Lindner Henry H
Private Practice, Tunkhannock, PA, United States.
Front Endocrinol (Lausanne). 2025 Jun 24;16:1529791. doi: 10.3389/fendo.2025.1529791. eCollection 2025.
The 2012 American endocrine associations' guidelines on hypothyroidism were a reiteration of the TSH-T4 Paradigm from the 1970s. They likewise defined hypothyroidism as hypothyroxinemia, assumed that almost all hypothyroidism was primary, and relied upon the thyroid stimulating hormone (TSH) test and inactive prohormone thyroxine (T4) for diagnosis and treatment. The guidelines' authors acknowledged many TSH and other "pitfalls" in the paradigm yet warned physicians against attending to patients' signs and symptoms and relative free T4 (FT4) and free triiodothyronine (FT3) levels-the only means by which to identify and avoid all pitfalls and provide individualized diagnosis and treatment. This inadequate paradigm has distorted medical practice and research for 50 years, including laboratories' FT4 and FT3 reference ranges. It produces overdiagnosis, underdiagnosis, inadequate treatment, and widespread patient dissatisfaction. Since the 1970s, our understanding of thyroid hormone production, transport, metabolism, reception, and signaling has increased greatly, as has our appreciation of the importance of optimal T3 effects for health and wellbeing. Hypothyroidism must be defined physiologically as insufficient T3 effect in some or all tissues. The best indicators of tissue T3 effect are the patient's signs and symptoms, and the best serum tests are FT4 and FT3, considered together. The TSH level is not a reliable indicator of T3 status in the untreated state and is oversuppressed by the peak levels that occur with once-daily oral T4 and/or T3. Normalizing an elevated TSH or low FT4 with T4 usually does not produce sufficient, let alone optimal, T3 effect and can leave some patients markedly hypothyroid. T4/T3 combination therapy is more physiological and effective than T4 monotherapy and must be guided by clinical criteria, not the TSH. Some patients cannot tolerate more T3 effect due to hypocortisolism, inflammation, and other disorders. There is no substitute for the practice of fully informed clinical medicine.
2012年美国内分泌学会关于甲状腺功能减退症的指南是对20世纪70年代促甲状腺激素 - 甲状腺素范式的重申。它们同样将甲状腺功能减退症定义为甲状腺素血症，假定几乎所有甲状腺功能减退症都是原发性的，并依靠促甲状腺激素（TSH）检测和无活性的甲状腺激素原甲状腺素（T4）进行诊断和治疗。该指南的作者承认该范式存在许多TSH及其他“陷阱”，但却警告医生不要关注患者的体征和症状以及游离甲状腺素（FT4）和游离三碘甲状腺原氨酸（FT3）的相对水平——这是识别和避免所有陷阱并提供个体化诊断和治疗的唯一方法。这种不充分的范式已经扭曲医学实践和研究达50年之久，包括实验室的FT4和FT3参考范围。它导致了过度诊断、诊断不足、治疗不充分以及患者普遍不满。自20世纪70年代以来，我们对甲状腺激素的产生、运输、代谢、受体和信号传导的理解有了极大的提高，我们对最佳T3效应对于健康和幸福的重要性的认识也是如此。甲状腺功能减退症必须在生理上定义为某些或所有组织中T3效应不足。组织T3效应的最佳指标是患者的体征和症状，而最佳的血清检测是FT4和FT3，综合考虑。在未经治疗的状态下，TSH水平不是T3状态的可靠指标，并且会被每日一次口服T4和/或T3时出现的峰值水平过度抑制。用T4使升高的TSH或低FT4正常化通常不会产生足够的，更不用说最佳的，T3效应，并且可能会使一些患者明显甲状腺功能减退。T4/T3联合治疗比T4单一治疗更符合生理且更有效，并且必须以临床标准而非TSH为指导。由于皮质醇缺乏、炎症和其他疾病，一些患者无法耐受更多的T3效应。充分知情的临床医学实践无可替代。
