Fluticasone and adrenal crisis

There have recently been several reports worldwide of adrenal insufficiency developing in children using inhaled corticosteroids. ADRAC has received 10 such reports from Australia. Eight involved the use of fluticasone, either alone (Flixotide) or in combination with salmeterol (Seretide).
In these 8 cases, the ages ranged from 3 to 10 years, and the doses of fluticasone from 250 to 1500µg daily; the daily dose was over 500µg in 6 of the reports. Six of the children had adrenal crisis, which was associated with hypoglycaemia in all cases, convulsions in 2, and coma in one. In 3 of the reports the adrenal crisis had been precipitated by an episode of gastroenteritis.
Adrenal crisis associated with inhaled corticosteroid use occurs because of the systemic absorption of the corticosteroid and consequent suppression of endogenous glucocorticoids, leaving insufficient adrenal reserve to respond to stress (for example, infection). It may also result from abrupt discontinuation or non-compliance with treatment, leading to acute steroid deficiency. It may present as hypoglycaemia, abdominal pain, tiredness or vomiting, with or without convulsions or coma.
Although adrenal insufficiency can occur with any inhaled corticosteroid, it may be more common with fluticasone because of its greater potency and hence lower equivalent dose (half the dose of budesonide or beclomethasone).
The Australian approved dose of inhaled fluticasone for children is 100-200µg daily. At this dose, adrenal suppression is unlikely. The use of higher doses, however, is common. The Thoracic Society of Australia and New Zealand recom-mends a maximum dose of 250µg daily in children up to 5 years, and 500µg daily in children over 5 years, before referral to a respiratory physician. The National Asthma Council recommends a maximum dose of 500µg daily for all children, before referral to a respiratory physician. Higher doses may not confer greater efficacy; a meta-analysis of trials of fluticasone in adolescents (=12 years) and adults indicated that in patients using regular, long-term inhaled corticosteroids, maximal efficacy was achieved at doses around 500 µg/day, but 90% of the benefit was achieved at doses of 100-250 µg/day.
Prescribers are reminded that inhaled corticosteroids should be given at the lowest effective dose and reviewed regularly, and should not be discontinued suddenly. Screening for adrenal insufficiency in children receiving high dose inhaled corticosteroids is generally not useful. Instead, parents of these children should be warned of the potential for adrenal suppression, and advised to seek medical attention if the child experiences any of the symptoms described above, particularly in the setting of an intercurrent illness.

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