Dubuis J M, Glorieux J, Richer F, Deal C L, Dussault J H, Van Vliet G
Research Unit on the Biology of Reproduction and Development, Sainte-Justine Hospital, Montreal, Quebec, Canada.
J Clin Endocrinol Metab. 1996 Jan;81(1):222-7. doi: 10.1210/jcem.81.1.8550756.
We have previously reported that despite neonatal screening, children with severe congenital hypothyroidism treated at 5 weeks of age with 6 micrograms/kg.day levothyroxine have clinically significant intellectual impairment, whereas those with the moderate form of the disease are indistinguishable from controls. The developmental outcome of children with severe congenital hypothyroidism treated earlier with higher initial doses of levothyroxine remained to be determined. In the present study, 45 infants with permanent congenital hypothyroidism detected by neonatal screening are described. For the group, the median age at starting treatment was 14 days, and the median initial dose of levothyroxine was 11.6 micrograms/kg.day. Based on the area of their knee epiphyses at diagnosis, the patients were divided into 2 subgroups: severe (< 0.05 cm2; n = 10) and moderate (> or = 0.05 cm2; n = 35). The psychomotor development of 8 patients in each subgroup, matched for the socioeducational level of their families, was assessed at 18 months. Mean plasma free T4 levels were supraphysiological during the first few months of life, but mean plasma T3 levels remained within the normal range, and there were no signs or symptoms of hyperthyroidism. The mean plasma TSH concentration was less than 4.5 mIU/L 4 weeks after starting treatment. Bone maturation remained delayed at 12 months in the severe cases and was not unduly advanced in the moderate cases. The mean (+/- SD) developmental quotients at 18 months were similar in severe and moderate cases (107 +/- 10 and 110 +/- 5, respectively). We conclude that with earlier treatment and a higher initial dose of levothyroxine, the early developmental outcome of infants with severe congenital hypothyroidism is now indistinguishable from that of infants with the moderate form of the disease who were used as controls.
我们之前曾报道，尽管进行了新生儿筛查，但5周龄时开始用6微克/千克·天左甲状腺素治疗的重度先天性甲状腺功能减退症患儿仍有临床上显著的智力损害，而中度患儿与对照组无差异。早期用更高初始剂量左甲状腺素治疗的重度先天性甲状腺功能减退症患儿的发育结局仍有待确定。在本研究中，描述了45例通过新生儿筛查发现的永久性先天性甲状腺功能减退症婴儿。该组开始治疗的中位年龄为14天，左甲状腺素的中位初始剂量为11.6微克/千克·天。根据诊断时膝部骨骺面积，将患者分为2个亚组：重度（<0.05平方厘米；n = 10）和中度（≥0.05平方厘米；n = 35）。在18个月时评估了每个亚组中8例家庭社会教育水平相匹配的患儿的精神运动发育情况。出生后头几个月平均血浆游离T4水平高于生理水平，但平均血浆T3水平仍在正常范围内，且无甲状腺功能亢进的体征或症状。开始治疗4周后平均血浆TSH浓度低于4.5 mIU/L。重度病例在12个月时骨成熟仍延迟，中度病例未过度提前。重度和中度病例在18个月时的平均（±标准差）发育商相似（分别为107±10和110±5）。我们得出结论，通过早期治疗和更高的左甲状腺素初始剂量，重度先天性甲状腺功能减退症婴儿的早期发育结局现在与作为对照的中度疾病婴儿无法区分。
