Strich David, Karavani Gilad, Levin Shimon, Edri Shalom, Gillis David
Specialist Pediatric Clinics, Clalit Health Services, Jerusalem, Israel.
Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem, Israel.
Clin Endocrinol (Oxf). 2016 Jul;85(1):110-5. doi: 10.1111/cen.12970. Epub 2015 Nov 24.
Thyroid-stimulating hormone (TSH) levels within populations do not follow Gaussian distribution, and normal limits are derived after mathematical normalization. The clinical relevance of these limits is unknown. The objective of this study was to compare upper and lower TSH limits by four data normalization methods with non-normalized data and assess their clinical relevance.
DESIGN, PATIENTS AND MEASUREMENTS: Results of blood samples taken by community physicians and stored in a computerized database were analysed after removing samples from patients with evidence of thyroid illness. TSH values were normalized by the Hoffmann and Tukey methods and each method with natural log transformation. Non-normalized data for TSH in the uppermost and lowermost percentile were also calculated. Clinical relevance was determined by alterations in thyroid hormone levels at, below and above the limits for each method.
The maximal reduction from non-normalized data for the upper normal limit (UNL) was by the Hoffman method 43% = 3·1 mIU/l). The maximal increase for the lower normal limit (LNL) was also by the Hoffman method (708% = 0·81 mIU/l). There was very limited difference in average FT3 and FT4 between patients with TSH within, below or above the normal range for all methods.
Different normalization methods alter the normal limits greatly. However, in individuals without thyroid illness, thyroid hormone values are stable over a wide range of TSH levels including beyond the UNL for all methods. Indeed, there may be no true universal upper TSH cut-off level and clinical decision-making cannot rely on these calculated limits.
人群中的促甲状腺激素（TSH）水平不遵循高斯分布，正常范围是通过数学归一化得出的。这些范围的临床相关性尚不清楚。本研究的目的是比较四种数据归一化方法与未归一化数据得出的TSH上限和下限，并评估它们的临床相关性。
设计、患者和测量方法：去除有甲状腺疾病证据患者的样本后，分析社区医生采集并存储在计算机数据库中的血样结果。TSH值通过霍夫曼方法和图基方法以及每种进行自然对数转换的方法进行归一化。还计算了TSH处于最高和最低百分位数时的未归一化数据。通过每种方法的上限、低于上限和高于上限时甲状腺激素水平的变化来确定临床相关性。
上限正常范围（UNL）未归一化数据的最大降幅是通过霍夫曼方法（43% = 3.1 mIU/l）。下限正常范围（LNL）的最大增幅也是通过霍夫曼方法（708% = 0.81 mIU/l）。对于所有方法，TSH处于正常范围、低于正常范围或高于正常范围的患者之间，平均游离三碘甲腺原氨酸（FT3）和游离甲状腺素（FT4）的差异非常有限。
不同的归一化方法会极大地改变正常范围。然而，在没有甲状腺疾病的个体中，甲状腺激素值在很宽的TSH水平范围内保持稳定，包括所有方法的上限正常范围以上。实际上，可能不存在真正通用的TSH上限截断值，临床决策不能依赖这些计算出的范围。
