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 μg/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.