Evaluating the low-dose ACTH stimulation test in neonates: Ideal times for cortisol measurement

Abstract

Context: Low-dose adrenocorticotropic hormone stimulation testing (LDST) can be used to diagnose central adrenal insufficiency. However, uncertainty remains over optimal times to draw serum cortisol levels. Objective: To determine optimal times to draw serum cortisol levels for the LDST in neonates. Design: A retrospective chart review of LDSTs performed on neonates from January 1, 2009 to September 30, 2017. Setting: Children's Hospital of Eastern Ontario (CHEO), a tertiary-care outborn pediatric center. Patients: Forty-nine patients were included: 23 (46.9%) born at term, 12 (24.5%) born very preterm to late preterm, and 14 (28.6%) born extremely preterm. Intervention: Cortisol levels were drawn at baseline and 15, 30, and 60 minutes following administration of Cortrosyn 1 mcg/kg (maximum dose 1 mcg). Main Outcome Measure: Timing of peak cortisol level and marginal value of drawing a second and third cortisol sample at 15, 30, or 60 minutes was determined. Results: Cortisol peaked at 15-, 30-, and 60-minute sampling times for 4%, 27%, and 69% of patients, respectively. The probability that a failed LDST changes to a pass by adding a 15- or 30-minute sample to the superior 60 minute sample is 5.6% (1% to 25.8%) and 11% (3.1% to 32.6%), respectively, for a cortisol pass threshold of 18.1mcg/dL (500 nmol/L). Conclusions: In contrast to studies of older children, we found that the majority of neonatal LDST cortisol peaks occurred at the 60-minute sampling time with the addition of a 30-minute sample providing substantial benefit. It is questionable if a 15-minute sample provides any benefit, making a case to revise LDST protocols to sample cortisol later for neonates.