Endocrine Abstracts

Introduction and aim: The purpose of replacement therapy in Adrenal Insufficiency (AI) is mimicking endogenous cortisol levels as closely as possible: dual release hydrocortisone (DR-HC) has been introduced to replicate the circadian cortisol rhythm. Multiple daily saliva collections could be used to assess the cortisol concentration during real-life: our aim was to study the salivary cortisol rhythm in AI.

Materials and methods: We prospectively evaluated, in an observational study, 18 outpatients with AI (11 primary and 7 secondary AI), switched from conventional treatment (conv-HC, 25 mg/day) to the same dose of DR-HC. We collected 6 samples of saliva in a day, measuring cortisol (F) and cortisone (E) with LC-MS/MS. 43 matched healthy subjects served as controls. To assess endogenous daily F exposure we computed the Area Under the Curve (AUC) for salivary F levels at the different time-points respect to the ground (SalAUC) according to the trapezoidal formula. We divided the day in two different parts, the first covering the morning (SalAUC^morning), and the second covering the afternoon and the evening (SalAUC^afternoon).

Results: F levels of patients during conv-HC and after switch to DR-HC were similar in the morning, and lower in the afternoon/evening with DR-HC. Considering daily cortisol exposure, SalAUC was lower with DR-HC despite assuming the same GC dose. Specifically, morning SalAUC^morning levels were similar among conv-HC and DR-HC, contrariwise SalAUC^afternoon was lower with DR-HC. Morning F was lower in patients than controls: a value <3 nmol/l presented 90% SE and 98% SP in detecting patients (AUC 0.979). Also morning E levels were able to differentiate AI from controls: E <9.45 nmol/l presented 95% SE and 94% SP to detect patients with AI (AUC 0.982). Cortisol rhythm in patients with DR-HC was closer to controls, especially in the afternoon/evening: normalization of evening cortisol exposure (SalAUC^afternoon) was observed only in patients with DR-HC. F to E ratio levels were similar between patients with conv-HC and DR-HC, and allowed us to exclude glucocorticoid contamination. A reduction of total cholesterol levels was observed with DR-HC; HbA1c levels dropped with DR-HC in diabetic patients (57 to 52 mmol/mol, P=0.045).

Conclusions: Salivary cortisol is a reliable tool to assess the improvement of cortisol profile in patients treated with DR-HC, and might provide new insights in the study of patients with AI.