Functional Gonadotroph Adenomas: A Single-Institution Case Series

Introduction: Functional gonadotroph adenomas (FGAs) are rare growths of the pituitary that secrete biochemically active levels of follicle stimulating hormone (FSH) and/or luteinizing hormone (LH). Due to their rarity, there exists a paucity in the literature regarding the diagnosis, characteristics, and management of FGAs.

Methods: A retrospective review of patients diagnosed with pituitary adenomas at a single institution was performed.

Results: Of 4,145 adenomas diagnosed between 1980 and 2021, eight were FGAs (6 macroadenomas, 2 microadenomas) based on elevated serum levels of FSH and/or LH. All FGA patients were men, with the mean age at diagnosis being 65 years. Preoperatively, all patients had elevated serum levels of FSH (mean = 21.2 mIU/mL; range = 14.1–33.9 mIU/mL; nl = 1.5–12.4 mIU/mL). Three patients also exhibited elevated LH levels. Two patients presented with low total testosterone (mean = 71.5 ng/dL; range = 20–123 ng/dL; nl = 300–1000 ng/dL) and one presented with low free testosterone (22.6 pg/mL; nl = 30–135 pg/mL). Additional concomitant endocrine dysfunction included hyperprolactinemia (n = 2) and hypothyroidism (n = 2). Seven patients were symptomatic, with the most common symptoms being headache (n = 3), memory issues (n = 3), fatigue (n = 2), and visual problems (n = 2). One patient presented with gynecomastia in the setting of normal prolactin. Five patients (4 macroadenomas, 1 microadenoma) underwent transsphenoidal resection. Gross total resection (GTR) was achieved for all 5 patients. Pathology staining was available for 3 FGAs. All 3 FGAs were positive for steroidogenic factor-1 (SF-1 stain) and negative for pituitary-specific transcription factor 1 (PIT-1), prolactin, thyroid stimulating hormone, human growth hormone, and adrenocorticotrophic hormone. K_i-67 (MIB-1) ranged from <1% to 2.2%. Postoperative FSH and LH levels were documented in four patients. One patient achieved fully normal postoperative pituitary functions, including resolution of his preoperative hypothyroidism and low free testosterone. The remaining three patients continued to exhibit elevated FSH levels postoperatively (mean = 24.5 mIU/mL; range = 17.4–31.0 mIU/mL; nl = 1.5–12.4 mIU/mL) despite radiographic GTR and intraoperative extracapsular dissection. Of these three postoperative patients with elevated FSH, one experienced normalization of LH, one experienced normalization of total testosterone, and one continued to exhibit an elevated LH (22.5 mIU/mL; nl = 1.6–15.2 mIU/mL). Sixty percent of surgical patients experienced resolution of all symptoms postoperatively, including the patient with gynecomastia. Postoperatively, headache resolved in 2 out of 3 patients and visual problems resolved in 2 out of 2 patients.

Conclusions: FGAs typically present in men with hypogonadal or non-specific symptoms. All our patients presented with elevated FSH levels, and a minority also exhibited elevated LH levels and/or other endocrine dysfunction. Transsphenoidal endoscopic surgery yielded complete resection in all our surgical cases. While most of our postoperative cases continued to exhibit elevated FSH levels, the majority also experienced normalization of at least one hormone level and resolution of symptoms. This case series helps guide postoperative expectations for FGAs.

Publication History

Article published online:
01 February 2023