Table 8.

Some reports of ICS-induced adrenal insufficiency in children and adolescents

Reference	Methodology	Findings
Todd et al. [151]	Low dose corticotropin test	A child presented with acute adrenal crisis after shift from fluticasone 1000 μg to budesonide 800 μg/day.
Gupta et al. [234]	Serum cortisol and tetracosactrin test	800 ug/day of BDP for 6 months led to subclinical HPA-axis suppression in one out of 7 children.
Drake et al. [235]	Standard short corticotropin test	Case series of 4 children on fluticasone ≥500 μg daily who presented with adrenal crises secondary to adrenal suppression.
Dunlop et al. [152]	Standard short corticotropin test	Case report of a 5 month old infant presenting with acute adrenal crisis secondary to reducing budesonide dose.
Todd et al. [153]	Variable (Standard short corticotropin test, glucagon stimulation test, decreased serum cortisol response to critical illness)	Based on surveys of doctors in the UK, 28 cases of adrenal crises in children and in adults. AI contributed to a death in one pediatric case.
Todd et al. [236]	Variable (Standard short corticotropin test, baseline serum ACTH levels)	Case series of 3 children and one adult who had adrenal crises secondary to change of ICS.
Macdessi et al. [237]	Standard short corticotropin test	Three children had adrenal crises secondary to high dose fluticasone >500 μg daily.
Santiago et al. [238]	Standard short corticotropin test	Case report of a 7 year old child on 220 μg daily who presented with acute adrenal crisis.
Skoner et al. [139]	Serum and 12 h urinary cortisol	Effects of several examined doses of mometasone furoate on cortisol levels were similar to the placebo group.
Schwartz et al. [155]	Variable (early morning basal cortisol, standard short corticotropin test, 24 h urinary cortisol)	14 children had secondary adrenal suppression with <500 μg daily fluticasone.
Smith et al. [156]	Morning serum cortisol and low dose ACTH stimulation test	Cohort study: 43 of 214 children had low early morning serum cortisol; 20 of whom had confirmed HPA suppression with low dose ACTH stimulation testing.
Zollner et al. [239]	Variable (Fasting morning serum cortisol, basal cortisol, metyrapone testing)	91 out of 143 asthmatic children had a subclinical degree of HPA axis dysfunction.
Allen et al. [240]	24 h serum and urinary cortisol at baseline and on day 42	Inhaled fluticasone furoate/vilanterol did not affect HPA axis in adolescents or adults.
Cavkaytar et al. [241]	Morning serum cortisol and low-dose ACTH stimulation test	HPA axis suppression in 7.7 % of a group of children taking ICS even at moderate doses.

Modified from Sannarangappa and Jalleh [148]

AI adrenal insufficiency, HPA-axis hypothalamic pituitary adrenal axis, ICS inhaled corticosteroids