To study the effects of 2 standard treatment-timing strategies for glucocorticoïd dosage on androgen concentration in CAH children

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disorder of adrenal steroid synthesis leading to cortisol deficiency and an increase in androgen production due to a lack of the negative feedback of cortisol on the ACTH production. Treatment in children consists of hydrocortisone substitution thereby also restoring the negative feedback on the pituitary gland and consequently normalize androgen production. However, mostly supra-physiological dosages of hydrocortisone are necessary to normalize the increased androgen production to prevent side effects of increased androgens such as early pubertal signs and reduced final height but with the risk of complications due to the high glucocorticoid dosages such as also decreased final height, obesity, and cardiovascular complications. There is still no evidence about the best timing of hydrocortisone use: The highest dosage of hydrocortisone in the morning will most likely simulate normal diurnal rythm of the adrenal gland, whereas the highest dosage at night may suppress the early morning increase of androgens (around 3.00 am) more effectively but with probably negative effects on blood pressure and sleep patterns.

Aim of the study:
To study the effects of 2 standard treatment timing strategies for glucocorticoid dosage on androgen concentration in CAH children: a. highest dosage in the morning, b. highest dosage in the evening.

Study design:
6 Weeks cross-over non randomized low-interventional trial (category A)

The intended research aims to evaluate whether a better suppression of adrenal androgens, so a better hormonal setting, can be achieved by changing the time of the highest dose in the morning or in the evening.

The duration of the study is for each subject 6 weeks.

After the informed consent procedure, each patient will recieve the same total daily medication dosage from their own initial pre-study treatment, starting with either the biggest dosage of hydrocortisone in the morning (dosage A: distribution daily dosage 2/4 - 1/4 - 1/4) or in the evening (dosage B: distribution daily dosage 1/4 - 1/4 - 2/4). The first dosage scheme (dosage A or B) will be their own usual medicatio scheme. Immediately after the first period, the next period of 3 weeks will start. On days 20 and 21 of each 3-week study period, saliva will be collected before taking the medication and one additional measurement at 5 am (a total of 4 samples per day).The patient will collect saliva at home and send the samples to our laboratory by mail. In saliva steroid hormone levels of 17OHP and A will be measured. In the third week of each treatment cycle, a 12-hour blood pressure profile measurement (19.00 - 7.00 h) will be performed. daily activities will be documented daily by the parents by asking the parents/ children to give a daily score (0 - 10) te measure daily activity and sleeping pattern.