Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom

Abstract

Background: Until recently, only two cases of acute adrenal crisis associated with inhaled corticosteroids (ICS) had been reported worldwide. We identified four additional cases and sought to survey the frequency of this side effect in the United Kingdom. Methods: Questionnaires were sent to all consultant paediatricians and adult endocrinologists registered in a UK medical directory, asking whether they had encountered asthmatic patients with acute adrenal crisis associated with ICS. Those responding positively completed a more detailed questionnaire. Diagnosis was confirmed by symptoms/signs and abnormal hypothalamic-pituitaryadrenal axis function test results. Results: From an initial 2912 questionnaires, 33 patients met the diagnostic criteria (28 children, five adults). Twenty-three children had acute hypoglycaemia (13 with decreased levels of consciousness or coma; nine with coma and convulsions; one with coma, convulsions and death); five had insidious onset of symptoms. Four adults had insidious onset of symptoms; one had hypoglycaemia and convulsions. Of the 33 patients treated with 500-2000 µg/day ICS, 30 (91%) had received fluticasone, one (3%) fluticasone and budesonide, and two (6%) beclomethasone. Conclusions: The frequency of acute adrenal crisis was greater than expected as the majority of these patients were treated with ICS doses supported by British Guidelines on Asthma Management. Despite being the least prescribed and most recently introduced ICS, fluticasone was associated with 94% of the cases. We therefore advise that the licensed dosage of fluticasone for children, 400 µg/day, should not be exceeded unless the patient is being supervised by a physician with experience in problematic asthma. We would also emphasise that until adrenal function has been assessed patients receiving high dose ICS should not have this therapy abruptly terminated as this could precipitate adrenal crisis.

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

“…However, cases of adrenal crises have been reported with ICS; of the 33 patients reported, 28 were children and most were taking doses of ICS within the recommended doses according to UK guidelines at that time. There is potential for ICS to cause adrenal suppression but this is not a common event, and clinicians need always to be aware of this idiosyncratic potentiality [186,187].…”

Categorizing Asthma Severity: An Overview of National Guidelines

“…Inhaled corticosteroids are known to suppress the hypothalamic-pituitary-adrenal axis, but are very rarely the cause of clinically recognizable adrenal insufficiency. 16 Parents are concerned that inhaled corticosteroids might affect the growth of their children. Growth velocity does transiently decrease with initiation of inhaled corticosteroid treatment in prepubertal children, but this effect does not seem to result in diminution of actual height attained.…”

Hair cortisol as a novel biomarker of HPA suppression by inhaled corticosteroids in children

“…Articles DISCUSSION Despite the perception that there is low systemic bioavailability of ICS compared with oral or intravenous steroids, there is evidence of unexpected ICS-induced adverse effects in children such as height deficits that persist into adulthood with long-term budesonide use (12). Moreover, children have been repeatedly documented as experiencing adrenal suppression, insufficiency, or crisis while receiving ICS (6,7,13). These adverse effects depend on the dose, duration of therapy, and age at the initiation of therapy.…”

“…However, in children, there are still concerns that chronic use of these agents may lead to adverse effects such as stunted growth (4), or HPA suppression (5), which is the focus of our research. Previous studies have found an association between ICS use in children and decreased salivary cortisol (6), as well as incidents of adrenal crisis, a potentially life-threatening condition (7).…”