Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy.
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, 41126 Modena, Italy.
Eur J Endocrinol. 2024 Jan 3;190(1):12-22. doi: 10.1093/ejendo/lvad172.
Despite having normal thyroid-stimulating hormone levels, many hypothyroid patients are dissatisfied with the treatment. The primary aim of this study was to evaluate the effect of twice-daily, combination therapy with levothyroxine (LT4) and liothyronine (LT3), at doses adapted according to TSH-level, on peripheral tissues as reflected by sex hormone binding globulin (SHBG) levels in totally thyroidectomized patients. Changes in other tissue markers and quality of life considering DIO2-rs225014 and MCT10-rs17606253 genetic variants were also assessed.
Double-blind, randomized, placebo-controlled.
One hundred and forty-one subjects were randomized to LT4 + LT3 group (LT4 + LT3 in the morning and LT3 in the evening; n = 70) or placebo group (LT4 in the morning and placebo in the evening; n = 71). Pituitary-thyroid axis compensation was assessed after 6, 12, and 24 weeks. Clinical parameters, quality of life, and tissue markers (sex hormone binding globulin, serum lipids, bone markers) were evaluated at 12 and 24 weeks. DIO2 and MCT10 single nucleotide polymorphisms were genotyped.
The LT4 + LT3 group was treated with mean daily LT3 doses of 5.00 µg, with a mean daily LT4 reduction of 15 µg. After 6 months of treatment, neither SHBG and other tissue markers nor quality of life differed significantly between groups. Combination treatment required greater dose adjustments than placebo (25% vs 54%, P < .001), due to thyroid-stimulating hormone reduction, without hyperthyroidism signs or symptoms. At the end of treatment, the LT4 + placebo group had significantly lower fT3/fT4 compared to the LT4 + LT3 group (0.26 ± 0.05 vs 0.32 ± 0.08, P < .001). No preference for combination therapy was found. Genetic variants did not influence any outcomes.
Six months of combination therapy with twice-daily LT3 dose adapted according to TSH-level do not significantly change peripheral tissue response or quality of life, despite an increase in the fT3/fT4 ratio.
尽管甲状腺刺激激素水平正常，许多甲状腺功能减退患者仍对治疗不满意。本研究的主要目的是评估根据 TSH 水平调整剂量的左甲状腺素（LT4）和三碘甲状腺原氨酸（LT3）联合治疗对甲状腺全部切除患者外周组织的影响，这种治疗方案反映在性激素结合球蛋白（SHBG）水平上。还评估了考虑 DIO2-rs225014 和 MCT10-rs17606253 遗传变异的其他组织标志物和生活质量的变化。
双盲、随机、安慰剂对照。
141 名受试者被随机分配到 LT4 + LT3 组（LT4 上午和 LT3 晚上；n = 70）或安慰剂组（LT4 上午和安慰剂晚上；n = 71）。6、12 和 24 周后评估垂体-甲状腺轴补偿情况。12 和 24 周时评估临床参数、生活质量和组织标志物（性激素结合球蛋白、血清脂质、骨标志物）。DIO2 和 MCT10 单核苷酸多态性进行基因分型。
LT4 + LT3 组每天接受平均 5.00 µg LT3 剂量，每天 LT4 减少 15 µg。治疗 6 个月后，两组间 SHBG 和其他组织标志物以及生活质量均无显著差异。与安慰剂相比，联合治疗需要更大的剂量调整（25%比 54%，P <.001），这是由于促甲状腺激素减少引起的，没有出现甲状腺功能亢进的迹象或症状。治疗结束时，LT4 + 安慰剂组的 fT3/fT4 显著低于 LT4 + LT3 组（0.26 ± 0.05 比 0.32 ± 0.08，P <.001）。未发现联合治疗有偏好。遗传变异对任何结果均无影响。
根据 TSH 水平调整剂量的每日两次 LT3 剂量联合治疗 6 个月，并未显著改变外周组织反应或生活质量，尽管 fT3/fT4 比值增加。
