Endocrine Abstracts

Background: Several evidences suggested that conventional glucocorticoids (CGCs) used as replacement treatment in adrenal insufficiency (AI) are inadequate to mimic physiological cortisol circadian rhythm (CCR), and that CCR disruption, represented by non-physiological pattern of peaks and troughs and elevated evening GC levels, might be responsible for the increased metabolic and, consequently, cardiovascular risk. It has been demonstrated that once daily dual-release-hydrocortisone (DR-HC), which better reproduces physiological CCR, significantly improves metabolic parameters in primary AI (PAI) and secondary AI (SAI) patients.

Aim: The aim of the current study was to evaluate CCR and metabolic profile in PAI and SAI patients switched from CGCs, particularly cortisone acetate and immediate-release hydrocortisone, to DR-HC.

Methods: Thirteen AI patients (7 SAI and 6 PAI, nine females and four males, 20–66 yrs) were enrolled. CCR (AUC_{0-24 hrs}) was explored by collecting cortisol blood samples at selected time points (0700−1000 h, 1300−1600−1900−2100 h, 0100−0400−0700 h), at baseline (CGCs) and 12 months after switching to DR-HC. Anthropometric and metabolic parameters were evaluated with standard procedures in a fasting status (1900 h) in the entire cohort;glucose and insulin at fasting and during oral glucose tolerance test (OGTT) were evaluated in a subgroup of nine patients; surrogate indexes of insulin sensitivity/resistance, derived from OGTT, were calculated according to homeostasis model assessment-insulin resistance (HOMA-IR) and Insulin Sensitivity Index (ISI) Matsuda.

Results: Cortisol AUC (1900 h−0100 h) was significantly lower with DR-HC than with CGCs (P = 0.033), and particularly, cortisol levels measured at 1900 h appeared lower with DR-HC than with CGCs (P = 0.042). After 12 months of treatment, DR-HC induced a significant improvement in waist circumference (P = 0.004), and a trend to a significant improvement in body mass index (P = 0.07); in the subgroup of patients evaluated with OGTT, DR-HC induced a significant reduction in fasting insulin levels (P = 0.039) and a significant increase in ISI_0’ (P = 0.012) and ISI_120’(P = 0.027).However, no significant correlation was found between cortisol secretion pattern and metabolic changes.

Conclusions: The switch from CGCs to DR-HC in AI patients induces a significant decrease of late evening GC overexposure associated with a significant improvement of visceral obesity and insulin sensitivity. Therefore, this change might induce a beneficial effect on cardiovascular risk in AI patients treated with GCs.