Pearce Simon H.S., Cheetham Timothy D., Wood Claire L., Gan Earn H., Perros Petros
Professor of Endocrinology, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
Professor of Paediatric Endocrinology, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
The diagnosis of Graves’ disease is mostly straightforward, depending on recognition of the cardinal features of the disease and confirmation by tests including serum TSH, free T4, and TSH receptor antibodies. The differential diagnosis includes other causes of thyrotoxicosis, such as secretory thyroid nodules, various forms of inflammatory or destructive thyroiditis, or thyrotoxicosis factitia. The mainstay of treatment of Graves’ disease for most patients remains thionamide antithyroid drugs, with radioiodine (I) and thyroidectomy surgery being necessary for patients whose hyperthyroidism is not controlled following one or more courses of antithyroid drug or for whom antithyroid drugs are unlikely to result in durable remission. As none of these treatment modalities have limitations, shared decision making should be used to determine each patient’s preference. Stratification of disease severity at presentation, based on patient age, goiter size, degree of hyperthyroidism, and concentration of TSH receptor antibodies reliably predicts prognosis and should be used to inform choice of primary therapy. Subclinical hyperthyroidism owing to Graves’ disease has a high progression rate to overt hyperthyroidism and antithyroid drug therapy should be the primary mode of therapy for most patients. Graves’ disease in children and young adults has a worse outcome than in adults and primary treatment with a prolonged course of antithyroid drugs is recommended, with many cases requiring eventual definitive treatment with thyroidectomy or radioiodine, when timing is appropriate to the educational and social situation. Other special situations including pregnancy and thyroid eye disease are also reviewed. As none of the existing therapies are ideal, there are a range of new therapeutic options currently in clinical trials, including approaches to deplete serum TSH receptor antibodies from plasma and to directly block TSH receptor signaling using both small molecule antagonists and biologics. These advances are likely to change the physician’s armamentarium for management of Graves’ disease substantially in the next decade. For complete coverage of all related areas of Thyroidology please visit our Free web-site https://www.thyroidmanager.org. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.
经典型格雷夫斯病的诊断并不困难，主要依据对该病主要特征的识别，并通过促甲状腺激素（TSH）和游离甲状腺素指数（FTI）等检查来确诊。鉴别诊断包括其他类型的甲状腺毒症，如结节性甲状腺肿伴发的甲状腺毒症、某些甲状腺肿瘤伴发的甲状腺毒症、人为性甲状腺毒症，以及非毒性甲状腺肿。能模仿甲状腺毒症症状的高代谢状态也必须纳入鉴别诊断范围。例如某些嗜铬细胞瘤、红细胞增多症、淋巴瘤及白血病病例。肺部疾病、感染、帕金森病、妊娠或肾炎可能引发甲状腺毒症的某些特征。格雷夫斯病的治疗目前尚无法针对病因，因为病因仍不明。若甲状腺毒症似乎是主要指征，则设法控制甲状腺毒症；若疾病的眼部病变显得更为紧迫，则针对眼部病变进行治疗。本文将对现有的治疗方式，包括手术、药物及放射性碘治疗进行综述。对于哪种治疗方式最佳，存在不同观点，但在很大程度上可以制定治疗选择的指导原则。抗甲状腺药物被广泛用于长期治疗。接受长期抗甲状腺治疗的患者中，约三分之一可实现永久性甲状腺功能正常。药物是儿童和年轻人首选的初始治疗方法。如果有优秀的外科医生，甲状腺次全切除术是一种令人满意的治疗方式，但在2016年较少使用。抗甲状腺药物与碘联合使用可使患者在手术前得到充分准备，手术死亡率已接近零。如果抗甲状腺药物治疗失败，许多年轻人会接受手术治疗。目前，大多数内分泌学家认为放射性碘治疗是成人的最佳治疗方法，并认为随之而来的甲状腺功能减退是一个小问题。经过五十多年的经验，迄今为止的证据表明晚期甲状腺癌的风险必定接近零。作者建议对大多数40岁以上的患者采用这种治疗方法，并认为在大约15岁以上使用并无禁忌。剂量根据摄取量和腺体大小计算。大多数患者一次治疗即可治愈。治疗后多年，甲状腺功能减退的发生率相当稳定，如果要通过碘-131治愈疾病，甲状腺功能减退可能是不可避免的。许多治疗医生将此视为治疗的预期结果。儿童甲状腺毒症最初最好采用抗甲状腺药物治疗。如果这种治疗未能治愈，可进行手术。一些医生接受放射性碘治疗作为替代治疗方式，尤其是随着年龄接近15岁时。新生儿甲状腺毒症较为罕见。可能需要使用抗甲状腺药物、普萘洛尔和碘剂数周，直到母体来源的抗体被代谢。应用这些治疗方式控制甲状腺毒症的医生还应关注患者的情感需求，以及其对休息、营养和特定抗甲状腺药物的需求。有关此主题及相关主题的完整内容，请查阅我们的免费网络书籍WWW.ENDOTEXT.ORG。我们注意到，目前有2份关于格雷夫斯病诊断和治疗的非常全面的指南——2016年美国甲状腺协会（ATA）指南---http://online.liebertpub.com/doi/pdfplus/10.1089/thy.2016.0229（270页），以及美国临床内分泌医师协会（AACE）2011年版关于甲状腺功能亢进及其他甲状腺毒症病因的指南（65页）--https://www.aace.com/files/hyperguidelinesapril2013.pdf。两者都非常值得一读。
