SAT-098 Diffuse hCG Expression in a Case of Pituitary Adenoma: A Diagnostic Challenge Mimicking Germ Cell Tumors

Abstract Disclosure: A.N. Mukhtar: None. M. Shahid: None. G.Y. Gandhi: None. C.A. Koch: Abbvie. Background: Pituitary adenomas can express FSH and LH. However, diffuse human chorionic gonadotropin (hCG) expression in pituitary adenomas is rare. These adenomas can mimic germ cell tumors Clinical Case: A 60-year-old woman presented with a 3-week history of headache and nausea. MRI revealed a 2.2 cm pituitary macroadenoma with cystic degeneration extending into the suprasellar region, causing compression of optic chiasm. The patient did not report any visual disturbances or galactorrhea. Hormonal evaluation showed mild prolactin elevation of 48.7 ng/mL and normal IGF-1, cortisol, alpha subunit, free T4, and TSH. After transsphenoidal resection, immunohistochemical analysis showed positive staining for synaptophysin and chromogranin A, diffuse hCG positivity, non-specific FSH staining, and less than 1% prolactin expression. The tumor was negative for GH, ACTH, and TSH. The ki-67 index was <2%, with a histopathological exam consistent with a non-functioning gonadotroph adenoma. Postoperative follow-up revealed a serum hCG <5 mIU/mL with no signs of hormonal hypersecretion or deficiency. MRI scans remained unremarkable Conclusion: The pituitary typically secretes small amounts of hCG, which is particularly relevant in postmenopausal women, where elevated gonadotropin levels can lead to mild increases in pituitary-derived hCG. Diffuse hCG expression in pituitary adenomas can be mistaken for germ cell tumors. However, pituitary adenomas expressing hCG tend to be less aggressive, as evident by a low Ki-67 index and the absence of elevated serum hCG. In this case, the stable clinical course, negative serum hCG, and no recurrence or residual mass further support this conclusion. Elevated FSH and LH in postmenopausal women often correlate with pituitary-derived hCG, which typically does not exceed 5.3 IU/L in serum. This threshold helps distinguish pituitary-derived hCG from that produced by other tumors. FSH levels ≥40 IU/L serve as a valuable indicator for distinguishing pituitary-origin hCG in postmenopausal women with serum hCG concentrations between 5.3 and 16 IU/L, helping avoid unnecessary interventions. The use of GnRH antagonists can help suppress gonadotropin production to confirm whether hCG is of pituitary origin. These antagonists are available in clinical practice for managing gonadotropin-dependent conditions. However, their role in confirming pituitary-origin hCG remains investigational. Due to their shared alpha subunit, cross-reactivity between LH and hCG may cause falsely elevated hCG levels in assays not designed to differentiate between LH and hCG. Therefore, modern immunoassays that do not show this cross-reactivity are essential for accurate diagnosis. Understanding the molecular distinctions between pituitary adenomas and germ cell tumors is critical for accurate diagnosis and management, preventing unnecessary oncologic investigations Presentation: Saturday, July 12, 2025