Long-acting intramuscular ACTH stimulation test for the diagnosis of secondary adrenal insufficiency in children

Abstract

Abstract Background The diagnosis of adrenal insufficiency (AI) is based on the basal and stimulated levels of serum cortisol in response to the short Synacthen test (SST). In patients with secondary AI (SAI) due to hypothalamic-pituitary-adrenal (HPA) axis defects, the SST has been validated against the insulin tolerance test (ITT), which is the gold standard. However, injection Synacthen is not easily available in some countries, and endocrinologists often use Acton-Prolongatum (intramuscular [IM] long-acting adrenocorticotropic hormone [ACTH]) in place of Synacthen. There are no studies validating the use of IM-ACTH in children with suspected AI. We evaluated the diagnostic value of the IM-ACTH test against the ITT for the diagnosis of SAI in children. Methods All children with suspected growth hormone deficiency (GHD) undergoing a routine ITT were evaluated using the IM-ACTH test within 1 week. Results Forty-eight patients (36 boys/12 girls, age range: 5–14 years) were evaluated using both the ITT and the IM-ACTH test. Twenty-eight patients had a normal cortisol response (≥18 μg/dL, 500 nmol/L) in the ITT and 20 had low values. In patients with a normal cortisol response on the ITT, the peak value obtained after the IM-ACTH test was higher than that on the ITT (28.7 μg/dL [± 8.8] vs. 23.8 μg/dL [± 4.54], respectively; p=0.0012). Compared to the ITT, the sensitivity and specificity of the IM-ACTH test for the diagnosis of SAI at cortisol cut-offs <18 μg/dL (500 nmol/L) and <22 μg/dL (600 nmol/L) were 57.1% and 92.8%, and 100% and 73.5%, respectively. Conclusions A peak cortisol value <18 μg/dL on the IM-ACTH test is highly suggestive of SAI, whereas a value >22 μg/dL rules out SAI.