Hypercortisolism: An Under-Recognised Pathway Linked to Multi-System Complications

The clinical understanding of hypercortisolism (HC) has evolved from a classic overt syndrome with florid Cushingoid features to a broader spectrum of disease that includes milder presentations, often referred to as mild autonomous cortisol secretion (MACS). This shift has lowered the threshold for screening and encouraged clinicians to consider HC even in the absence of classic physical findings, particularly in patients presenting with common features, including metabolic, cardiovascular, musculoskeletal and neuropsychiatric comorbidities. Chronic cortisol excess is associated with substantial morbidity and increased mortality through widespread effects on glucose metabolism, lipid homeostasis, cardiovascular function, blood pressure control, bone and muscle health, reproductive function, cognition and mental health. Importantly, many of these complications are frequently seen in patients with MACS, particularly in association with difficult-to-control diabetes and hypertension, emphasising the importance of earlier disease recognition. Recent data suggest that this abnormality may be more common than previously recognised, and its identification can have important implications for patient management. Emerging evidence may also help identify individuals at higher risk through relatively simple screening tests. Recognising this abnormality, particularly in patients with common chronic diseases that are difficult to control, represents a novel and clinically important concept that may lead to more targeted evaluation and management strategies.