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

Division of Developmental Medicine, University of Glasgow, Royal Hospital for Sick Children, Glasgow G3 8SJ, Scotland, UK.
Archives of Disease in Childhood (Impact Factor: 2.9). 10/2006; 91(10):808-13. DOI: 10.1136/adc.2005.087247
Source: PubMed


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.
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).
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.
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.

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    • "No of cases Symptoms and signs Triggering cause of adrenal crisis Duration of glucocorticoid therapy Glucocorticoid dose Confirmation of adrenal crisis Reference 1 Severe weakness, dizziness, nauseated and shaking No known stressors 24 months Prednisone 20 mg/d tapered and discontinued 2 weeks before Basal cortisol = 0 nmol/L Krasner 1999 [22] 33 (1 fatal) Hypoglycaemia (n = 23), decreased level of consciousness or coma (n = 13), vomiting (n = 2), insidious onset of symptoms (n = 5) Sepsis (fatal case), surgery (1 case), infections, exacerbation of asthma, reduction or discontinuation of ICS >3 years: 5 patients 1–2 years: 14 patients b1 year: 6 patients Inhaled glucocorticoids (91% fluticasone) 500–2000 μg/day and b 21 days with oral glucocorticoids in previous year (one patient more) Synacthen® test (n = 30) and/or low basal cortisol Todd et al. 2002 [11] 1 Hypoglycaemia, seizures Influenza vaccine Long-term (only 32 months old child) Inhaled fluticasone 440–1320 μg/day Synacthen® test Kennedy et al. 2002 [67] 1 Unconscious, unresponsive to stimulation, cyanosed, hypothermic, cushingoid features, hypoglycemia, seizure Respiratory infection 14 months Inhaled budesonide 1 mg × 4 Synacthen® test Dunlop et al. 2002 [68] 3 (with 1–3 episodes) Vomiting, abdominal pain, lethargy, hypoglycemia, hyponatremia Intercurrent illness Long-term Inhaled fluticasone 500–1500 μg/day Synacthen® test Macdessi et al. 2003 [69] 3 Weakness, malaise, fever, gastrointestinal symptoms, hypotension Sepsis (A + C), Infection (B) 1 × 5 weeks (A + B), 1 × 5 + 1 + 3 weeks (C) + 9 days tapering (all) All: prednisolone 60 mg/m 2 /day, A: tapered and discontinued 4 1/2 months before crisis, C: last 3 weeks dexamethasone 10 mg/m 2 /day Synacthen® test Rix et al. 2005 [31] 1 Tiredness, poor weight gain, mild encephalopathy, hypoglycemia Tonsillitis Not reported Inhaled fluticasone 1000 μg/day (no oral glucocorticoids) Synacthen® test Paton et al. 2006 [70] "
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