Endocrine Abstracts

JOINT3621

Introduction: Multiple endocrine neoplasia are rare, with a prevalence of 1 in 200,000 in the general population. The diagnosis is confirmed by identifying a genetic mutation. However, in sporadic cases, this mutation remains undetected.

Case Report: We report the case of a 74-year-old female patient with a family history of papillary thyroid carcinoma in her daughter. She has been followed in our department for 10 years due to recurrent primary hyperparathyroidism. She underwent three surgical interventions for primary hyperparathyroidism over a 10-year period, each time revealing a parathyroid adenoma. This condition was complicated by osteoporosis. Suspicion of multiple endocrine neoplasia (MEN) prompted further investigations: Bilateral adrenal nodular thickening was observed. Hormonal evaluation of these nodules revealed ACTH-independent Cushing’s syndrome. Pituitary imaging identified a 7 mm left-sided, non-secreting pituitary microadenoma. Genetic analysis for MEN1, AIP, CDKNIB, CaR, CDC73, and GNA11 was negative. The patient was started on calcimimetics for her primary hyperparathyroidism. Medical treatment is planned for her ACTH-independent Cushing’s syndrome.

Discussion: The association of primary hyperparathyroidism, bilateral adrenal adenomas with ACTH-independent Cushing’s syndrome, and a pituitary microadenoma supports the diagnosis of multiple endocrine neoplasia type 1 (MEN1). However, genetic testing for MEN1 mutations was negative. Indeed, in 5-10% of MEN1 cases, no mutation is detected. In such instances, the simultaneous occurrence of endocrine tumors typically associated with MEN1 mutations may result in a phenocopy. Other genetic mutations could be responsible for a MEN1-like phenotype, such as CDKN1B mutations, which cause multiple endocrine neoplasia type 4. Additionally, mutations in CaSR, AlP, and CDC73 have been implicated in MEN1-like syndromes. However, genetic testing for all these genes in our patient was negative. This case could represent a MEN1-like phenotype due to an unidentified etiology or the coincidental occurrence of multiple endocrine tumors.