Background: We present a boy with classical adrenal hyperplasia (CAH) and constantly increased 17-OH-progesterone (17-OH-P) values despite multiple dose adjustments of hydrocortisone up to 18 mg/m2 body surface and addition of fludrocortisone. After puberty, therapy was changed from hydrocortisone to prednisone without improvement of the 17-OH-P values. Non-compliance was suspected as cause of the inadequately controlled CAH. Alternatively, an atypical steroid metabolism was considered.
Objective and hypotheses: To distinguish between non-compliance with insufficient intake of prednisone and an atypical metabolism of prednisone/prednisolone pharmacological studies were initiated.
Method: A 24 h pharmacokinetic study of prednisone and prednisolone metabolism was performed with concomitant monitoring of 17-OH-P, ACTH, and androstendione. A second pharmacokinetic study was performed after changing from prednisone to prednisolone with individually adapted dosing intervals during the day and introduction of a modulated release prednisone formulation at night time.
Results: The first pharmacokinetic study revealed an impaired conversion of prednisone to prednisolone with an increased clearance of prednisolone. Due to the atypically decreased half-life of prednisolone, inadequate suppression of 17-OH-P was observed in our patient. Based on these results the therapy was changed from prednisone to prednisolone with dosing intervals of only 4 h during daytime and a modulated release formulation of prednisone at night time. Due to this individually tailored therapy, 17-OH-P values were markedly improved in a second pharmacokinetic study during follow-up.
Conclusion: Before blaming a patient with CAH on non-compliance due to raised 17-OH-P a pharmacokinetic study might be helpful to detect patients with atypical steroid metabolism. Modulated release prednisone formulation is a helpful tool to cover the longer period at night time and avoid the raise of 17-OH-P and ACTH in the early morning.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology