FSH-secreting Giant Pituitary Macroadenoma with Aggressive Clinical Behavior

We describe a case of a 51-year-old woman with a 15-year history of a functional gonadotroph adenoma (FGA) secreting FSH, characterized by persistent hormonal hypersecretion, progressive tumor growth despite multiple surgeries, and anterior hypopituitarism. She initially presented at age 35 with menorrhagia and diplopia and underwent transsphenoidal surgery (TSS) abroad. Upon relocating to the United States 3 years later, she presented with recurrent menorrhagia, elevated FSH and estradiol, and a 3.2 cm invasive macroadenoma, requiring repeat TSS. Pathology demonstrated isolated FSH immunopositivity with a low Ki-67 index (≤3%). The postoperative course was complicated by central hypothyroidism and adrenal insufficiency. Despite a trial of bromocriptine, she experienced ongoing menorrhagia and tumor growth to 6.8 cm, requiring a third TSS and hysterectomy. Management was further complicated by inconsistent follow-up and hesitancy toward recommended radiotherapy. Fifteen years after her initial presentation, the residual tumor exceeded 8 cm, causing seizures, hallucinations, and vision loss despite persistently low Ki-67 proliferation (<3%). This case highlights the diagnostic and therapeutic challenges of FGAs, especially when tumor behavior is discordant with low-grade histologic features. It underscores the need for improved prognostic markers and earlier consideration of multimodal therapy, including radiotherapy and chemotherapy, in refractory cases.