Adrenal responses to low dose synthetic ACTH (Synacthen) in children receiving high dose inhaled fluticasone

Background and Aims: Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) > 400 mu g/day, the maximum dose licensed for use in children with asthma. Following two cases of serious adrenal insufficiency ( one fatal) attributed to FP, adrenal function was evaluated in children receiving FP outwith the licensed dose. Methods: Children recorded as prescribed FP >= 500 mg/day were invited to attend for assessment. Adrenal function was measured using the low dose Synacthen test ( 500 ng/1.73 m(2) intravenously) and was categorised as: biochemically normal ( peak cortisol response > 500 nmol/l); impaired ( peak cortisol <= 500 nmol/l); or flat ( peak cortisol <= 500 nmol/l with increment of < 200 nmol/l and basal morning cortisol < 200 nmol/l). Results: A total of 422 children had been receiving FP alone or in combination with salmeterol; 202 were not investigated (137 FP within license; 24 FP discontinued); 220 attended and 217 ( age 2.6 - 19.3 years) were successfully tested. Of 194 receiving FP >= 500 mg/day, six had flat responses, 82 impaired responses, 104 were normal, and in 2 the LDST was unsuccessful. Apart from the index child, the other five with flat responses were asymptomatic; a further child with impairment (peak cortisol 296 nmol/l) had encephalopathic symptoms with borderline hypoglycaemia during an intercurrent illness. The six with flat responses and the symptomatic child were all receiving FP doses of >= 1000 mg/day. Conclusion: Overall, flat adrenal responses in association with FP occurred in 2.8% of children tested, all receiving >= 1000 mg/ day, while impaired responses were seen in 39.6%. Children on above licence FP doses should have adrenal function monitoring as well as a written plan for emergency steroid replacement.