Adrenal responses to low dose synthetic ACTH (Synacthen) in children receiving high dose inhaled fluticasone.
OBJECTIVE
Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) > 400 microg/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 > or = 500 microg/day were invited to attend for assessment. Adrenal function was measured using the low dose Synacthen test (500 ng/1.73 m2 intravenously) and was categorised as: biochemically normal (peak cortisol response > 500 nmol/l); impaired (peak cortisol < or = 500 nmol/l); or flat (peak cortisol < or = 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 > or = 500 microg/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 > or = 1000 microg/day.


CONCLUSIONS
Overall, flat adrenal responses in association with FP occurred in 2.8% of children tested, all receiving > or = 1000 microg/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.
Division of Developmental Medicine, University of Glasgow, Royal Hospital for Sick Children, Glasgow G3 8SJ, Scotland, UK. J.Y.Paton@clinmed.gla.ac.uk
J
J
Paton
E
E
Jardine
E
E
McNeill
S
S
Beaton
P
P
Galloway
D
D
Young
M
M
Donaldson
D000293:Adolescent; D000304:Adrenal Cortex Function Tests / Q000379:methods; D000309:Adrenal Insufficiency / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001249:Asthma / Q000097:blood / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003366:Cosyntropin; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000068298:Fluticasone; D006801:Humans; D006854:Hydrocortisone / Q000097:blood
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D003366:Cosyntropin; C006418:adrenocorticotropin zinc; D000068298:Fluticasone; D006854:Hydrocortisone