1、1 1 Thyroid 2015 American Thyroid Association DOI: 10.1089/thy.2015.0020 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer The American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated
2、 Thyroid CancerBryan R. Haugen, M.D.1 (Chair)*, Erik K. Alexander, M.D.2, Keith C. Bible, M.D., Ph.D.3, Gerard M. Doherty, M.D.4, Susan J. Mandel, M.D., M.P.H.5, Yuri E. Nikiforov, M.D., Ph.D.6, Furio Pacini, M.D.7, Gregory W. Randolph, M.D.8, Anna M. Sawka, M.D., Ph.D.9, Martin Schlumberger, M.D.10
3、, Kathryn Schuff, M.D.11, Steven I. Sherman, M.D.12, Julie Ann Sosa, M.D.13, David L. Steward, M.D.14, R. Michael Tuttle, M.D.15, and Leonard Wartofsky, M.D.16 *Authors are listed in alphabetical order and were appointed by ATA to independently formulate the content of this manuscript. None of the s
4、cientific or medical content of the manuscript was dictated by the ATA. 1 University of Colorado School of Medicine, Aurora, Colorado. 2Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusettes. 3The Mayo Clinic, Rochester, Minnesota. 4Boston Medical Center, Boston, Massachusettes.
5、 5 Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 6University of Pittsburgh Medical Center, Pittsburgh, Pennsylvannia. 7 The University of Siena, Siena, Italy. 8Massachusettes Eye and Ear Infirmary, Massachusettes General Hospital, Harvard Medical School, Boston
6、, Massachusettes. 9University Health Network, University of Toronto , Toronto, Canada. 10Institute Gustave Roussy and University Paris Sud, Villejuif, France. 11Oregon Health and Science University, Portland, Oregon. 12University of Texas M.D. Anderson Cancer Center, Houston, Texas. 13Duke Universit
7、y School of Medicine, Durham, North Carolina. 14University of Cincinnati Medical Center, Cincinnati, Ohio. 15Memorial Sloan-Kettering Cancer Center, New York, New York. 16MedStar Washington Hospital Center, Washington, DC. Running title: ATA Thyroid Nodule/DTC Guidelines Page 1 of 411 Thyroid2015 Am
8、erican Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer (doi: 10.1089/thy.2015.0020)This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published versio
9、n may differ from this 2 2 ABSTRACT Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Associations guidelines for the management of these disorders were revised in 2009, significant scientific a
10、dvances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addre
11、ssed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including: electronic database searching, review and selection of relevant citations, and critical appra
12、isal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians (ACP) Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a sim
13、ilarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed and communicated to the ATA and task force members.
14、 Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers and management of benign
15、thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and Page 2 of 411 Thyroid2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Canc
16、er (doi: 10.1089/thy.2015.0020)This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this 3 3 risk assessment, surgical management, radioiodine remnant ablation and therapy, and TSH suppr
17、ession therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using imaging and serum thyroglobulin, thyroid hormone therapy, management of recurrent and metastatic disease, considerati
18、on for clinical trials and targeted therapy, as well as directions for future research. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporar
19、y optimal care for patients with these disorders. Page 3 of 411 Thyroid2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer (doi: 10.1089/thy.2015.0020)This article has been peer-reviewed and accepted for publication, but h
20、as yet to undergo copyediting and proof correction. The final published version may differ from this 4 4 INTRODUCTION THYROID NODULES are a common clinical problem. Epidemiologic studies have shown the prevalence of palpable thyroid nodules to be approximately 5% in women and 1% in men living in iod
21、ine-sufficient parts of the world (1;2). In contrast, high-resolution ultrasound (US) can detect thyroid nodules in 1968% of randomly selected individuals with higher frequencies in women and the elderly (3;4). The clinical importance of thyroid nodules rests with the need to exclude thyroid cancer,
22、 which occurs in 715% depending on age, sex, radiation exposure history, family history, and other factors (5;6). Differentiated thyroid cancer (DTC), which includes papillary and follicular cancer, comprises the vast majority (90%) of all thyroid cancers (7). In the United States, approximately 63,
23、000 new cases of thyroid cancer were predicted to be diagnosed in 2014 (8) compared with 37,200 in 2009 when the last ATA guidelines were published. The yearly incidence has nearly tripled from 4.9 per 100,000 in 1975 to 14.3 per 100,000 in 2009 (9). Almost the entire change has been attributed to a
24、n increase in the incidence of papillary thyroid cancer (PTC). Moreover, 25% of the new thyroid cancers diagnosed in 1988-89 were 2.5-fold more likely to file for bankruptcy than Page 4 of 411 Thyroid2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and
25、Differentiated Thyroid Cancer (doi: 10.1089/thy.2015.0020)This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this 5 5 those without a cancer diagnosis. Patients with thyroid cancer had
26、 one of the highest risks for filing bankruptcy (approximately 3.5-fold), suggesting that the increasing incidence and treatment of thyroid cancer can carry many risks. Optimization of long-term health outcomes and education about potential prognosis for individuals with thyroid neoplasms is critica
27、lly important. In 1996, the American Thyroid Association (ATA) published treatment guidelines for patients with thyroid nodules and DTC (13). Over the last 15-20 years, there have been many advances in the diagnosis and therapy of both thyroid nodules and DTC, but clinical controversy exists in many
28、 areas. A long history of insufficient peer-reviewed research funding for high quality clinical trials in the field of thyroid neoplasia, may be an important contributing factor to existing clinical uncertainties (12). Methodologic limitations or conflicting findings of older studies present a signi
29、ficant challenge to modern-day medical decision-making in many aspects of thyroid neoplasia. Although not a specific focus of these guidelines, we recognize that feasibility and cost considerations of various diagnostic and therapeutic options also present important clinical challenges in many clini
30、cal practice settings. AIM AND TARGET AUDIENCE Our objective in these guidelines is to inform clinicians, patients, researchers, and health policy makers about the best available evidence (and its limitations), relating to the diagnosis and treatment of adult patients with thyroid nodules and differ
31、entiated thyroid cancer. These guidelines should not be applied to children (1 cm should be evaluated, since they have a greater potential to be clinically significant cancers. Occasionally, there may be nodules 1 cm that require evaluation because of suspicious US findings, associated lymphadenopat
32、hy, or other high-risk clinical factors such as a history of childhood head and neck irradiation or a history of thyroid cancer in one or more first-degree relatives. Occasionally, there may be nodules 1 cm that require further evaluation because of clinical symptoms or associated lymphadenopathy. I
33、n very rare cases, some nodules 1 cm in any diameter or diffuse or focal thyroidal uptake on F18-flurodeoxyglucose positron emission tomography (18FDG-PET) scan, a serum TSH level should be obtained. If the serum TSH is subnormal, a radionuclide thyroid scan should be obtained to document whether th
34、e nodule is hyperfunctioning (“hot”, i.e., tracer uptake is greater than the surrounding normal thyroid), isofunctioning (“warm”, i.e., tracer uptake is equal to the surrounding thyroid), or nonfunctioning (“cold”, i.e., has uptake less than the surrounding thyroid tissue) (44). Since hyperfunctioni
35、ng nodules rarely harbor malignancy, if one is found that corresponds to the nodule in question, no cytologic evaluation is necessary. If overt or subclinical hyperthyroidism is present, additional evaluation is required. A higher serum TSH level, even within the upper part of the reference range, i
36、s associated with increased risk of malignancy in a thyroid nodule, as well as more advanced stage thyroid cancer (45;46). A5 Serum thyroglobulin measurement RECOMMENDATION 3 Routine measurement of serum Tg for initial evaluation of thyroid nodules is not Page 15 of 411 Thyroid2015 American Thyroid
37、Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer (doi: 10.1089/thy.2015.0020)This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ fr
38、om this 16 16 recommended. (Strong recommendation, Moderate-quality evidence) Serum Tg levels can be elevated in most thyroid diseases and are an insensitive and nonspecific test for thyroid cancer (47-49). A6 Serum calcitonin measurement RECOMMENDATION 4 The panel cannot recommend either for or aga
39、inst routine measurement of serum calcitonin in patients with thyroid nodules. (No recommendation, Insufficient evidence) The utility of serum calcitonin has been evaluated in a series of prospective, non-randomized studies (50-54). These data suggest that the use of routine serum calcitonin for scr
40、eening may detect C-cell hyperplasia and medullary thyroid cancer (MTC) at an earlier stage and overall survival consequently may be improved. However, most studies relied on pentagastrin stimulation testing to increase specificity. This drug is not available in the United States, Canada and some ot
41、her countries, and there remain unresolved issues of sensitivity, specificity, assay performance, cut-offs using calcium stimulation (55) and cost-effectiveness. Two retrospective studies have shown improved survival in patients diagnosed with MTC after routine calcitonin testing compared with histo
42、rical controls (53;56), but were unable to show a decreased number of MTC related deaths. A cost-effectiveness analysis suggested that calcitonin screening would be cost effective in the United States (57). However, prevalence estimates of MTC in this analysis included patients with C-cell hyperplas
43、ia and microMTC, which have uncertain clinical significance. Based on the retrospective nature of the survival Page 16 of 411 Thyroid2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer (doi: 10.1089/thy.2015.0020)This arti
44、cle has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this 17 17 data, unresolved issues of assay performance, lack of availability of pentagastrin in North America, and potential biases in the co
45、st-effective analysis, the task force cannot recommend for or against the routine measurement of serum calcitonin as a screening test in patients with thyroid nodules, although there was not uniform agreement on this recommendation. There was, however, agreement that serum calcitonin may be consider
46、ed in the subgroup of patients where an elevated calcitonin may change the diagnostic or surgical approach (i.e. patients considered for less than total thyroidectomy, patients with suspicious cytology not consistent with PTC). If the unstimulated serum calcitonin determination has been obtained and
47、 the level is greater than 50-100 pg/mL, a diagnosis of MTC is common (58). There is emerging evidence that a calcitonin measurement from a thyroid nodule FNA washout may be helpful in the preoperative evaluation of patients with a modestly elevated basal serum calcitonin (20-100 pg/ml) (59). A7 18F
48、DG-PET scan RECOMMENDATION 5 A) Focal 18FDG-PET uptake within a sonographically confirmed thyroid nodule conveys an increased risk of thyroid cancer, and fine needle aspiration is recommended for those nodules 1 cm. (Strong recommendation, Moderate-quality evidence) B) Diffuse 18FDG-PET uptake, in c
49、onjunction with sonographic and clinical evidence of chronic lymphocytic thyroiditis, does not require further imaging or fine needle aspiration. (Strong recommendation, Moderate-quality evidence) Page 17 of 411 Thyroid2015 American Thyroid Association Management Guidelines for Adult Patients with T
50、hyroid Nodules and Differentiated Thyroid Cancer (doi: 10.1089/thy.2015.0020)This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this 18 18 18FDG-PET is increasingly performed during th
