Kaplowitz P B, D'Ercole A J, Utiger R D
J Clin Endocrinol Metab. 1981 Nov;53(5):958-63. doi: 10.1210/jcem-53-5-958.
Peripheral resistance to thyroid hormone, a syndrome characterized by elevated serum total and free thyroid hormone levels and abnormal TSH suppression without manifestations of hyperthyroidism, was studied in a clinically euthyroid 6-month-old infant. Initial serum concentrations of T4, T3, and TSH were 22.1 micrograms/dl, 334 ng/dl, and 7.6 microunits/ml, respectively; infusion of synthetic TRH increased the serum TSH to 47.4 microunits/ml, an exaggerated response. Pituitary insensitivity to T3 was investigated by measuring these parameters in response to consecutive 7-day courses of increasing doses of T3. Four times the calculated replacement dose of T3 (40 micrograms/day) was required to normalize the serum T4 and the serum TSH response to TRH. After administration of 80 micrograms/day T3, the serum TSH response to TRH was virtually abolished, but no clinical signs of thyroid hormone excess were observed. High doses of T4 blunted the serum TSH response to TRH in a manner similar to T3. Prednisone also decreased the TSH response to TRH but had no effect on serum thyroid hormone concentrations. In an attempt to determine the mechanism of thyroid hormone resistance, specific nuclear T3 binding was compared in cultured skin fibroblasts from the patient and a normal infant. Normal fibroblast nuclei had a single binding site with a Ka of 3.1 X 10(9) M-1. In contrast, the Scatchard plot of the patient's T3 binding was curvilinear, compatible with a high affinity site that had a Ka (4.2 X 10(9) M-1) similar to that of the normal fibroblasts and a second low affinity site (Ka = 2.7 X 10(8) M-1). Supraphysiological concentrations of T3 elicited a dose-related increase in fibroblast glucose consumption, which was similar in cells from both the patient and from a normal infant. In conclusion, pituitary and peripheral resistance to thyroid hormone has been demonstrated in this infant, but despite the abnormality of nuclear T3 binding, the cellular mechanisms remain unclear.
在一名临床甲状腺功能正常的6个月大婴儿中，对甲状腺激素外周抵抗进行了研究。甲状腺激素外周抵抗是一种综合征，其特征为血清总甲状腺激素和游离甲状腺激素水平升高以及TSH抑制异常，但无甲状腺功能亢进表现。初始血清T4、T3和TSH浓度分别为22.1微克/分升、334纳克/分升和7.6微单位/毫升；注射合成促甲状腺激素释放激素（TRH）后，血清TSH升高至47.4微单位/毫升，这是一种过度反应。通过测量这些参数对连续7天递增剂量T3疗程的反应，研究了垂体对T3的不敏感性。需要四倍于计算出的T3替代剂量（40微克/天）才能使血清T4和血清TSH对TRH的反应恢复正常。给予80微克/天T3后，血清TSH对TRH的反应几乎消失，但未观察到甲状腺激素过量的临床体征。高剂量T4以类似于T3的方式减弱了血清TSH对TRH的反应。泼尼松也降低了TSH对TRH的反应，但对血清甲状腺激素浓度无影响。为了确定甲状腺激素抵抗的机制，比较了该患者和一名正常婴儿培养的皮肤成纤维细胞中特异性核T3结合情况。正常成纤维细胞核有一个单一结合位点，解离常数（Ka）为3.1×10⁹ M⁻¹。相比之下，患者T3结合的Scatchard图呈曲线，与一个高亲和力位点相符，该位点的Ka（4.2×10⁹ M⁻¹）与正常成纤维细胞相似，还有一个低亲和力位点（Ka = 2.7×10⁸ M⁻¹）。超生理浓度的T3引起成纤维细胞葡萄糖消耗呈剂量相关增加，患者和正常婴儿细胞中的情况相似。总之，已在该婴儿中证实存在垂体和外周甲状腺激素抵抗，但尽管核T3结合存在异常，细胞机制仍不清楚。
