Adrenal suppression from high-dose inhaled fluticasone propionate in children with asthma

This cross-sectional study was designed to examine the prevalence of adrenocortical suppression in children with asthma treated with high-dose inhaled fluticasone propionate (FP). Children and adolescents (n=50) with asthma, treated with inhaled FP at a dose of ≥1,000 mg a day for ≥6 months, were enrolled. Early morning serum cortisol was performed. Subjects with a serum cortisol of <400 nmol·L−1 had a tetracosactrin stimulation test. Fifty subjects of mean age 13.1 yrs were treated with a mean dose of 924.7 µg·m−2·day−1 FP for a mean duration of 2 yrs. Of the 50 subjects, 36 (72%) had serum cortisol levels of <400 nmol·L−1 and underwent tetracosactrin stimulation test. Of these, 6 (17%) demonstrated a less than two-fold increase in serum cortisol from baseline and peak cortisol level of ≤550 nmol·L−1 at 30 or 60 min poststimulation. There was a significant negative correlation between the dose of FP·m−2 and stimulated peak cortisol level. Biochemical evidence of adrenocortical insufficiency was demonstrated in 12% of the subjects, indicating that high-dose fluticasone propionate use may be associated with dose-dependent adrenocortical suppression.

[1]  Arl Medford,et al.  British Thoracic Society , 2004 .

[2]  S. Crowley.  Inhaled glucocorticoids and adrenal function: an update. , 2003, Paediatric respiratory reviews.

[3]  A. Buist.  Guidelines for the management of chronic obstructive pulmonary disease. , 2002, Respiratory medicine.

[4]  M. Zacharin,et al.  Growth and adrenal suppression in asthmatic children on moderate to high doses of fluticasone propionate , 2002, Journal of paediatrics and child health.

[5]  John W. Wilson,et al.  Asthma Management Handbook , 2002 .

[6]  R. Voutilainen,et al.  Adrenal suppression, evaluated by a low dose adrenocorticotropin test, and growth in asthmatic children treated with inhaled steroids. , 2000, The Journal of clinical endocrinology and metabolism.

[7]  D. Zimmerman,et al.  Adrenal suppression secondary to inhaled fluticasone propionate. , 1999, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[8]  B. Lipworth.  Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis. , 1999, Archives of internal medicine.

[9]  P. Hindmarsh,et al.  Tests of adrenal insufficiency , 1999, Archives of disease in childhood.

[10]  F. Versteegh,et al.  Efficacy and safety of high-dose inhaled steroids in children with asthma: a comparison of fluticasone propionate with budesonide. , 1999, The Journal of pediatrics.

[11]  R. Clayton,et al.  Comparison of the low dose short synacthen test (1 microg), the conventional dose short synacthen test (250 microg), and the insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in patients with pituitary disease. , 1999, The Journal of clinical endocrinology and metabolism.

[12]  G. Todd.  Side-effects of high-dose fluticasone propionate in children. , 1999, The European respiratory journal.

[13]  P. O'Byrne,et al.  Measuring efficacy and safety of different inhaled corticosteroid preparations. , 1998, The Journal of allergy and clinical immunology.

[14]  B. Meibohm,et al.  The clinical pharmacology of fluticasone propionate , 1998 .

[15]  P. V. van Asperen,et al.  Fluticasone propionate 750 μg/day versus beclomethasone dipropionate 1500 μg/day: comparison of efficacy and adrenal function in paediatric asthma , 1998 .

[16]  D. Wherrett,et al.  Adrenal suppression in two patients with asthma treated with low doses of the inhaled steroid fluticasone propionate. , 1998, The Journal of allergy and clinical immunology.

[17]  J. Paulson,et al.  Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects. , 2003, British journal of clinical pharmacology.

[18]  C. Macarthur,et al.  Effectiveness of prophylactic inhaled steroids in childhood asthma: a systemic review of the literature. , 1997, The Journal of allergy and clinical immunology.

[19]  B. Lipworth,et al.  Adrenocortical activity with repeated twice daily dosing of fluticasone propionate and budesonide given via a large volume spacer to asthmatic school children. , 1997, Thorax.

[20]  P. Stephenson.  Statement concerning the second revision of the British guidelines on asthma management , 1997 .

[21]  G. Todd,et al.  Growth and adrenal suppression in asthmatic children treated with high-dose fluticasone propionate , 1996, The Lancet.

[22]  J. Barron.  Diagnosis of Adrenal Insufficiency , 1996, Annals of clinical biochemistry.

[23]  S. Hurel,et al.  The short Synacthen and insulin stress tests in the assessment of the hypothalamic–pituitary–adrenal axis , 1996, Clinical endocrinology.

[24]  E. Hägg,et al.  A low dose ACTH test to assess the function of the hypothalamic–pituitary–adrenal axis , 1996, Clinical endocrinology.

[25]  S. Holgate,et al.  Growth of prepubertal children with mild asthma treated with inhaled beclomethasone dipropionate. , 1995, American journal of respiratory and critical care medicine.

[26]  N. Stern,et al.  The role of the low dose (1 microgram) adrenocorticotropin test in the evaluation of patients with pituitary diseases. , 1995, The Journal of clinical endocrinology and metabolism.

[27]  Y. Weisman,et al.  Low-dose adrenocorticotropin test reveals impaired adrenal function in patients taking inhaled corticosteroids. , 1995, The Journal of clinical endocrinology and metabolism.

[28]  B. Lipworth,et al.  New perspectives on inhaled drug delivery and systemic bioactivity , 1995 .

[29]  L. Jonetz-Mentzel,et al.  Establishment of Reference Ranges for Cortisol in Neonates, Infants, Children and Adolescents , 1993, European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies.

[30]  G. Crompton,et al.  Screening for hypothalamo-pituitary-adrenal axis suppression in asthmatics taking high dose inhaled corticosteroids. , 1991, Respiratory medicine.

[31]  P. Hindmarsh,et al.  The use of low doses of ACTH in the investigation of adrenal function in man. , 1991, The Journal of endocrinology.

[32]  A. Milner,et al.  Adrenal function in asthma. , 1990, Archives of disease in childhood.

[33]  S. Clarke,et al.  Deposition and clinical efficacy of terbutaline sulphate from Turbuhaler, a new multi-dose powder inhaler. , 1989, The European respiratory journal.

[34]  A. Millar,et al.  Improvement of pressurised aerosol deposition with Nebuhaler spacer device. , 1984, Thorax.

[35]  C. Brook.  Clinical Paediatric Endocrinology , 1973 .