Different hepatic responses to thyroxine replacement in spontaneous and 131I-induced primary hypothyroidism

The serum levels of a range of analytes known to change with thyroid status were measured in two groups of patients with primary hypothyroidism commencing T4 replacement therapy. One group (group 1; n = 9) had spontaneous hypothyroidism whilst in the second (group 2; n = 10), hypothyroidism had resulted from radioiodine therapy. The replacement dose was increased in 50 micrograms increments each month to 200 micrograms/day; this produced similar serum concentrations of thyroid hormones and TSH in the two groups at each dose. Dose-dependent increases in glutathione S-transferase (GST) were seen in both groups but changes in alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) activities occurred only in group 1 patients. Group 1 patients had significantly higher levels of GST than group 2 at the 150 micrograms (P less than 0.01) and the 200 micrograms (P less than 0.005) doses of T4, and they had higher activities of ALT (P less than 0.01) and GGT (P less than 0.02) at the 200 micrograms dose. Seven patients in group 1 had abnormalities in GST and four had high levels of ALT, whereas three patients from group 2 had high GST concentrations and all had ALT activities within reference limits. The concentrations of the other analytes measured in serum showed the same response to T4 in the two groups, particularly the concentrations of certain transport proteins whose serum concentrations depend on hepatic protein synthesis. These data suggest that patients with spontaneous primary hypothyroidism are more susceptible to hepatocellular damage than patients who have radioiodine-induced primary hypothyroidism when given oral doses of thyroxine greater than 150 micrograms/day.