Evaluating the Low-Dose ACTH Stimulation Test in Children: Ideal Times for Cortisol Measurement

Context Central adrenal insufficiency (AI) can be diagnosed with the low-dose ACTH stimulation test (LDST). Protocols determining timing of cortisol sampling vary, with 30 minutes after stimulation being most common. Objectives To determine optimal times to draw cortisol levels and factors predicting timing of peak cortisol levels in children undergoing LDST. Design Retrospective chart review of LDSTs between February 2014 and September 2017. Setting The Children’s Hospital of Eastern Ontario. Patients Patients 3 months to 20 years who underwent LDSTs. Intervention LDSTs were performed with cortisol levels at 0, 15, 30, and 60 minutes after 1 μg cosyntropin. Cortisol values <18 μg/dL (500 nmol/L) determined AI. Main Outcome Measures The incremental value of testing cortisol at 15 or 60 minutes, in addition to the standard 30-minute sample, was estimated. Results A total of 221 patients met inclusion criteria. The mean age was 9.7 years, and 32% were female. Peak cortisol levels were 19%, 67%, and 14% at 15, 30, and 60 minutes, respectively. One false positive LDST result would be prevented for every 24 (95% CI, 13 to 46) or 55 (95% CI, 22 to 141) patients tested at 15 or 60 minutes in addition to the standard 30-minute test. Of the 122 patients who passed the LDST, discontinuing the 15- and 60-minute samples would have misdiagnosed 12 patients (9.8%). Glucocorticoid exposure, age, and body mass index z scores were independent predictors of peak cortisol timing. Conclusion Although the majority of patients peak 30 minutes after cosyntropin administration, testing cortisol levels at 15 and 60 minutes reduces the risk of false positive LDSTs.