Steroid dose, age and gender affect adrenal responses to a low dose short Synacthen test in children with asthma
Daniel Hawcutt1, Andrea Jorgensen1, Christopher Gardner2, Matthew Peak2, Jonathan Couriel2, David Lacy3, Paul Newland2, Mohamed Didi2, Munir Pirmohamed1, Rosalind Smith1 & Joanne Blair2
Background: The activity of the hypothalamicpituitaryadrenal axis (HPA) during inhaled corticosteroid (ICS) treatment of asthma has been studied extensively. To date patient populations have been too small or homogeneous to identify relationships between steroid exposure, patient characteristics and HPA activity. In this abstract we report data from a large, heterogeneous cohort of patients recruited to observational and pharmacogenomic studies.
Patients and methods: A simplified low dose short Synacthen test (Synacthen dose 500 ng/1.73 m2, sampling at 0, 15, 25, and 35 min) was performed in 332 subjects (201 M, age 11.2±3.3 years) treated with ICS for >3 months. Patients treated with prednisolone daily were excluded. Total steroid exposure (TSE; inhaled+intranasal+oral) was calculated as beclomethasone equivalent in ratios of 1:1 (clenil modulate, budesonide), 2:1 (fluticasone) and 3:20 (prednisolone) and adjusted for body surface area (BSA). Median TSE was 813 (25th/75th percentile: 400/1183) μg/day.
Results: Cortisol response was impaired (peak cortisol <500 nmol/l) in 115 subjects (34.6%). Basal (252±140 nmol/l) and peak (554±154 nmol/l) cortisol correlated negatively with BSA adjusted TSE (P=0.009). Age and gender associated positively with basal and peak cortisol (age: P=0.0002, gender: all ages P=0.015, age >12 years P=0.003). Time to peak cortisol was positively associated with value of peak cortisol (P=0.003).
Discussion: To our knowledge this is the first study to consider the effect of TSE rather than ICS in isolation. Our observation that female gender and greater age are associated with higher basal cortisol may reflect an oestrogen driven rise in cortisol binding globulin during female puberty. We speculate that the relationship between time and magnitude of cortisol peak reflects more rapid depletion of cortisol in adrenals with lower cortisol reserve. These data give interesting insights into the maturation of the HPA during childhood and adolescence.