Background: Benign adrenal tumours (AT) can be non-functioning (NFAT) or associated with cortisol excess, as indicated by failure to suppress serum morning cortisol to <50 nmol/l in the 1mg-dexamethasone suppression test (1 mg-DST). The latter group divides into patients with clinically overt signs of cortisol excess (adrenal Cushings syndrome, CUSH) and patients lacking CUSH signs (mild autonomous cortisol excess, MACE). Smaller series and a recent meta-analysis reported a high prevalence of obesity, type 2 diabetes and hypertension in MACE. However, large-scale prospective data investigating the metabolic impact of MACE are lacking.
Methods: We included 1309 prospectively recruited patients with benign ATs who underwent 1 mg-DST assessment as part of the ENSAT EURINE-ACT study. All patients provided a 24-h urine for mass spectrometry-based urine steroid excretion profiling. Results were compared to 127 healthy controls, using a sex-, BMI- and age-adjusted linear regression model.
Results: NFAT, MACE and CUSH were diagnosed in 50%, 45% and 5% of patients, respectively. Prevalence of metabolic disease increased with the degree of cortisol excess (hypertension: NFAT 64%, MACE 76%, CUSH 72%; type 2 diabetes: NFAT 20%, MACE 28%, CUSH 26%; osteoporosis: NFAT 33%, MACE 47%, CUSH 63%; all P<0.01 by Fishers exact test). Urine steroid metabolome analysis identified specific signatures that correlated with the degree of cortisol excess and clinical outcomes. Patients with cortisol excess, hypertension and diabetes had higher urinary glucocorticoid excretion than those without comorbidities. Patients with cortisol excess and osteoporosis had decreased urinary androgens, suggesting a more pronounced glucocorticoid-induced adrenal suppression.
Conclusions: Cortisol excess is highly prevalent in benign ATs and associated with an increased burden of metabolic comorbidities. The urinary adrenal steroid metabolome provides a tool for metabolic risk stratification and may identify those patients who can benefit from definitive treatment of cortisol excess, e.g. tumour removal in patients with MACE.