Midnight serum cortisol as a marker of increased cardiovascular risk in patients with a clinically inapparent adrenal adenoma.

OBJECTIVE: There is scant information on the morbidity associated with subclinical Cushing's syndrome in patients with a clinically inapparent adrenal adenoma. In the present study, we have determined the prevalence of alterations of the hypothalamic-pituitary-adrenal axis in such patients and examined whether any correlation between endocrine data and the clinical phenotype exists. DESIGN AND METHODS: A multi-institutional retrospective study was carried out on 210 patients (135 women and 75 men aged 19-81 years) with an adrenal adenoma detected serendipitously between 1996 and 2000 in four referral centers in Italy.
RESULTS: Hypertension was observed in 53.8%, obesity in 21.4% and hyperglycemia in 22.4% of patients. The 47 patients with midnight serum cortisol >5.4 microg/dl, a value corresponding to the 97th centile of 100 controls, were older and displayed greater fasting glucose (120.4+/-52.2 mg/dl vs 105.1+/-39.2 mg/dl, P = 0.04) and systolic blood pressure (148.3+/-14.6 mmHg vs 136.4+/-16.2 mmHg, P = 0.0009) than the 113 patients with normal cortisol levels. The difference in systolic blood pressure remained statistically significant (P = 0.009) when age was used as a covariate. The percentage of hypertensive patients undergoing treatment was not different between the two groups (90.5 and 97.1%) but the percentage of patients with controlled hypertension was significantly lower among the hypercortisolemic patients (12.5 vs 32.4%, P = 0.04). Glycated haemoglobin (HbA1c) levels were higher in the hypercortisolemic diabetic patients (8.9+/-1.1% vs 7.1+/-1.3%, P = 0.005).
CONCLUSIONS: Elevated midnight cortisol concentration is a reliable test to select a subgroup of patients with a clinically inapparent adrenal adenoma with an adverse cardiovascular risk profile.