ESPE Abstracts

Background: Children with classical congenital adrenal hyperplasia (CAH) require glucocorticoid replacement. The measurement of cortisol and steroid precursors in saliva is particularly suitable for pediatric endocrinology. Data on salivary cortisol measurements in patients with CAH is limited.

Objective and hypothesis: The cortisol in saliva shows a circadian rhythm even under steroid substitution. This is independent of the treatment regimen.

Method: In this retrospective analysis of 22 patients with salt-wasting CAH, we aimed to investigate the kinetics of cortisol in saliva in relation to the treatment regimen. Saliva samples were obtained in the morning, at noon and in the evening, always before intake of hydrocortisone and fludrocortisone.

Results: We analyzed 153 daily profiles (459 samples) of salivary cortisol from 22 patients. The following values were found in the total group (median and 25th/75th percentiles): morning 3.9 ng/ml (1.35 – 21.6), noon 1.7 ng/ml (0.7 – 5.35) and evening 1.15 ng/ml (0.6 – 2.6). The reverse-circadian treated children showed the following values: morning 3.3 ng/ml (1.15 – 14.5), noon 1.4 ng/ml (0.65 – 5.05) and evening 0.9 ng/ml (0.53 – 2.05). Non-reverse-circadian treated children: morning 5.1 ng/ml (1.43 – 30.0), noon 1.8 ng/ml (0.9 – 5.38) and evening 1.45 ng/ml (0.6 – 4.08). Our study shows a difference between cortisol in the morning compared to noon/evening. The values show similar levels at noon and evening. However, the values in the morning are higher. These findings are independent of the therapy regimen (total group, reverse circadian or non-reverse-circadian treatment). In reverse circadian treated children, the morning values are (statistically non-significantly) lower compared to other regimens.

Conclusion: Cortisol follows a circadian rhythm even under different therapy regimens. With a half-life of hydrocortisone of a few hours, the higher concentrations of cortisol in the morning cannot be explained sufficiently by pharmacokinetics. Assuming that the pharmacokinetics are the same during the day and at night, the cortisol level should be the lowest in the morning. One possible cause could be a different metabolisation of hydrocortisone at different times of the day. The role of corticosteroid binding globulin (CBG) in this context remains unclear. CBG could be subject to circadian rhythmicity and circadian binding capacity. The physiological ACTH peak, which is also present in patients with CAH, causes increased hepatic clerence of cortisol. Patients with CAH regularly have elevated ACTH levels. This could be also a partial explanation for the reduced cortisol clearance during the night.