Background. Adrenal insufficiency requires life long corticosteroid therapy, but optimal dosing of hydrocortisone replacement has not received adequate attention.Chronic over or under treatment predisposes to morbidity and mortality.
Objective.To examine the variables determiming hydrocortisone disposition and develop practical protocols for individualised prescribing and monitoring of treatment.
Design. Prospective open study.
Setting. Ward of a public hospital.
Patients. Sixty cortisol insufficient patients.
Intervention. Patients were given either a fixed dose of oral hydrocortisone or a 'body surface area adjusted' (BSA) dose in the fasted or fixed state.
Measurements. Serum cortisol profiles were measured in patients and endogenous cortisol levels measured in healthy control subjects. Pharmacokinetic analysis was performed using the the P-Pharm software, and computer simulations were used to assess the likely population distribution of the data.
Results. Body weight was the most important predictor of hydrocortisone clearance. A fixed dose of 10mg over exposed patients to cortisol by 6.3%, whereas weigth adjusted dosing decreaesd inter patient variability in maximum serum cortisol concentration from 31 to 7% and in area under the curve (AUC)from 50 to 22% (p<0.05), and reduced over exposure to <5%. Food taken before hydrocortisone dosing delayed absorption and increased variability. A blood sample taken four hours after hydrocortisone dosing predicted serum cortisol AUC (r2=0.78; p<0.001).
Conclusions. Using current preparations of hydrocortisone we recommend weight adjusted dosing of thrice daily befoer food, monitored with a single measurement of serum cortisol using a nomogram. Optimal treatment awaits the development of a delayed and sustained release hydrocortisone preparation.
03 - 05 Nov 2003
Society for Endocrinology