Sequential liver and bone biochemical changes in hyperthyroidism: prospective controlled follow-up study.

OBJECTIVE

To reexamine the prevalence and sequential changes of liver and bone biochemical abnormalities in patients with hyperthyroidism.

METHODS

A consecutive series of 95 patients with hyperthyroidism and 66 controls with euthyroid goiter seen during same period were studied. The patients were treated with propylthiouracil (PTU) 300 mg/day for 2 months, followed by 100-150 mg/day for 3 months and a subsequent maintenance dose of 100 mg/day. Serum aspartate amino-transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin, ALP isoenzymes, and hepatitis markers were studied before therapy and at 2 and 5 months after PTU therapy was begun.

RESULTS

Seventy-two [75.8%, confidence interval (CI) 67.2-84.4%] of the 95 patients had at least one biochemical abnormality. AST, ALT, ALP, GGT, and bilirubin were elevated in 27.4%, 36.8%, 64.2%, 16.8%, and 5.3%, respectively. Of the 34 patients with ALT elevation, 62% showed gradual normalization of ALT, whereas 38% (CI 21.9-54.5%) showed transient, asymptomatic, but significant (p < 0.025) further elevation of ALT during PTU therapy. Overt hepatitis developed in one patient. None of these changes was due to hepatitis A, B, C, or delta virus infection or autoimmune hepatitis. Changes of serum GGT parallel those of ALT. In contrast, serum ALP (primarily bone isoenzyme) rose significantly (p < 0.01) as T4 and T3 levels declined at 2 months after therapy.

CONCLUSIONS

The results suggest that hyperthyroidism is often associated with abnormal biochemical tests, particularly ALP elevation, and thus may pose diagnostic confusion. The increase of bone isoenzyme accounts for the elevations in total ALP level before and during therapy. Serum ALT and GGT abnormalities usually subside during PTU therapy, but transient asymptomatic PTU hepatotoxicity occurs in one-third of the patients. Discontinuation of PTU is not required unless overt hepatitis develops.