Thyroid Research Group, Division of Infection and Immunity, Cardiff University, Cardiff, UK.
Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, Netherlands.
Lancet. 2024 Oct 5;404(10460):1347-1364. doi: 10.1016/S0140-6736(24)01614-3.
Hypothyroidism, the deficiency of thyroid hormone, is a common condition worldwide. It affects almost all body systems and has a wide variety of clinical presentations from being asymptomatic to, in rare cases, life threatening. The classic symptoms of hypothyroidism include fatigue, lethargy, weight gain, and cold intolerance; however, these symptoms are non-specific and the diagnosis is typically made on biochemical grounds through serum thyroid function tests. The most common cause of hypothyroidism is chronic autoimmune thyroiditis (Hashimoto's thyroiditis), although other causes, including drugs (such as amiodarone, lithium, and immune checkpoint inhibitors), radioactive-iodine treatment, and thyroid surgery, are frequent. Historically, severe iodine deficiency was the most common cause. Reference ranges for thyroid function tests are based on fixed percentiles of the population distribution, but there is increasing awareness of the need for more individualised reference intervals based on key factors such as age, sex, and special circumstances such as pregnancy. Levothyroxine monotherapy is the standard treatment for hypothyroidism; it is safe and inexpensive, restores thyroid function tests to within the reference range, and improves symptoms in the majority of patients. However, 10% of patients have persistent symptoms of ill health despite normalisation of thyroid function tests biochemically and a substantial proportion of patients on levothyroxine have thyroid-stimulating hormone concentrations outside the reference range. Ongoing symptoms despite levothyroxine treatment has led to some patients using liothyronine or desiccated thyroid extract. Taken together, these factors have led to intense debate around the treatment thresholds and treatment strategies for hypothyroidism. In this Seminar, we review the epidemiology, genetic determinants, causes, and presentation of hypothyroidism; highlight key considerations and controversies in its diagnosis and management; and provide future directions for research.
甲状腺功能减退症，即甲状腺激素缺乏，是一种全球范围内常见的疾病。它影响几乎所有的身体系统，临床表现多种多样，从无症状到极少数情况下的危及生命。甲状腺功能减退症的典型症状包括疲劳、乏力、体重增加和畏寒；然而，这些症状并不具有特异性，诊断通常基于生化指标，即通过血清甲状腺功能检测。甲状腺功能减退症最常见的原因是慢性自身免疫性甲状腺炎（桥本甲状腺炎），尽管其他原因，包括药物（如胺碘酮、锂和免疫检查点抑制剂）、放射性碘治疗和甲状腺手术，也很常见。历史上，严重碘缺乏是最常见的原因。甲状腺功能检测的参考范围基于人群分布的固定百分位数，但越来越多的人意识到需要根据年龄、性别和特殊情况（如妊娠）等关键因素制定更个体化的参考区间。左甲状腺素单药治疗是甲状腺功能减退症的标准治疗方法；它安全且廉价，可将甲状腺功能检测恢复至参考范围内，并改善大多数患者的症状。然而，尽管生物化学上甲状腺功能检测正常，仍有 10%的患者持续存在健康状况不佳的症状，并且相当一部分接受左甲状腺素治疗的患者的促甲状腺激素浓度超出参考范围。尽管接受了左甲状腺素治疗，但症状仍持续存在，这导致一些患者使用三碘甲状腺原氨酸或甲状腺干制剂。综上所述，这些因素引发了关于甲状腺功能减退症治疗阈值和治疗策略的激烈争论。在本次研讨会上，我们回顾了甲状腺功能减退症的流行病学、遗传决定因素、病因和表现；强调了其诊断和管理中的关键考虑因素和争议；并为未来的研究提供了方向。
