Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore, Singapore.
Bergmannsheil University Hospitals, Ruhr University of Bochum, Bochum, Germany.
J Endocrinol Invest. 2021 May;44(5):969-977. doi: 10.1007/s40618-020-01390-7. Epub 2020 Aug 17.
The homeostatic euthyroid set point of the hypothalamus-pituitary-thyroid axis of any given individual is unique and oscillates narrowly within substantially broader normal population ranges of circulating free thyroxine (FT4) and thyroid-stimulating hormone (TSH), otherwise termed 'thyroid function test (TFT)'. We developed a mathematical algorithm codenamed Thyroid-SPOT that effectively reconstructs the personalized set point in open-loop situations and evaluated its performance in a retrospective patient sample.
We computed the set points of 101 patients who underwent total thyroidectomy for non-functioning thyroid disease using Thyroid-SPOT on each patient's own serial post-thyroidectomy TFT. Every predicted set point was compared against its respective healthy pre-operative euthyroid TFT per individual and their separation (i.e. predicted-observed TFT) quantified.
Bland-Altman analysis to measure the agreement between each pair of an individual's predicted and actual set points revealed a mean difference in FT4 and TSH of + 3.03 pmol/L (95% CI 2.64, 3.43) and - 0.03 mIU/L (95% CI - 0.25, 0.19), respectively. These differences are small compared to the width of the reference intervals. Thyroid-SPOT can predict the euthyroid set point remarkably well, especially for TSH with a 10-16-fold spread in magnitude between population normal limits.
Every individual's equilibrium euthyroid set point is unique. Thyroid-SPOT serves as an accurate, precise and reliable targeting system for optimal personalized restoration of euthyroidism. This algorithm can guide clinicians in L-thyroxine dose titrations to resolve persistent dysthyroid symptoms among challenging cases harbouring "normal TFT" within the laboratory ranges but differing significantly from their actual euthyroid set points.
每个人下丘脑-垂体-甲状腺轴的稳态甲状腺功能正常设定点是独特的，并在广泛的循环游离甲状腺素 (FT4) 和促甲状腺激素 (TSH) 正常人群范围内狭窄波动，否则称为“甲状腺功能测试 (TFT)”。我们开发了一种名为 Thyroid-SPOT 的数学算法，该算法可在开环情况下有效地重建个性化设定点，并在回顾性患者样本中评估其性能。
我们使用 Thyroid-SPOT 计算了 101 名因非功能性甲状腺疾病行甲状腺全切除术的患者的设定点，这些患者的甲状腺功能减退术后 TFT 均为患者自身的连续序列。将每个预测的设定点与每个个体的相应健康术前甲状腺功能正常的 TFT 进行比较，并量化它们的分离（即预测-观察 TFT）。
Bland-Altman 分析用于测量个体预测和实际设定点之间的每对差异，结果显示 FT4 和 TSH 的平均差异分别为 +3.03 pmol/L（95% CI 2.64，3.43）和-0.03 mIU/L（95% CI -0.25，0.19）。与参考区间的宽度相比，这些差异很小。Thyroid-SPOT 可以很好地预测甲状腺功能正常的设定点，特别是对于 TSH，人群正常范围之间的幅度相差 10-16 倍。
每个人的平衡甲状腺功能正常设定点都是独特的。Thyroid-SPOT 是一种准确、精确和可靠的靶向系统，可实现最佳个性化甲状腺功能正常的恢复。该算法可以指导临床医生进行 L-甲状腺素剂量滴定，以解决在实验室范围内存在“正常 TFT”但与实际甲状腺功能正常设定点显著不同的具有挑战性病例中持续存在的甲状腺功能亢进症状。
