Beck-Peccoz P, Chatterjee V K
Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore IRCCS, Italy.
Thyroid. 1994 Summer;4(2):225-32. doi: 10.1089/thy.1994.4.225.
Thyroid hormone resistance syndrome (RTH) is a rare disorder characterized by elevated levels of circulating free thyroid hormones, inappropriate TSH secretion, and reduced peripheral tissue responses to iodothyronine action. On the basis of clinical features, at least two different forms of RTH have been described: generalized resistance (GRTH) in which patients are asymptomatic with few clinical signs and pituitary resistance (PRTH) where patients present with some signs and symptoms associated with thyrotoxicosis. However, a review of the literature and our own experience indicates that there is a wide overlap of symptoms and signs exhibited by individuals with GRTH or PRTH. Assessments using biochemical and physiological indices of thyroid hormone action are useful, but limited by their lack of precision and also show an overlap between values recorded in GRTH and PRTH. In addition, we have observed significant temporal variations in clinical signs as well as in parameters of thyroid hormone action in the same individuals, with no correlation with their subjective symptoms. Recent genetic analyses indicate that patients with either GRTH or PRTH are heterozygous for mutations in the thyroid hormone receptor beta (TR beta) gene. Indeed, different clinical features have been observed in affected individuals within a kindred harboring the same Tr beta mutation, and identical mutations have been identified in unrelated kindreds classified as GRTH or PRTH. These data support the view that GRTH and PRTH are variable manifestations of a single genetic entity. Nevertheless, this clinical distinction will remain useful as a guide to the most appropriate treatment. The variable phenotypic spectrum of thyroid hormone resistance may be related to factors other than mutations in Tr beta that have yet to be elucidated.
甲状腺激素抵抗综合征（RTH）是一种罕见的疾病，其特征为循环游离甲状腺激素水平升高、促甲状腺激素（TSH）分泌异常以及外周组织对碘甲状腺原氨酸作用的反应降低。根据临床特征，至少已描述了两种不同形式的RTH：全身性抵抗（GRTH），患者无症状且几乎没有临床体征；垂体抵抗（PRTH），患者表现出一些与甲状腺毒症相关的体征和症状。然而，文献综述及我们自己的经验表明，GRTH或PRTH患者所表现出的症状和体征有很大重叠。使用甲状腺激素作用的生化和生理指标进行评估是有用的，但因其缺乏精确性而受到限制，并且在GRTH和PRTH中记录的值也存在重叠。此外，我们观察到同一患者的临床体征以及甲状腺激素作用参数存在显著的时间变化，且与他们的主观症状无关。最近的基因分析表明，GRTH或PRTH患者在甲状腺激素受体β（TRβ）基因上存在杂合突变。实际上，在携带相同Trβ突变的家族中，受影响个体表现出不同的临床特征，并且在分类为GRTH或PRTH的无关家族中也鉴定出了相同的突变。这些数据支持GRTH和PRTH是单一遗传实体的可变表现这一观点。尽管如此，这种临床区分作为最恰当治疗的指南仍将有用。甲状腺激素抵抗的可变表型谱可能与Trβ突变以外尚未阐明的因素有关。
