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ARTICLE: Leonard B. Bacharier, Hengameh H. Raissy, Laura Wilson, Bennie McWilliams, Robert C. Strunk, and H. William Kelly Long-Term Effect of Budesonide on Hypothalamic-Pituitary-Adrenal Axis Function in Children With Mild to Moderate Asthma Pediatrics 2004; 113: 1693-1699 [Abstract] [Full text] [PDF]

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Physiological dose of ACTH

Brian J Lipworth   (14 June 2004)

Response to Dr. Lipworth's Comments

Leonard B Bacharier, Robert C Strunk, H William Kelly, and Hengameh H. Raissy   (15 June 2004)

Physiological dose of ACTH 14 June 2004
Brian J Lipworth, Professor of allergy and pulmonology Asthma and Allergy Research Group,Ninewells University Hospital,Dundee Send letter to journal: Re: Physiological dose of ACTH b.j.lipworth{at}dundee.ac.uk Brian J Lipworth	The authors concluded that budesonide 400ug daily was safe because no effects were seen on the 250ug ACTH stimulated cortisol response or on 24 hour urinary cortsiol .It is well recognised that the standard dose of ACTH is 250 times the dose (ie 1ug ) required to elicit a physiological cortisol response [1,2].Thus when using a supraphysiological 250ug dose of ACTH ,it is possible that an impaired response may have been missed in those susceptible children who exhibit increased glucocorticoid receptor senstivity to systemically absorbed exogenous budesonide. This has previously been shown with a physiological 1 ug /Kg dose of CRH in susceptible children taking budesonide 400ug/day [3]. Moreover the use of 24 hour urinary cortisol is likely to be flawed due to compliance with collections in this age group . While the results of the CAMP study are on the whole reassuring , precribers should still be vigilant when using long term inhaled cortcosteroids ,particularly in children who are also taking concomitant intranasal corticosteroid ,which may add to the overall systemic burden in susceptible individuals. References 1.Broide J,Soferman R ,Kivity S,et al .Low dose adrenocorticotropin test reveals impaired adrenal function in patients taking inhaled corticosteroids .J Clin Endocrinol Metab 1995;80:1243-1246 2.Rasmuson S,Olsson T,Hagg E.A low dose ACTH test to assess the function of the hypothalamic pituitary adrenal axis .Clin Endocrinol 1996;44:151-156 3.Pescollderungg L,Radetti G,Gottardi E, et al .Systemic activity of inhaled corticosteroid treatment in asthmatic children :corticotrophin releasing hormone test .Thorax 2003;58:227-30
Response to Dr. Lipworth's Comments 15 June 2004
Leonard B Bacharier, Pediatric Allergy/Pulmonary Medicine Washington University/St. Louis Children's Hospital, Robert C Strunk, H William Kelly, and Hengameh H. Raissy Send letter to journal: Re: Response to Dr. Lipworth's Comments bacharier_l{at}kids.wustl.edu Leonard B Bacharier, et al.	We concur with Dr. Lipworth that the standard dose of ACTH (250 mcg) may be less sensitive in detecting subtle levels of adrenal gland hyporesponsiveness than the low dose ACTH (1 mcg). When CAMP was started in 1994, the standard dose ACTH test was considered the standard biochemical approach for assessment of adrenal gland responsiveness. Furthermore, while the low dose ACTH test may detect lesser degrees of adrenal suppression (although this is not universally accepted), interpretation of the low dose test is complicated by a lack of a threshold which indicates an impaired adrenal response to illness or other stressors (1). In addition, authors have suggested that mildly abnormal low-dose ACTH stimulation tests be followed up by either an insulin- induced hypoglycemia or metyrapone test (2, 3). We recognized the issues related to 24 hour urine collections, and for this reason hospitalized these children in the General Clinical Research Centers to assure appropriate and complete urine collection. We believe our results are reassuring to the practicing physician, but remind readers that our findings apply to a subgroup of young children with mild-moderate asthma treated with low-moderate dose inhaled corticosteroids. Physicians must remain vigilant for evidence of steroid- related side effects in other populations with more severe disease or who use higher doses of inhaled corticosteroids, often in combination with intranasal corticosteroids. References: 1. Allen DB. Sense and sensitivity: assessing inhaled corticosteroid effects on the hypothalamic-pituitary-adrenal axis. Ann Allergy Asthma Immunol 2002;89(6):537-9. 2. Krasner AS. Glucocorticoid-Induced Adrenal Insufficiency. JAMA 1999;282(7):671-676. 3. Kelly HW. Potential adverse effects of the inhaled corticosteroids. J Allergy Clin Immunol 2003;112(3):469-78; quiz 479.