title: Liver injury may increase the risk of diazoxide toxicity: a case report.
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  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.
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Children's Hospital of Pittsburgh, 4401 Penn Ave, Pittsburgh, PA, 15224, USA, emir.tas@chp.edu.
authors.forename: Emir
authors.initials: E
authors.lastname: Tas
authors.forename: Burhanuddin
authors.initials: B
authors.lastname: Mahmood
authors.forename: Luigi
authors.initials: L
authors.lastname: Garibaldi
authors.forename: Mark
authors.initials: M
authors.lastname: Sperling
mesh_terms: D000418:Albumins / Q000378:metabolism*; D001786:Blood Glucose / Q000187:drug effects*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D003981:Diazoxide / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D007003:Hypoglycemia / Q000097:blood / Q000188:drug therapy; D007231:Infant, Newborn; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D012131:Respiratory Insufficiency / Q000139:chemically induced; D014665:Vasodilator Agents / Q000009:adverse effects
chemical_list: D000418:Albumins; D001786:Blood Glucose; D014665:Vasodilator Agents; D003981:Diazoxide