如果患者出现以下症状,则需要进行甲状腺疾病评估:原因不明的体重减轻、心悸、心房颤动或其他室上性心动过速、震颤、全身性近端肌无力、或原因不明的眼球突出。[2]Smith TJ, Hegedüs L. Graves' disease. N Engl J Med. 2016 Oct 20;375(16):1552-65.http://www.ncbi.nlm.nih.gov/pubmed/27797318?tool=bestpractice.com[7]Boelaert K, Torlinska B, Holder RL, et al. Older subjects with hyperthyroidism present with a paucity of symptoms and signs – a large cross-sectional study. J Clin Endocrinol Metab. 2010 Jun;95(6):2715-26.http://press.endocrine.org/doi/full/10.1210/jc.2009-2495http://www.ncbi.nlm.nih.gov/pubmed/20392869?tool=bestpractice.com[47]Pearce EN. Diagnosis and management of thyrotoxicosis. BMJ. 2006 Jun 10;332(7554):1369-73.http://www.ncbi.nlm.nih.gov/pubmed/16763249?tool=bestpractice.com 对甲状腺弥漫性肿大应该进行检查,特别是在出现杂音时。以下症状也可能与甲状腺功能亢进症有关:女性出现潮湿和松软的皮肤、脱发、甲剥离、月经紊乱;男性出现乳房发育或勃起功能障碍。[2]Smith TJ, Hegedüs L. Graves' disease. N Engl J Med. 2016 Oct 20;375(16):1552-65.http://www.ncbi.nlm.nih.gov/pubmed/27797318?tool=bestpractice.com[47]Pearce EN. Diagnosis and management of thyrotoxicosis. BMJ. 2006 Jun 10;332(7554):1369-73.http://www.ncbi.nlm.nih.gov/pubmed/16763249?tool=bestpractice.com
诸如原因不明的体重下降和全身乏力等症状可能会使患者担忧潜在的恶性病因。如果出现不能用其他原因解释的任何恶性肿瘤症状,则应安排相应检查,并遵循患者安全保障程序 (patient safety-netting procedure)。
在针对其他指征的常规检查时,许多无症状患者可能被诊断出由 Graves 病导致的亚临床甲状腺功能亢进。详细的临床病史(包括自身免疫性疾病的家族史)、体格检查以及在 8 至 12 周内反复进行甲状腺功能检测与促甲状腺激素 (thyroid-stimulating hormone, TSH) 受体抗体检测,将有助于确定生化异常是暂时性的(例如由非甲状腺疾病所致)还是由自身免疫反应所致。
实验室检查
血清 TSH 检测是首选的实验室筛查项目。大多数有症状的甲状腺功能亢进症 Graves 病患者的血清 TSH 低于第三代检测法的检测下限(如<0.01 mIU/L)。[48]Baskin HJ, Cobin RH, Duick DS, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract. 2002 Nov-Dec;8(6):457-69.http://www.ncbi.nlm.nih.gov/pubmed/15260011?tool=bestpractice.com 亚临床疾病患者的血清 TSH 水平低于正常,外周血甲状腺激素水平正常。[10]Mitchell AL, Pearce SH. How should we treat patients with low serum thyrotropin concentrations? Clin Endocrinol (Oxf). 2010 Mar;72(3):292-6.http://www.ncbi.nlm.nih.gov/pubmed/19744106?tool=bestpractice.com[11]Col NF, Surks MI, Daniels GH. Subclinical thyroid disease: clinical applications. JAMA. 2004 Jan 14;291(2):239-43.http://www.ncbi.nlm.nih.gov/pubmed/14722151?tool=bestpractice.com[12]Biondi B, Palmieri EA, Klain M, et al. Subclinical hyperthyroidism: clinical features and treatment options. Eur J Endocrinol. 2005 Jan;152(1):1-9.http://www.ncbi.nlm.nih.gov/pubmed/15762182?tool=bestpractice.com 依据血清游离 T4、T3 或游离 T3 增高,可确诊甲状腺功能亢进。[2]Smith TJ, Hegedüs L. Graves' disease. N Engl J Med. 2016 Oct 20;375(16):1552-65.http://www.ncbi.nlm.nih.gov/pubmed/27797318?tool=bestpractice.com[47]Pearce EN. Diagnosis and management of thyrotoxicosis. BMJ. 2006 Jun 10;332(7554):1369-73.http://www.ncbi.nlm.nih.gov/pubmed/16763249?tool=bestpractice.com 轻度 Graves 病患者的游离 T4 水平可能正常,但是 T3 升高(“T3 毒症”)。总 T4 和 T3 检测结果可能具有误导性,因为它们受到一些因素的影响,这些因素会改变 T4 与甲状腺素结合球蛋白的结合。通过免疫测定法或生物测定法检测到 TSH 受体抗体可确诊绝大多数病例的 Graves 病。通常没有必要测定其他甲状腺抗体。[49]Bojarska-Szmygin A, Janicki K, Pietura R, et al. Changes in TSH receptor antibody levels (TRAb) as markers of effectiveness of various therapies in Graves-Basedow's disease. Ann Univ Mariae Curie Sklodowska [Med]. 2003;58(1):248-53.http://www.ncbi.nlm.nih.gov/pubmed/15314994?tool=bestpractice.com[50]Orgiazzi J. Anti-TSH receptor antibodies in clinical practice. Endocrinol Metab Clin North Am. 2000 Jun;29(2):339-55.http://www.ncbi.nlm.nih.gov/pubmed/10874533?tool=bestpractice.com[51]Rubello D, et al. Prognostic value of anti-TSH receptor antibodies assay in 85 patients treated for Graves' disease. The thyroid gland, environment and autoimmunity: proceedings of the International Symposium on Thyroid Gland, Environment & Autoimmunity, 1989. Amsterdam: Elsevier Science Publishers; 1990:263-8. 在禁用放射性碘摄取(例如妊娠期或哺乳期)时,计算总 T3/T4 或游离 T3/T4 比值可能有助于鉴别甲状腺炎与 Graves 病和毒性结节性甲状腺肿。[52]Amino N, Yabu Y, Miki T, et al. Serum ratio of triiodothyronine to thyroxine, and thyroxine-binding globulin and calcitonin concentration in Graves' disease and destruction-induced thyrotoxicosis. J Clin Endocrinol Metab. 1981 Jul;53(1):113-6.http://www.ncbi.nlm.nih.gov/pubmed/6165731?tool=bestpractice.com 存在高 T3/T4 比率提示 Graves 病而非甲状腺炎。[53]Yoshimura Noh J, Momotani N, Fukada S, et al. Ratio of serum free triiodothyronine to free thyroxine in Graves' hyperthyroidism and thyrotoxicosis caused by painless thyroiditis. Endocr J. 2005 Oct;52(5):537-42.https://www.jstage.jst.go.jp/article/endocrj/52/5/52_5_537/_articlehttp://www.ncbi.nlm.nih.gov/pubmed/16284430?tool=bestpractice.com[54]Sriphrapradang C, Bhasipol A. Differentiating Graves' disease from subacute thyroiditis using ratio of serum free triiodothyronine to free thyroxine. Ann Med Surg (Lond). 2016 Aug 8;10:69-72.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990637/http://www.ncbi.nlm.nih.gov/pubmed/27570620?tool=bestpractice.com[55]Shigemasa C, Abe K, Taniguchi S, et al. Lower serum free thyroxine (T4) levels in painless thyroiditis compared with Graves' disease despite similar serum total T4 levels. J Clin Endocrinol Metab. 1987 Aug;65(2):359-63.http://www.ncbi.nlm.nih.gov/pubmed/3110204?tool=bestpractice.com
影像学检查
对于存在甲状腺毒性生化结果和 TSH 受体抗体升高的患者,则无需进行放射学检测。测量放射性碘(I-131 或 I-123)或锝 (Tc-99) 的甲状腺摄取率有助于排除摄取率低的甲状腺功能亢进综合征,例如无痛性甲状腺炎,还有助于鉴别 Graves 病(弥散性摄取)与毒性多结节性甲状腺肿(局灶区域摄取增加)。[2]Smith TJ, Hegedüs L. Graves' disease. N Engl J Med. 2016 Oct 20;375(16):1552-65.http://www.ncbi.nlm.nih.gov/pubmed/27797318?tool=bestpractice.com[47]Pearce EN. Diagnosis and management of thyrotoxicosis. BMJ. 2006 Jun 10;332(7554):1369-73.http://www.ncbi.nlm.nih.gov/pubmed/16763249?tool=bestpractice.com 如果出现结节,则需要进行甲状腺超声检查;而彩色血流多普勒可用于区分 Graves 病(血流增加)与无痛性甲状腺炎(血流减少),类似于将其用于鉴别胺碘酮诱发甲状腺功能亢进的原因。[2]Smith TJ, Hegedüs L. Graves' disease. N Engl J Med. 2016 Oct 20;375(16):1552-65.http://www.ncbi.nlm.nih.gov/pubmed/27797318?tool=bestpractice.com[47]Pearce EN. Diagnosis and management of thyrotoxicosis. BMJ. 2006 Jun 10;332(7554):1369-73.http://www.ncbi.nlm.nih.gov/pubmed/16763249?tool=bestpractice.com[56]Bogazzi F, Vitti P. Could improved ultrasound and power Doppler replace thyroidal radioiodine uptake to assess thyroid disease? Nat Clin Pract Endocrinol Metab. 2008 Feb;4(2):70-1.http://www.ncbi.nlm.nih.gov/pubmed/17984981?tool=bestpractice.com
[Figure caption and citation for the preceding image starts]: 碘摄取扫描。甲状腺炎中不存在摄取的典型表现(上图)。Graves 病中弥散性摄取增加(左下图)。多结节性甲状腺肿中摄取增加和减少的区域(中下图)。毒性腺瘤中摄取增加的单个区域(右下图)由 Dr. Petros Perros 提供 [Citation ends].
眼眶病/皮肤病
双侧眼球突出和眼睑退缩是典型的临床特征,同时伴有甲状腺功能亢进,即足以作出 Graves 眼病的诊断。对于甲状腺功能正常的单侧眼病或其他非典型表现(例如既往或当前无甲状腺功能异常的证据、不存在上眼睑回缩、外斜视、仅表现复视或在白天快要结束时复视加重),需要进行眼眶横断面成像(例如 CT 或 MRI 扫描),成像显示典型眼肌增厚,才能排除其他诊断。TSH 受体抗体水平升高会使诊断 Graves 眼病的可能性增加,但是,如果怀疑其他诊断结果,不可使用此方法替代眼眶影像学检查。[3]Prabhakar BS, Bahn RS, Smith TJ. Current perspective on the pathogenesis of Graves' disease and ophthalmopathy. Endocrine Rev. 2003 Dec;24(6):802-35.http://www.ncbi.nlm.nih.gov/pubmed/14671007?tool=bestpractice.com[4]Bahn RS. Pathogenesis of Graves ophthalmopathy: the role of orbital thyroid-stimulating hormone receptor expression. Curr Opin Endocrinol Diabetes. 2003 Oct;10(5):353-6.[6]Eckstein AK, Johnson KT, Thanos M, et al. Current insights into the pathogenesis of Graves' orbitopathy. Horm Metab Res. 2009 Jun;41(6):456-64.http://www.ncbi.nlm.nih.gov/pubmed/19530272?tool=bestpractice.com[57]Bartalena L, Marocci C, Tanda ML, et al. An update on medical management of Graves' ophthalmopathy. J Endocrinol Invest. 2005 May;28(5):469-78.http://www.ncbi.nlm.nih.gov/pubmed/16075933?tool=bestpractice.com 依据甲状腺皮肤病的临床表现伴 Graves 眼病,可诊断为 Graves 病。皮肤病和/或杵状指不伴有眼眶病极其罕见,应当怀疑引起皮肤和指甲改变的其他原因。对于可疑病例需要进行皮肤活检。[58]Schwartz KM, Fatourechi V, Ahmed DD, et al. Dermopathy of Graves' disease (pretibial myxedema): long-term outcome. J Clin Endocrinol Metab. 2002 Feb;87(2):438-46.http://www.ncbi.nlm.nih.gov/pubmed/11836263?tool=bestpractice.com[59]Fatourechi V, Ahmed DDF, Schwartz KM. Thyroid acropachy: report of 40 patients treated at a single institution in a 26-year period. J Clin Endocrinol Metab. 2002 Dec;87(12):5435-41.http://www.ncbi.nlm.nih.gov/pubmed/12466333?tool=bestpractice.com 因为存在变态反应和结膜炎,Graves 眼眶病经常被延迟诊断或误诊,尤其是眼部症状在确诊 Graves 病之前出现时。
目前尚不清楚轻度 Graves 眼病是慢性复发缓解的过程,还是病程中的一过性事件。[60]Anagnostis P, Boboridis K, Adamidou F, et al. Natural course of mild Graves' orbitopathy: is it a chronic remitting or a transient disease? J Endocrinol Invest. 2017 Mar;40(3):257-61.http://www.ncbi.nlm.nih.gov/pubmed/27664101?tool=bestpractice.com
DiaGO(Graves 眼眶病诊断)测试是一项 20 分的评估工具,可由临床医生(包括非眼科医生)使用,可以帮助鉴别 Graves 眼眶病患者。[61]Mitchell AL, Goss L, Mathiopoulou L, et al. Diagnosis of Graves' orbitopathy (DiaGO): results of a pilot study to assess the utility of an office tool for practicing endocrinologists. J Clin Endocrinol Metab. 2015 Mar;100(3):E458-62.http://www.ncbi.nlm.nih.gov/pubmed/25485725?tool=bestpractice.com 已经发布了关于 Graves 眼眶病早期检测和管理的指南。[62]Perros P, Dayan CM, Dickinson AJ, et al. Management of patients with Graves' orbitopathy: initial assessment, management outside specialised centres and referral pathways. Clin Med (Lond). 2015 Apr;15(2):173-8.http://www.clinmed.rcpjournal.org/content/15/2/173.longhttp://www.ncbi.nlm.nih.gov/pubmed/25824071?tool=bestpractice.com[63]Bartalena L, Baldeschi L, Boboridis K, et al. The 2016 European Thyroid Association/European Group on Graves' Orbitopathy guidelines for the management of Graves' orbitopathy. Eur Thyroid J. 2016 Mar;5(1):9-26.http://www.karger.com/Article/FullText/443828#http://www.ncbi.nlm.nih.gov/pubmed/27099835?tool=bestpractice.com
[Figure caption and citation for the preceding image starts]: 眼睑回缩、轻度眼球突出和轻度球结膜水肿Vahab Fatourechi 医生提供 [Citation ends].
[Figure caption and citation for the preceding image starts]: 通过 Graves 眼眶病患者眼眶的轴向 CT 扫描,显示内直肌增厚由 Dr. Petros Perros 提供 [Citation ends].
[Figure caption and citation for the preceding image starts]: 眼眶病和象皮病Vahab Fatourechi 医生提供 [Citation ends].
总结
Graves 甲状腺功能亢进症的诊断标准包括:TSH 受体抗体水平升高(或甲状腺对放射性碘/锝-99 摄取率升高),同时 TSH 降低伴游离 T4 或 T3 升高。
静脉穿刺和抽血的动画演示
关于如何进行心电图的动画演示