Lazarus J H
Department of Medicine, University of Wales College of Medicine, Cardiff, UK.
Thyroid. 1998 Oct;8(10):909-13. doi: 10.1089/thy.1998.8.909.
Lithium is used in the prophylaxis of bipolar depressive disorder in augmentation treatment of depression and in the therapy of some cases of unipolar depression. Lithium affects cell function via its inhibitory action on adenosine triphosphatase (ATPase) activity, cyclic adenosine monophosphate (cAMP), and intracellular enzymes. The inhibitory effect of lithium on inositol phospholipid metabolism affects signal transduction and may account for part of the action of the cation in manic depression. Lithium also alters the in vitro response of cultured cells to thyrotropin-releasing hormone (TRH) and can stimulate DNA synthesis. Lithium is concentrated by the thyroid and inhibits thyroidal iodine uptake. It also inhibits iodotyrosine coupling, alters thyroglobulin structure, and inhibits thyroid hormone secretion. The latter effect is critical to the development of hypothyroidism and goiter. Effects on brain deiodinase enzymes and alterations in thyroid hormone receptor concentration in the hypothalamus are under investigation in relation to the therapeutic effect of lithium. The ion affects many aspects of cellular and humoral immunity in vitro and in vivo. This accounts for a rise in antithyroid antibody titer in patients having these antibodies before lithium administration whereas there is no induction of thyroid antibody synthesis de novo. Goiter, due to increased thyrotropin (TSH) after inhibition of thyroid hormone release, occurs at various reported incidence rates from 0%-60% and is smooth and nontender. Subclinical and clinical hypothyroidism due to lithium is usually associated with circulating anti-thyroid peroxidase (TPO) antibodies but may occur in their absence. Iodine exposure, dietary goitrogens, and immunogenetic background may all contribute to the occurrence of goiter and hypothyroidism during long-term lithium therapy. It is currently unclear whether the reported association of lithium therapy and hyperthyroidism are causal, although there is suggestive epidemiological evidence. Finally, lithium therapy is associated with exaggerated response of both TSH and prolactin to TRH in 50%-100% of patients, although basal levels are not usually high. It is probable that the hypothalamic pituitary axis adjusts to a new setting in patients receiving lithium.
锂用于双相抑郁障碍的预防、抑郁症的增效治疗以及某些单相抑郁症的治疗。锂通过对三磷酸腺苷酶（ATPase）活性、环磷酸腺苷（cAMP）和细胞内酶的抑制作用来影响细胞功能。锂对肌醇磷脂代谢的抑制作用会影响信号转导，这可能是该阳离子在躁狂抑郁症中发挥作用的部分原因。锂还会改变培养细胞对促甲状腺激素释放激素（TRH）的体外反应，并能刺激DNA合成。锂会在甲状腺中蓄积并抑制甲状腺对碘的摄取。它还会抑制碘酪氨酸偶联、改变甲状腺球蛋白结构并抑制甲状腺激素分泌。后一种作用对甲状腺功能减退和甲状腺肿的发展至关重要。关于锂的治疗效果，目前正在研究其对脑脱碘酶的影响以及下丘脑甲状腺激素受体浓度的改变。该离子在体外和体内会影响细胞免疫和体液免疫的多个方面。这解释了在服用锂之前就已有抗甲状腺抗体的患者中抗甲状腺抗体滴度会升高，而不会从头诱导甲状腺抗体合成。由于甲状腺激素释放受抑制后促甲状腺激素（TSH）增加而导致的甲状腺肿，其报道的发生率在0%至60%之间，且甲状腺肿光滑无压痛。锂导致亚临床和临床甲状腺功能减退通常与循环抗甲状腺过氧化物酶（TPO）抗体有关，但也可能在没有这些抗体的情况下发生。碘暴露、饮食中的致甲状腺肿物质和免疫遗传背景都可能导致长期锂治疗期间甲状腺肿和甲状腺功能减退的发生。目前尚不清楚所报道的锂治疗与甲状腺功能亢进之间的关联是否具有因果关系，尽管有提示性的流行病学证据。最后，锂治疗与50%至100%的患者中TSH和催乳素对TRH的反应过度有关，尽管基础水平通常不高。接受锂治疗的患者下丘脑 - 垂体轴可能会适应新的状态。
