（十一）Tg测定
初始治疗后的血清Tg监测对疾病下一步的评估提供了重要的预测价值。当术后131I成像为阴性，甲状腺激素状态下测不到血清的Tg可作为治愈的完美指标[115]。相反，若Tg值持续升高，则还需要进一步临床评估，包括131I治疗后的全身放射性碘扫描及影像学检查，其目的是发现复发病灶的位置，并提供合适的治疗手段[116]。
参考文献
[1] Davies L, Welch H G.Current thyroid cancer trends in the United States[J].JAMA Otolaryngol Head Neck Surg,2014,140(4):317-322.
[2] Lewis E.Braverman, David Cooper.Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text [M].Lippincott Williams & Wilkins, 2012.
[3] Ahn H S, Kim H J, Welch H G.Korea’s thyroid-cancer“epidemic”-screening and overdiagnosis[J].N Engl J Med,2014,371(19):1765-1767.
[4] Oh C M, Won Y J, Jung K W.Cancer Statistics in Korea:Incidence, Mortality, Survival, and Prevalence in 2013[J].Cancer Res Treat, 2016,48(2):436-450.
[5] 刘玉琴， 张书全， 陈万青.中国2003—2007年甲状腺癌发病死亡现状及流行趋势分析 [J].中华流行病学杂志，2012，33（10）：1044-1048.
[6] 孙嘉伟，许晓君，蔡秋茂.中国甲状腺癌发病趋势分析[J].中国肿瘤，2013，22 （9）：690-693.
[7] Chen W,Zheng R, Baade P D.Cancer statistics in China,2015[J].CA Cancer J Clin,2016, 66(2):115-132.
[8] Agate L, Lorusso L, Elisei R.New and old knowledge on differentiated thyroid cancer epidemiology and risk factors[J].Endocrinol Invest, 2012,35.
[9] 肖海鹏，洪澍彬，喻爽.甲状腺癌流行趋势及其影响因素[J].内科理论与实践， 2013，8（6）： 383-387.
[10] Leslie J.De Groot.Endocrinology[J].W B Saunders, 1995.
[11] Enewold L, Zhu K, Ron E, et al.Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980—2005[J].Cancer Epidemiol Biomarkers Prev,2009,18:784-791.
[12] 史晓光，杨雯晴，滕卫平.甲状腺癌的“过度诊断”和“过度治疗”[J].中华内分泌代谢杂志， 2016，32（6）：443-447.
[13] 张太平，徐强，赵玉沛.也谈甲状腺癌的过度诊断[J].国际外科学杂志，2015，2（42）：73-75.
[14] 滕卫平.我国面临甲状腺癌“过度诊断”的挑战[J].中华内分泌代谢杂志，2016，7（32）：531-532.
[15] Pacini F.Thyroid?microcarcinoma[J].Best Pract Res Clin Endocrinol Metab,2012,26(3):381-389.
[16] Stroup A M, Harrell C J, Herget K A.Long-term survival in young women: hazards and competing risks after thyroid cancer[J].Cancer Epidemiol, 2012, 2012:641372.
[17] Hollenbeak C S, Boltz M M, Schaefer E W, et al.Recurrence of differentiated thyroid cancer in the elderly[J].Eur J Endocrinol,2013,168(4):549-556.
[18] Chan J K C, Saw D.The grooved nucleus: A useful diagnostic criterion of papillary carcinoma of the thyroid[J] .Am J Surg Pathol, 1986, 10:672-679.
[19] Grebe S K, Hay I D.Thyroid cancer nodal metastases:Biologic significance and therapeutic considerations[J].Surg Oncol Clin N Am, 1996, 1:43-63.
[20] Elisei R, Molinaro E, Agate L, et al.Are the clinical and pathological features of differentiated thyroid carcinoma really changed over the last 35 years? Study on 4187 patients from a single Italian institution to answer this question[J] .Clin Endocrinol Metab, 2010, 95:1516-1527.
[21] Tielens E T, Sherman S I, Hruban R H, et al.Follicular variant of papillary thyroid carcinoma[J].Cancer, 1994,73:424-431.
[22] Koo J S, Hong S, Park C S.Diffuse sclerosing variant is a major subtype of papillary thyroid carcinoma in the young[J].Thyroid, 2009, 19:1225-1231.
[23] Sobrinho-Simoes M, Nesland J M, Johannessen JV.Columnar cell carcinoma: Another variant of poorly differentiated carcinoma of the thyroid[J].Am J Clin Pathol, 1988, 89:264-267.
[24] Ganly I, Ibrahimpasic T, Rivera M, et al.Prognostic implications of papillary thyroid carcinoma with tall cell features[J].Thyroid, 2014, 24(4):662-670.
[25] Rivera M, Tuttle R M, Patel S, et al.Encapsulated papillary thyroid carcinoma: A clinico-pathologic study of 106 cases with emphasis on its morphologic subtypes(histologic growth pattern)[J].Thyroid, 2009, 19:119-127.
[26] Pacini F, Cetani F, Miccoli P, et al.Outcome of 309 patients with metastatic differentiated thyroid carcinoma treated with radioiodine[J].World J Surg, 1994, 18:600-604.
[27] Sywak M, Pasieka J L, Ogilvie T.A review of thyroid cancer with intermediate differentiation[J].Surg Oncol,2004, 86:44-54.
[28] Goffredo P, Roman S A, Sosa J A.Hurthle cell carcinoma:A population-level analysis of 3311 patients[J].Cancer,2013, 119:504-511.
[29] Fernandez I J, Piccin O, Sciascia S, et al.Clinical significance of BRAF mutation in thyroid papillary cancer[J].Otolaryngol Head Neck Surg, 2013, 148:919-925.
[30] Bronner M P, Livolsi V A.Oxyphilic (Askanazy/Hürthle cell) tumors of the thyroid: Microscopic features predict biologic behaviour[J].Surg Pathol, 1988, 1:137-150.
[31] Rabes H M, Demidchik E P, Sidorow J D, et al.Pattern of radiation induced RET and NTRK1 rearrangements in 191 post-Chernobyl papillary thyroid carcinomas:Biological, phenotypic, and clinical implications [J].Clin Cancer Res, 2000, 6:1093-1103.
[32] Nikiforov Y E.RET/PTC rearrangement in thyroid tumors[J].Endocr Pathol, 2002, 13:3-16.
[33] Nikiforova M N, Lynch R A, Biddinger P W, et al.RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: Evidence for distinct molecular pathways in thyroid follicular carcinoma[J].Clin Endocrinol Metab, 2003, 88:2318-2326.
[34] National Council on Radiation Protection and Measurement.Risks to the thyroid from ionizing radiation[R].Report No.159.Bethesda, MD: National Council on Radiation Protection and Measurement, 2009.
[35] National Research Council.Health risks from exposure to low levels of ionizing radiation: BEIR Ⅶ phase 2[M].Washington, DC: National Academy Press, 2006.
[36] Ron E, Lubin J H, Shore R E, et al.Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies[J].Radiat Res, 1995, 141:259-277.
[37] Preston D L, Ron E, Tokuoka S, et al.Solid cancer incidence in atomic bomb survivors: 1958-1998[J].Radiat Res, 2007, 168:1-64.
[38] Richardson D B.Exposure to ionizing radiation in adulthood and thyroid cancer incidence[J].Epidemiology,2009, 20:181-187.
[39] Hayashi Y, Lagarde F, Tsuda N, et al.Papillary microcarcinoma of the thyroid among atomic bomb survivors: tumor characteristics and radiation risk[J].Cancer, 2010, 116:1646-1655.
[40] Tronko M D, Howe G R, Bogdanova T I, et al.A cohort study of thyroid cancer and other thyroid diseases after the Chernobyl accident: thyroid cancer in Ukraine detected during first screening[J].J Natl Cancer Inst,2006, 98:897- 903.
[41] Zablotska L B, Ron E, Rozhko A V, et al.Thyroid cancer risk in Belarus among children and adolescents exposed to radioiodine after the Chernobyl accident[J].Br J Cancer, 2011, 104:181-187.
[42] Williams E D, Abrosimov A, Bogdanova T, et al.Thyroid carcinoma after Chernobyl latent period, morphology and aggressiveness[J].Br J Cancer, 2004, 90:2219-2224.
[43] Williams E D, Abrosimov A, Bogdanova T, et al.Morphologic characteristics of Chernobyl-related childhood papillary thyroid carcinomas are independent of radiation exposure but vary with iodine intake[J].Thyroid, 2008, 18:847-852.
[44] Shipler D B, Napier B A, Farris W T, et al.Hanford environmental dose reconstruction project: an overview[J].Health Phys, 1996, 71:532-544.
[45] Ron E.Thyroid cancer incidence among people living in areas contaminated by radiation from the Chernobyl accident[J].Health Phys, 2007, 93:502-511.
[46] Davis S, Kopecky K J, Hamilton T E, et al.Thyroid neoplasia, autoimmune thyroiditis, and hypothyroidism in persons exposed to iodine 131 from the Hanford Nuclear Site[J].J Am Med Assn, 2004, 292:2600-2613.
[47] Cooper D S.Radioiodine for hyperthyroidism-Where do we stand after 50 years? [J].JAMA,1998, 280:375-376.
[48] Franklyn J A, Maisonneuve P, Sheppard M, et al.Cancer incidence and mortality after radioiodine treatment for hyperthyroidism: a population-based cohort study[J].Lancet, 1999, 353:2111-2115.
[49] Holm L-E, Hall P, Wiklund K, et al.Cancer risk after iodine-131 therapy for hyperthyroidism[J].J Natl Cancer Inst, 1991, 83:1072-1077.
[50] Hall P, Furst C J, Mattsson A, et al.Thyroid nodularity after diagnostic administration of iodine-131[J].Radiat Res, 1996, 146:673-682.
[51] Hall P, Mattsson A, Boice J D.Thyroid cancer after diagnostic administration of iodine-131[J].Radiat Res,1996, 145:86-92.
[52] Franklyn J A, Maisonneuve P, Sheppard M C, et al.Mortality after the treatment of hyperthyroidism with radioactive iodine[J].N Engl J Med, 1998, 338:712-718.
[53] Schneider A B, Sarne D H.Long-term risks for thyroid cancer and other neoplasms after exposure to radiation[J].Nat Clin Pract Endocrinol Metab, 2005, 1:82-91.
[54] Lin Z, Wu W, Lin J, et al.A longitudinal study on the radiation-induced thyroid gland changes after external beam radiotherapy of nasopharyngeal carcinoma [J].Thyroid, 2011, 21:19-23.
[55] Armstrong G T, Stovall M, Robison L L.Long-term effects of radiation exposure among adult survivors of childhood cancer: results from the Childhood Cancer Survivor Study[J].Radiat Res, 2010, 174:840-850.
[56] Chow E J, Friedman D L, Stovall M, et al.Risk of thyroid dysfunction and subsequent thyroid cancer among survivors of acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study[J].Pediatr Blood Cancer, 2009, 53:432-437.
[57] Favus M, Schneider A, Stachura M, et al.Thyroid cancer occurring as a late consequence of head-and-neck irradiation[J].N Engl J Med, 1976,294:1019- 1025.(https://www.daowen.com)
[58] O’Kane P, Shelkovoy E, McConnell RJ, et al.Frequency of undetected thyroid nodules in a large I-131-exposed population repeatedly screened by ultrasonography:results from the Ukrainian-American cohort study of thyroid cancer and other thyroid diseases following the Chernobyl accident[J].Thyroid, 2010, 20:959-964.
[59] Cooper D S, Doherty G M, Haugen B R, et al.Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer[J].Thyroid, 2009, 19:1167-1214.
[60] Mihailescu D V, Collins B J, Wilbur A, et al.Ultrasounddetected thyroid nodules in radiation-exposed patients:changes over time[J].Thyroid, 2005, 15:127-133.
[61] Fogelfeld L, Wiviott M B T, Shore-Freedman E, et al.Recurrence of thyroid nodules after surgical removal in patients irradiated in childhood for benign conditions[J].N Engl J Med, 1989, 320:835-840.
[62] Dotto J, Nose V.Familial thyroid carcinoma: a diagnostic algorithm[J].Adv Anat Pathol, 2008, 15:332-349.
[63] Nose V.Thyroid cancer of follicular cell origin in inherited tumor syndromes[J].Adv Anat Pathol, 2010, 17:428-436.
[64] Herraiz M, Barbesino G, Faquin W, et al.Prevalence of thyroid cancer in familial adenomatous polyposis syndrome and the role of screening ultra-sound examinations.[J].Clin Gastroenterol Hepatol, 2007,5:367-373.
[65] Jarrar A M, Milas M, Mitchell J, et al.Screening for thyroid cancer in patients with familial adenomatous polyposis[J].Ann Surg, 2011, 253:515-521.
[66] Cetta F, Chiappetta G, Melillo R M, et al.The ret/ptc1 oncogene is activated in familial adenomatous polyposisassociated thyroid papillary carcinomas[J].Clin Endocrinol Metab, 1998, 83:1003-1006.
[67] Nose V.Familial follicular cell tumors: classification and morphological characteristics[J].Endocr Pathol, 2010,21:219-226.
[68] Charkes N D.On the prevalence of familial nonmedullary thyroid cancer in multiply affected kindreds[J].Thyroid,2006, 16:181-186.
[69] Gudmundsson J, Sulem P, Gudbjartsson D F, et al.Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations[J].Nat Genet,2009, 41:460-464.
[70] Wegelin C.Malignant disease of the thyroid and its relation to goiter in men and animals[J].Cancer Rev,1928, 3:297.
[71] Sehestedt T, Knudsen N, Perrild H, et al.Iodine intake and incidence of thyroid cancer in Denmark[J].Clin Endocrinol (Oxf) , 2006, 65:229-233.
[72] Bacher-Stier C, Riccabona G, Totsch M, et al.Incidence and clinical characteristics of thyroid carcinoma after iodine prophylaxis in an endemic goiter country[J].Thyroid, 1997, 7:733-741.
[73] Besic N, Hocevar M, Zgajnar J.Lower incidence of anaplastic carcinoma after higher iodination of salt in Slovenia[J].Thyroid, 2010, 20:623-626.
[74] Bosetti C, Kolonel L, Negri E, et al.A pooled analysis of case-control studies of thyroid cancer.VI.Fish and shellfish consumption[J].Cancer Cause Control , 2001,12:375-382.
[75] Bosetti C, Negri E, Kolonel L, et al.A pooled analysis of case-control studies of thyroid cancer.VII.Cruciferous and other vegetables (International)[J].Cancer Cause Control, 2002, 13:765-775.
[76] Meinhold C L, Park Y, Stolzenberg-Solomon R Z, et al.Alcohol intake and risk of thyroid cancer in the NIHAARP diet and health study[J].Br J Cancer, 2009,101:1630-1634.
[77] Kreiger N, Parkes R.Cigarette smoking and the risk of thyroid cancer[J].Eur J Cancer, 2000, 36:1969-1973.
[78] Capen C C.Mechanistic data and risk assessment of selected toxic end points of the thyroid gland[J].Toxicol Pathol, 1997, 25:39-48.
[79] Wong E Y, Ray R, Gao D L, et al.Reproductive history,occupational exposures, and thyroid cancer risk among women textile workers in Shanghai, China[J].Int Arch Occup Environ Health, 2006, 79:251-258.
[80] Leenhardt L, Grosclaude P, Chérié-Challine L.Thyroid Cancer Committee: Increased incidence of thyroid carcinoma in France: A true epidemic or thyroid nodule management effects? Report from the French Thyroid Cancer Committee[J].Thyroid, 2004, 14:1056-1060.
[81] Lin J D, Huang B Y, Chao T C, et al.Diagnosis of occult thyroid carcinoma by thyroid ultrasonography with fine needle aspiration cytology[J].Acta Cytol, 1997, 41:1751-1756.
[82] 中华医学会内分泌学分会，中华医学会外科学分会内分泌学组， 中国抗癌协会头颈肿瘤专业委员会，等.甲状腺结节和分化型甲状腺癌诊治指南[J].中华内分泌代谢杂志， 2012， 28（10）：779-796.
[83] HegedtisL．Clinical practice．The thyroid nodule[J]．N Engl J Med, 2004, 351:1764-1771．
[84] Fiore E, Vitti P．Semm TSH and Risk of Papillary Thyroid Cancer in Nodular Thyroid Disease [J].Clin Endoerinol Metab, 2012, 97:1134-1145．
[85] Baskin H J.Ultrasound of thyroid nodules.In: Baskin HJ,ed.Thyroid Ultrasound and Ultrasound-Guided FNA Biopsy[M].Boston.MA: Kluwer Academic Publishers,2000, 71-86．
[86] Cappeui C, Castellano M, Pimla I, et a1.The Predjctive value of ultIasound findings in the management ofthyroid nodules[J].QJM, 2007, 100: 29-35．
[87] Rago T, santini F, scutari M, et a1．Elastography: new developments in ultrasound for predicting malignancy in thymid nodules [J].Clin Endocrinol Metab, 2007, 92:2917-2922．
[88] Boelaen K, Horacek J, Holder R L, et a1.Serum thyrotropin concentration as a novel predictor of Malignancy in thyroid nodules investigated by fineneedle aspiration [J].Clin Endo Metab, 2006, 91:4295-4301．
[89] Noguchi S, Yamashita H, Uchno S, et al.Papillary microcarcinoma[J].World J Surg, 2008, 32:747-753．
[90] Se Lee Yoon, Lim Yun-Sung, Lee Jin-Choon, et al.Nodal status of central lymph nodes as a negative prognostic factor for papillary thyroid carcinoma[J].Surg Oncol,2013, 107:777-782.
[91] Mercante G, Frasoldati A, Pedroni C, et al.Prognostic factors affecting neck lymph node recurrence and distant metastasis in papillary microcarcinoma of the thyroid:Results of a study in 445 patients[J].Thyroid, 2009,19:707-716.
[92] Bosetti C, Bertuccio P, Levi F, et al.Cancer mortality in the European Union, 1970—2003, with a joinpoint analysis[J].Ann Oncol, 2008, 19:631-640.
[93] McConahey W M, Hay I D, Woolner L B, et al.Papillary thyroid cancer treated at the Mayo Clinic, 1946 through 1970: Initial manifestation, pathologic findings, therapy,and outcome[J].Mayo Clin Proc, 1986, 61:978-996.
[94] Lang W, Choritz H, Hundeshagen H.Risk factors in follicular thyroid carcinomas: A retrospective followup study covering a 14-year period with emphasis on morphological findings[J].Am J Surg Pathol, 1986,10:246-255.
[95] Hazard J B, Hawk W A, Crile J r G.Medullary (solid)carcinoma of the thyroid: A clinicopathologicentity[J] .Clin Endocrinol Metab,1959,19:152-161.
[96] Melvin K E W, Miller H H, Tashjian A H.Early diagnosis of medullary carcinoma of the thyroid gland by means of calcitonin assay[J].N Engl J Med, 1971, 285:1115-1120.
[97] Pacini F, Romei C, Miccoli P, et al.Early treatment of hereditary medullary thyroid carcinoma after attribution of multiple endocrine neoplasia type 2 gene carrier status by screening for ret gene mutations[J].Surgery, 1995,118:1031-1035.
[98] Harada T, Ito K, Shimaoka K, et al.Fatal thyroid carcinoma:Anaplastic transformation of adenocarcinoma[J].Cancer,1977, 39:2588-2596.
[99] Rodriguez J M, Parrilla P, Moreno A, et al.Insular carcinoma: An infrequent subtype of thyroid cancer[J].Am Coll Surg, 1998, 187:503-508.
[100] Elisei R, Molinaro E, Agate L, et al.Are the clinical and pathological features of differentiated thyroid carcinoma really changed over the last 35 years? Study on 4187 patients from a single Italian institution to answer this question [J].Clin Endocrinol Metab, 2010, 95:1516-1527.
[101] Nilubol N, Zhang L, Kebebew E.Multivariate analysis of the relationship between male sex, disease-specifc survival, and features of tumor aggressiveness in thyroid cancer of follicular cell origin[J].Thyroid, 2013,23:695-702.
[102] Friguglietti C U, Dutenhefner S E, Brandaõ L G, et al.Classifcation of papillary thyroid microcarcinoma according to size and fneneedle aspiration cytology:Behavior and therapeutic implications[J].Head Neck, 2011, 33:696-701.
[103] Shaha A R.Treatment of thyroid cancer based on risk groups[J].Surg Oncol, 2006, 94:683-691.
[104] Rivera M, Ricarte-Filho J, Tuttle R M, et al.Molecular,morphologic, and outcome analysis of thyroid carcinomas according to degree of extrathyroid extension[J].Thyroid, 2010, 20:1085-1093.
[105] Rivera M, Tuttle R M, Patel S, et al.Encapsulated papillary thyroid carcinoma: A clinicopathologic study of 106 cases with emphasis on its morphologic subtypes(histologic growth pattern)[J].Thyroid,2009;19:119-127.
[106] Pacini F, Mariotti S, Formica N, et al.Thyroid autoantibodies in thyroid cancer: Incidence and relationship with tumour outcome[J].Acta Endocrinol(Copenh) , 1988, 119:373-380.
[107] Kim E Y, Kim W G, Kim W B, et al.Coexistence of chronic lymphocytic thyroiditis is associated with lower recurrence rates in patients with papillary thyroid carcinoma[J].Clin Endocrinol (Oxf) , 2009, 71(4):581-586.
[108] Park Y J, Kim Y A, Lee Y J, et al.Papillary microcarcinoma in comparison with larger papillary thyroid carcinoma in BRAF(V600E) mutation,clinicopathological features, and immunohistochemical fndings[J].Head Neck,2010,32:38-45.
[109] Mazzaferri E L.Impact of initial tumor features and treatment selected on the long-term course of differentiated thyroid cancer[J].Thyroid Today, 1995,18:1-13.
[110] Hung-Hin Lang B, Pun Wong K, Cheung C Y, et al.Evaluating the prognostic factors associated with cancer-specifc survival of differentiated thyroid carcinoma presenting with distant metastasis[J].Ann Surg Oncol, 2013, 20:1329-1335.
[111] Xing M, Alzahrani A S, Carson K A, et al.Association between BRAFV600E mutation and mortality in patients with papillary thyroid cancer[J].JAMA, 2013,309:1493-1501.
[112] De Groot L J, Kaplan E L, McCormick M, et al.Natural history,treatment, and course of papillary thyroid carcinoma [J] .Clin Endocrinol Metab, 1990, 71:414-424.
[113] Mazzaferri E L.Papillary thyroid carcinoma: Factors affecting prognosis and current therapy[J].Semin Oncol,1987, 14:315-332.
[114] Castagna M G, Cevenini G, Theodoropoulou A, et al.Post-surgical thyroid ablation with low or high radioiodine activities results in similar outcomes in intermediate risk differentiated thyroid cancer patients[J].Eur J Endocrinol, 2013, 169:23-29.
[115] Pacini F, Ceccarelli C, Elisei R, et al.Serum thyroglobulin determination in thyroid cancer: A ten years experience.In: Nagataki S,Torizuka K, eds[M].The Thyroid.New York: Elsevier, 1988,685.
[116] Pacini F, Lippi F, Formica N, et al.Therapeutic doses of iodine-131 reveal undiagnosed metastases in thyroid cancer patients with detectable serum thyroglobulin levels[J].Nucl Med, 1987, 28:1888-1891.