Tas Emir, Mahmood Burhanuddin, Garibaldi Luigi, Sperling Mark
Division of Pediatric Endocrinology and Diabetes, Children's Hospital of Pittsburgh, 4401 Penn Ave, Pittsburgh, PA, 15224, USA,
Eur J Pediatr. 2015 Mar;174(3):403-6. doi: 10.1007/s00431-015-2488-6. Epub 2015 Jan 25.
Stress-related hyperinsulinism (HI) may lead to recalcitrant hypoglycemia for weeks or months following perinatal stress, often in premature newborn infants. Diazoxide is an effective and usually safe medication to treat this type and other types of neonatal HI. We report a male infant born at 35-week gestation with severe respiratory distress who developed prolonged hypoglycemia requiring high glucose infusion rates. He also had abnormal liver function tests, including hypoalbuminemia. Laboratory tests were consistent with HI, which responded to diazoxide treatment (10 mg/kg/day started at 10 days of age). The patient developed cardiorespiratory failure, hepatomegaly, worsening liver function tests, and hyperglycemia 7 weeks after the initiation of therapy. Diazoxide was discontinued with rapid resolution of the cardiorespiratory failure and without recurrence of hypoglycemia.
We hypothesize that low albumin level may increase the toxicity of diazoxide, possibly by increasing the free diazoxide concentration, as this compound is typically >90% bound to plasma proteins.
Diazoxide binds to plasma proteins >90% and excreted in urine. Dose adjustment is recommended in patients with impaired kidney functions. What is New: Literature is not available regarding diazoxide dose adjustment in patients with liver injury. Diazoxide toxicity is not dose-dependent.
与应激相关的高胰岛素血症（HI）可能导致围产期应激后数周或数月出现顽固性低血糖，常见于早产新生儿。二氮嗪是治疗此类及其他类型新生儿HI的有效且通常安全的药物。我们报告一名孕35周出生的男婴，患有严重呼吸窘迫，出现持续性低血糖，需要高葡萄糖输注速率。他还存在肝功能检查异常，包括低白蛋白血症。实验室检查结果符合HI，对二氮嗪治疗有反应（10天龄开始，剂量为10mg/kg/天）。治疗开始7周后，患者出现心肺功能衰竭、肝肿大、肝功能检查恶化及高血糖。停用二氮嗪后，心肺功能衰竭迅速缓解，且未再出现低血糖。
我们推测低白蛋白水平可能增加二氮嗪的毒性，可能是通过增加游离二氮嗪浓度，因为该化合物通常>90%与血浆蛋白结合。
二氮嗪与血浆蛋白结合>90%，经尿液排泄。肾功能受损患者建议调整剂量。新情况：关于肝损伤患者二氮嗪剂量调整的文献尚无报道。二氮嗪毒性与剂量无关。
