The cortisol production rate in children: Implications for therapy

We studied the daily cortisol production rate in 33 normal children and adolescents, ages 8–17 years, using a stable isotope-dilution technique employing high-performance liquid chromatography-mass spectrometry. Two indwelling intravenous catheters were inserted and deuterated cortisol was infused continuously for 30 hours. After 6 hours of tracer infusion to establish equilibrium, blood was obtained every 20 minutes for 24 hours for the measurement of deuterated cortisol. The cortisol production rate was calculated from the relative abundance of the deuterated cortisol. The cortisol production rate was 9.5 ± 2.5 mg/day or 6.8 ± 1.9 mg/M²/day (mean ± SD). Cortisol production rate did not vary with gender or pubertal stage (9.8 ± 2.8 mg/day or 7.3 ± 1.8 mg/M²/day in the girls and 9.1 ± 2.2 mg/day or 6.1 ± 1.8 mg/M²/day in the boys). These results suggest that the cortisol production rate in children and adolescents is only about half of that estimated by earlier studies using less discriminating techniques. Thus, the physiologic replacement dose of hydrocortisone for children may be lower than previously believed. This finding has implications for the treatment of diseases such as adrenal insufficiency and congenital adrenal hyperplasia.