Conventional hydrocortisone dosing does not mimic the normal cortisol circadian rhythm making treatment optimisation difficult in patients with adrenal insufficiency. We described the first use of a continuous variable subcutaneous hydrocortisone infusion (CSHI) via an insulin pump to replace cortisol in a patient with congenital adrenal hyperplasia (CAH) to mimic the normal plasma cortisol circadian rhythm. We report the long term experience of CSHI in seven patients with adrenal insufficiency (5M) aged at start of therapy between 14 and 21 years with adrenal insufficiency (2 CAH, 4 Addison, 1 hypopituitarism). Median duration of therapy - 6 years (range 1 14). Indications for therapy were rapid clearance (2), gastric problems (2) and loss of energy (1), difficulty managing diabetes (2). Cortisol half-life was calculated from intravenous studies (median value of 67.5 min (range 40120)). Clearance was used to estimate pump delivery rates to match hourly plasma cortisol concentrations derived from 24 hour plasma cortisol profiles obtained in 80 adults. Cortisol replacement was compared to the normal dataset and in addition in those with CAH, 17OHP and Addisons ACTH. CSHI therapy was well tolerated and over 42 patient-years there was one cannula site problem due to thigh insertion and one allergy to Efcort resolved by Solucortef substitution. There have been no pump failures or hospitalisations and all patients managed sick days using increased infusion rates successfully. Data from the normal subjects were translated into z scores for each hourly measurement so that each time point was 0±1. Compared to the normative set 24h plasma cortisol profiles obtained yearly had a mean z score of −0.2±0.15 indicating a normal circadian rhythm. 17OHP was measurable within the normal range (<5 nmol/l) but was not suppressed. 0800 h ACTH averaged 15 pg/ml and none were suppressed or above the normal range. All patients reported a vast improvement in quality of life, as well as energy levels, reduction in headaches, concentration, stamina and school and work performance. CSHI is the only method currently available to reproduce the cortisol circadian rhythm. The therapy is effective both clinically and economically and improves quality of life.
07 - 09 Nov 2018
British Society for Paediatric Endocrinology and Diabetes