An Analysis of Post-Adrenalectomy Dynamics in MACS (Mild Autonomous Cortisol Secretion)-Positive Adrenal Tumours: The Biomarkers and Clinical Impact

Abstract

Background/Objective: One third of “non-functioning adrenal tumours” (NFAs) have mild autonomous cortisol secretion (MACS). An updated analysis of the hormonal biomarkers profile, including risk factors and the rate of post-surgery adrenal insufficiency (PSAI), the duration of restoring the normal adrenocortical function in MACS/NFA and potential impacts on clinical comorbidities. Methods: Comprehensive review based on PubMed search (January 2020–January 2025). Results: The studies (n = 14) included 2623 patients (N = 1158 underwent unilateral adrenalectomy), aged 18–93 (mean = 57.49 years), with a female-to-male ratio = 1.54. Post-adrenalectomy (n = 9, N = 753) analysis: the PSAI risk correlated with the severity of baseline hypercortisolism. PSAI incidence: 50% of MAC. The rate after 4–6 weeks follow-up was 71.9% (adrenal Cushing’s syndrome) vs. 50% (MACS) vs. 14.4% (NFA). PSAI duration was up to 35 months. Early PSAI diagnosis was reflected by post-operative cortisol assay on day 1 (cut-off ≤ 5 µg/dL) and an ACTH (Cosyntropin) stimulation test (CST) (cortisol cut-off ≤ 14 µg/dL). Pre-operatory PSAI predictors: higher serum cortisol-DST (1 mg dexamethasone testing) and lower baseline plasma ACTH (not all studies agreed). Conclusions: A stratified strategy is encouraged following a unilateral adrenalectomy in MACS; PSAI is expected in almost half of patients, with a potential improvement of hypertension. Serum cortisol assays serve as most useful biomarker as pre-operatory PSAI predictor (after DST) and, potentially, in addition with baseline ACTH. Post-surgery basal cortisol measurement (± CST) helps the decision of glucocorticoids replacement since first post-operative day and during follow-up, serial testing at 3 months is a useful tool.