MON-077 Endogenous Suppression of Prolactinoma Hypersecretion by a Dopamine Secreting Paraganglioma

Abstract Disclosure: T.J. Fox: None. L. Needleman: None. K. Bharani: None. F. Mihm: None. J.P. Annes: None. J.J. Chang: None. Introduction: Prolactinomas are benign pituitary adenomas/neuroendocrine tumors (PitNET) that are typically treated first-line with dopamine agonists to inhibit prolactin secretion and reduce tumor size. Dopamine-secreting pheochromocytoma and paragangliomas (PPGL) are an exceptionally rare subtype of neuroendocrine tumor arising from sympathetic and parasympathetic paraganglia and often do not present with symptoms of catecholamine excess. Although overlapping genetic drivers have been described for paragangliomas and PitNETs, biochemical crosstalk between coexisting tumors is underexplored. Case Description: A 52-year-old male presented with a 6-month history of cerebrospinal fluid rhinorrhea which prompted brain imaging finding an invasive, 4.2 cm pituitary mass with modestly elevated prolactin (130.8 ng/mL, reference range 2-18 ng/mL), the remainder of his pituitary hormonal panel was unremarkable aside from hypogonadotropic hypogonadism. Additional imaging discovered an anterior mediastinal mass suspicious for a thoracic paraganglioma with biochemical screening demonstrating marked elevation of plasma and urinary dopamine. He was started on alpha blockade with doxazosin and underwent successful resection of the mediastinal mass. Pathology confirmed a paraganglioma with immunohistochemical staining positive for synaptophysin, GATA3 and S100 sustentacular cell staining. Following resection of the paraganglioma, his dopamine normalized but prolactin rose significantly (877.8 ng/mL), suggesting an endogenous dopamine-agonist-like effect from the paraganglioma which suppressed prolactin hypersecretion from the presumed prolactinoma. He was started on cabergoline, which suppressed prolactin again. He later underwent transsphenoidal surgery for CSF leak repair with partial pituitary tumor resection. Pituitary pathology was notable for a PIT1-lineage PitNET with absent immunohistochemical staining for prolactin. Germline sequencing for hereditary PPGL susceptibility genes was negative for MEN1, RET, NF1, VHL, SDHB and SDHD but did identify a monoallelic variant of uncertain significance (VUS) in the gene encoding SDHC (SDHC c.155T>C). Given the presence of a germline SDHC VUS, SDHB immunohistochemistry was performed on the PGL tissue and was normally retained. Conclusions: In this case, we report the first case involving feedback signaling between dopamine-secreting PPGL and prolactinoma and highlight challenges in the diagnosis and management of these two rare NETs. Endogenous dopamine production originating from hyperfunctioning PPGL can suppress PitNET prolactin secretion. In our case, the pituitary pathology showed PIT1 staining but was negative for prolactin. Immature PIT1-lineage PitNETs are less differentiated, possess variable hormone immunostaining and secretion, and tend to be relatively larger and more aggressive. Presentation: Monday, July 14, 2025