Endocrine Abstracts

Background: MACS is defined as hypercortisolism not suppressed by dexamethasone in patients without overt Cushing’s syndrome (CS) features. In patients with bilateral macronodular adrenal disease (BMAD), excess cortisol production is frequently due to aberrant cortisol responses leading to perturbed cortisol rhythmicity, yet in some patients cortisolemia is suppressed by dexamethasone.

Aim: To describe the clinical characteristics and management of patients with BMAD and dexamethasone-suppressible cortisolemia.

Results: 10 patients (8F/2M) out of 104 patients evaluated between 2015-2024 for incidentally-discovered bilateral adrenal masses were identified. Median age at diagnosis was 62 yrs (range 42-74). Prevalence of overweight/obesity was 70%, diabetes mellitus 50%, arterial hypertension 90%, osteoporosis 20%, obstructive sleep apnoea 20%. Cortisolemia was <50 nmol/L after 1mg DST or LDDST at the initial evaluation. UFC was elevated only in one patient (M, 42yo). Midnight serum cortisol was elevated in 8/9 patients (90.5-344 nmol/L). Morning ACTH was <10 pg/mL in 50% of patients (range 5.02-24.66). All patients tested (7) demonstrated aberrant cortisol responses: to food (all), GnRH agonist (2/7) and orthostatism (1/7); 2 patients showing multiple responses. 4 patients had increased ARR, 2 with confirmed primary hyperaldosteronism. Median follow-up was 33 months (range 0-108). No patient manifested cyclical CS. Progression of hypercortisolism was discrete: baseline ACTH decreased and dexamethasone suppression was lost in 2 patients. One patient (M, 42yo) underwent unilateral adrenalectomy, with improvement of diabetes and hypertension control and remission of concomitant hyperaldosteronism. The remaining patients were monitored for comorbidities attributable to hypercortisolism, without intervention.

Conclusion: Patients with dexamethasone-suppressible BMAD have a high morbidity burden. Demonstration of autonomous cortisol production requires additional tests (midnight cortisolemia/screening for aberrant adrenal receptors). Management remains predominantly conservative, in line with current guideline, although these patients are candidates for treatment with inhibitors of steroidogenesis (chronotherapy/block and replace).