CARBOHYDRATE AND LIPID-METABOLISM IN ENDOGENOUS HYPERCORTISOLISM - SHARED FEATURES WITH METABOLIC SYNDROME-X AND NIDDM

Carbohydrate and lipid metabolism was cross-sectionally assessed in 16 patients with endogenous hypercortisolism (endogenous Gushing syndrom e). Five patients (31%) had fasting glucose levels over 6.6 mmol/l and a HbA1c over 7.5%. Six patients (38%) had diabetes mellitus based on an abnormal 75 g oral glucose tolerance test (OGTT) and two additional patients (13%) had impaired glucose tolerance based on an OGTT. Compa red to obese individuals, patients with Gushing syndrome had an elevat ed glucose but no elevated insulin response to the OGTT. Regression an alysis showed positive correlations between 24-h urinary free cortisol (UFC) and fasting blood glucose (P<0.0005), UFC and OGTT glucose area under the curve (AUC) (P<0.01), and UFC and HbA1c (P<0.005). UFC leve ls were negatively correlated (P<0.05) with OGTT insulin AUC and insul in/glucose ratios. Eleven (69%) patients required anti-hypertensive th erapy for blood pressure control. Total cholesterol and triglycerides were elevated in patients with Gushing syndrome compared to obese cont rols, while LDL and HDL cholesterol, and Lp(a) were similar in the two groups. We conclude that impaired glucose tolerance and/or diabetes i n patients with endogenous Gushing syndrome is due to the hyperglycemi c effects of cortisol with relative insulinopenia. Thus, Gushing syndr ome shares features with both the Metabolic Syndrome X and NIDDM, incl uding impaired glucose uptake, hyperlipidemia and hypertension. Howeve r, in Gushing syndrome, a relative insulinopenia occurs, while in Meta bolic Syndrome X and NIDDM, insulin excess is observed. In Gushing syn drome, as the hypercortisolemia exacerbates, insulinopenia becomes mor e paramount, suggesting that cortisol exerts a direct or indirect ''to xic'' effect on the beta-cell.