SAT604 An Extensively Invasive Giant Prolactinoma Associated With CDH23 Mutation

Abstract

Abstract Disclosure: B. Alghamdi: None. L.A. Alobaid: None. M. Alswailem: None. E.O. Othman: None. M. Dababo: None. O. Alsagheir: None. A.S. Alzahrani: None. Pituitary adenomas (PA), renamed recently pituitary neuroendocrine neoplasms, are common and prolactinomas are the most common subtype of these tumors. The vast majority of PA are sporadic but they can also be due to germline (∼ 5%), mosaic (<1%) or somatic mutations (∼40%). PA with germline mutations might be part of a syndrome such as MEN1 or apparently sporadic, either due to de novo mutations or because of low penetrance of the underlying gene (e.g. AIP). Among the several genes that have been identified, CDH23 was reported to be associated with familial PA in a single study that included 12 families with PA (33% of them had CDH23 variants) and 125 sporadic PA (15 (12%) of them harbored CDH23 variants) compared to only 0.8% of 260 healthy controls. In this report, we describe a middle-aged woman who was incidentally found to have a huge macroprolactinoma with extensive invasion. Genetic testing revealed a novel germline CDH23 variant. Case report: A 53-year-old woman who with hypertension, diabetes and chronic renal insufficiency diagnosed 4 years before. She accidentally fell down on the back of her head. A CT and subsequent MRI scans of the head showed a huge mass extensively involving the Sella, suprasellar space, the cavernous sinuses and middle fossae. This mass extends inferiorly to the sphenoid and parasellar sinuses, nasopharynx, and appears at the nostrils. The patient reported chronic headaches, snoring and congested nose, and worsening hearing and vision over the last 4 years. She denied history of galactorrhea and her periods ceased 8 years before. She never got married and has no children. Her family history is negative for any pituitary or other tumors. The mass was initially thought to be a nasopharyngeal cancer. However, a bedside biopsy from the protruding mass in the right nostril revealed a pituitary tissue strongly positive for prolactin and weakly positive for growth hormone (GH). An undiluted serum prolactin level was 47 ug/l (3.4-24). After several dilutions for the hook effect, the level was 578,000 ug/l (3.4-24). IGF-1 253 ng/ml (93-245), random GH 4.7 ng/ml, TSH 1.9 mU/l (0.4-4.2), FT4 11.4 pmol/l (12-22), AM cortisol 235 nmol/l (159-620), ACTH 27.6 (5-60). Whole exome sequencing followed by Sanger sequencing revealed a novel variant in CDH23 (c.2621C>A, p.Ala874Asp). Several in silico analyses suggest that this variant is pathogenic and it is assigned variant of unknown significance (VUS) according to American College of Medical Genetics (ACMG) classification. It is not reported in EXAC and 1000G databases. All other known PA-associated genes and cancer-associated genes revealed no pathogenic variants. Conclusion: We report a massive prolactinoma, likely due to a novel CDH23 variant. This is the second report on the likely pathogenic role of this gene in PA. In the case reported here, it is associated with a huge and highly invasive pituitary macroadenoma. Presentation: Saturday, June 17, 2023