Endocrinology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma - Università Cattolica del Sacro CuoreLargo Gemelli 8, I - 00167, Roma, Italy.
Institute of Biochemistry and Clinical Biochemistry, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma Largo Gemelli 8, I - 00167, Roma, Italy.
Front Biosci (Landmark Ed). 2020 Jan 1;25(2):201-228. doi: 10.2741/4803.
Iodothyronine deiodinases are selenoproteins that regulate thyroid hormone metabolism. Of the three types of deiodinases, type 2 is the major regulator of intracellular triiodothyronine concentration in both the hypothalamus and pituitary, and therefore the major regulator of thyrotropin secretion. A defect in iodothyronine deiodinase activity can lead to a reduced sensitivity to thyroid hormones action and the most recent literature includes these defects in the so-called "syndromes of reduced sensitivity to thyroid hormones". To date, the pathogenic variants of the selenocysteine insertion sequence-binding protein 2 () gene are the first and only inherited disorder of iodothyronine metabolism described. Moreover, there is a growing interest in understanding the possible role of polymorphisms of and genes in some pathological conditions and in determining the requirement of levothyroxine replacement and the role of combined levothyroxine-liothyronine therapy in carrying subjects affected by hypothyroidism and who need replacement therapy. Results on this topic are still conflicting and more studies are needed to assess the efficacy of combined levothyroxine-liothyronine replacement therapy in this subset of patients.
碘甲状腺原氨酸脱碘酶是调节甲状腺激素代谢的硒蛋白。在三种脱碘酶中，脱碘酶 2 是下丘脑和垂体细胞内三碘甲状腺原氨酸浓度的主要调节剂，也是促甲状腺素分泌的主要调节剂。碘甲状腺原氨酸脱碘酶活性的缺陷可导致对甲状腺激素作用的敏感性降低，最近的文献将这些缺陷包括在所谓的“甲状腺激素敏感性降低综合征”中。迄今为止，硒代半胱氨酸插入序列结合蛋白 2 () 基因的致病性变异是描述的第一种也是唯一一种遗传性碘甲状腺原氨酸代谢紊乱。此外，人们越来越关注理解 和 基因多态性在某些病理情况下的可能作用，以及确定左甲状腺素替代治疗的需求以及左甲状腺素-三碘甲状腺原氨酸联合治疗在携带甲状腺功能减退症且需要替代治疗的受影响患者中的作用。关于这个主题的结果仍然存在争议，需要更多的研究来评估联合左甲状腺素-三碘甲状腺原氨酸替代治疗在这部分患者中的疗效。
