CONTEXT: Hydrocortisone treatment of young patients with 21-hydroxylase deficiency (21OHD) is given thrice-daily, but there is debate about the optimal timing of highest hydrocortisone dose, either mimicking the physiological diurnal rhythm (morning), or optimally suppressing androgen activity (evening).
OBJECTIVE: We aimed to compare two standard hydrocortisone timing strategies, either highest dosage in the morning or evening, with respect to hormonal status throughout the day, nocturnal blood pressure, sleep and activity scores.
DESIGN AND SETTING: Six-week cross-over study.
PATIENTS: Thirty-nine patients (4-19 years) with 21OHD.
INTERVENTIONS: Patients were treated for three weeks with highest hydrocortisone dose in the morning, followed by three weeks with highest dose in the evening (n=21), or vice-versa (n=18). Androstenedione (A4) and 17-hydroxyprogesterone (17OHP) levels were quantified in saliva collected at 5.00am; 7.00am; 3.00pm; and 11.00pm during the last two days of each treatment period.
MAIN OUTCOME MEASURE: Comparison of saliva 17OHP and A4 levels between two treatment strategies.
RESULTS: Administration of the highest dose in the evening resulted in significantly lower 17OHP levels at 5.00am, whereas the highest dose in the morning resulted in significantly lower 17OHP and A4 levels in the afternoon. The two treatment dose regimens were comparable with respect to averaged daily hormone levels, nocturnal blood pressure, and activity- and sleep scores.
CONCLUSION: No clear benefit for either treatment schedule was established. Given the variation in individual responses we recommend to individually optimize dose distribution and monitoring disease control at multiple timepoints.
|Journal||The Journal of clinical endocrinology and metabolism|
|Publication status||E-pub ahead of print - 12 Nov 2021|