Improved urinary cortisol metabolome in addison disease: A prospective trial of dual-release hydrocortisone

CONTEXT: Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy has demonstrated an improved metabolic profile compared to conventional 3-times-daily (TID-HC) among patients with primary adrenal insufficiency. This effect might be related a more physiological cortisol profile, but also modified pattern of metabolism. OBJECTIVE: work aimed study metabolism during DR-HC and TID-HC. DESIGN: A randomized, 12-week, crossover was conducted. INTERVENTION AND PARTICIPANTS: DC-HC same daily dose TID-HC were administered insufficiency (n = 50) vs healthy individuals (n = 124) as controls. MAIN OUTCOME MEASURES: Urinary corticosteroid metabolites measured by gas chromatography/mass spectrometry at 24-hour urinary collections. RESULTS: Total decreased (P < .001) reached control values (P = .089). During DR-HC, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity tetrahydrocortisol + 5α-tetrahydrocortisol/tetrahydrocortisone ratio reduced (P < .05), remained increased controls (P < .001). 11β-HSD2 free cortisone/free (P < .01) normalized (P = .358). 5α- 5β-reduced Tetrahydrocortisol/5α-tetrahydrocortisol both treatments, suggesting 5β-reductase activity. CONCLUSIONS: The metabolome shows striking abnormalities in receiving therapy, 11β-HSD1 that may account for the unfavorable phenotype Its change toward normalization mediate beneficial effects. serve tool assess optimal therapy.