Comparison of low‐dose and high‐dose cosyntropin stimulation testing in children

Background: There is no consensus among pediatric endocrinologists in using low‐dose (LD) versus high‐dose (HD) cosyntropin to test for secondary/tertiary adrenal insufficiency. This paper compares LD and HD cosyntropin stimulation testing in children for evaluation of hypothalamic‐pituitary‐adrenal axis (HPAA) and suggests a new peak cortisol cut‐off value for LD stimulation testing to avoid false positivity. Methods: Data of 36 children receiving LD (1 µg) and HD (249 µg) cosyntropin consecutively during growth hormone (GH) stimulation testing were analyzed in two groups. Group A were patients who passed GH stimulation testing and were not on oral, inhaled or intranasal steroids (intact hypothalamic‐pituitary axis, n= 19). Group B were patients who failed GH stimulation testing and/or were on oral, inhaled or intranasal steroids (impaired hypothalamic‐pituitary axis, n= 17). Results: In group A, the mean peak cortisol response in LD cosyntropin was 18.5 ± 2.4 µg/dL and that for the HD cosyntropin was 24.8 ± 3.1 µg/dL (r: 0.76, P≤ 0.05). In group B, the mean peak cortisol response in LD cosyntropin was 15.7 ± 6.1 µg/dL and that for HD cosyntropin was 21.7 ± 7.9 µg/dL (r: 0.98, P≤ 0.05). When a standard cut‐off of 18 µg/dL was used, 37% of the patients with intact HPAA failed LD cosyntropin testing, but a cut‐off of 14 µg/dL eliminated false positive results. Conclusions: LD cosyntropin stimulation testing results should be interpreted cautiously when used alone to prevent unnecessary long‐term treatment. Using a lower cut‐off for LD (≥14 µg/dL) seems to avoid false positive results and still detects most cases of impaired HPAA.