Skip to main content
NCBI home page
Thorax logoLink to Thorax
. 2003 Mar;58(3):227–230. doi: 10.1136/thorax.58.3.227

Systemic activity of inhaled corticosteroid treatment in asthmatic children: corticotrophin releasing hormone test

L Pescollderungg 1, G Radetti 1, E Gottardi 1, D Peroni 1, A Pietrobelli 1, A Boner 1
PMCID: PMC1746598  PMID: 12612299

Abstract

Background: A study was undertaken to assess the function of the hypothalamic-pituitary-adrenal axis (HPA) in a group of asthmatic children before and after treatment with inhaled corticosteroids.

Methods: Thirty prepubertal patients of mean (SD) age 6.7 (1.8) years were treated with inhaled corticosteroids. All children underwent a corticotrophin releasing hormone (CRH) test with evaluation of serum cortisol and adrenocorticotrophin hormone (ACTH) levels before and after 3 months of treatment. Twenty four hour urine samples were also collected to measure free cortisol (UFC) excretion.

Results: Subjects showed no difference between basal serum cortisol levels (mean change –18; 95% CI –41 to 5; p=0.118) and delta (peak minus basal) levels (mean change –13; 95% CI –38 to 12; p=0.308) before and after treatment, whereas the peak cortisol level (mean change –31; 95% CI –55 to –7; p=0.013) and area under the curve (AUC) (mean change –175; 95% CI –288 to –63; p=0.003) after CRH were significantly lower following treatment. Basal, peak and AUC ACTH were significantly lower after treatment (p<0.05, p=0.004 and p=0.003, respectively), while delta ACTH was similar before and after treatment ((mean change –12; 95% CI – 31 to –7; p=0.199). No significant reduction in 24 hour UFC was observed after the treatment period (before 14.9 (7.1), after 15.0 (11.6); mean change 0.1, 95% CI –5.2 to 5.4; p=0.967). No correlation was found between UFC and any of the parameters of cortisol excretion following the CRH test, either before or after treatment.

Conclusions: These data suggest that, at the dosage and for the treatment period used, inhaled steroids do not seem to suppress the HPA axis in the majority of patients. The CRH test may be more sensitive than 24 hour UFC and morning plasma cortisol levels in evaluating systemic activity of inhaled corticosteroid treatment.

Full Text

The Full Text of this article is available as a PDF (133.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barrett Bruce P., Brown Roger L., Locken Kristin, Maberry Rob, Bobula James A., D'Alessio Donn. Treatment of the common cold with unrefined echinacea. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2002 Dec 17;137(12):939–946. doi: 10.7326/0003-4819-137-12-200212170-00006. [DOI] [PubMed] [Google Scholar]
  2. Bazzy-Asaad A. Safety of inhaled corticosteroids in children with asthma. Curr Opin Pediatr. 2001 Dec;13(6):523–527. doi: 10.1097/00008480-200112000-00005. [DOI] [PubMed] [Google Scholar]
  3. Boner A. L. Effects of intranasal corticosteroids on the hypothalamic-pituitary-adrenal axis in children. J Allergy Clin Immunol. 2001 Jul;108(1 Suppl):S32–S39. doi: 10.1067/mai.2001.115564. [DOI] [PubMed] [Google Scholar]
  4. Broide J., Soferman R., Kivity S., Golander A., Dickstein G., Spirer Z., Weisman Y. Low-dose adrenocorticotropin test reveals impaired adrenal function in patients taking inhaled corticosteroids. J Clin Endocrinol Metab. 1995 Apr;80(4):1243–1246. doi: 10.1210/jcem.80.4.7714095. [DOI] [PubMed] [Google Scholar]
  5. Casale T. B., Nelson H. S., Stricker W. E., Raff H., Newman K. B. Suppression of hypothalamic-pituitary-adrenal axis activity with inhaled flunisolide and fluticasone propionate in adult asthma patients. Ann Allergy Asthma Immunol. 2001 Nov;87(5):379–385. doi: 10.1016/S1081-1206(10)62918-3. [DOI] [PubMed] [Google Scholar]
  6. Chrousos G. P., Harris A. G. Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid therapy. 1. General principles. Neuroimmunomodulation. 1998 Nov-Dec;5(6):277–287. doi: 10.1159/000026348. [DOI] [PubMed] [Google Scholar]
  7. Chrousos G. P., Harris A. G. Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid therapy. 2. Review of the literature. Neuroimmunomodulation. 1998 Nov-Dec;5(6):288–308. doi: 10.1159/000026349. [DOI] [PubMed] [Google Scholar]
  8. Clark D. J., Lipworth B. J. Evaluation of corticotropin releasing factor stimulation and basal markers of hypothalamic-pituitary-adrenal axis suppression in asthmatic patients. Chest. 1997 Nov 5;112(5):1248–1252. doi: 10.1378/chest.112.5.1248. [DOI] [PubMed] [Google Scholar]
  9. Dupont W. D., Plummer W. D., Jr Power and sample size calculations. A review and computer program. Control Clin Trials. 1990 Apr;11(2):116–128. doi: 10.1016/0197-2456(90)90005-m. [DOI] [PubMed] [Google Scholar]
  10. Fink Richard S., Pierre Lisa N., Daley-Yates Peter T., Richards David H., Gibson Anthony, Honour John W. Hypothalamic-pituitary-adrenal axis function after inhaled corticosteroids: unreliability of urinary free cortisol estimation. J Clin Endocrinol Metab. 2002 Oct;87(10):4541–4546. doi: 10.1210/jc.2002-020287. [DOI] [PubMed] [Google Scholar]
  11. Holt P. R., Lowndes D. W., Smithies E., Dixon G. T. The effect of an inhaled steroid on the hypothalamic-pituitary-adrenal axis--which tests should be used? Clin Exp Allergy. 1990 Mar;20(2):145–149. doi: 10.1111/j.1365-2222.1990.tb02659.x. [DOI] [PubMed] [Google Scholar]
  12. Honour J. W. Hypothalamic-pituitary-adrenal axis. Respir Med. 1994 Aug;88 (Suppl A):9–15. doi: 10.1016/s0954-6111(05)80035-6. [DOI] [PubMed] [Google Scholar]
  13. Iwasaki T., Tamura G., Sano K., Ohkawara Y., Haneda K., Shirato K. [Comparison of CRH test and ACTH test in patients with bronchial asthma]. Arerugi. 1999 Jun;48(6):632–638. [PubMed] [Google Scholar]
  14. Kannisto S., Korppi M., Remes K., Voutilainen R. Adrenal suppression, evaluated by a low dose adrenocorticotropin test, and growth in asthmatic children treated with inhaled steroids. J Clin Endocrinol Metab. 2000 Feb;85(2):652–657. doi: 10.1210/jcem.85.2.6336. [DOI] [PubMed] [Google Scholar]
  15. Lipworth B. J. Adrenal suppression with inhaled corticosteroids. Ann Allergy Asthma Immunol. 2001 Nov;87(5):359–361. doi: 10.1016/S1081-1206(10)62914-6. [DOI] [PubMed] [Google Scholar]
  16. Lipworth B. J., Clark D. J., McFarlane L. C. Adrenocortical activity with repeated twice daily dosing of fluticasone propionate and budesonide given via a large volume spacer to asthmatic school children. Thorax. 1997 Aug;52(8):686–689. doi: 10.1136/thx.52.8.686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lipworth B. J. Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis. Arch Intern Med. 1999 May 10;159(9):941–955. doi: 10.1001/archinte.159.9.941. [DOI] [PubMed] [Google Scholar]
  18. O'Byrne P. M., Pedersen S. Measuring efficacy and safety of different inhaled corticosteroid preparations. J Allergy Clin Immunol. 1998 Dec;102(6 Pt 1):879–886. doi: 10.1016/s0091-6749(98)70322-7. [DOI] [PubMed] [Google Scholar]
  19. Ringdal N., Lundbäck B., Alton M., Rak S., Eivindson A., Bratten G., Kjaersgaard P. Comparable effects of inhaled fluticasone propionate and budesonide on the HPA-axis in adult asthmatic patients. Respir Med. 2000 May;94(5):482–489. doi: 10.1053/rmed.1999.0758. [DOI] [PubMed] [Google Scholar]
  20. Rolland-Cachera M. F., Cole T. J., Sempé M., Tichet J., Rossignol C., Charraud A. Body Mass Index variations: centiles from birth to 87 years. Eur J Clin Nutr. 1991 Jan;45(1):13–21. [PubMed] [Google Scholar]
  21. Soule S., Van Zyl Smit C., Parolis G., Attenborough S., Peter D., Kinvig S., Kinvig T., Coetzer E. The low dose ACTH stimulation test is less sensitive than the overnight metyrapone test for the diagnosis of secondary hypoadrenalism. Clin Endocrinol (Oxf) 2000 Aug;53(2):221–227. doi: 10.1046/j.1365-2265.2000.01057.x. [DOI] [PubMed] [Google Scholar]
  22. Stewart P. M., Corrie J., Seckl J. R., Edwards C. R., Padfield P. L. A rational approach for assessing the hypothalamo-pituitary-adrenal axis. Lancet. 1988 May 28;1(8596):1208–1210. doi: 10.1016/s0140-6736(88)92020-x. [DOI] [PubMed] [Google Scholar]
  23. Suliman Abdulwahab M., Smith Thomas P., Labib Mourad, Fiad Tarek M., McKenna T. Joseph. The low-dose ACTH test does not provide a useful assessment of the hypothalamic-pituitary-adrenal axis in secondary adrenal insufficiency. Clin Endocrinol (Oxf) 2002 Apr;56(4):533–539. doi: 10.1046/j.1365-2265.2002.01509.x. [DOI] [PubMed] [Google Scholar]
  24. Tanner J. M., Whitehouse R. H., Takaishi M. Standards from birth to maturity for height, weight, height velocity, and weight velocity: British children, 1965. II. Arch Dis Child. 1966 Dec;41(220):613–635. doi: 10.1136/adc.41.220.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Volovitz B., Amir J., Malik H., Kauschansky A., Varsano I. Growth and pituitary-adrenal function in children with severe asthma treated with inhaled budesonide. N Engl J Med. 1993 Dec 2;329(23):1703–1708. doi: 10.1056/NEJM199312023292305. [DOI] [PubMed] [Google Scholar]
  26. Warner J. O., Naspitz C. K. Third International Pediatric Consensus statement on the management of childhood asthma. International Pediatric Asthma Consensus Group. Pediatr Pulmonol. 1998 Jan;25(1):1–17. doi: 10.1002/(sici)1099-0496(199801)25:1<1::aid-ppul1>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  27. Wilson A. M., Lipworth B. J. Dose-response evaluation of the therapeutic index for inhaled budesonide in patients with mild-to-moderate asthma. Am J Med. 2000 Mar;108(4):269–275. doi: 10.1016/s0002-9343(99)00435-0. [DOI] [PubMed] [Google Scholar]
  28. Wilson A. M., Sims E. J., Lipworth B. J. Dose response with fluticasone propionate on adrenocortical activity and recovery of basal and stimulated responses after stopping treatment. Clin Endocrinol (Oxf) 1999 Mar;50(3):329–335. doi: 10.1046/j.1365-2265.1999.00652.x. [DOI] [PubMed] [Google Scholar]
  29. Zimmerman B., Gold M., Wherrett D., Hanna A. K. Adrenal suppression in two patients with asthma treated with low doses of the inhaled steroid fluticasone propionate. J Allergy Clin Immunol. 1998 Mar;101(3):425–426. doi: 10.1016/S0091-6749(98)70260-X. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES