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.
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