Fine-needle Aspiration Biopsy
Fine-needle aspiration biopsy (FNAB) has become the cornerstone in the evaluation of solitary thyroid nodules and dominant nodules within multinodular goiters.[1] It is a procedure that requires skill and experience by the individual who performs the procedure, as well as by the cytopathologist who interprets the aspirate. If the procedure is done properly, it should have a false-negative rate of less than 5% and a false-positive rate of approximately 1%.[2] Generally, 1 of 4 types of interpretations may be reported, although the nomenclature of classification may vary among institutions: (1) benign, (2) malignant, (3) suspicious for a follicular or Hürthle cell tumor, and (4) insufficient for a diagnosis. If the lesion is either clearly benign or malignant, the management strategy is relatively straightforward. If there is insufficient material for diagnosis, a repeated FNAB should be considered. Insufficient biopsy findings may be owing to poor biopsy technique or cytologic preparations or to the presence of cyst fluid. Even in skilled hands, however, approximately 10% of biopsy findings are nondiagnostic.
A diagnosis of a follicular or Hürthle cell tumor requires further evaluation and management, since the cytologic features of benign follicular or Hürthle cell tumors and low-grade follicular or Hürthle cell cancer are similar.[3] The 2 entities can only be distinguished by the presence or absence of capsular or vascular invasion on histologic examination of surgical specimens. Follicular and Hürthle cell tumors, diagnosed by using FNAB, have a malignancy rate of 10% to 20%.
Blood Tests
Patients with a nodular goiter should have their serum thyrotropin (thyroid-stimulating hormone) concentrations measured in an assay that is sensitive enough to differentiate among euthyroid, hypothyroid (elevated thyrotropin level), and hyperthyroid (suppressed thyrotropin level) states. If the thyrotropin level is elevated, a serum antithyroperoxidase level (formerly called antimicrosomal antibody) may be obtained to confirm Hashimoto thyroiditis, although a neoplasm may coexist as an independent lesion. If the thyrotropin level is suppressed, a measurement of free thyroxine or its estimate should be obtained to document the presence and degree of hyperthyroidism. If the free thyroxine (estimate) is normal and the thyrotropin level is suppressed, a serum total triiodothyronine (T3) or free T3 (estimate) may be obtained to rule out "T3 toxicosis." A suppressed thyrotropin level, with or without an elevation in free thyroxine or free T3, suggests that the thyroid nodule is benign, but an iodine 123-labeled scan should be performed to confirm the presence of a hyperfunctioning ("hot") nodule, since a hypofunctioning nodule may coexist in the context of underlying hyperthyroidism.
If there is a family history of medullary thyroid cancer (MTC) or MEN II, a basal serum calcitonin level should be obtained, and if it is elevated, MTC is probably present. In such patients, the presence of a pheochromocytoma should also be excluded. If the family history is noncontributory, routine serum calcitonin measurements are not cost-effective, nor are serum thyroglobulin (Tg) measurements, which do not discriminate between benign and malignant disease.
Imaging of the Thyroid Gland
Radionuclide Scans. Iodine 123 or technetium Tc 99m pertechnetate are useful imaging agents for thyroid nodules, although most specialists who treat patients with thyroid disease prefer iodine 123. While nodules that are hyperfunctioning with iodine 123 and technetium Tc 99m pertechnetate are almost invariably benign, such lesions constitute less than 10% of all nodules. An occasional nodule that is functioning with technetium Tc 99m pertechnetate will be hypofunctioning with iodine 123. Therefore, all nodules that are hot with technetium Tc 99m pertechnetate should be rescanned with iodine 123. Nodules that are either hypofunctioning or eufunctioning with iodine 123 or technetium Tc 99m pertechnetate also are usually benign, but malignancy cannot be excluded. Thus, with the exception of hyperfunctioning nodules, the thyroid scan will not help to differentiate benign from malignant lesions. For this reason, many endocrinologists no longer advocate obtaining thyroid scans as part of the routine initial evaluation of a nodular goiter, and they prefer to perform an FNAB first. However, there are circumstances in which the thyroid scan is useful, including (1) determining if a nodule in a hyperthyroid patient (eg, Graves disease or multinodular goiter) is functioning, since functioning lesions are rarely malignant; (2) determining the functional status of a nodule that has been shown to be a follicular neoplasm by using FNAB; and (3) differentiating the functional status of nodules in a multinodular goiter. In addition, the radionuclide thyroid scan may be helpful when findings on palpation may be difficult to characterize, especially if there is some question about multinodularity, thyroid gland irregularity, or substernal extension.
Ultrasonography. Ultrasonography of the thyroid gland has been commonly used in the initial evaluation of a nodular goiter, but it does not differentiate between benign and malignant lesions. Pure simple cysts are usually benign, but since a vast majority of nodules are solid or have solid components on ultrasonography, the routine use of this procedure generally does not add significant information in easily palpable lesions. It may be useful, however, in selected patients who are undergoing an FNAB (eg, those with complex cysts, those with lesions that are difficult to palpate, or those whose cysts or lesions have been detected fortuitously by using other imaging procedures). Ultrasonography of the thyroid gland also may have utility if there is some question with regard to multinodularity. However, nonpalpable single or multiple nodules (size, <1 cm) that are detected only by using ultrasonography usually have a benign clinical course and generally do not require further evaluation but may be followed with ultrasonography at periodic intervals. Some clinicians suggest that ultrasound examinations should be obtained in individuals with a history of head or neck irradiation.
Other Imaging Modalities. Other imaging tests (eg, computed tomography or magnetic resonance imaging) have virtually no role in the initial evaluation of the patient with a thyroid nodule. Computed tomography or magnetic resonance imaging may be helpful, however, in determining the extent of a substernal goiter or the presence or degree of tracheal compression.
