AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS (AACE), ASSOCIAZIONE MEDICI ENDOCRINOLOGI (AME), AND EUROPEAN THYROID ASSOCIATION (ETA) MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND MANAGEMENT OF THYROID NODULES

Abstract

This document was prepared as a collaborative effort between the American Association of Clinical Endocrinologists (AACE), the 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 thyroid cancer management. The AACE protocol for standardized production of clinical practice guidelines was followed to rate the evidence 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), corresponding to the best conclusive evidence found, accompanies the recommendation grade. All AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS (AACE), ASSOCIAZIONE MEDICI ENDOCRINOLOGI (AME), AND EUROPEAN THYROID ASSOCIATION (ETA) MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND MANAGEMENT OF THYROID NODULES a Hossein Gharib, Enrico Papini, Ralf Paschke, Daniel S. Duick, Roberto Valcavi, Laszlo Hegedus, Paolo Vitti, and the AACE/AME/ETA Task Force on Thyroid Nodules (see Appendix) Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota; Endocrinology and Metabolism Unit, Regina Apostolorum Hospital, Albano, Rome, Italy; Medizinische Klinik, Universitat Leipzig, Leipzig, Germany; Endocrinology Association, Phoenix, Arizona; Endocrine Unit, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark; Department of Endocrinology, University of Pisa, Pisa, Italy. Hot Thyroidol. 4/10 Gharib et al, 2 Online ISSN: 2075-2202 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 recommendations 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), sensitive thyrotropin (TSH) assay, and fine-needle aspiration (FNA) biopsy is the basis for management of thyroid nodules. 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-deficient 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 of anti–thyroid peroxidase antibodies if the TSH value is above the normal range. A single, nonstimulated calcitonin measurement can be used in the initial work-up of thyroid 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 guidance because of the increase in diagnostic accuracy of the procedure. US-guided FNA (UGFNA) biopsy is recommended for nodules <10 mm if clinical information or US features are suspicious. Cytologic smears or liquid-based cytology should be interpreted by a pathologist 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 cytochemical or genetic marker is specific and sensitive enough to replace the morphologic diagnosis of follicular lesion or suspicious for neoplasm. However, use of these markers may be considered in selected cases. Hormone determination on washout from FNA biopsy may increase the diagnostic 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 routine levothyroxine suppressive therapy, it may be considered 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. Hot Thyroidol. 4/10 Gharib et al, 3 Online ISSN: 2075-2202 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. Key-words and abbreviations: AFTN = autonomously functioning thyroid nodule; BEL = best evidence level; CNB = core-needle biopsy; CT = computed tomography; EL = evidence level; FNA = fine-needle aspiration; LNB = large-needle biopsy; MEN2 = multiple endocrine neoplasia type 2; MeSH = Medical Subject Headings; MNG = multinodular goiter; MRI = magnetic resonance imaging; MTC = medullary thyroid carcinoma; PEI = percutaneous ethanol injection; PLA = percutaneous laser ablation; PTC = papillary thyroid carcinoma; RFA = radiofrequency ablation; rhTSH = recombinant human TSH; TPOAb = anti–thyroid peroxidase antibody; TRAb = anti–TSH-receptor antibody; TSH = thyrotropin (thyroid-stimulating hormone); UGFNA = US-guided FNA; US = ultrasonography, ultrasonographic