We review the cases of hepatic injury from propylthiouracil, methimazole and carbimazole in the English language literature and compare them to cases of agranulocytosis in a recent review. The data on hepatotoxicity confirm the findings for agranulocytosis that low-dose methimazole is safer than propylthiouracil and that methimazole toxicity is more common over 40 years old. In contrast, propylthiouracil hepatotoxicity often occurs in younger patients. Most cases of hepatic injury occur in the first few months of drug therapy as with agranulocytosis. The reason that methimazole typically causes cholestatic hepatitis while propylthiouracil causes cytotoxic hepatitis remains unknown.
Recent reports suggest that 14% to 23% of thyrotoxic patients have silent (painless) thyroiditis, a newly described syndrome characterized by transient thyrotoxicosis with a low radioactive iodine uptake. A three-year review at a Brooklyn (NY) hospital showed only one definite and three possible cases of silent thyroiditis among 86 thyrotoxic patients. At most, 4% to 5% of thyrotoxic patients had silent thyroiditis. We suggest a geographic variation in this syndrome. Most cases and the largest series are from Japan and the Great Lakes area of North America. The latter may be related to increased iodine intake over many years in a previously endemic area of hypoiodidism and goiter, although other local factors may also be involved.
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