The Functional Side of Multiple Endocrine Neoplasia Type 1-Associated Adrenal Disease: Mild Autonomous Cortisol Secretion.

Background/

Objectives

Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary syndrome characterized by primary hyperparathyroidism, duodeno-pancreatic and pituitary neuroendocrine tumors. Adrenal lesions are acknowledged manifestations of MEN1, but their functional characterization remains limited. Mild autonomous cortisol secretion (MACS) is associated with cardiometabolic risk and skeletal involvement in sporadic adrenal incidentaloma, significantly impacting patient morbidity, but data in MEN1 are lacking. The aims of the study were to estimate the prevalence of MACS in adult patients with MEN1 and radiological evidence of adrenal involvement, and to evaluate the associated biochemical, cardiometabolic, and skeletal features.

Methods

This retrospective single-center observational study included adult patients with clinical, familial, or genetic MEN1 and adrenal involvement. MACS was defined as serum cortisol >1.8 µg/dL after a 1 mg overnight dexamethasone suppression test in the absence of overt Cushing syndrome. Cardiometabolic and skeletal characteristics were compared according to MACS status.

Results

Among 101 MEN1 patients, 38 had adrenal involvement and 22 underwent complete hormonal evaluation. MACS was identified in 15 of the 22 patients (68.2%). Patients with MACS had significantly lower baseline ACTH concentrations and showed a trend toward a higher prevalence of metabolic syndrome. No significant differences were observed in osteoporosis or fracture prevalence.

Conclusions

This is the first study specifically evaluating the prevalence of MACS in MEN1 patients with adrenal lesions. MACS appears to be more common than in sporadic adrenal incidentalomas and may represent an important factor for improving clinical characterization and tailoring patient management. Larger prospective studies are needed to define the optimal follow-up strategy.