Subcutaneous hydrocortisone administration for emergency use in adrenal insufficiency

Aims: Despite careful patient education, patients with adrenal insufficiency are at risk of adrenal crisis, with evidence of increased mortality. Self administration of parenteral hydrocortisone in case of impending crisis holds potential to reduce crisis associated morbidity and mortality. Objective: Evaluation of the pharmacokinetics and safety of subcutaneous hydrocortisone injection for use in adrenal emergency. Design: Single center open label, sequence randomized, cross over study. Patients and methods: Twelve Patients with chronic Addison's disease. Comparison of hydrocortisone pharmacokinetics after subcutaneous (sc) and intramuscular (im) injection (100 mg), and after administration of sodium chloride (0.9%) subcutaneously, respectively, at three different visits. Main Outcome Measure: Maximum serum cortisol (Cmax), time to Cmax (t max ), and time to serum cortisol > 36 µg/dl (t Serum-Cortisol > 36 µg/dl ) after subcutaneous administration compared to intramuscular administration, safety and patient preference. Results: Serum cortisol increased rapidly and substantially after both im and sc injection (Cmax: 110 ± 29 vs. 97 ± 28 µg/dl, p = 0.27); t max 66 ± 51 vs. 91 ± 34 min, p = 0.17, and t Serum-Cortisol > 36 µg/dl 11 ± 5 vs. 22 ± 11 min, p = 0.004, respectively). Both, im and sc injections were well tolerated. Eleven patients (91.7%) preferred sc injection, whereas one patient did not have any preference. Conclusions: Subcutaneous administration of 100 mg hydrocortisone shows excellent pharmacokinetics for emergency use with only a short delay in cortisol increase compared to intramuscular injection. It has a good safety profile and is preferred by patients over intramuscular injection.