Todd GR, Acerini CL, Ross-Russell R, et al. Arch Dis Child. 2002;87:457–461
Purpose of the Study.
Rare reports of acute adrenal crisis associated with inhaled corticosteroid (ICS) use have been published. How commonly does this occur? To which patients? At what dose? With which drugs?
Patients of pediatricians and endocrinologists in the United Kingdom were studied.
Questionnaires were sent to the physicians, asking whether they had encountered asthmatic patients with acute adrenal crises associated with ICS use. Physicians who responded positively completed a more detailed questionnaire. Patients receiving orally administered corticosteroids were excluded, and the case definition required both symptoms of an adrenal crisis and abnormal hypothalamic-pituitary-adrenal axis function test results.
Thirty-three patients met the case definition criteria for acute adrenal crises developing in relation to ICS therapy, including 28 children (mean age: 6.4 years; range: 3.3–10 years) and 5 adults. Twenty-three children presented with acute hypoglycemia (13 with decreased levels of consciousness or coma, 9 with coma and convulsions, and 1 with coma, convulsions, and death). The remainder of the children and the majority of the adults presented with a more insidious onset of symptoms, such as lassitude, weakness, nausea, and dizziness. There were 37 total episodes of adrenal crisis among the 33 patients. There was no obvious precipitating cause in 24 cases (65%), there was evidence of infection (mostly respiratory) in 8 cases (21%), the ICS had been stopped, reduced, or changed to a lower-potency ICS in 4 cases (11%), and 1 episode (3%) occurred postoperatively. The vast majority of child and adult patients (30 of 33 patients) were treated with fluticasone; 1 child was treated with both fluticasone and budesonide, and 1 adult and 1 child were treated with beclomethasone. The mean dose of fluticasone among children was 980 μg/day (range: 500–2000 μg/day), and the mean dose among adults was 1380 μg/day (range: 1000–2000 μg/day). The mean durations of ICS treatment were 1.7 years for children and 3.3 years for adults.
The frequency of acute adrenal crises was greater than expected. Despite being the least prescribed and most recently introduced ICS, fluticasone was associated with 94% of the cases.
Clearly ICSs can cause adrenal suppression and consequent adrenal crises. This appears to be especially true with fluticasone. The author of an editorial that accompanied this article explained that, although fluticasone has high first-pass hepatic metabolism, which decreases the systemic bioavailability of the swallowed portion of the dose, it also has high lipophilicity, allowing the pulmonary portion of the dose to be easily absorbed, which, “combined with its high receptor affinity and prolonged duration of activity, ensure systemic potency and accumulation.” Once again, we are reminded to use the lowest effective dose of ICS. Furthermore, when higher doses are required, perhaps an ICS other than fluticasone would be a better choice.