胎儿甲状腺激素状态紊乱对甲状腺和中枢性先天性甲状腺功能减退症的治疗具有长期影响。

Disturbance of the fetal thyroid hormone state has long-term consequences for treatment of thyroidal and central congenital hypothyroidism.

作者信息

Kempers M J E, van Trotsenburg A S P, van Tijn D A, Bakker E, Wiedijk B M, Endert E, de Vijlder J J M, Vulsma T

机构信息

Emma Children's Hospital Academic Medical Center, University of Amsterdam, Department of Pediatric Endocrinology, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.

出版信息

J Clin Endocrinol Metab. 2005 Jul;90(7):4094-100. doi: 10.1210/jc.2005-0197. Epub 2005 Apr 12.

DOI:10.1210/jc.2005-0197

PMID:15827096

Abstract

BACKGROUND

During T(4) supplementation of patients with thyroidal (primary) congenital hypothyroidism (CH) TSH concentrations are frequently elevated despite free T(4) (FT(4)) concentrations being well within the reference range. To examine the thyroid's regulatory system, we analyzed thyroid function determinants in children with congenital and acquired thyroid disorders and in controls.

METHODS

Retrospectively, plasma FT(4), TSH, and T(3) concentrations were analyzed in T(4)-supplemented children aged 0.5-20.0 yr with thyroidal CH, central (secondary or tertiary) CH, or autoimmune thyroid disease and in control children with type 1 diabetes mellitus.

RESULTS

When TSH was within the reference range (0.4-4.0 mU/liter), mean FT(4) in thyroidal CH [1.65 ng/dl; 95% confidence interval (CI), 1.62-1.67] was significantly higher than in autoimmune thyroid disease (1.15 ng/dl; 95% CI, 1.11-1.19) and diabetes (1.08 ng/dl; 95% CI, 1.06-1.10). In central CH, when TSH was less than or equal to 0.02 mU/liter, mean FT(4) was 1.27 ng/dl (95% CI, 1.24-1.29). When FT(4) was within the reference range (0.78-1.79 ng/dl), 43% of the TSH measurements in thyroidal CH were more than 4.0 mU/liter, compared with 18% in autoimmune thyroid disease and 0% in type 1 diabetes mellitus; in central CH, 95% of TSH measurements were less than 0.4 mU/liter.

CONCLUSIONS

In T(4)-supplemented patients with thyroidal CH, when TSH concentrations are established within the reference range, FT(4) concentrations tend to be elevated, and vice versa. Because this phenomenon could not be observed in acquired thyroidal hypothyroidism, we hypothesize that a pre- and/or perinatal hypothyroid state shifts the setpoint of the thyroid's regulatory system. In central CH, when FT(4) concentrations are established within the reference range, the pituitary secretes only minute amounts of TSH. For monitoring T(4) supplementation, reference ranges for FT(4) and TSH should be adapted to the etiology of hypothyroidism.

摘要

背景

在对甲状腺（原发性）先天性甲状腺功能减退症（CH）患者补充T4期间，尽管游离T4（FT4）浓度完全在参考范围内，但促甲状腺激素（TSH）浓度仍经常升高。为了研究甲状腺的调节系统，我们分析了先天性和后天性甲状腺疾病患儿以及对照组的甲状腺功能决定因素。

方法

回顾性分析了年龄在0.5 - 20.0岁、接受T4补充治疗的甲状腺CH、中枢性（继发性或三发性）CH或自身免疫性甲状腺疾病患儿以及1型糖尿病对照患儿的血浆FT4、TSH和T3浓度。

结果

当TSH在参考范围内（0.4 - 4.0 mU/升）时，甲状腺CH患儿的平均FT4[1.65 ng/dl；95%置信区间（CI），1.62 - 1.67]显著高于自身免疫性甲状腺疾病患儿（1.15 ng/dl；95% CI，1.11 - 1.19）和糖尿病患儿（1.08 ng/dl；95% CI，1.06 - 1.10）。在中枢性CH患儿中，当TSH小于或等于0.02 mU/升时，平均FT4为1.27 ng/dl（95% CI，1.24 - 1.29）。当FT4在参考范围内（0.78 - 1.79 ng/dl）时，甲状腺CH患儿中43%的TSH测量值大于4.0 mU/升，而自身免疫性甲状腺疾病患儿中这一比例为18%，1型糖尿病患儿中为0%；在中枢性CH患儿中，95%的TSH测量值小于0.4 mU/升。

结论

在接受T4补充治疗的甲状腺CH患者中，当TSH浓度在参考范围内时，FT4浓度往往会升高，反之亦然。由于在后天性甲状腺功能减退症中未观察到这种现象，我们推测产前和/或围产期甲状腺功能减退状态会改变甲状腺调节系统的设定点。在中枢性CH中，当FT4浓度在参考范围内时，垂体仅分泌微量的TSH。为了监测T4补充治疗，FT4和TSH的参考范围应根据甲状腺功能减退的病因进行调整。