Use of the Low-Dose Corticotropin Stimulation Test for the Monitoring of Children with Asthma Treated with Inhaled Corticosteroids

Abstract

Objective: Subnormal hypothalamic-pituitary-adrenal (HPA) function and rare cases of adrenal crisis have been reported in asthmatic children treated with inhaled corticosteroids. We investigated subnormal HPA activity and followed up affected patients until recovery of normal HPA functions. Study Design: 100 children with persistent asthma underwent low-dose corticotropin testing, with the administration of 1 µg of 1–24 ACTH intravenously. Treatments were beclomethasone dipropionate as a metered-dose inhaler, n = 14, budesonide as a dry-powder inhaler, n = 16, fluticasone propionate as a metered-dose inhaler n = 31 or a dry-powder inhaler n = 39. The mean commercially labelled dose was 520 ± 29 µg/day (mean ± SEM, range: 160–1,000) and the equipotent dose (which compares the efficiency of these drugs for treating asthma and their responsibility for systemic effects) was 890 ± 55 µg/day (range: 200–2,000). Results: The mean stimulated cortisol level ± SEM (and range) of the patient was 482 ± 12 (148–801), and that of 40 age-matched controls was 580 ± 12.5 (439–726), (SD = 79). The result was subnormal (more than 2 SD below the mean of the controls) in28 of the 100 patients. One–four stepwise decreases of 10–100% in the daily equipotent doses received by the patients with abnormal low-dose corticotropin testing results led to normal results in subsequent low-dose corticotropin testing in 27 retested patients. The mean time interval between two tests was 5 months (range: 2–6 months) and the mean period required for normalization of the test was 13 months (range: 2–21). Only one case of asthma exacerbation and no adrenal crisis were observed over these periods. Conclusions: Decreasing daily equipotent doses led to recovery of normal HPA function without asthma exacerbation. Thus, a revision of the doses of inhaled corticosteroids used in asthmatic children with a progressive decrease to the consensus-recommended doses should decrease the systemic effects of inhaled corticosteroids, while minimizing the risk of asthma exacerbation.

Adrenal insufficiency after glucocorticoid withdrawal in children with rheumatic diseases

“…An overview of similar studies investigating adrenal function after GC therapy is given in Table 1. Impaired adrenal responsiveness during or after GC treatment and withdrawal has been described previously and ranged from 28% to 100% (13–19). Similar to our study, follow‐up tests of insufficient responders generally show a recovery of adrenal function over time (14,15,19).…”

“…Despite the high prevalence of adrenal insufficiency in biochemical tests, clinical manifestations of adrenal insufficiency after GC therapy/withdrawal seem to be rare (13,14,16–18). One may even argue that the ‘subclinical adrenal insufficiency’ by laboratory testing is of no obvious clinical concern.…”

Lack of sensitivity of the 1‐μg low‐dose ACTH stimulation test in a paediatric population with suboptimal cortisol responses to insulin‐induced hypoglycaemia

“…Many paediatric patients now undergo a 1‐μg LDSST, and use of the ITT has diminished . Data from a meta‐analysis of predominantly adult studies suggested that a peak cortisol <600 n m on LDSST necessitates a definitive test such as the ITT or oral metyrapone test .…”

“…39 Many paediatric patients now undergo a 1-lg LDSST, and use of the ITT has diminished. 19,[22][23][24][25][26] Data from a meta-analysis of predominantly adult studies suggested that a peak cortisol <600 nM on LDSST necessitates a definitive test such as the ITT or oral metyrapone test. 12 Our data suggest that in children and adolescents, using a 1-lg LDSST, this threshold may need to be even higher, and we cannot endorse it as a screening test for secondary adrenal insufficiency.…”

“…12,21 At our institution, we aimed to retrospectively evaluate the use of a 1-lg LDSST as an alternative assessment of adrenal reserve in a paediatric and adolescent patient population using an abnormal cortisol response to ITT as the gold standard for HPA axis dysfunction. This Synacthen TM dose is being used increasingly in paediatric practice, 19,[22][23][24][25][26] and a recent unpublished survey indicated that it is the LDSST dose used by 44% of Paediatric Endocrinologists in the United Kingdom (available at http://www.endocrine-abstracts.org/ea/0023/AbstractBook.pdf page 23 P18). Despite the frequency with which this test is carried out, to date there are only data comparing 1-lg LDSST to ITT in eight children.…”