Thyroid nodules are a common clinical condition. In 1996, the American Thyroid Association (ATA) issued guidelines for the treatment of thyroid nodules and thyroid cancer, and in the past decade, much more recent evidence has emerged regarding the diagnosis and treatment of thyroid nodules and differentiated thyroid cancer. In response, the ATA appointed a task force to reconsider the current clinical management strategies for these two diseases and to develop a new version of the clinical guidelines based on the principles of evidence-based medicine. Thyroid nodules A thyroid nodule is an isolated, palpable lesion within the thyroid gland that can be distinguished from surrounding thyroid tissue by ultrasonography. Some palpable lesions do not have corresponding imaging abnormalities, while other nonpalpable thyroid nodules are readily detected on ultrasound or other imaging analysis that reveals anatomical structures. Nonpalpable nodules have the same probability of malignancy as palpable nodules of the same size. In general, only nodules >1 cm in diameter need to be evaluated because of their potential for malignancy. Nodules <1 cm in diameter should also be evaluated when ultrasound findings are suspicious, or when the patient has a history of head and neck radiation exposure, or a positive family history of thyroid cancer. Once a patient is found to have a thyroid nodule, a complete medical history should be collected and a detailed examination of the thyroid gland and adjacent cervical lymph nodes should be performed. Some relevant medical histories, such as history of head, neck, or total body radiation exposure for bone marrow transplantation, family history of thyroid cancer in a first-degree relative, rapid growth of the mass, and hoarseness, are indicative of malignant nodules. Vocal cord paralysis, enlarged cervical lymph nodes on the same side of the nodule and relative fixation with surrounding tissues also indicate that the nodule may be malignant. When a thyroid nodule is >1 cm in diameter, serum thyroid stimulating hormone (TSH) levels should be checked. If TSH is low, a radionuclide thyroid scan should be performed to determine whether the nodule is functional, isofunctional (“warm nodules”), or nonfunctional. Functional nodules are rarely malignant; therefore, cytologic evaluation of such nodules is not necessary. If serum TSH is not suppressed, a diagnostic thyroid ultrasound should be performed, which will help to clarify such questions as: whether a nodule consistent with a palpable lesion is indeed present, whether the cystic portion of the nodule is >50%, and whether the nodule is located in the posterior aspect of the thyroid. The latter two conditions reduce the accuracy of fine-needle aspiration biopsy (FNA). FNA is recommended even if TSH is elevated because the rate of malignancy in normal thyroid tissue is similar to that of nodules in tissue involved in Hashimoto’s thyroiditis. Serum thyroglobulin levels are elevated in most thyroid disorders and this indicator is neither sensitive nor specific for thyroid cancer. Serum calcitonin is a meaningful indicator, and routine testing of serum calcitonin may improve the overall survival of such patients by early detection of parathyroid cell hyperplasia and medullary thyroid carcinoma. Serum calcitonin >100 pg/ml in the unstimulated setting suggests the possibility of medullary thyroid cancer. FNA is the most accurate and has the highest efficacy ratio for the evaluation of thyroid nodules. Traditionally, FNA biopsy results are classified into four categories: inconclusive, malignant, indeterminate (or suspicious for new organisms), and benign. Indeterminate refers to biopsy results that do not meet specific existing diagnostic criteria, in which case a repeat biopsy under ultrasound guidance is required. Some cystic nodules that are consistently undiagnosed on the basis of cytologic findings during repeated biopsies are likely to be diagnosed as malignant at the time of surgery. The risk of malignancy in multiple thyroid nodules is the same as in isolated nodules. Ultrasonography should be performed to determine the morphology of the multiple nodules. If only the “dominant” nodule or the largest nodule is biopsied by needle aspiration, thyroid cancer may be missed. If the ultrasound shows a solid nodule with microcalcifications, hypoechogenicity, and an abundant blood supply between the nodules, the nodule is likely to be malignant. Even if a thyroid nodule is diagnosed as benign, patients need to be followed up because the false negative rate of FNA can be up to 5%, which is a small but not negligible percentage of patients. Benign nodules become smaller in diameter, while malignant nodules increase in size, albeit slowly. Nodule growth itself is not an indication for malignant lesions, but it is an indication for a repeat biopsy. Initial treatment of differentiated thyroid cancer The fundamental treatment of differentiated thyroid cancer is aimed at: 1. Removal of the primary tumor, the diseased tissue that has spread outside the thyroid envelope, and the involved cervical lymph nodes. 2. To reduce the rate of disability associated with treatment and disease. 3.Precise staging of the tumor. 4.Easy to perform 131I radiotherapy at the appropriate time after surgery. 5.It is convenient for physicians to accurately monitor the recurrence of the disease in the long term after surgery. 6.It is beneficial to control the risk of tumor recurrence and metastasis to the minimum. It is known by standard pathological examination that 20% to 50% of patients with differentiated thyroid cancer (especially papillary carcinoma) have cervical lymph node involvement, even if the primary tumor is small or confined to the thyroid gland. Postoperative ultrasonography can detect suspicious lymph nodes in the neck in 20% to 31% of patients, and surgical options may be altered as a result. Accurate staging of the tumor is essential both to determine prognosis and to guide treatment; however, unlike other tumors, the presence of metastases does not mean that the primary site of differentiated thyroid cancer cannot be removed. Metastatic foci are sensitive to 131I radiotherapy, therefore, even if metastatic foci are present, the primary thyroid tumor and the surrounding tissues that may be involved should be removed during initial treatment. Surgical options for thyroid cancer include thyroid lobectomy, subtotal thyroidectomy [removal of most of the visible thyroid tissue with only a small amount of tissue (approximately 1 g) around the area where the recurrent laryngeal nerve enters the cricothyroid muscle] and total thyroidectomy (removal of all visible thyroid tissue). Subtotal thyroidectomy with preservation of the posterior thyroid tissue (>1 g) on the side of the lesion is not indicated for the treatment of thyroid cancer. Subtotal or total thyroidectomy is recommended if: (i) the tumor is >1 cm in diameter; (ii) there are thyroid nodules on the opposite side of the tumor; (iii) there are local or distal metastases; (iv) the patient has a history of head and neck radiation therapy; (v) the patient has a first-degree relative with a history of differentiated thyroid cancer. Patients who are older (>45 years old) have a higher recurrence rate, and the above procedure is also recommended. Local lymph node metastasis is present in 20% to 90% of patients with papillary thyroid cancer at the time of diagnosis, while the metastasis rate is lower in patients with other types of tumors. Bilateral central (zone VI) lymph node dissection may improve survival and reduce the rate of lymph node recurrence. Total thyroidectomy should be performed if the thyroid lobe is removed due to an undiagnosed diagnosis or if a non-diagnostic biopsy confirms a malignant lesion. Total thyroidectomy should be performed in patients with multiple thyroid cancers to ensure complete removal of the lesion and to prepare for 131I radiotherapy. American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) TNM staging Postoperative staging of thyroid cancer can be used to: (1) determine the individual prognosis of patients with differentiated thyroid cancer; (2) guide postoperative adjuvant therapy, including 131I radiotherapy and TSH suppressive therapy, to reduce the recurrence rate and mortality of patients; (3) determine the timing and frequency of follow-up, with more intensive follow-up for high-risk patients; and (4) help patients and their physicians follow-up; and ④ help patients communicate better with their physicians. The AJCC/UICC classification system based on TNM parameters is applicable to all types of tumors, including thyroid cancer, because it provides an effective and convenient way to describe the extent of tumors. This classification scheme takes into account a number of predictors of regression, the most meaningful of which are the presence of distant metastases, patient age and tumor extent.