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

Abstract

Inhibition of thyrotropin (TSH) release by chronic treatment with small quantities of triiodothyronine (T₃) and thyroxine (T₄) 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 T₃ + T₄ had been given for 3-4 wk. Treatment of eight normal subjects with 15 μg T₃ + 60 μg T₄ reduced the maximum increase in serum TSH above baseline (maximum ΔTSH) by 76% in response to 400 μg TRH and by 87% in response to 25 μg TRH. The average serum T₃ level during a 24 hr period in normal subjects who had been taking 15 μg T₃ + 60 μg T₄ 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 T₄ level was unchanged from the pretreatment level. Treatment of the same subjects with 30 μg T₃ + 120 μg T₄ reduced the maximum ΔTSH further. Six patients with primary hypothyroidism were treated, sequentially, with 15 + 60, 22.5 + 90, and 30 μg T₃ + 120 μg T₄. For each patient there was one increase in dosage of 7.5 μg T₃ + 30 μg T₄ which abruptly converted a maximum ΔTSH 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 T₃ level increased only from 105±5 to 129±9 ng/100 ml, and the mean serum T₄ level increased only from 4.9±0.8 to 6.3±0.5 μg/100 ml. These data demonstrate the extreme sensitivity of TRH-induced TSH release to inhibition by the chronic administration of quantities of T₃ + T₄ which do not raise serum T₃ and T₄ levels above the normal ranges.