Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland.
Clin Exp Pharmacol Physiol. 2021 Sep;48(9):1215-1223. doi: 10.1111/1440-1681.13532. Epub 2021 Jun 21.
Subjects with both subclinical hypothyroidism and autoimmune thyroiditis are frequently diagnosed with metabolic syndrome. The purpose of the current study was to investigate whether insulin sensitivity determines levothyroxine action on thyroid antibody titres and hypothalamic-pituitary-thyroid axis activity in young women with autoimmune subclinical hypothyroidism. The study population consisted of three age-, thyroid antibody- and thyrotropin-matched groups of women with autoimmune subclinical hypothyroidism: metformin-naive women with insulin resistance (group A, n=31), women receiving metformin treatment because of insulin resistance (group B, n=32), as well as metformin-naive women with normal insulin sensitivity (group C, n=35). Throughout the study, all subjects were treated with levothyroxine. Titres of thyroid peroxidase and thyroglobulin antibodies, as well as circulating levels of glucose, insulin, lipids, thyrotropin, free thyroid hormones, prolactin, high-sensitivity C-reactive protein (hsCRP) and 25-hydroxyvitamin D were determined at the beginning of the study and 6 months later. Except for two individuals, all patients completed the study. At baseline, group A differed from groups B and C in circulating levels of glucose, HDL-cholesterol, triglycerides, hsCRP, 25-hydroxyvitamin D and the homeostatic model assessment 1 of insulin resistance (HOMA1-IR). Although levothyroxine reduced thyroid antibody titres, decreased thyrotropin levels and increased free thyroid hormone levels in all studied groups, the effect on antibody titres and thyrotropin levels was more pronounced in groups B and C than in group A. The impact of levothyroxine on thyroid antibody titres correlated with baseline and treatment-induced changes in HOMA1-IR, thyrotropin, hsCRP and 25-hydroxyvitamin D. The results of the current study suggest that the impact of exogenous levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity is determined by insulin sensitivity.
患有亚临床甲状腺功能减退症和自身免疫性甲状腺炎的患者常被诊断为代谢综合征。本研究旨在探讨年轻女性自身免疫性亚临床甲状腺功能减退症患者中，胰岛素敏感性是否决定左甲状腺素对甲状腺抗体滴度和下丘脑-垂体-甲状腺轴活性的作用。研究人群由三组年龄、甲状腺抗体和促甲状腺激素匹配的自身免疫性亚临床甲状腺功能减退症女性组成：胰岛素抵抗的二甲双胍初治组（A 组，n=31）、因胰岛素抵抗接受二甲双胍治疗的女性（B 组，n=32），以及胰岛素敏感性正常的二甲双胍初治组（C 组，n=35）。在整个研究过程中，所有受试者均接受左甲状腺素治疗。在研究开始时和 6 个月后，测定甲状腺过氧化物酶和甲状腺球蛋白抗体滴度、循环血糖、胰岛素、血脂、促甲状腺激素、游离甲状腺激素、催乳素、高敏 C 反应蛋白（hsCRP）和 25-羟维生素 D 水平。除了 2 人外，所有患者均完成了研究。基线时，A 组与 B 组和 C 组的循环血糖、高密度脂蛋白胆固醇、甘油三酯、hsCRP、25-羟维生素 D 和胰岛素抵抗的稳态模型评估 1（HOMA1-IR）水平不同。尽管左甲状腺素降低了所有研究组的甲状腺抗体滴度、降低了促甲状腺激素水平并增加了游离甲状腺激素水平，但在 B 组和 C 组的作用比 A 组更为明显。左甲状腺素对甲状腺抗体滴度的影响与基线和治疗诱导的 HOMA1-IR、促甲状腺激素、hsCRP 和 25-羟维生素 D 的变化相关。本研究结果表明，外源性左甲状腺素对甲状腺自身免疫和下丘脑-垂体-甲状腺轴活性的影响取决于胰岛素敏感性。
