1、RESEARCH ARTICLERevised American Thyroid Association ManagementGuidelines for Patients with Thyroid Nodulesand Differentiated Thyroid CancerThe American Thyroid Association (ATA) Guidelines Taskforceon Thyroid Nodules and Differentiated Thyroid CancerDavid S. Cooper, M.D.1(Chair)*, Gerard M. Doherty
2、, M.D.,2Bryan R. Haugen, M.D.,3Richard T. Kloos, M.D.,4Stephanie L. Lee, M.D., Ph.D.,5Susan J. Mandel, M.D., M.P.H.,6Ernest L. Mazzaferri, M.D.,7Bryan McIver, M.D., Ph.D.,8Furio Pacini, M.D.,9Martin Schlumberger, M.D.,10Steven I. Sherman, M.D.,11David L. Steward, M.D.,12and R. Michael Tuttle, M.D.13
3、Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becomingincreasingly prevalent. Since the publication of the American Thyroid Associations guidelines for the man-agement of these disorders was published in 2006, a large amount of new information has be
4、come available,prompting a revision of the guidelines.Methods: Relevant articles through December 2008 were reviewed by the task force and categorized by topic andlevel of evidence according to a modified schema used by the United States Preventative Services Task Force.Results: The revised guidelin
5、es for the management of thyroid nodules include recommendations regardinginitial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needleaspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initialman
6、agement of thyroid cancer include those relating to optimal surgical management, radioiodine remnantablation, and suppression therapy using levothyroxine. Recommendations related to long-term management ofdifferentiated thyroid cancer include those related to surveillance for recurrent disease using
7、 ultrasound andserum thyroglobulin as well as those related to management of recurrent and metastatic disease.Conclusions: We created evidence-based recommendations in response to our appointment as a an independenttask force by the American Thyroid Association to assist in the clinical management o
8、f patients with thyroidnodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for pa-tients with these disorders.Thyroid nodules are a common clinical problem. Epi-demiologic studies have shown the prevalence of palpa-ble thyroid nodules to be approximat
9、ely 5% in women and 1%in men living in iodine-sufficient parts of the world (1,2). Incontrast, high-resolution ultrasound (US) can detect thyroidnodules in 1967% of randomly selected individuals withhigher frequencies in women and the elderly (3). The clinicalimportance of thyroid nodules rests with
10、 the need to excludethyroid cancer which occurs in 515% depending on age, sex,radiation exposure history, family history, and other factors*Authors are listed in alphabetical order and were appointed by ATA to independently formulate the content of this manuscript. None ofthe scientific or medical c
11、ontent of the manuscript was dictated by the ATA.1The Johns Hopkins University School of Medicine, Baltimore, Maryland.2University of Michigan Medical Center, Ann Arbor, Michigan.3University of Colorado Health Sciences Center, Denver, Colorado.4The Ohio State University, Columbus, Ohio.5Boston Unive
12、rsity Medical Center, Boston, Massachusetts.6University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.7University of Florida College of Medicine, Gainesville, Florida.8The Mayo Clinic, Rochester, Minnesota.9The University of Siena, Siena, Italy.10Institute Gustave Roussy, Paris, Fra
13、nce.11University of Texas M.D. Anderson Cancer Center, Houston, Texas.12University of Cincinnati Medical Center, Cincinnati, Ohio.13Memorial Sloan-Kettering Cancer Center, New York, New York.THYROIDVolume 19, Number 11, 2009 Mary Ann Liebert, Inc.DOI: 10.1089=thy.2009.01101(4,5). Differentiated thyr
14、oid cancer (DTC), which includespapillary and follicular cancer, comprises the vast majority(90%) of all thyroid cancers (6). In the United States, approx-imately 37,200 new cases of thyroid cancer will be diagnosedin 2009 (7). The yearly incidence has increased from 3.6 per100,000 in 1973 to 8.7 pe
15、r 100,000 in 2002, a 2.4-fold increase( p1 cm should be evaluated, sincethey have a greater potential to be clinically significant can-cers. Occasionally, there may be nodules 1 cm in any diameter ordiffuse or focal thyroidal uptake on18FDG-PET scan, a serumTSH level should be obtained. If the serum
16、 TSH is subnormal,a radionuclide thyroid scan should be obtained to documentwhether the nodule is hyperfunctioning (i.e., tracer uptake isgreater than the surrounding normal thyroid), isofunctioningor warm (i.e., tracer uptake is equal to the surroundingthyroid), or nonfunctioning (i.e., has uptake
17、less than thesurrounding thyroid tissue). Since hyperfunctioning nodulesrarely harbor malignancy, if one is found that corresponds tothe nodule in question, no cytologic evaluation is necessary. Ifovert or subclinical hyperthyroidism is present, additionalevaluation is required. Higher serum TSH, ev
18、en within theupper part of the reference range, is associated with increasedrisk of malignancy in a thyroid nodule (26).e.g., a nodule found incidentallyon computed tomography (CT) or magnetic resonance im-aging (MRI) or thyroidal uptake on18FDG-PET scan.Thyroid US can answer the following questions
19、: Is theretruly a nodule that corresponds to the palpable abnormal-ity? How large is the nodule? Does the nodule have benignor suspicious features? Is suspicious cervical lymphade-nopathy present? Is the nodule greater than 50% cystic? Isthe nodule located posteriorly in the thyroid gland? Theselast
20、 two features might decrease the accuracy of FNA bi-opsy performed with palpation (27,28). Also, there maybe other thyroid nodules present that require biopsy basedon their size and appearance (18,29,30). As already noted,FNA is recommended especially when the serum TSHis elevated because, compared
21、with normal thyroid glands,the rate of malignancy in nodules in thyroid glandsinvolved with Hashimotos thyroiditis is as least as high orpossibly higher (31,32).history of external beam radiation as a child; exposure toionizing radiation in childhood or adolescence; prior hemithyroidectomy with disc
22、overy of thyroid cancer,18FDG avidity on PET scanning;MEN2=FMTC-associated RET protooncogene mutation, calcitonin 100 pg=mL. MEN, multiple endocrine neoplasia; FMTC, familial medullarythyroid cancer.bSuspicious features: microcalcifications; hypoechoic; increased nodular vascularity; infiltrative ma
23、rgins; taller than wide on transverse view.cFNA cytology may be obtained from the abnormal lymph node in lieu of the thyroid nodule.dSonographic monitoring without biopsy may be an acceptable alternative (see text) (48).eUnless indicated as therapeutic modality (see text).REVISED ATA THYROID CANCER
24、GUIDELINES 7thyroid nodule (48,51,52). In a recent study, only 1 of 360malignant nodules demonstrated this appearance (48) and inanother report, a spongiform appearance had a negative pre-dictive value for malignancy of 98.5% (52). Elastography is anemerging and promising sonographic technique that
25、requiresadditional validation with prospective studies (53).Routine FNA is not recommended for subcentimeter nod-ules. However, the presence of a solid hypoechoic nodule withmicrocalcifications is highly suggestive of PTC. Although mostmicropapillary carcinomas may be incidental findings, a sub-set
26、may be more clinically relevant, especially those 5mmindiameter (54). These include nodules that have abnormallymph nodes detected clinically or with imaging at presenta-tion (55,56). Therefore, after imaging a subcentimeter nodulewith a suspicious appearance, sonographic assessment of lat-eral neck
27、 and central neck lymph nodes (more limited due tothe presence of the thyroid) must be performed. Detection ofabnormal lymph nodes should lead to FNA of the lymph node.Other groups of patients for whom consideration of FNA of asubcentimeter nodule may be warranted include those with ahigher likeliho
28、od of malignancy (high risk history): 1) familyhistory of PTC (57); 2) history of external beam radiation ex-posure as a child (58); 3) exposure to ionizing radiation inchildhood or adolescence (59); 4) history of prior hemi-thyroidectomy with discovery of thyroid cancer; and 5)18FDG-PETpositive thy
29、roid nodules.Mixed cysticsolid nodules and predominantly cystic with50% cystic component are generally evaluated by FNA withdirected biopsy of the solid component (especially the vas-cular component.) Cyst drainage may also be performed, es-pecially in symptomatic patients.levels II and IV are above
30、 and belowlevel III, respectively. The level I node compartment includes the submental and submandibular nodes, above the hyoid bone,and anterior to the posterior edge of the submandibular gland. Finally, the level V nodes are in the posterior triangle, lateralto the lateral edge of the sternocleido
31、mastoid muscle. Levels I, II, and V can be further subdivided as noted in the figure. Theinferior extent of level VI is defined as the suprasternal notch. Many authors also include the pretracheal and paratrachealsuperior mediastinal lymph nodes above the level of the innominate artery (sometimes re
32、ferred to as level VII) in central neckdissection (166).12 COOPER ET AL.thyroid nodules present or regional or distant metastases arepresent, the patient has a personal history of radiation therapyto the head and neck, or the patient has first-degree familyhistory of DTC. Older age (45 years) may al
33、so be a criterionfor recommending near-total or total thyroidectomy evenwith tumors 1.0 cm (156). When examined sepa-rately, even patients with 1.02.0 cm tumors who underwentlobectomy, had a 24% higher risk of recurrence and a 49%higher risk of thyroid cancer mortality ( p0.04 and p1 cm, the initial
34、 surgicalprocedure should be a near-total or total thyroidectomyunless there are contraindications to this surgery. Thyroidlobectomy alone may be sufficient treatment for small(45 years, distant metastasis, and large tumor sizesignificantly predicted poor outcome on multivariate analysis(163). All-c
35、ause survival at 14 years was 82% for PTC withoutlymph node and 79% with lymph node metastases (p2to4cmT3 Primary tumor diameter 4 cm limited to the thyroid or with minimal extrathyroidal extensionT4aTumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, larynx,
36、trachea,esophagus, or recurrent laryngeal nerveT4bTumor invades prevertebral fascia or encases carotid artery or mediastinal vesselsTX Primary tumor size unknown, but without extrathyroidal invasionNO No metastatic nodesN1aMetastases to level VI (pretracheal, paratracheal, and prelaryngeal=Delphian
37、lymph nodes)N1bMetastasis to unilateral, bilateral, contralateral cervical or superior mediastinal nodesNX Nodes not assessed at surgeryMO No distant metastasesM1 Distant metastasesMX Distant metastases not assessedStagesPatient age 1.5 cm, or with residualdisease following surgery, while lower-risk
38、 patients do notshow evidence for benefit (122,159,213). The National ThyroidCancer Treatment Cooperative Study Group (NTCTCSG) re-port (214) of 2936 patients found after a median follow-up of 3years, that near-total thyroidectomy followed by RAI therapyand aggressive thyroid hormone suppression the
39、rapy pre-dicted improved overall survival of patients with NTCTCSGstage III and IV disease, and was also beneficial for patientswith NTCTCSG stage II disease. No impact of therapy wasobserved in patients with stage I disease. It should be notedthat the NTCTCSG staging criteria are similar but not id
40、en-tical to the AJCC criteria. Thus, older patients with micro-scopic extrathyroidal extension are stage II in the NTCTCSGsystem, but are stage III in the AJCC system. There are recentdata suggesting a benefit of RAI in patients with moreaggressive histologies (215). There are no prospective ran-dom
41、ized trials that have addressed this question (209). Un-fortunately, many clinical circumstances have not beenexamined with regard to the efficacy of RAI ablative therapy.Table 5 presents a framework for deciding whether RAI isworthwhile, solely based on the AJCC classification, andprovides the rati
42、onale for therapy and the strength of existingevidence for or against treatment.In addition to the major factors listed in Table 5, severalother histological features may place the patient at higher riskof local recurrence or metastases than would have been pre-dicted by the AJCC staging system. The
43、se include worrisomehistologic subtypes (such as tall cell, columnar, insular, andsolid variants, as well as poorly differentiated thyroid cancer),the presence of intrathyroidal vascular invasion, or the find-ing of gross or microscopic multifocal disease. While many ofthese features have been assoc
44、iated with increased risk, thereare inadequate data to determine whether RAI ablation has abenefit based on specific histologic findings, independent oftumor size, lymph node status, and the age of the patient.Therefore, while RAI ablation is not recommended for allpatients with these higher risk hi
45、stologic features, the pres-ence of these features in combination with size of the tumor,lymph node status, and patient age may increase the risk ofrecurrence or metastatic spread to a degree that is high en-ough to warrant RAI ablation in selected patients. However,in the absence of data for most o
46、f these factors, clinical judg-ment must prevail in the decision-making process. For mi-croscopic multifocal papillary cancer, when all foci are 4 cm even in the absence of other higherrisk features (see Table 5 for strength of evidence).(b) RAI ablation is recommended for selected patientswith 14 c
47、m thyroid cancers confined to the thyroid,Table 5. Major Factors Impacting Decision Making in Radioiodine Remnant AblationExpected benefitFactors DescriptionDecreasedrisk ofdeathDecreasedrisk ofrecurrenceMay facilitateinitial stagingand follow-upRAI ablationusuallyrecommendedStrengthofevidenceT1 1 c
48、m or less, intrathyroidal ormicroscopic multifocalNo No Yes No E12 cm, intrathyroidal No Conflicting dataaYes Selective useaIT2 24 cm, intrathyroidal No Conflicting dataaYes Selective useaCT3 4cm45 years old Conflicting data Conflicting dataaYes Selective useaCM1 Distant metastasis present Yes Yes Y
49、es Yes AaBecause of either conflicting or inadequate data, we cannot recommend either for or against RAI ablation for this entire subgroup.However, selected patients within this subgroup with higher risk features may benefit from RAI ablation (see modifying factors in the text).16 COOPER ET AL.who have documented lymph node metastases, orother higher risk features (see preceding paragraphs)when the combination of age, tumor size, lymph nodestatus, and individual histology predicts an interme-diate to high risk of recurrence or death from thyroidcancer (see Table 5 for strength
