Endocrine Abstracts

Background: Adrenal involvement in multiple endocrine neoplasia type 1 (MEN1) has been reported, its prevalence varying from 9 to 73%. The aim of this study was to characterize the adrenal phenotype and the prevalence and clinical significance of cortisol hypersecretion in a cohort of MEN1 patients.

Methods: We retrospectively analyzed data of 36 adult patients with germline menin mutation (20 females; mean age 50±17.4 years) in regular follow-up at our Endocrinology Unit between 2000 and 2023. All study participants underwent periodical MRI abdominal imaging and evaluation of adrenal glands. If adrenal lesions were present hormonal evaluation was carried out and included: 1 mg dexamethasone overnight suppression test (DST), urinary free cortisol (UFC) levels and salivary cortisol levels assessed on 3 consecutive nights; aldosterone, renin levels and urinary metanephrines were assessed when hypertension was present. Patients were also screened for hypercortisolism-related comorbidities (cardiovascular events, hypertension, glucose and lipid metabolism, osteoporosis).

Results: 13 patients (36%) had radiological evidence of adrenal lesions: 4 had hyperplasia (30.7%, 3 females) of which 2 unilateral and 2 bilateral, 4 had bilateral macronodular hyperplasia (30.7%, 3 males) and 5 had unilateral nodular lesions (38.5%, 4 males). The mean diameter of lesions was 15.7±6 mm. One patient with macronodular bilateral hyperplasia had adrenal hemorrhage. Of these 13 patients, 9 (69.2%) had at least one test suggestive for hypercortisolism. 6 had serum cortisol levels after 1 mg DST ≥1.8 µg/l (mean 3.12±1 µg/l), 4 had elevated UFC levels (median 1.3 IQR 1.1-1.4 ULN) and 1 had 2/3 elevated salivary cortisol levels. Median ACTH levels were 11.6 IQR 7.2-18.8 ng/l. Only one patient had both unsuppressed cortisol levels after 1 mgDST and elevated UFC on multiple occasions, thus medical therapy with metyrapone was started. One patient underwent surgical adrenalectomy. Of the 9 patients 4 had hyperplasia, 2 had macronodular hyperplasia and 3 had unilateral nodules. None had clinical signs of overt Cushing syndrome. We compared the prevalence of hypercortisolism-associated comorbidities between patients with possible cortisol autonomous secretion and without and found no significant difference (cardiovascular events 0 vs 1; hypertension 2 vs 2; mean BMI 24.6±2.6 vs 27.9±7.2 kg/m²; diabetes 3 vs 1; IFG 0 vs 4; dyslipidemia 1 vs 1, osteoporosis 3 vs 1). No patients had hyperaldosteronism or pheochromocytoma.

Conclusion: Our data, with the limitation of a small series, suggest that there is a high frequency of biochemical evidence of hypercortisolism, however this does not seem to be associated with clinical signs or with increased frequency of typically related comorbidities.