenopausal women: clinical and molecular characterization and review of the literature. Pituitary 25, 454–467 (2022). https://doi.org/10.1007/s11102-021-01205-9

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