Growth and puberty in the diagnosis of MEN1-related manifestations during childhood

Abstract

Introduction MEN1 syndrome exhibits early manifestations including primary hyperparathyroidism (pHPT), pituitary adenomas (PA) and neuroendocrine gastrointestinal tumors (PanNET). While these manifestations are often asymptomatic before age 19, symptomatic cases may require intervention. Current guidelines recommend annual clinical and laboratory assessments with additional imaging for PA and PanNET.

Purpose To determine age-dependent penetrance of the primary MEN1 manifestations and investigate the efficacy of relying solely on symptoms, growth assessment and pubertal development to detect clinically relevant manifestations.

Methods We conducted a retrospective study on a cohort from the Dutch MEN1Study Group (DMSG), comprising of MEN1 patients from UMC/WKZ. The study involved periodic screening during childhood and adolescence, collecting additional data on growth and pubertal development, and symptoms. Age-dependent penetrance of MEN1 manifestations was estimated using Kaplan-Meier analysis. Linear growth, onset of puberty, manifestations and intervention were visually represented through plots.

Results Among 44 patients, 52% developed pHPT before age 19, 30% had PA and 21% had PanNET. Patients with manifestations exhibited varied linear growth. Out of 22 patients identified for growth/pubertal development analysis, two, with MEN1-related manifestations, displayed decelerated growth during puberty, necessitating intervention for functioning PA.

Conclusion The predominant MEN1 manifestation was pHPT, followed by PA and PanNET. Symptomatology was minimally indicative for pHPT and not for PanNET. Patients with functioning PA exhibited delayed puberty and growth deceleration. Monitoring growth and biochemical parameters exclusively can indicate functioning PA in this cohort. Further research in a larger cohort is necessary to establish the contributory value for patients.