Role of thyrotropin in triiodothyronine generation in hypothyroidism

Most of the circulating T3 is generated by monodeiodination of T4 in extrathyroidal tissue with only minor contribution by the thyroid gland. Since T3 is the main active thyroid hormone and TSH is the major modulator of its synthesis and release by the thyroid gland, TSH may also play a significant role in synthesis and release of T3 by the peripheral tissues as documented in recent in vitro animal studies. However, the data regarding its influence on T4 metabolism in humans is lacking. Hypothyroidism may provide an appropriate environment for assessing the influence of TSH in synthesis and release of T3 by the extrathyroidal tissues, since circulating T3 is almost totally derived via peripheral conversion of T4, and serum TSH varies from subnormal levels in central hypothyroidism to a wide range of supernormal concentration in the primary variety. This study determined the relationship between serum TSH concentration and T3 and T4 ratio, a reliable index of conversion of T4 into T3 in peripheral tissues, in 75 subjects with hypothyroidism including both the primary and the central types. Serum T3 was significantly higher (p < 0.001) in primary hypothyroidism (1.48 +/- 0.13 mM/l) in comparison with the central type (0.71 +/- 0.09 mM/l) despite almost equally low serum T4 concentration in both groups. In primary hypothyroidism, T3:T4 ratio (0.026 +/- 0.0012) was significantly higher (p < 0.01) than normal (0.017 +/- 0.0010) along with supernormal TSH (71 +/- 6.4 mU/L) concentration prior to initiation of LT4 replacement therapy and normalized (0.015 +/- 0.0008) on achieving euthyroid state with correction of serum TSH level (3.8 +/- 0.3 mU/L).(ABSTRACT TRUNCATED AT 250 WORDS)