Menzaghi C, Balsamo A, Di Paola R, Gallone G, Rossi C, Tassi V, Fonzo D, De Filippis V
Clinical Division and Research Unit of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Thyroid. 1999 Jan;9(1):1-6. doi: 10.1089/thy.1999.9.1.
Resistance to thyroid hormone (RTH) is a rare syndrome characterized by reduced sensitivity to thyroid hormone due to thyroid hormone receptor-beta (TRbeta) gene mutations or deletion. RTH has been classified on the basis of clinical features into generalized (GRTH) and pituitary (PRTH) resistance. There is, however, overlap of clinical and biochemical findings in patients with the two forms of resistance, and similar TRbeta gene mutations have been identified in both. The 2 subtypes of RTH, therefore, are considered to be different manifestations of a single genetic entity. We report a mutation of the TRbeta gene, an arginine to leucine substitution at codon 338 (R338L), in 2 unrelated RTH kindreds of northern Italian ancestry. The same mutation was already reported in a single unrelated kindred affected by PRTH. Five individuals, 3 in the first and 2 in the second family, were clinically evaluated and followed for 3-11 years. During the long-term follow-up, the patients manifested symptoms and signs of hyperthyroidism including palpitations, fine tremors, heat intolerance, increased sweating, increased deep tendon reflexes, moist and warm skin, cardiac rhythm abnormalities, reduced body weight, and reduced bone mineral density. The clinical features of these kindreds are consistent with a predominant PRTH phenotype.
甲状腺激素抵抗（RTH）是一种罕见的综合征，其特征是由于甲状腺激素受体β（TRβ）基因突变或缺失导致对甲状腺激素的敏感性降低。RTH已根据临床特征分为全身性（GRTH）和垂体性（PRTH）抵抗。然而，这两种抵抗形式的患者在临床和生化检查结果上存在重叠，并且在两者中都发现了相似的TRβ基因突变。因此，RTH的这两种亚型被认为是单一遗传实体的不同表现形式。我们报告了在两个具有意大利北部血统的无关RTH家族中发现的TRβ基因突变，即密码子338处的精氨酸被亮氨酸取代（R338L）。在一个受PRTH影响的单一无关家族中已经报道过相同的突变。对5名个体进行了临床评估并随访了3至11年，其中3名来自第一个家族，2名来自第二个家族。在长期随访期间，患者表现出甲状腺功能亢进的症状和体征，包括心悸、细微震颤、不耐热、出汗增多、深腱反射亢进、皮肤湿润温暖、心律失常、体重减轻和骨密度降低。这些家族的临床特征与主要的PRTH表型一致。
