Oral glucose tolerance testing but not intravenous glucose administration uncovers hyper-responsiveness of hypothalamo-pituitary-adrenal axis in patients with adrenal incidentalomas

OBJECTIVE: Modern imaging techniques are detecting adrenal incidentalomas with increasing frequency. Recent data suggests food-dependent hypercortisolism in a subgroup of patients with bilateral macronodular hyperplasia due to aberrant adrenal responsiveness to gastric inhibitory polypeptide (GIP). We studied the putative influence of food intake on the hypothalamo-pituitary-adrenal (HPA) axis in patients with adrenal incidentalomas and possible mediation by GIP.

PATIENTS AND MEASUREMENTS: We examined 15 mildly obese patients with adrenal incidentalomas, eight healthy, lean subjects, and seven obese patients with the metabolic syndrome, who were matched for body weight and age. Each individual underwent oral glucose tolerance testing (OGTT, 75 g glucose), i.v. glucose administration (IVGTT, 30 g glucose over 1 h) and i.v. glucose plus GIP infusion (body weight adapted leading to physiological postprandial GIP serum levels) on three occasions. Plasma glucose, ACTH and cortisol were measured from blood samples taken every 15 minutes from time - 30 minutes to + 75 minutes.

RESULTS: OGTT, i.v. glucose administration and GIP infusion led to comparable glucose values within the groups. In contrast to normal subjects and patients with the metabolic syndrome, patients with adrenal incidentalomas had significantly higher mean cortisol values after oral glucose intake as compared to i.v. glucose administration or GIP infusion. The increase in cortisol levels was preceded by a corresponding ACTH increase. No significant effect of GIP administration on cortisol or on ACTH secretion could be detected.

CONCLUSIONS: Patients with adrenal incidentalomas showed an abnormal responsiveness of the pituitary-adrenal axis to oral glucose administration. The cortisol peaks in these patients seemed to be ACTH-mediated and were not induced by GIP.