TOPLINE

Patients with adrenal tumours and mild autonomous cortisol secretion (MACS) had a higher risk for subsequent psychiatric disorders, particularly substance use disorders, than those with non-functional adrenal tumours (NFATs). The risk for subsequent psychiatric disorders increased with higher cortisol concentrations after the dexamethasone suppression test (DST).

METHODOLOGY

• Researchers in Sweden utilised national health registers and laboratory data to track how often psychiatric disorders were diagnosed before and after an adrenal tumour diagnosis in relation to cortisol levels after a DST.
• They included 3195 patients (median age, 64 years; 58.9% women) who received a benign adrenal tumour diagnosis between 2005 and 2018 and had undergone a 1-mg DST. Of these patients, 1216 had MACS (post-DST cortisol level > 50 nmol/L), and 1979 had NFATs (post-DST cortisol level ≤ 50 nmol/L).
• Cortisol levels after the DST were analysed in three ways: using the standard cutoff of 50 nmol/L to classify patients into two groups, dividing patients into four groups on the basis of cortisol levels (≤ 50, 51-82, 83-138, and > 138 nmol/L), and treating the cortisol level as a continuous measure to assess potential dose-response associations.
• The primary outcome was the risk for any psychiatric disorder, whereas secondary outcomes were anxiety (including stress-related), mood, psychotic, and substance use disorders.
• Patients were followed up for a median of 4.7 years.

TAKEAWAY

• At baseline, the prevalence of psychiatric diagnoses was slightly higher with MACS than with NFATs (adjusted odds ratio [aOR], 1.35; 95% CI, 1.11-1.64), with this difference mainly driven by substance use disorders (aOR, 2.22; 95% CI, 1.67-2.90).
• During follow-up, patients with MACS showed a higher risk for incident psychiatric disorders than those with NFATs (adjusted hazard ratio [aHR], 1.79; 95% CI, 1.43-2.23), and the risk was highest for substance use disorders (aHR, 2.50; 95% CI, 1.79-3.49). MACS was also associated with incident anxiety and mood disorders, but these associations did not remain significant after correction for multiple comparisons.
• The risk for any psychiatric disorder increased with higher post-DST cortisol concentrations, with aHRs ranging from 1.63 at concentrations of 51-82 nmol/L to 2.16 at concentrations > 138 nmol/L. When cortisol was treated as a continuous measure, the risk for any psychiatric disorder increased with higher cortisol concentrations (aHR, 1.003; 95% CI, 1.002-1.005).
• The risk for any psychiatric disorder was higher among men than among women (aHR, 2.43 vs 1.51) and was highest among men younger than 65 years (aHR, 3.11; 95% CI, 1.87-5.18).

IN PRACTICE

"These results suggest that neuropsychiatric morbidity may be part of the clinical burden of mild cortisol autonomy and should be considered in the broader assessment of patients with MACS," the authors wrote.

SOURCE

This study was led by Hadis Mirzaei, MD, MSc, Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden. It was published online on October 12, 2026, in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS

Cortisol status was assessed using a single DST, possibly limiting the evaluation of long-term cortisol exposure. The registry mostly included psychiatric disorders diagnosed in specialist care. The possibility of residual confounding could not be completely ruled out.

DISCLOSURES

This study received support from Stockholm Läns Landsting and Karolinska Institutet. The authors declared having no conflicts of interest. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.