LAUSR

Introduction Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy provides a more physiological cortisol profile than conventional thrice-daily (TID) therapy and has demonstrated improved metabolic profile among patients with adrenal insufficiency (AI). The mechanisms by which this metabolic improvement occurs may be due to less total exposure, changed cortisol time exposure profile, but also modified metabolism of cortisol. Objective To study cortisol metabolism during DR-HC and TID. Methods Patients with primary AI received DR-HC or an equal total daily dose of TID in a crossover multi-center study. Cortisol metabolites were measured by gas chromatography/mass spectrometry on 24 h urinary collections after both treatments and in controls. Results Fifty patients (22 females, mean age 47 years) and 124 healthy controls (73 females, mean age 48 years) were included in the study. Total cortisol metabolites were significantly decreased during DR-HC [median: 6380 μg/24 h] compared to TID [8825 μg/24 h]; P P  = 0.089). Compared to controls, the urinary THF + 5αTHF/THE ratio reflecting 11βHSD1 activity was increased during both DR-HC ( P P P P P  = 0.358). The urinary 5αTHF/THF ratio was increased during both treatments (controls: 1.3; TID: 2.3, P P P Conclusion The urinary cortisol metabolome may be a more sensitive marker of “optimal cortisol replacement”. Abnormal cortisol metabolites excretion and cortisol metabolism are observed in patients receiving TID. This abnormal profile improves with DR-HC. Especially, reduced 11βHSD1 activity during DR-HC may mediate some of the beneficial metabolic effects previously observed with this treatment.