'Chemical hyperthyroidism': the significance of elevated serum thyroxine levels in L-thyroxine treated individuals

We have previously reported that L-thyroxine treated patients may often have elevated serum T4 concentrations and yet show no clinical signs of hyperthyroidism. We found that such patients had normal serum T3 concentrations. The present study explored the relationship between serum T3 and T4 and dosage of L-thyroxine. Retrospective analysis of 99 patient records was performed. There was an increase of serum T4, serum T3 resin uptake (T3R), and T3 with increasing dose of L-thyroxine. The T3/T4 ratio decreased with increasing dose of L-thyroxine and with increasing T4. This phenomenon was analysed prospectively by starting 23 individuals on L-thyroxine and progressively incrementing the dose until either symptoms of hyperthyroidism developed or T4 levels exceeded the upper unit of the normal range. Once again, there was a progressive increase in serum T4, T3R, and T3 with increasing dose of L-thyroxine. At even the lowest dose of L-thyroxine (0.05 mg), there was a marked fall in T3/T4 ratio as compared to untreated individuals. The T3/T4 ratio fell further with increasing dose but with a fairly weak correlation. The decrease in T3/T4 ratio showed a much stronger correlation with serum T4. Of the 23 individuals, all exceeded the upper limit of the normal range of serum T4. No individual with elevated T4 developed clinical signs of hyperthyroidism unless serum T3 was also elevated beyond the normal range. Of eight individuals who reached elevated T3 levels, six demonstrated clinical signs of hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)