7214 A Retrospective Cohort Study on Prevalence Of Pituitary Adenomas in MEN2

Abstract Disclosure: R. Ghosh: None. N. Behiri: None. J. Glod: None. S. Gubbi: None. J. Klubo-Gwiezdzinska: None. Background: Multiple endocrine neoplasia (MEN) syndromes are autosomal dominant and present with tumors in at least two or more endocrine organs. MEN2 syndromes that are driven by germline rearranged during transfection (RET) gene pathogenic variants are divided into 2A consisting of medullary thyroid carcinoma (MTC), parathyroid adenomas and pheochromocytoma and 2B presenting with MTC, pheochromocytoma, marfanoid habitus, mucosal neuromas and gastrointestinal ganglioneuromatosis. Pituitary adenomas have been rarely described in MEN2 and hence we conducted a retrospective chart review to determine their prevalence in MEN2. Methods: Retrospective chart screening of MEN2 patients followed at a tertiary referral center between August 1999- August 2022 was done to evaluate the prevalence of pituitary adenomas using biochemical hormonal evaluation and magnetic resonance imaging (MRI) of pituitary based on screening of clinical symptoms. Results: The study consisted of 91 patients (43 MEN2A and 48 MEN2B), aged 35.3±16.9 years (MEN2A) and 18.6±6.4 years (MEN2B), 20/43 (46.5%) women in MEN2A and 24/48 (50%) women in MEN2B. These patients were followed for median duration of 6.5 years (3.3-22) in MEN2A and 8.5 years (5.4-14.6) in MEN2B. RET mutation status was unavailable for 1 MEN2A patient out of 91 patients. Among MEN2A patients, majority (53.5%) were positive for RET C634X mutation followed by RET 804, 609, 631,620 and 666 mutations in the descending order. While in MEN2B cohort all patients were positive for M918T RET mutation. A total of 4/91 (4.4%) patients were found to have pituitary adenomas (3 MEN2B and 1 MEN2A). One patient had clinically symptomatic ACTH producing microadenoma which was surgically resected, and others have asymptomatic non-functioning adenomas. The patient with Cushing’s disease underwent three transsphenoidal resections leading to complete resolution but developed panhypopituitarism. Prevalence of pituitary adenomas in our cohort was significantly higher than the general population screened based on clinical suspicion (p<0.001). Conclusion: Prevalence of clinically symptomatic pituitary adenomas is 1 in 1000 in the general population (1). It is rarely associated with MEN2 syndromes and only few cases are reported in the literature (2). However, screening of all patients with MEN2 for pituitary adenomas, regardless of clinical suspicion, might lead to incidental discovery of asymptomatic pituitary pathology and can provide the actual prevalence. Further studies are needed to evaluate the genetics of these pituitary adenomas in MEN2 syndromes to investigate whether RET protooncogene is indeed the dominant molecular driver of these tumors. References: 1) Daly AF et al. The Epidemiology of Pituitary Adenomas. Endocrinol Metab Clin North Am. 2020 Sep;49(3):347-55 2)Tatsi C et al. The Genetics of Pituitary Adenomas. J Clin Med. 2019 Dec 21;9(1):30 Presentation: 6/1/2024