title: Hepatic injury during propylthiouracil therapy in patients with hyperthyroidism. A cohort study.
abstract: OBJECTIVE
  To evaluate the incidence, severity, and course of propylthiouracil-induced hepatic injury in patients with hyperthyroidism.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Outpatient clinic of a university-based hospital.
  
  
  METHODS
  Fifty-four patients with normal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values and a definite diagnosis of hyperthyroidism.
  
  
  METHODS
  Treatment with propylthiouracil, 300 mg/d for 2 months followed by 100 to 150 mg/d for 3 months and a subsequent maintenance dose of 100 mg/d.
  
  
  METHODS
  Liver biochemical tests were studied before therapy and 2 months and 5 months after starting propylthiouracil therapy. The patients were monitored with clinical evaluation and weekly liver biochemical tests after AST or ALT levels became abnormal. Serologic markers of hepatitis A, B, C, and delta virus infection were also studied when appropriate.
  
  
  RESULTS
  Fifteen (28%; 95% CI, 16% to 42%) of the 54 patients showed ALT elevations 2 months after propylthiouracil therapy. The mean peak ALT level for these patients was 1.35 mu kat/L (range, 0.65 3.85 mu kat/L). None of these patients had symptoms or hyperbilirubinemia. Liver biopsy in three patients showed mild perivenular focal necrosis or ill-defined granuloma composed of foamy histiocytes with ceroid pigment and mild fatty metamorphosis. Despite continued propylthiouracil therapy at a reduced dose, ALT levels returned to normal in 13 of 15 patients in the following 3 months. None of these ALT elevations resulted from hepatitis A, B, C, or delta virus infection. No statistical difference was seen in the pretreatment characteristics between patients with and those without ALT elevation, except that the former had a higher pretreatment T4 level (270 +/- 12.9 compared with 237 +/- 7.72 nmol/L, P = 0.027) and T3 level (7.22 +/- 0.72 compared with 5.85 +/- 0.39 nmol/L, P = 0.048).
  
  
  CONCLUSIONS
  Propylthiouracil-induced subclinical liver injury is common and is usually transient and asymptomatic. Therapy with propylthiouracil may be continued with caution in the absence of symptoms and hyperbilirubinemia.
authors.affiliation: Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Y F
authors.initials: YF
authors.lastname: Liaw
authors.forename: M J
authors.initials: MJ
authors.lastname: Huang
authors.forename: K D
authors.initials: KD
authors.lastname: Fan
authors.forename: K L
authors.initials: KL
authors.lastname: Li
authors.forename: S S
authors.initials: SS
authors.lastname: Wu
authors.forename: T J
authors.initials: TJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury; D004796:Clinical Enzyme Tests; D015331:Cohort Studies; D005260:Female; D006525:Hepatitis, Viral, Human / Q000453:epidemiology; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy*; D015994:Incidence; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000175:diagnosis / Q000453:epidemiology; D008297:Male; D011441:Propylthiouracil / Q000009:adverse effects* / Q000627:therapeutic use; D012720:Severity of Illness Index
chemical_list: D011441:Propylthiouracil; D000410:Alanine Transaminase