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Adrenal crisis associated with high dose inhaled steroids is more common than previously thought

A UK survey has warned that acute adrenal crisis associated with high dose inhaled corticosteroids is more common— particularly in children—than previously reported. 
 
A group of researchers from several UK hospitals sent questionnaires to all 2912 consultant paediatricians and adult endocrinologists registered in a UK medical directory identifying tertiary care physicians, asking whether they had seen patients with asthma who had had acute adrenal crisis associated with inhaled corticosteroids. Fifty five (2% in all) of the 709 (24%) respondents reported one or more possible cases of acute adrenal crisis . 
 
Thirty three patients (28 children and 5 adults) met the criteria for acute adrenal crisis defined by the research team. The results showed that 23 of the children had presented with acute hypoglycaemia—13 with reduced levels of consciousness or coma, nine with coma and convulsions, and one with coma, convulsions, and death. Five of the patients—mainly adult—had insidious onset of symptoms, which were mainly lethargy and nausea. 
 
Almost all of the cases of acute adrenal crisis identified in the survey involved high doses of inhaled steroids, but most were within accepted treatment guidelines for cases of severe persistent asthma. The dosage range was 500-2000 mg a day. One inhaled corticosteroid, fluticasone, was associated with 94% of the cases of acute adrenal crisis. 
 
In more than three quarters (78%) of cases the dosages used were up to 1000 mg a day, the amount recommended for severe asthma by the British asthma guidelines, although this is higher than recommended by the manufacturer 
 
Clinically significant side effects with inhaled corticosteroids are uncommon, and before 1999 only two cases of acute adrenal crisis associated with these drugs had been reported worldwide. Acute adrenal crisis can occur when there is markedly suppressed production of endogenous cortisol caused by administration of exogenous steroids, so adrenal reserve is insufficient to respond to stressful stimuli that the body can usually cope with, such as respiratory infection. 
 
Lead investigator Geoffrey Todd of Antrim Area Hospital, Antrim, Northern Ireland, explained that the study was prompted by finding four additional cases. He said: “It is clear that the frequency of acute adrenal crisis associated with inhaled corticosteroids is greater than previously assumed.” 
 
The researchers acknowledged that the benefits of controlling symptoms in severe asthma often outweigh the risk of side effects, supporting the use of higher daily doses of inhaled corticosteroids. 
 
However, they concluded: “We advise that the licensed dosage of fluticasone for children—400 mg/day, should not be exceeded unless the patient is being supervised by a physician with experience in problematic asthma.” They added that high dose inhaled steroids should not be stopped abruptly until adrenal function has been assessed, as this could precipitate adrenal crisis.