The Figure outlines a suggested strategy for the evaluation and management of thyroid nodules. An iodine 123-tagged scan may be helpful when a follicular neoplasm has been found on FNAB, since benign hyperfunctioning nodules may be cytologically indistinguishable from nonfunctioning benign follicular neoplasms and follicular cancer.[1] As noted earlier, hyperfunctioning nodules are almost never malignant.
Patients with thyroid nodules in whom malignancy has been excluded or determined to be improbable require long-term periodic clinical observation with judicious use of laboratory tests, imaging procedures, needle biopsy, and levothyroxine sodium suppression therapy. The goals of follow-up are (1) to recognize progressive enlargement that could result in local compressive complications or cosmetic concerns or may also be signs of malignancy, (2) to diagnose associated clinical or subclinical thyroid dysfunction, and (3) to identify patients in whom there may be an undiagnosed or subsequent thyroid malignant neoplasm.
Periodic assessment should include a history that is focused to identify (1) progressive nodule or goiter enlargement; (2) local compressive and invasive symptoms (ie, dysphagia, dyspnea, cough, pain, hoarseness); (3) other local neck, pulmonary, or skeletal symptoms that would suggest metastatic disease from an undetected thyroid malignant neoplasm; and (4) symptoms that would suggest hyperthyroidism or hypothyroidism, particularly in individuals with functioning adenomas or Hashimoto thyroiditis, respectively.
Follow-up should also include a physical examination that is relevant to the patient's clinical status. The size of the nodule or gland should be quantified and recorded, and evidence of tracheal deviation or regional lymphadenopathy should also be recorded.
The frequency of periodic clinical assessments can and should vary both among patients and over time, from as often as weekly (rarely necessary) to as infrequently as every other year. Factors that govern the frequency of follow-up visits include (1) the degree of diagnostic certainty that the thyroid nodule or goiter is benign, (2) the level of confidence that the nodule or goiter is stable in size, (3) the likelihood of subsequent development of thyroid dysfunction, and (4) the presence of other medical conditions that are potentially complicated by the thyroid disorder.
Typically, relatively few diagnostic tests are needed to manage most patients with thyroid nodules and goiter that are previously thought to be benign. Serial imaging procedures should generally be limited to patients in whom the lesions cannot be readily palpated and in whom the size of the nodule cannot be reliably determined by palpation. In these circumstances, thyroid ultrasonography for lesions that are limited to the neck, and either computed tomography (preferably without contrast) or magnetic resonance imaging for goiters that are located substernally, may be required. Radionuclide scanning is relatively imprecise for the assessment of the size of the nodule or goiter, although there may be a limited role for radionuclide scans to define the function of newly appearing nodules.
Periodic thyroid function testing is necessary in patients with functioning adenomas, multinodular goiters, or coexistent autoimmune thyroiditis. The serum thyrotropin measurement, in an assay with a functional sensitivity of 0.1 mU/L or less, is the most sensitive test to identify individuals with thyroid dysfunction. Periodic serum thyrotropin measurements are also indicated in patients who are treated with levothyroxine. Serial monitoring of serum antithyroid antibody levels is not useful. During the course of follow-up, repeated FNAB may be appropriate to reassess thyroid nodules or goiters under several circumstances as follows: (1) when the lesion continues to enlarge or fails to decrease in size with thyrotropin suppressive therapy; (2) when new clinical features develop that suggest possible malignancy; (3) when the previous cytologic diagnosis was indeterminate, or (4) when there is insufficient material for cytologic diagnosis. Routine repetitive FNAB of lesions that were previously shown to be benign is rarely indicated.
Some patients with benign nodules may benefit from thyrotropin-suppressive therapy with levothyroxine, which may shrink some lesions and prevent progressive enlargement in others.[5] The appropriate duration of thyrotropin-suppressive therapy can vary widely. For some individuals, lifelong thyroid hormone therapy may be justifiable. Regardless of the duration of previous treatment, patients who are taking levothyroxine for thyrotropin suppression should be reevaluated clinically and with a sensitive thyrotropin measurement. Ultrasonography of the thyroid gland may be helpful in determining a change in the size of the nodule, especially with lesions that are difficult to palpate. The potential benefits and risks of therapy should be reassessed at least annually.
