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Endogenous and Exogenous Glucocorticoids in Cushingoid Patients

The pharmacokinetics of prednisone/prednisolone and the time-course of endogenous hydrocortisone were investigated in 15 stable renal transplant patients and 12 patients with oral mucocutaneous vesiculoerosive diseases. All 27 patients were given their usual prednisone dose orally on one occasion, and 24 were given an equivalent amount of prednisolone intravenously on another occasion. After dosing, 8-14 plasma samples were obtained for the determination of total prednisolone, prednisone, and hydrocortisone concentrations by high performance liquid chromatography and unbound prednisolone concentrations by equilibrium dialysis. The bioavailability of prednisone, the interconversion of prednisone into prednisolone, the total and unbound prednisolone clearances, the prednisolone binding capacity of albumin and transcortin, and the affinity of albumin for prednisolone were not different when the 14 patients without cushingoid side effects were compared with the 13 cushingoid patients. Patients with cushingoid side effects had a higher affinity constant for prednisolone binding to transcortin, more frequently exhibited peak hydrocortisone levels within the normal range, and more often had measurable (greater than 10 ng/ml) hydrocortisone in the plasma samples collected during the kinetic studies, as compared with those not showing side effects. The data suggest that endogenous hydrocortisone production is not as suppressed in patients with visible cushingoid signs as in noncushingoid patients and that no significant difference in the pharmacokinetics of exogenous glucocorticoids exists between patients with and without cushingoid side effects.