SUN-018 - Plurihormonal Pituitary Adenoma Presenting as Cushing Disease

Background:

Cushing disease is typically caused by monohormonal corticotroph adenomas. Plurihormonal pituitary neuroendocrine tumors (PitNETs) co-expressing ACTH, prolactin, and FSH are exceedingly rare, occurring in 5-10% of corticotroph adenomas. Recognition is critical for post-operative surveillance and long-term management.

Case Presentation:

A 40-year-old woman developed progressive hypercortisolism over one year. Biochemical testing confirmed ACTH-dependent hypercortisolism with mildly elevated prolactin initially attributed to stalk effect. Pituitary MRI identified a sellar lesion consistent with macroadenoma abutting the optic chiasm. Inferior petrosal sinus sampling demonstrated a marked central-to-peripheral ACTH gradient at baseline and after desmopressin, confirming pituitary ACTH hypersecretion. Following transsphenoidal resection, immunohistochemistry revealed a plurihormonal PitNET immunopositive for ACTH, prolactin, and FSH. Transcription factor analysis showed predominant TPIT with focal PIT-1 positivity, confirming plurihormonal differentiation, despite an ACTH-driven clinical phenotype. Postoperatively the patient experienced symptomatic and biochemical remission and was transitioned to physiologic glucocorticoid replacement.

Discussion:
This case illustrates the critical discordance between immunohistochemical findings and clinical presentation. The preoperative prolactin elevation, initially dismissed as stalk effect, may well have been tumor-derived, highlighting the importance of considering plurihormonal tumors in the differential diagnosis. Despite immunopositivity for prolactin and FSH, only ACTH hypersecretion was functionally active, demonstrating that immunohistochemistry does not reliably predict hormonal secretion.
Transcription factor profiling revealed predominant TPIT (corticotroph lineage) with focal PIT-1 (lactotroph/somatotroph/thyrotroph lineage) consistent with derivation from multipotent progenitor cells. This plurihormonal differentiation necessitates extended surveillance for evolving hormonal activity. Long-term follow-up should include monitoring of cortisol, prolactin, and gonadotropins to detect evolving hormone excess. Recognition of plurihormonal differentiation aids risk stratification and patient counseling. This case highlights the heterogeneity of pituitary tumors and supports the role of multipotent progenitor cells in tumorigenesis.

Conclusion:
Cushing disease can rarely arise from plurihormonal PitNETs. Awareness of these variants is crucial for individualized postoperative surveillance, early detection of evolving hormone excess, and long-term patient counseling.

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