Inhibition of thyrotropin response to thyrotropin-releasing hormone by small quantities of thyroid hormones

Inhibition of thyrotropin (TSH) release by chronic treatment with small quantities of triiodothyronine (T(3)) and thyroxine (T(4)) was evaluated by determining the serum TSH response to thyrotropin-releasing hormone (TRH) in normal subjects and hypothyroid patients. Response to TRH was determined before treatment and after each dosage of a synthetic combination of T(3) + T(4) had been given for 3-4 wk. Treatment of eight normal subjects with 15 mug T(3) + 60 mug T(4) reduced the maximum increase in serum TSH above baseline (maximum DeltaTSH) by 76% in response to 400 mug TRH and by 87% in response to 25 mug TRH. The average serum T(3) level during a 24 hr period in normal subjects who had been taking 15 mug T(3) + 60 mug T(4) for 3-4 wk was 129+/-10 ng/100 ml (mean +/-SEM), well within the normal range, 70-150 ng/100 ml, although higher than the pretreatment level, 98+/-7 ng/100 ml. The average serum T(4) level was unchanged from the pretreatment level. Treatment of the same subjects with 30 mug T(3) + 120 mug T(4) reduced the maximum DeltaTSH further.Six patients with primary hypothyroidism were treated, sequentially, with 15 + 60, 22.5 + 90, and 30 mug T(3) + 120 mug T(4). For each patient there was one increase in dosage of 7.5 mug T(3) + 30 mug T(4) which abruptly converted a maximum DeltaTSH that was greater than, or at the upper limit of, normal to one that was subnormal. Concurrent with these six abrupt changes in TSH response, the mean serum T(3) level increased only from 105+/-5 to 129+/-9 ng/100 ml, and the mean serum T(4) level increased only from 4.9+/-0.8 to 6.3+/-0.5 mug/100 ml. These data demonstrate the extreme sensitivity of TRH-induced TSH release to inhibition by the chronic administration of quantities of T(3) + T(4) which do not raise serum T(3) and T(4) levels above the normal ranges.