Lamberg B A, Liewendahl K
Ann Clin Res. 1980 Oct;12(5):243-53.
General resistance to the action of thyroid hormones is characterized by increased levels of thyroid hormones and normal thyroid hormone binding proteins but clinical euthyroidism. There is a wide clinical spectrum ranging from patients with congenital goitre and signs of subclinical hypothyroidism to subjects with no physical abnormality. In the most affected patients special physical features have been described. Serum thyrotrophin (TSH) and the response to thyrotrophin releasing hormone (TRH) is mostly normal but may fluctuate being at times elevated and even markedly increased values may be encountered. Studies on lymphocytes and fibroblasts indicate that a decreased affinity of thyroid hormones for nuclear receptors, a decreased binding capacity of the receptors or some post-receptor mechanism may be responsible for these changes. Hitherto, six families, comprising 24 patients and seven single cases, have been described. The pedigrees are compatible with dominant inheritance. Selective refractoriness of the pituitary thyrotrophs to thyroid hormones has been described in five patients with hyperthyroidism. Excessive secretion of TSH is the cause of hyperthyroidism. In four of the cases reported TRH caused an exaggerated TSH response and TSH was partially suppressible by additional exogenous thyroid hormone. The response of TSH and the behaviour of the alpha- and beta-subunits of TSH distinguish this syndrome from TSH-induced hyperthyroidism due to pituitary tumours. The underlying mechanisms are unknown.
对甲状腺激素作用的普遍抵抗的特征是甲状腺激素水平升高、甲状腺激素结合蛋白正常，但临床甲状腺功能正常。临床表现范围广泛，从患有先天性甲状腺肿和亚临床甲状腺功能减退体征的患者到无身体异常的个体。在受影响最严重的患者中，已描述了特殊的身体特征。血清促甲状腺激素（TSH）以及对促甲状腺激素释放激素（TRH）的反应大多正常，但可能会波动，有时会升高，甚至可能出现明显升高的值。对淋巴细胞和成纤维细胞的研究表明，甲状腺激素与核受体的亲和力降低、受体的结合能力降低或某些受体后机制可能是这些变化的原因。迄今为止，已描述了六个家族，包括24名患者和7例散发病例。家系图谱符合显性遗传。在五名甲状腺功能亢进患者中描述了垂体促甲状腺细胞对甲状腺激素的选择性不应性。促甲状腺激素分泌过多是甲状腺功能亢进的原因。在所报道的4例病例中，TRH引起TSH反应过度，额外的外源性甲状腺激素可部分抑制TSH。TSH的反应以及TSH的α和β亚基的行为将该综合征与垂体肿瘤引起的TSH诱导的甲状腺功能亢进区分开来。其潜在机制尚不清楚。
