期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 102, 期 5, 页码 1440-1446出版社
OXFORD UNIV PRESS INC
DOI: 10.1210/jc.2016-4048
关键词
-
资金
- National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK079970]
- National Institutes of General Medical Sciences [R01GM063666]
- National Center for Research Resources [UL1TR000003]
- National Center for Advancing Translational Sciences, National Institutes of Health
- National Children's Research Centre, Dublin, Ireland
Context: The P450 enzyme CYP24A1 is the principal inactivator of vitamin D metabolites. Biallelic loss-of-function mutations in CYP24A1 are associated with elevated serum levels of 1,25-dihydroxyvitamin D-3 with consequent hypercalcemia and hypercalciuria and represent the most common form of idiopathic infantile hypercalcemia (IIH). Current management strategies for this condition include a low-calcium diet, reduced dietary vitamin D intake, and limited sunlight exposure. CYP3A4 is a P450 enzyme that inactivates many drugs and xenobiotics and may represent an alternative pathway for inactivation of vitamin D metabolites. Objective: Our goal was to determine if rifampin, a potent inducer of CYP3A4, can normalize mineral metabolism in patients with IIH due to mutations in CYP24A1. Methods: We treated two patients with IIH with daily rifampin (10 mg/kg/d, up to a maximum of 600 mg). Serum calcium, phosphorus, parathyroid hormone (PTH), liver, and adrenal function and vitamin D metabolites, as well as urinary calcium excretion, were monitored during treatment of up to 13 months. Results: Prior to treatment, both patients had hypercalcemia, hypercalciuria, and nephrocalcinosis with elevated serum 1,25-dihydroxyvitamin D-3 and suppressed serum PTH. Daily treatment with rifampin was well tolerated and led to normalization or improvement in all clinical and biochemical parameters. Conclusion: These observations suggest that rifampin-induced overexpression of CYP3A4 provides an alternative pathway for inactivation of vitamin D metabolites in patients who lack CYP24A1 function.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据