Subcutaneous hydrocortisone administration for emergency use in adrenal insufficiency

Objective: Evaluation of the pharmacokinetics and safety of s.c. hydrocortisone injection for use in adrenal emergency. Design: Single-center, open-label, sequence-randomized, crossover study in a tertiary care center. Patients and methods: Twelve patients with chronic Addison's disease. Comparison of hydrocortisone pharmacokinetics after s.c. and i.m. injection (100 mg) and after s.c. administration of sodium chloride (0.9%) respectively at three different visits. Main outcome measure: maximum serum cortisol (C-max), time to C-max (t(max)), and time to serum cortisol > 36 mu g/dl (t(serum) cortisol > 36 mg/dl) after s.c. administration compared with i.m. administration, safety, and patient preference. Results: Serum cortisol increased rapidly and substantially after both i.m. and s.c. injections (C-max: 110 +/- 29 vs 97 +/- 28 mu g/dl, P=0.27, t(max): 66 +/- 51 vs 91 +/- 34 min, P=0.17, and t(serum cortisol >) (36 mu g/dl): 11 +/- 5 vs 22 +/- 11 min, P=0.004 respectively). Both i.m. and s.c. injections were well tolerated. Eleven (91.7%) patients preferred s.c. injection, whereas one patient did not have any preference. Conclusions: S.c. administration of 100 mg hydrocortisone shows excellent pharmacokinetics for emergency use with only a short delay in cortisol increase compared with i.m. injection. It has a good safety profile and is preferred by patients over i.m. injection.