Evaluation of Hypothalamic-Pituitary-Adrenal Axis Suppression following Cutaneous Use of Topical Corticosteroids in Children: A Meta-Analysis

Abstract

Background/Aims: A meta-analysis was performed to determine the likelihood of hypothalamic-pituitary-adrenal (HPA) axis suppression following short-term cutaneous treatment of atopic dermatitis with topical corticosteroids (TCS) in pediatric patients. Methods: All published pediatric clinical trials evaluating TCS use with pre- and post-treatment HPA axis assessment by cosyntropin stimulation testing were included. Results: Of 128 eligible trials, 12 were selected for meta-analysis with a total of 522 participants. There were 20 observed cases of HPA axis suppression (3.8%, 95% CI 2.4–5.8). The percentage of HPA axis suppression with low- (classes 6–7), medium- (classes 3–5) and high-potency (classes 1–2) TCS use was 2% (3 of 148 patients, 95% CI 0.7–5.8), 3.1% (7 of 223 patients, 95% CI 1.5–6.3), and 6.6% (10 of 151 patients, 95% CI 3.6–11.8), respectively. Conclusion: There is a low rate of reversible HPA axis suppression with the use of mid- to low-potency TCS compared to more potent formulations. In pediatric clinical practice, the limited use of mid- to low-potency TCS is rarely associated with clinically significant adrenal insufficiency or adrenal crisis. In the absence of signs and symptoms of adrenal insufficiency, there is little need to test the HPA axis of these patients.

Safety and efficacy of fixed‐dose combination calcipotriol (50 μg/g) and betamethasone dipropionate (0.5 mg/g) cutaneous foam in adolescent patients (aged 12 to <17 years) with plaque psoriasis: results of a phase II, open‐label trial

“…Lastly, hypothalamic–pituitary–adrenal (HPA) axis suppression has been noted with long‐term use of corticosteroids; thus, HPA‐axis dysregulation with BD is a concern. The adrenocorticotropic–hormone (ACTH) challenge is used to assess HPA‐axis suppression in children with psoriasis, with a serum cortisol value ≤18 μg/dL at 30 min post‐ACTH challenge suggestive of potential adrenal‐cortisol insufficiency …”

Adrenal suppression from glucocorticoids: preventing an iatrogenic cause of morbidity and mortality in children

“…While the use of low to moderate potency topical corticosteroids is rarely associated with a risk of AS,39 there have been case reports of symptomatic AS and cushingoid features in infants receiving potent topical GCs for >1 month with misuse of the medication 40. Symptomatic AS associated with cushingoid features has also been reported with ocular GCs 41.…”

<p>Current Perspectives on the Management of Infantile Atopic Dermatitis</p>

“…A meta-analysis of 12 clinical trials determined that the incidence of adrenal insufficiency in children (including those younger than age 3 years) using TCS is low, and thus, routine testing of the HPA axis following up to 4 weeks of TCS usage is not recommended unless symptoms of adrenal insufficiency arise. 45 Regardless of TCS application frequency and potency, no detrimental growth parameter effects were demonstrated in a study comparing age versus predicted parental heights. 46 …”