Snyder P J, Utiger R D
J Clin Invest. 1972 Aug;51(8):2077-84. doi: 10.1172/JCI107014.
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.
通过测定正常受试者和甲状腺功能减退患者血清促甲状腺激素（TSH）对促甲状腺激素释放激素（TRH）的反应，评估小剂量三碘甲状腺原氨酸（T₃）和甲状腺素（T₄）长期治疗对促甲状腺激素（TSH）释放的抑制作用。在治疗前以及给予T₃ + T₄的合成组合每次剂量3 - 4周后，测定对TRH的反应。用15μg T₃ + 60μg T₄治疗8名正常受试者，对400μg TRH反应时，血清TSH高于基线的最大增加值（最大ΔTSH）降低了76%，对25μg TRH反应时降低了87%。在服用15μg T₃ + 60μg T₄ 3 - 4周的正常受试者中，24小时期间的平均血清T₃水平为129±10 ng/100 ml（均值±标准误），虽高于治疗前水平98±7 ng/100 ml，但仍在正常范围内70 - 150 ng/100 ml。平均血清T₄水平与治疗前水平无变化。用30μg T₃ + 120μg T₄治疗相同受试者，最大ΔTSH进一步降低。6例原发性甲状腺功能减退患者依次接受15 + 60、22.5 + 90和30μg T₃ + 120μg T₄治疗。对于每位患者，剂量增加一次7.5μg T₃ + 30μg T₄，这使最大ΔTSH从高于正常或处于正常上限突然转变为低于正常。与TSH反应的这6次突然变化同时发生的是，平均血清T₃水平仅从105±5升高至129±9 ng/100 ml，平均血清T₄水平仅从4.9±0.8升高至6.3±0.5μg/100 ml。这些数据表明，长期给予不使血清T₃和T₄水平高于正常范围的T₃ + T₄量，对TRH诱导的TSH释放具有极强的抑制敏感性。
