8710 “The Refractory Giant”: Functional FSH-Producing Pituitary Adenoma, A Case Report

Abstract Disclosure: M. Manolas: None. J. Samavedam: None. S. Stefan: None. Introduction: Gonadotroph pituitary adenomas are common but typically hormonally silent. Functioning gonadotroph adenomas (FGAs) are rare, accounting for less than 1% of pituitary adenomas, and pose unique clinical challenges. We report a rare case of a functional FSH-producing pituitary macroadenoma refractory to multiple resections. Clinical Case: A 50-year-old woman with a long history of FSH-producing pituitary macroadenoma, complicated by central adrenal insufficiency and hypothyroidism, was admitted for altered mental status and complete vision loss. Brain MRI revealed a residual pituitary mass over 8cm in size with multi-directional extension. She initially presented at age 35 with menorrhagia and diplopia. She underwent transsphenoidal resection (TSS) in Jamaica with no records of hormonal assessments or pathology available from that procedure. In 2012, brain MRI showed residual invasive 3.2cm tumor compressing the optic chiasm. Laboratory results revealed high FSH of 74.5 mIU/mL (RR: Follicular, days 2-3 - 3.0-14.4; Follicular, midcycle - 5.8-21.0; Luteal - 1.2-9.0), low LH of 2.68 mIU/mL (RR: Follicular, days 2-3 - 1.1-11.6; Follicular, midcycle - 17.0-77.0; Luteal - 1.0-14.7), and significantly elevated Estradiol of 1800 pg/mL (RR: 6.0-490) concerning for a functional, FSH-producing adenoma. Pathology from repeat TSS confirmed isolated FSH immunopositivity. She was started on Bromocriptine but given refractory menorrhagia required total hysterectomy and bilateral salpingo-oophorectomy, after which her Estradiol level was undetectable. Between 2014 and 2020 the tumor grew from 3.8cm to 6.8cm, resulting in ongoing visual field defects necessitating a third TSS. Surprisingly, the tumor consistently demonstrated a Ki-67 index of 3% or less. Despite a low mitotic index, it eventually exceeded 8cm in size, causing hallucinations, seizures, memory deficits, and complete vision loss due to progressive extrasellar extension with mass effect on the right temporal lobe. The family is engaged in discussions to weigh the risks and benefits of further tumor debulking. Conclusion: In premenopausal women, FGAs may present with menstrual irregularities, menorrhagia, or ovarian hyperstimulation syndrome as a consequence of hypothalamic-pituitary-gonadal axis dysregulation. They often go undiagnosed or misdiagnosed until the patient develops symptoms of mass effect. Standard treatment for FGAs is tumor resection. While dopamine agonists can help reduce estradiol levels and ovarian size, they do not appear to decrease pituitary tumor size. Existing literature shows that FSH-producing FGAs typically respond well to surgical resection. However, our case is exceptional due to the unusual size of the tumor, its rapid regrowth, and its resistance to multiple resections despite a low Ki-67 index. This atypical case warrants reporting and further discussion. Presentation: 6/2/2024