Endogenous and exogenous glucocorticoids in cushingoid patients

Area of Science:

• Pharmacology
• Endocrinology
• Nephrology

Background:

• Prednisone and its active metabolite, prednisolone, are commonly used glucocorticoids.
• Understanding their pharmacokinetics is crucial for optimizing patient outcomes, especially in renal transplant recipients.
• Cushingoid side effects are a known complication of glucocorticoid therapy.

Purpose of the Study:

• To investigate the pharmacokinetics of prednisone/prednisolone and the time-course of endogenous hydrocortisone.
• To compare these parameters between patients with and without cushingoid side effects.
• To explore potential differences in glucocorticoid metabolism and endogenous hormone suppression.

Main Methods:

• 15 renal transplant patients and 12 patients with vesiculoerosive diseases received oral prednisone and intravenous prednisolone.
• Plasma samples were analyzed for total and unbound prednisolone, prednisone, and hydrocortisone using HPLC and equilibrium dialysis.
• Pharmacokinetic parameters, including bioavailability, interconversion, clearance, and protein binding, were assessed.

Main Results:

• No significant differences in prednisone/prednisolone bioavailability, interconversion, clearance, or albumin binding were observed between cushingoid and non-cushingoid patients.
• Patients with cushingoid side effects exhibited a higher affinity for prednisolone binding to transcortin.
• Cushingoid patients more frequently had normal peak hydrocortisone levels and measurable hydrocortisone during kinetic studies.

Conclusions:

• Exogenous glucocorticoid pharmacokinetics do not significantly differ between patients with and without cushingoid side effects.
• Endogenous hydrocortisone production appears less suppressed in patients exhibiting cushingoid signs.
• These findings suggest potential alterations in the hypothalamic-pituitary-adrenal (HPA) axis regulation in patients with glucocorticoid-induced side effects.