J Korean Soc Endocrinol.  2000 Oct;15(4-5):554-560.

Hepatic Injury during Treatment with Antithyroid Drugs in Patients with Hyperthyroidism

• Lee KY
• Lee YJ
• Hong SH
• Jung SK
• Lee HE
• Seo CJ
• Jung YS
• Lee SK
• Kim HK
• Park HY
• Kang MH

Abstract

BACKGROUND
Propylthiouracil (PIV) and methimazole (MMI) were widely used for the treatment of hyperthyroidism. Hepatic injury caused by these agents is a rare but serious complication. This study is to investigate the clinical features of hepatotoxicity from antithyroid drugs.
METHODS
We reviewed 17 cases of hepatic injury during treatment with antithyroid drugs in patients with hyperthyroidism. Included were 6 cases we experienced and 11 cases reported in Korean literature from 1986 to 1999. We analyzed the clinical features of hepatic injury.
RESULTS
Of 17 cases of hepatic injury, 12 were PTU cases and 5 MMI cases. The mean age of PTU cases was 40 years with 6/12 patients over 40 years old and 2/5 MMI cases were over 40 years old. The dose of PTU was 300 mg/d or more in 10/12 cases (83%) and the dose of MMI was 30 mg/d in 3/5 cases (60%). The hepatic injury occurred within 3 months in 8/12 PTU cases (67%) and within 2 months in 4/5 MMI cases (80%). The duration of hepatic injury tended to be longer in MMI cases than in PTV cases (median; 80 vs 41 days, p=0.102). In PTU cases, the duration of hepatic injury was correlated with the duration of drug use before hepatic injury (p<0.05). All of 8 biopsied cases who took PTU had predominantly hepatocellular necrosis. Two biopsied cases who took MMI had cholestatic jaundice and nonspecific abnormality, respectively. Biochemical findings of all MMI cases were compatible with cholestatic jaundice. As to the treatment of hyperthyroidism after hepatic injury, 4/12 PTU cases were treated with RAI therapy, 5 with MMI and one with surgery, and treatment was unknown in two. On the other hand 3/5 MMI cases interestingly entered into spontaneous remission after hepatic injury and 2/5 had RAI therapy. Hepatic dysfunction recurred in each one whom treatment by changing to MMI or PTU was tried on.
CONCLUSION
Most of hepatic injury during treatment with antithyroid drugs developed within two to three months of drug use. The hepatic injury related to PTU was mainly cytotoxic whereas that related to MMI was cholestatic. Since there is a cross-reaction between PTU and MMI in hepatotoxicity, RAI therapy or operation shoud be considered as an alternative treatment of hyperthyroidism after hepatic injury.

MeSH Terms

Adult
Antithyroid Agents*
Hand
Humans
Hyperthyroidism*
Jaundice, Obstructive
Methimazole
Necrosis
Propylthiouracil
Remission, Spontaneous
Antithyroid Agents
Methimazole
Propylthiouracil