美国内分泌协会及欧洲甲状腺协会甲状腺结节诊治指南

ENDOCRINE PRACTICE Vol 16 (Suppl 1) May/June 2010 1 AACE/AME/ETA Guidelines AMERICAN ASSOCIATION Of ClINICAl ENDOCRINOlOgISTS, ASSOCIAzIONE MEDICI ENDOCRINOlOgI, AND EuROPEAN ThyROID ASSOCIATION MEDICAl guIDElINES fOR ClINICAl PRACTICE fOR ThE DIAgNOSIS AND MANAgEMENT Of ThyROID NODulES Hossein Gharib, MD, MACP, MACE; Enrico Papini, MD, FACE; Ralf Paschke, MD; Daniel S. Duick, MD, FACP, FACE; Roberto Valcavi, MD, FACE; Laszlo Hegedüs, MD; Paolo Vitti, MD; for the AACE/AME/ETA Task Force on Thyroid Nodules* American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules are systemati- cally developed statements to assist health care professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this informa- tion in conjunction with their best clinical judgment. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances. *Task Force Committee Members are listed on the second page and in the Acknowledgment. Published as a Rapid Electronic Article in Press at http://www. endocrine practice.org on May 24, 2010. DOI: 10.4158/10024.GL © 2010 AACE. These guidelines are based on Endocr Pract. 2006 Jan-Feb;12(1):63-102. Used with permission. 2 AACE/AME/ETA Thyroid Nodule guidelines, Endocr Pract. 2010;16(Suppl 1) WRITING COMMITTEE Primary Authors Hossein Gharib, MD, MACP, MACE* Enrico Papini, MD, FACE* Ralf Paschke, MD* Daniel S. Duick, MD, FACP, FACE Roberto Valcavi, MD, FACE Laszlo Hegedüs, MD Paolo Vitti, MD AACE/AME/ETA TASK FORCE COMMITTEE MEMBERS Sofia Tseleni Balafouta, MD Zubair Baloch, MD Anna Crescenzi, MD Henning Dralle, MD Roland Gärtner, MD Rinaldo Guglielmi, MD Jeffrey I. Mechanick, MD, FACP, FACN, FACE Christoph Reiners, MD Istvan Szabolcs, MD, PhD, DSc Martha A. Zeiger, MD, FACS Michele Zini, MD *Cochairpersons. AACE/AME/ETA Thyroid Nodule guidelines, Endocr Pract. 2010;16(Suppl 1) 3 Abbreviations: AACE = American Association of Clinical Endocrinologists; AFTN = autonomously function- ing thyroid nodule; AME = Associazione Medici Endocrinologi; BEL = best evidence level; CNB = core-needle biopsy; CT = computed tomography; EL = evidence level; ETA = European Thyroid Association; FNA = fine-needle aspiration, LNB = large-needle bi- opsy; MEN 2 = multiple endocrine neoplasia type 2; MeSH = Medical Subject Headings; MNG = multi- nodular goiter; MRI = magnetic resonance imaging; MTC = medullary thyroid carcinoma; PEI = percuta- neous ethanol injection; PLA = percutaneous laser ab- lation; PTC = papillary thyroid carcinoma; RFA = ra- diofrequency ablation; rhTSH = recombinant human TSH; TPOAb = anti–thyroid peroxidase antibody; TRAb = anti–TSH-receptor antibody; TSH = thyro- tropin (thyroid-stimulating hormone); UGFNA = US- guided FNA; US = ultrasonography, ultrasonographic INTRODUCTION This document was prepared as a collabora- tive effort between the American Association of Clinical Endocrinologists (AACE), the Associazione Medici Endocrinologi (Italian Association of Clinical Endocrinologists) (AME), and the European Thyroid Association (ETA). This guideline covers diagnostic and therapeutic aspects of thyroid nodular disease but not thy- roid cancer management. The AACE protocol for standardized production of clinical practice guidelines was followed to rate the evi- dence level of each reference (on a scale of 1 to 4) and to link the guidelines to the strength of recommendations on the basis of grade designations A (action based on strong evidence) through D (action not based on any evidence or not recommended). The best evidence level (BEL), corre- sponding to the best conclusive evidence found, accom- panies the recommendation grade. All recommendations resulted from a consensus among the AACE, AME, and ETA primary writers and were influenced by input from the Task Force members and reviewers. Some recommenda- tions were upgraded or downgraded on the basis of expert opinion. In these cases, subjective factors such as clinical experience, cost, risks, and regional availability of specific technologies and expertise took priority over the reported BEL. The use of high-resolution ultrasonography (US), sen- sitive thyrotropin (TSH) assay, and fine-needle aspiration (FNA) biopsy is the basis for management of thyroid nod- ules. Thyroid scintigraphy is not necessary for diagnosis in most cases. However, it may be warranted in patients with a low serum TSH value or a multinodular gland to detect functional autonomy, most common in iodine-defi- cient areas. Measurement of serum TSH is the best initial laboratory test of thyroid function and should be followed by measurement of free thyroxine and triiodothyronine if the TSH value is decreased, and measurement of anti–thy- roid peroxidase antibodies (TPOAb) if the TSH value is above the reference range. A single, nonstimulated calcito- nin measurement can be used in the initial workup of thy- roid nodules and is recommended before thyroid nodule surgery. Although thyroid nodules are a common incidental finding, US should not be performed as a screening test. Most patients with thyroid nodules are asymptomatic, but the absence of symptoms does not rule out malignancy; thus, clinical and US risk factors for malignant disease should always be reviewed. All patients with a palpable thyroid nodule or with clinical risk factors should undergo US examination. Thyroid FNA biopsy is best performed under US guid- ance because of the increase in diagnostic accuracy of the procedure. US-guided FNA (UGFNA) biopsy is recom- mended for nodules smaller than 10 mm if clinical infor- mation or US features are suspicious. Cytologic smears or liquid-based cytology should be interpreted by a patholo- gist with specific experience. A classification scheme in 5 cytologic diagnostic categories is recommended for the cytologic report: nondiagnostic, benign, follicular lesion, suspicious, or malignant. Currently, no single cytochemi- cal or genetic marker is specific and sensitive enough to re- place the morphologic diagnosis of follicular lesion or sus- picious for neoplasm. However, use of these markers may be considered in selected cases. Hormone determination on washout from FNA biopsy may increase the diagnos- tic accuracy of FNA biopsy in suspicious node metastasis or hyperplastic parathyroid glands. US-guided core-needle biopsy should be reserved for patients with neck masses and uncertain FNA biopsy diagnosis. Patients with benign thyroid nodules should undergo clinical and US follow-up. Symptomatic goiters, whether euthyroid or hyperthyroid, may be treated surgically or with radioiodine. Although we do not recommend rou- tine levothyroxine suppressive therapy, it may be consid- ered for small nodular goiters in young patients living in iodine-deficient regions. Percutaneous ethanol injection is useful in the treatment of benign cystic thyroid lesions. Symptomatic patients with benign nodules who decline surgery or who are at surgical risk may benefit from US- guided thermal ablation. Malignant or suspicious nodules should be treated surgically. Preoperative evaluation with US and UGFNA biopsy is recommended for appropriate surgical planning. Suggestions for thyroid nodule management during pregnancy and childhood are also presented. 4 AACE/AME/ETA Thyroid Nodule guidelines, Endocr Pract. 2010;16(Suppl 1) 1. THYROID NODULES: THE SCOPE OF THE PROBLEM Thyroid nodules are a common clinical finding, with an estimated prevalence on the basis of palpation that ranges from 3% to 7% (1,2). The prevalence of clinically inapparent thyroid nodules is estimated with US at 20% to 76% in the general population, with a prevalence similar to that reported from autopsy data (3-5). Moreover, 20% to 48% of patients with 1 palpable thyroid nodule are found to have additional nodules on US investigation (5,6). Thyroid nodules are more common in elderly persons, in women, in those with iodine deficiency, and in those with a history of radiation exposure. The estimated annual incidence rate of 0.1% in the United States suggests that 300 000 new nod- ules are detected in this country every year (7,8). This guideline covers diagnostic and therapeutic as- pects of thyroid nodular disease but does not cover thyroid cancer management. 2. CLINICAL EVALUATION AND DIAGNOSIS 2.1. History and Physical Examination Both benign and malignant disorders can cause thy- roid nodules (Box 1) (9). Hence, the clinical importance of newly diagnosed thyroid nodules is primarily the exclusion of malignant thyroid lesions (6,10) (Box 2). In iodine-de- ficient areas, however, local symptoms, functional auton- omy, and hyperthyroidism are common clinical problems (11). 2.1.1. History During examination, patients should be asked about a family history of benign or malignant thyroid disease. Familial medullary thyroid carcinoma (MTC), multiple en- docrine neoplasia type 2 (MEN 2), familial papillary thy- roid tumors, familial polyposis coli, Cowden disease, and Gardner syndrome should be considered (12-14). Previous disease or treatments involving the neck (head and neck irradiation during childhood), recent preg- nancy, and rapidity of onset and rate of growth of the neck swelling should be documented. Presence of thyroid nod- ules during childhood and adolescence should induce cau- tion because the malignancy rate is 3- to 4-fold higher than in adult patients (15). The risk of thyroid cancer is also higher in older persons and in men (3,9). 2.1.2. Symptoms and Signs Most patients with thyroid nodules have few or no symptoms, and usually no clear relationship exists be- tween nodule histologic features and the reported symp- toms. Thyroid nodules are often discovered incidentally on physical examination, color Doppler evaluation of the carotid artery, or imaging studies performed for unrelated reasons (16). In symptomatic patients, a detailed history and a com- plete physical examination may guide the selection of ap- propriate clinical and laboratory investigations. Slow but progressive growth of the nodule (during weeks or months) is suggestive of malignant involvement. Sudden pain is commonly due to hemorrhage in a cystic nodule. In patients with progressive and pain- ful enlargement of a thyroid nodule, however, anaplastic carcinoma or primary lymphoma of the thyroid should be considered (17). Symptoms such as a choking sensation, cervical tenderness or pain, dysphagia, or hoarseness may be perceived as attributable to thyroid disease, but in most patients, these symptoms are caused by nonthyroid disor- ders. Slow-onset cervical symptoms and signs caused by the compression of vital structures of the neck or upper thoracic cavity usually occur if thyroid nodules are embed- ded within large goiters. When observed in the absence of a multinodular goiter (MNG), the symptoms of tracheal compression (cough and dysphonia) suggest an underlying malignant lesion. Surgical treatment should be considered in patients with growth of a thyroid mass and vocal cord paresis even if cytologic results are negative for malig- nancy (18,19). Differentiated thyroid carcinomas rarely cause airway obstruction, vocal cord paralysis, or esopha- geal symptoms at their clinical presentation. Hence, the absence of local symptoms does not rule out a malignant tumor (20). Small differentiated thyroid cancers are frequently devoid of alarming characteristics on physical evaluation (21-23). However, a firm or hard, solitary or dominant thy- roid nodule that clearly differs from the rest of the gland suggests an increased risk of malignant involvement (17). Therefore, despite the low predictive value of palpation (23,24), a careful inspection and palpation of the thyroid Box 1 Causes of Thyroid Nodules Benign nodular goiter Chronic lymphocytic thyroiditis Simple or hemorrhagic cysts Follicular adenomas Subacute thyroiditis Papillary carcinoma Follicular carcinoma Hürthle cell carcinoma Poorly differentiated carcinoma Medullary carcinoma Anaplastic carcinoma Primary thyroid lymphoma Sarcoma, teratoma, and miscellaneous tumors Metastatic tumors AACE/AME/ETA Thyroid Nodule guidelines, Endocr Pract. 2010;16(Suppl 1) 5 gland and the anterior and lateral nodal compartments of the neck should always be done (Box 2). Suppressed or low levels of thyrotropin (thyroid-stim- ulating hormone; TSH) are associated with a decreased probability of malignancy (25), and autonomously func- tioning thyroid nodules (AFTNs) in adults need no further cytologic evaluation because the incidence of malignancy is exceedingly low (26). Hyperfunctioning MNGs, how- ever, may harbor both hyperfunctioning areas and cold (potentially malignant) lesions (22). Nodules appearing in patients with Graves disease or Hashimoto thyroiditis should be managed in the same way as in any other patients (27). 2.2. Thyroid Incidentaloma Thyroid lesions discovered on computed tomography (CT) or magnetic resonance imaging (MRI) performed for other reasons have an uncertain risk of malignancy and should undergo US evaluation before considering evalua- tion with FNA biopsy (28,29). Nodules are detected infre- quently by 18F-fluorodeoxyglucose positron emission to- mography, but when found have a high risk of malignancy (30,31). Such lesions should undergo focused US evalua- tion followed by FNA biopsy. Focal lesions detected by technetium Tc 99m sesta- mibi scans have a high risk of malignancy (32) and should be evaluated by US. 2.3. Key Recommendations 2.3.1. History • Record the following information (Grade B; BEL 2): o Age o Family history of thyroid disease or cancer o Previous head or neck irradiation o Rate of growth of the neck mass o Dysphonia, dysphagia, or dyspnea o Symptoms of hyperthyroidism or hypothyroidism o Use of iodine-containing drugs or supplements • Most nodules are asymptomatic, and absence of symptoms does not rule out malignancy (Grade C; BEL 3) 2.3.2. Physical Examination • A careful physical examination of the thyroid gland and cervical lymph nodes is mandatory (Grade A; BEL 3) • Record (Grade C; BEL 3): o Location, consistency, and size of the nodule(s) o Neck tenderness or pain o Cervical adenopathy • The risk of cancer is similar in patients with a solitary nodule or with MNG (Grade B; BEL 2) 3. US AND OTHER DIAGNOSTIC IMAGING STUDIES 3.1. When to Perform Thyroid US High-resolution US is the most sensitive test avail- able to detect thyroid lesions, measure their dimensions, identify their structure, and evaluate diffuse changes in the thyroid gland (33,34). If results of palpation are normal, US should be per- formed when a thyroid disorder is suspected on clinical grounds or if risk factors have been recognized (Box 2). The physical finding of suspicious neck adenopathy war- rants US examination of both lymph nodes and thyroid gland because of the risk of a metastatic lesion from an otherwise unrecognized papillary microcarcinoma (35). In all patients with palpable thyroid nodules or MNGs, US should be performed to accomplish the following: • Help with the diagnosis in difficult cases (as in chronic lymphocytic thyroiditis) Box 2 Factors Suggesting Increased Risk of Malignant Potential History of head and neck irradiation Family history of medullary thyroid carcinoma, multiple endocrine neoplasia type 2, or papillary thyroid carcinoma Age <14 or >70 years Male sex Growing nodule Firm or hard consistency Cervical adenopathy Fixed nodule Persistent dysphonia, dysphagia, or dyspnea 6 AACE/AME/ETA Thyroid Nodule guidelines, Endocr Pract. 2010;16(Suppl 1) • Look for coincidental thyroid nodules or diffuse thyroid gland changes • Detect US features suggestive of malignant growth and select the lesions to be recommended for FNA biopsy • Choose the gauge and length of the biopsy needle • Obtain an objective measure of the baseline vol- ume of the thyroid gland and of lesions that will be assigned to follow-up or medical therapy Standardized US reporting criteria should be fol- lowed, indicating position, shape, size, margins, content, and echogenic and vascular pattern of the nodule. Nodules with malignant potential should be carefully described. 3.2. US Criteria for FNA Biopsy of Palpable Nodules The risk of cancer is not significantly higher for pal- pable solitary thyroid nodules than for multinodular glands or nodules embedded in diffuse goiters (22,23). Moreover, in 50% of thyroid glands with a “solitary” nodule on the basis of palpation, other small nodules are discovered by US (24). For MNGs, the cytologic sampling should be fo- cused on lesions with suspicious US features rather than on larger or clinically dominant nodules (34,36). US and color Doppler features have varying abili- ties to predict the risk of malignancy. The reported speci- ficities for predicting malignancy are 41.4% to 92.2% for marked hypoechogenicity, 44.2% to 95.0% for microcalci- fications (small, intranodular, punctate, hyperechoic spots with scanty or no posterior acoustic shadowing), 48.3% to 91.8% for irregular or microlobulated margins, and about 80% for chaotic arrangement or intranodular vascular im- ages (37,38). The value of these features for predicting cancer is partially blunted by the low sensitivities, how- ever, and no US sign independently is fully predictive of a malignant lesion (21). A rounded appearance or a “more tall (anteroposterior) than wide (transverse)” shape of the nodule is an additional US pattern suggestive of malignant potential (39,40). The coexistence of 2 or more suspicious US criteria greatly increases the risk of thyroid cancer (21,39-41). Large neoplastic lesions may be characterized by de- generative changes and multiple fluid-filled areas, findings rarely noted in microcarcinomas. Although most complex thyroid nodules with a dominant fluid component are be- nign, UGFNA biopsy should always be performed because papillary thyroid carcinoma (PTC) can be partially cystic (42). Extension of irregular hypoechoic lesions beyond the thyroid capsule, invasion of prethyroid muscles, and infil- tration of the recurrent laryngeal nerve are infrequent but threatening US findings that demand immediate cytologic assessment (34). The presence of enlarged lymph nodes with no hilum, cystic changes, and microcalcifications is highly suspicious (43,44). Rounded appearance and chaotic hypervascular- ity are more common but less specific findings (44). Such nodes and any coexistent thyroid nodules, whatever their size, always warrant UGFNA biopsy. 3.3. US Criteria for FNA Biopsy of Impalpable Nodules and Nodular Goiters Clinically inapparent thyroid lesions were detected by US in about half of the women in several studies (2,8). The prevalence of cancer reported for nonpalpable thyroid le- sions ranges from 5.4% to 7.7% (21,37,45) and appears to be similar to that reported for palpable lesions (5.0%- 6.5%) (22,37,44-46). Clinical criteria for a malignant nod- ule are lacking for most nonpalpable lesions (20). Hence, it is essential to determine which thyroid lesions have a high malignant potential on the basis of their US features. The US c