Patients with adrenal tumours that quietly overproduce cortisol face a significantly higher risk of developing psychiatric disorders — especially substance use disorders — compared to those with non-functioning tumours. A large Swedish registry study found the overall risk nearly doubled, and was 2.5 times higher for substance use disorders specifically. The association was dose-dependent, with higher cortisol levels tied to greater psychiatric risk.
A new study out of Sweden adds a psychiatric dimension to the clinical picture of mild autonomous cortisol secretion (MACS) — a condition where adrenal tumours subtly overproduce cortisol without causing full-blown Cushing's syndrome. Researchers tracked over 3,000 patients with benign adrenal tumours and found that those with MACS were significantly more likely to develop psychiatric disorders after diagnosis compared to those with non-functional adrenal tumours (NFATs).
The risk was particularly striking for substance use disorders, which were 2.5 times more likely in MACS patients. The association also followed a dose-response pattern — the higher the post-dexamethasone suppression test (DST) cortisol level, the greater the psychiatric risk. Men under 65 were the most vulnerable subgroup, with a more than threefold increased risk.
By the Numbers:
Why it matters: Clinicians managing adrenal incidentalomas often focus on the metabolic and cardiovascular risks of mild cortisol excess. This study signals that neuropsychiatric screening — particularly for substance use disorders in younger men — should also be part of routine care for MACS patients.
