Institute for Experimental Pediatric Endocrinology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Sozial-Pädiatrisches Zentrum, Charité Universitätsmedizin Berlin, Berlin, Germany.
J Clin Endocrinol Metab. 2018 Apr 1;103(4):1459-1469. doi: 10.1210/jc.2017-01937.
The optimal levothyroxine (LT4) dose to treat congenital hypothyroidism (CH) remains unclear, with debate over whether higher starting doses (>10 µg/kg) are necessary and safe for a normal intelligence quotient (IQ).
To examine psychomotor, metabolic, and quality of life (QoL) outcomes in patients with CH treated with a mean high initial LT4 dose.
DESIGN, SETTINGS, PARTICIPANTS: A cross-sectional cohort study of patients with CH identified in the Berlin newborn screening program from 1979 to 2003; 76 patients with CH (mean age, 18 years; mean initial LT4 dose, 13.5 µg/kg) and 40 siblings completed the study.
Psychomotor (Wechsler Intelligence Test, CNS Vital Signs), QoL (short form-36 Health Survey), anthropometric (body mass index, height), and metabolic (intima media thickness, laboratory parameters) outcomes were compared with those of healthy siblings. Mean values and percentage of episodes of elevated thyroxine (T4) and tri-jod-thyronin (T3) and suppressed thyrotropin (TSH) before age 2 years were analyzed. A meta-analysis of CH treatment studies was performed.
There were no significant differences in IQ, QoL, or other outcome measures in patients with CH compared with controls. Most T4 levels were high before age 2 years and during subsequent testing, but mean T3 and TSH levels remained normal. The meta-analysis showed a significant IQ difference in severe vs mild CH cases only when treatment started with an LT4 dose <10 µg/kg.
High initial LT4 dosing was effective and safely achieved optimal cognitive development in patients with CH, including those severely affected. Supranormal T4 values during infancy were not associated with impaired IQ in adolescence.
治疗先天性甲状腺功能减退症（CH）的最佳左甲状腺素（LT4）剂量仍不清楚，对于是否需要更高的起始剂量（>10μg/kg）以及对于正常智商（IQ）是否安全存在争议。
检查用平均高初始 LT4 剂量治疗的 CH 患者的精神运动、代谢和生活质量（QoL）结果。
设计、地点、参与者：这是一项对 1979 年至 2003 年柏林新生儿筛查计划中发现的 CH 患者进行的横断面队列研究；76 名 CH 患者（平均年龄 18 岁；平均初始 LT4 剂量 13.5μg/kg）和 40 名兄弟姐妹完成了这项研究。
精神运动（韦氏智力测验、CNS 生命体征）、QoL（简短形式 36 健康调查）、人体测量学（体重指数、身高）和代谢（内中膜厚度、实验室参数）结果与健康兄弟姐妹进行了比较。分析了 2 岁前升高的甲状腺素（T4）和三碘甲状腺原氨酸（T3）和抑制的促甲状腺素（TSH）的平均值和发作次数。对 CH 治疗研究进行了荟萃分析。
与对照组相比，CH 患者的 IQ、QoL 或其他结果测量值没有差异。大多数 T4 水平在 2 岁之前和随后的测试中较高，但平均 T3 和 TSH 水平仍正常。荟萃分析显示，仅在 LT4 剂量<10μg/kg 开始治疗的严重 CH 病例与轻度 CH 病例之间存在显著的 IQ 差异。
高初始 LT4 给药在包括严重受影响的 CH 患者在内的患者中是有效且安全的，可实现最佳认知发育。婴儿期的 T4 水平过高与青春期的 IQ 受损无关。
