Clinical features of MEN1 in children, adolescents, and young adults: a single-center study

Multiple endocrine neoplasia type 1 (MEN1) can present during childhood and adolescence, yet data on the full endocrine and non-endocrine phenotype in young patients remain limited.

We conducted a retrospective single-center study of genetically confirmed MEN1 patients diagnosed at ≤21 years and followed between 2001 and 2024. Clinical features, surveillance findings, treatments, and outcomes were extracted from medical records.

The cohort included 21 patients (52% males), with a median age at genetic diagnosis of 15 years and a median follow-up of 9 years. At first evaluation, 33% were asymptomatic MEN1 pathogenic/likely pathogenic variant carriers. During follow-up, primary hyperparathyroidism (PHPT) developed in 71% (median age 18 years) and was frequently complicated by renal and skeletal involvement (hypercalciuria, silent nephrolithiasis, and reduced bone mass). Parathyroidectomy was performed in 33% of patients with PHPT, with variable surgical approaches. Both postoperative hypoparathyroidism and persistent or recurrent disease were documented. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) occurred in 48% (median age ~19.5 years), predominantly non-functioning and pancreatic, with surgery in <40% and no metastatic disease. Pituitary adenomas were detected in 52% (mostly non-functioning); one pediatric prolactinoma responded to cabergoline. Adrenal involvement (14%), cutaneous lesions (angiofibromas 33%; lipomas 19%), and thoracic neuroendocrine lesions (19%, all >21 years) broadened the early-life MEN1 phenotype.

In MEN1 patients diagnosed at ≤21 years, early disease expression is common and clinically meaningful. PHPT represents the earliest and most prevalent manifestation and is frequently associated with renal and skeletal morbidity despite sometimes mild biochemical abnormalities. GEP-NETs and pituitary adenomas are also prevalent by late adolescence/young adulthood and are often indolent, suggesting structured, age-adapted multidisciplinary surveillance and early cascade genetic testing in at-risk families.