Mild Autonomous ACTH Secretion: A Narrative Review of 52 Cases from the Literature

Mild autonomous ACTH secretion (MAAS) is an autonomous pituitary-derived hypercortisolism occurring in the absence of overt signs and symptoms of Cushing's syndrome (CS). MAAS is still an underdiagnosed and poorly understood condition. We systematically collected 52 cases of MAAS published in the literature from 1994 to 2026 with the purpose to outline MAAS onset, clinical and biochemical features, pituitary-imaging findings, therapy and clinical outcome, histological and molecular features. MAAS affects a wide age range (18-83 years), with a predominance in women (60%). It is found in about 5% of patients with pituitary adenomas and should not be overlooked in patients with acromegaly. It is associated with significant metabolic complications including hypertension (56%) and type 2 diabetes (57%). A 1mg-dexamethasone suppression tests (DST) value >1.8 μg/dL with non-suppressed ACTH levels support the diagnosis of MAAS, while low dose DST and 24 hours free urinary cortisol may have limited sensitivity in this setting. MAAS may present with pituitary microadenomas, macroadenomas, or even radiologically occult lesions. Surgery often leads to improvements in glycemic control and blood pressure while clinical follow up may be essential in case of non-identifiable lesion. Further prospective research is needed to better clarify clinical, biochemical and molecular feature of MAAS.