Endocrine Abstracts

Introduction: Current management of intercurrent illness (ICI) in adrenal insufficiency (AI) is inadequate. We attempted to optimise ICI regimens with pharmacokinetic simulations of a dual-release (DR) hydrocortisone (HC) and tested them in a formal clinical trial.

Methods: This work consisted of: i) dosing recommendations in episodes of mild ICI with DR-HC using simulations with a population pharmacokinetic model, ii) collection of ICI episodes with increased cortisol use and outcome assessment using quality-of-life (QoL; Fatigue Impact Scale, Short-Form 36), and iii) exposure-response model for probability of developing an ICI based on logistic regression.

Data was collected from a 3-month cross-over trial comparing once-daily DR-HC with immediate-release (IR) HC given TID using the same daily dose of HC. Further safety data for DR-HC were available for 80 patients over 27 months.

Results: Cortisol profiles were obtained in 62 patients after administration of DR-HC on 116 occasions, and in 16 healthy volunteers. Simulations showed that an additional DR-HC dose at 8±2 h after the morning dose or TID with 8 h intervals provided greater 24 h coverage IR-HC TID.

There was no difference in ICI episodes between DR-HC and IR-HC in mean percentage of days with extra doses, 2.5 and 1.6% respectively (median both 0.0). QoL after an ICI episode was not different between DR-HC and IR-HC. The total experience with DR-HC in mild ICI corresponded to 145 patient years (293 episodes).

There was no correlation between total HC exposure (AUC _{0–24 h}) and numbers of AEs The estimated probability of at least one adverse event episode was not associated with total (AUC _{0–24 h}) HC exposure; DR-HC (P=0.64) and IR-HC (TID) (P=0.52).

Conclusions: In this first prospective study in ICI, the suggested DR-HC regimens were successfully implemented in the clinical management of AI patients. Simulations suggested DR-HC regimens gave greater coverage over 24 h than IR-HC.