MON-045 Discordance Between Profound Hyperprolactinemia And Hormone Immunostaining In A PIT1-positive Pituitary Neuroendocrine Tumor. A Rare Case Report.

Abstract Disclosure: A. Arif: None. R. Osman: None. We present a rare case of a functioning macroprolactinoma with negative hormone immunohistochemistry (IHC) but positive PIT1 transcription factor staining. This case highlights the diagnostic value of transcription factor IHC when clinical and biochemical findings are discordant with hormone staining. An 18-year-old female with unremarkable medical history presented with high prolactin levels, galactorrhea, and amenorrhea for 6 months. She was not on any medications, and was not sexually active, or trying to conceive. Prolactin levels were markedly elevated (462, 1,067, and 1,282 ng/mL). MRI showed a 13×12×14 mm T2-hyperintense, slightly cystic pituitary macroadenoma with suprasellar extension and optic chiasm compression, but no cavernous sinus invasion (Knosp 0). Rest of the pituitary hormonal evaluation was normal. She was diagnosed with macroprolactinoma with secondary amenorrhea and galactorrhea. Given Knosp grading, growth pattern, and her young age, she had transsphenoidal resection. Postoperatively, prolactin normalized to 14.4 ng/ml, although not predictive of remission. Her menstrual cycle resumed, and galactorrhea resolved. Postoperative MRI showed a small residual tumor. Pathology showed a Pituitary neuroendocrine tumor, null type. IHC staining was negative for prolactin, ACTH, FSH, LH, TSH, hGH, GFAP, and p53. Ki-67 index was up to 20%. Given hyperprolactinemia and negative IHC staining for prolactin, additional IHC for PIT1 was requested and was positive, confirming PIT1-lineage PitNET. According to the 2022 WHO classification, PitNETs are categorized by transcription factor expression—PIT1, TPIT, or SF1—in addition to hormone staining, to better define cell lineage. PIT1 is associated with differentiation of lactotrophs, somatotrophs, and thyrotrophs.A high percentage of PitNETs are clinically non-functioning (presenting due to mass effect), often so-called silent pituitary adenomas. They can remain positive for hormones or transcription factors by IHC without clinically significant hormonal overproduction. A rare presentation is PIT1-positive PitNETs that are clinically functioning, yet IHC negative for GH, PRL, and TSH. They are distinct from null cell adenomas (lack all transcription factors and hormones). A study by Hong et al. found 4% of PIT1-positive tumors lacked hormone expression; about half still showed biochemical hormone excess, often attributed to stalk effect (typically prolactin <150 ng/mL). We did not find any cases of functioning PitNET with prolactin >150, hormone negative, and PIT1 positive. In our case, prolactin >1000 ng/ml indicates true hormonal secretion. It illustrates an unusual presentation between clinical hyperprolactinemia and negative hormone IHC in a PIT1-positive tumor. It emphasizes the importance of transcription factor staining in PitNETs and the need for ongoing endocrine follow up in such patients. Presentation: Monday, July 14, 2025