Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency

• Published in: European journal of endocrinology Vol. 171; no. 3; pp. 369 - 377
• Main Authors: Nilsson, A G, Marelli, C, Fitts, D, Bergthorsdottir, R, Burman, P, Dahlqvist, P, Ekman, B, Engström, B Edén, Olsson, T, Ragnarsson, O, Ryberg, M, Wahlberg, J, Lennernäs, H, Skrtic, S, Johannsson, G
• Format: Journal Article
• Language: English
• Published: Bristol Bioscientifica Ltd 01.09.2014; BioScientifica
• Subjects: [S-35]GTP gamma S autoradiography; adiponectin; administration & dosage; Adrenal Insufficiency; Adrenal Insufficiency - blood; Adrenal Insufficiency - diagnosis; Adrenal Insufficiency - drug therapy; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adult; adverse effects; Biological and medical sciences; blood; CB1 receptors; chemically induced; Clinical Medicine; Clinical Study; Cross-Over Studies; diagnosis; Drug Administration Schedule; drug therapy; Endocannabinoid; Endocrinology and Diabetes; Endocrinopathies; Endokrinologi och diabetes; Female; Follow-Up Studies; Fructose; Fundamental and applied biological sciences. Psychology; Headache; Headache - chemically induced; Headache - diagnosis; Humans; Hydrocortisone; Hydrocortisone - administration & dosage; Hydrocortisone - adverse effects; Klinisk medicin; leptin; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Nasopharyngitis; Nasopharyngitis - chemically induced; Nasopharyngitis - diagnosis; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Prospective Studies; Vertebrates: endocrinology; Endocrinopathy; Human; Corticosteroid; Evaluation; Steroid hormone; Toxicity; Antiinflammatory agent; Patient; Replacement; Hydrocortisone; Glucocorticoid; Long term; Prospective; Daily; Adrenal insufficiency; Adrenal hormone; Adrenal gland diseases; Safety; Endocrinology; Release
• ISSN: 0804-4643; 1479-683X; 1479-683X
• DOI: 10.1530/EJE-14-0327

ObjectiveThe objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI).DesignRandomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden.MethodsSixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20–40 mg once daily and hydrocortisone 20–40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness).ResultsIn stage 1, patients had a median 1.5 (range, 1–9) intercurrent illness events with DR-HC and 1.0 (1–8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1–3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure.ConclusionsThis long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy.