Department of Endocrinology, Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, The Netherlands.
Thyroid. 2013 Feb;23(2):160-5. doi: 10.1089/thy.2011.0262.
A major problem in the treatment of patients with congenital hypothyroidism (CHT) is that the optimal individual target values of thyrotropin (TSH) and free thyroxine (fT(4)) are unknown. We investigated whether patients with CHT have during treatment considered optimal stable fT(4) and TSH steady-state concentrations (SSCs) that can be used as target values, and whether TSH or fT(4) is more useful in guiding decisions regarding therapy.
From 60 early-treated patients with CHT, TSH and fT(4) follow-up samples within the age interval 1.5-132 months (postinitial period) and within TSH interval 0.5-10 mU/L were selected. TSH and fT(4) SSCs were estimated by taking the individual mean values of a series of determinations, under the most euthyroid conditions possible (n=1257), for the whole age and TSH intervals, as well as for the age intervals 1.5-24, 25-72, and 73-132 months, as well as, for fT(4), for the two split TSH intervals 0.5-4.49 and 4.5-10 mU/L. For all SSCs, the within-subject coefficient of variation (CV(w)) was determined. Further, fT(4) SSCs were assessed for the first 6 weeks after therapy initiation.
For both TSH and fT(4), individual SSCs differed significantly (p<0.001). The 95% confidence interval for TSH SSCs was 1.1-5.7 mU/L and for fT(4) SSCs 16.6-28.7 pmol/L. Mean CV(w) values for TSH and fT(4) SSCs were 60.9% and 13.1%, respectively. Individual fT(4) and TSH SSCs were reproducible when assessed for the three age intervals, both slightly decreasing with age (p≤0.033), and fT(4) SSCs were reproducible for the two split TSH intervals, with a slight fT(4) difference (p<0.001). fT(4) SSCs were largely independent of the administered LT(4) dosage (range 2.4-6.1 μg/kg). fT(4) SSCs of the initial period were comparable to those of postinitial period with a mean±SD difference of 1.0±3.5 pmol/L, p=0.07.
Our study suggests that in CHT during therapy considered optimal, stable TSH and fT(4) SSCs can be found slightly decreasing with age and largely independent of the administered LT(4) dosage (range 2.4-6.1 μg/kg). In clinical follow-up, fT(4) SSCs may be more valuable as individual target values than TSH SSCs.
在先天性甲状腺功能减退症（CHT）患者的治疗中，一个主要问题是促甲状腺激素（TSH）和游离甲状腺素（fT(4)）的最佳个体目标值未知。我们研究了 CHT 患者在治疗期间是否具有可作为目标值的考虑最佳的稳定 fT(4)和 TSH 稳态浓度（SSC），以及 TSH 或 fT(4)在指导治疗决策方面是否更有用。
从 60 例早期治疗的 CHT 患者中，选择年龄在 1.5-132 个月（初始后期间）和 TSH 间隔在 0.5-10 mU/L 内的 TSH 和 fT(4)随访样本。在尽可能最甲状腺功能正常的条件下，通过连续多次测定的个体平均值来估计 TSH 和 fT(4) SSC（n=1257），用于整个年龄和 TSH 间隔，以及年龄间隔 1.5-24、25-72 和 73-132 个月，以及对于 fT(4)，用于两个分裂的 TSH 间隔 0.5-4.49 和 4.5-10 mU/L。对于所有 SSC，确定了个体内变异系数（CV(w)）。此外，在治疗开始后的前 6 周评估了 fT(4) SSC。
TSH 和 fT(4)的个体 SSC 均有显著差异（p<0.001）。TSH SSC 的 95%置信区间为 1.1-5.7 mU/L，fT(4) SSC 的 95%置信区间为 16.6-28.7 pmol/L。TSH 和 fT(4) SSC 的平均 CV(w)值分别为 60.9%和 13.1%。当评估三个年龄间隔时，个体 fT(4)和 TSH SSC 是可重复的，并且随着年龄的增长略有下降（p≤0.033），fT(4) SSC 对于两个分裂的 TSH 间隔是可重复的，并且 fT(4) 略有差异（p<0.001）。fT(4) SSC 与给予的 LT(4)剂量（范围 2.4-6.1 μg/kg）基本无关。初始期间的 fT(4) SSC 与初始后期间的 fT(4) SSC 相当，平均差异±SD 为 1.0±3.5 pmol/L，p=0.07。
我们的研究表明，在 CHT 治疗期间，考虑到最佳状态，可发现 TSH 和 fT(4) SSC 略有下降，并且与给予的 LT(4)剂量（范围 2.4-6.1 μg/kg）基本无关。在临床随访中，fT(4) SSC 可能比 TSH SSC 更有价值作为个体目标值。
