You are in: eMedicine Specialties > Endocrinology > Thyroid Thyroid NoduleArticle Last Updated: Sep 20, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 7
  Author: Steven K Dankle, MD, Clinical Associate Professor, Department of Otolaryngology, Medical College of Wisconsin Steven K Dankle is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Medical Association, and State Medical Society of Wisconsin Editors: Steven R Gambert, MD, Program Director, Physician-in-Chief, Professor, Department of Internal Medicine, Sinai Hospital, Johns Hopkins University School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Don S Schalch, MD, Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics; Mark Cooper, MD, Head, Vascular Division, Baker Medical Research Institute; Professor of Medicine, Monash University; George T Griffing, MD, Professor of Medicine, Director of General Internal Medicine, St Louis University Author and Editor Disclosure Synonyms and related keywords: colloid nodule, degenerative cyst, hyperplasia, thyroiditis, benign neoplasm, malignancy, malignant thyroid nodule, Hashimoto thyroiditis, Hashimoto's thyroiditis, hypothyroidism, hyperthyroidism, thyroid-stimulating hormone, TSH, fine-needle aspiration biopsy, FNAB BACKGROUNDSection 2 of 7
  Nodular disease of the thyroid gland is prevalent in the United States. The lifetime risk for developing a palpable thyroid nodule is estimated to be 5-10%, and the condition affects more women than men. In general, nodular disease of the thyroid is common; however, malignancy of the thyroid occurs in only 0.004% of the American population annually (12,000 new cases per y). Roughly 5% of thyroid nodules are malignant; the remainder represent a variety of benign diagnoses, including colloid nodules, degenerative cysts, hyperplasia, thyroiditis, or benign neoplasms. A rational approach to management of a thyroid nodule is based on the clinician's ability to distinguish the more common benign diagnoses from malignancy in a highly reliable and cost-effective manner. CLINICAL OUTLINESection 3 of 7
A comprehensive history and physical examination provides the foundation for decision making in the management of thyroid nodules. A number of features in the patient's history and physical examination significantly influence the statistical probability of malignancy in a thyroid nodule. Factors suggesting a malignant diagnosis include the following:
Factors suggesting a benign diagnosis include the following:
Of importance, the factors mentioned above are only guidelines to assist in decision-making, and they do not provide absolute diagnostic information. For example, a historical axiom is that a multinodular goiter without a dominant nodule or a solitary cyst suggests a benign diagnosis. Data from contemporary studies, including those incorporating image-guided fine-needle aspiration biopsy (FNAB), have raised questions about this axiom. Furthermore, the sonographic size of a solid thyroid nodule may have some diagnostic importance because nodules larger than 3 cm are thought to have an increased risk of malignancy. However, recent findings suggest that nonpalpable nodules (incidentalomas) incidentally found on high-resolution ultrasonography may have a risk of malignancy comparable to that of palpable nodules. DIAGNOSTIC WORKUPSection 4 of 7
The most important laboratory test is a sensitive thyroid-stimulating hormone (TSH) assay, which is used to screen for hypothyroidism or hyperthyroidism. In addition, obtaining serum thyroxine (T4) and triiodothyronine (T3) levels may be helpful (eg, when TSH levels are low-normal or high-normal). In most cases of solitary thyroid nodules, the TSH level is normal. In cases of a solitary thyroid nodule with a normal TSH value, no additional laboratory studies may be required in the diagnostic evaluation unless autoimmune disease (eg, Hashimoto thyroiditis) is suspected. When the patient's history and physical findings reveal a family history or raise clinical suspicion for Hashimoto thyroiditis, obtain serum antithyroid peroxidase (anti-TPO) antibody and antithyroglobulin (anti-Tg) antibody levels. A diagnosis of Hashimoto thyroiditis does not exclude the possibility of malignancy. Additional laboratory studies are unnecessary in the routine initial diagnostic evaluation of a solitary thyroid nodule.
Thyroid scintigraphy In most centers, the routine initial diagnostic evaluation of a solitary thyroid nodule no longer includes imaging studies. In the past, radionuclide scanning was an important imaging study performed routinely in the initial assessment of a thyroid nodule. Nuclear imaging can be used to describe a nodule as being hot, warm, or cold on the basis of its relative uptake of radioactive isotope. Hot nodules indicate autonomously functioning nodules, warm nodules suggest normal thyroid function, and cold nodules indicate hypofunctional or nonfunctional thyroid tissue. Hot nodules are rarely malignant; however, 5-8% of warm or cold nodules are malignant. Ultrasonography Because of recent advances in technology, ultrasonography is highly sensitive in determining the size and number of thyroid nodules. By itself, ultrasonography cannot reliably be used to distinguish a benign nodule from a malignant nodule. However, combining high-resolution sonography with Doppler and spectral analysis of the vascular characteristics of a thyroid nodule holds promise as a useful tool in screening thyroid nodules for malignancy. Studies have shown that the risk of malignancy is lower in nodules with a predominantly perinodular pattern than in nodules with an exclusively central vascular pattern. Furthermore, if the vascular characteristics of thyroid nodules are combined with their ultrasonographic parameters, including a halo, microcalcifications, cross-sectional diameter, and echogenicity, the predictive value of this imaging approach may increase. Thyroid ultrasonography can be helpful in certain cases when it is used to guide FNAB. Recent data have suggested that sonography-guided FNAB may be preferable to palpation-guided FNAB. Although sensitivity and specificity are not clearly and significantly between the approaches to FNAB, many authors consider image-guided FNAB to hold certain advantages. For example, image-guided FNAB may be particularly helpful in the assessment of nonpalpable or small nodules, nodules with cystic components, or nodules that are difficult to access (eg, posterior or substernal nodules). Ultrasonography-guided FNAB, combined with on-site cytologic verification of the adequacy of the specimen by a cytotechnologist or pathologist, may likely provide the highest sensitivity and specificity. Whether this is the most cost-effective approach for all thyroid nodules remains an issue. CT, MRI, and positron emission tomography CT or MRI is generally not cost-effective in the initial evaluation of solitary thyroid nodules. Such studies may be useful in the assessment of thyroid masses that are largely substernal. Also, in some cases CT-guided FNAB may be helpful. Positron-emission-tomography (PET) with 18F-fluorodeoxyglucose is at present primarily an investigational tool, but it might have some role in thyroid imaging in the future, particularly in the evaluation of metastatic disease. In the past, nuclear imaging studies of the thyroid, often combined with ultrasonography, were routinely performed in initial assessment of thyroid nodules. Because only 10% of solitary thyroid nodules are hot and because 90% of cold nodules are not malignant, nuclear imaging with or without ultrasonography typically offers a low yield of cancer diagnoses in surgical specimens when their results are used as the main guides for referral to a surgeon.
Fine-needle aspiration biopsy FNAB has emerged as the most important step in the diagnostic evaluation of thyroid nodules. Data from numerous studies have established FNAB as highly accurate, with mean sensitivity higher than 80% and mean specificity higher than 90%. The accuracy of FNAB in diagnosing thyroid conditions highly depends on the cytopathologist's expertise and experience and the technical skill of the physician performing the biopsy. In addition, FNAB is highly cost-effective compared with traditional workups that heavily depended on nuclear imaging and ultrasonography. Routine use of FNAB in the evaluation of thyroid nodules can reduce the need for diagnostic thyroidectomy by 20-50% while increasing the yield of cancer diagnoses in thyroid specimens by 15-45%. Provided that adequate cellular material is available, FNAB of thyroid nodules can be used to categorize tissue into the following diagnostic categories: malignant, benign, thyroiditis, follicular neoplasm, suspicious, or nondiagnostic. In the malignant category, FNAB can be used to distinguish papillary carcinoma, medullary carcinoma, anaplastic carcinoma, and carcinoma metastatic to the thyroid gland, and it can be used to distinguish malignant lymphoma from other disease. FNAB can also help in reliably diagnosing colloid nodules, Hashimoto thyroiditis, and subacute thyroiditis. The main weakness of FNAB involves hypocellular aspirates and aspirates with high follicular cellularity. Hypocellular aspirates may be observed in cystic nodules, or they may be related to biopsy technique. The addition of ultrasonography to guide FNAB sometimes reduces technical errors. In addition, on-site verification of the adequacy of the specimen by a cytotechnologist or a pathologist is likely to reduce the rate of nondiagnostic specimens. Aspirates characterized by high follicular cellularity suggest follicular neoplasm; however, FNAB cannot be used reliably to distinguish a benign follicular neoplasm from a malignant neoplasm. In addition, aspirates that are highly cellular with Hürthle cells can be observed with benign or malignant Hürthle-cell neoplasms and with some cases of Hashimoto thyroiditis. Advances in cytologic analysis may increase the predictive value of FNAB of thyroid nodules in the future. For example, the incorporation of immunocytochemical studies, as well as genetic and molecular profiling of aspirates, may improve the accuracy of minimally invasive diagnostic techniques. MANAGEMENT OF THYROID NODULESSection 5 of 7
The most important routine aspects of the diagnostic evaluation of solitary thyroid nodules include thorough history taking and physical examination, measurement of the serum TSH level, and FNAB of the nodule if the patient has access to an experienced cytopathologist. Subsequent management of a solitary thyroid nodule largely depends on the diagnosis from FNAB. Malignant cytopathology is usually an indication for surgical referral. Exceptions may be made in the case of malignant lymphoma, which is typically not managed surgically, and in cases of anaplastic carcinoma, in which surgical intervention may be futile. Most thyroid nodules associated with benign cytopathology on FNAB can be managed without routine surgical referral, provided that adequate follow-up is possible. Although the incidence of false-negative results with FNAB is low, most physicians recommend repeat FNAB for confirmation 6-12 months after an initial diagnosis of a benign lesion or if the characteristics of the nodule change on follow-up examination. When a benign diagnosis is confirmed, referral to a surgeon is reasonable for patients with symptoms, such as dysphagia or discomfort, or concerns about cosmesis. Patients with suggestive or follicular cytopathology on FNAB should be referred to a surgeon because 20-30% of such nodules are malignant. When findings from the aspirate are nondiagnostic, repeat the aspiration, possibly with ultrasonographic guidance. Nodules for which aspirates are repeated nondiagnostic may ultimately require surgical management. SPECIAL CONSIDERATIONSSection 6 of 7
Incidentally discovered thyroid nodules Advances in imaging technology have increased the potential for the incidental discovery of nonpalpable thyroid nodules. When the history and physical findings result in a low index of suspicion for malignancy, periodic follow-up evaluation with high-resolution ultrasonography is appropriate. Specific guidelines regarding such evaluation have not been established, but findings have raised concern that the incidence of malignancy in nonpalpable nodules may approach that of palpable nodules. For this reason, if sequential sonograms (eg, obtained at 6-mo intervals) reveal an increase in nodular size, ultrasonography-guided FNAB may be appropriate, even if the nodule remains nonpalpable. Autonomously functioning thyroid nodules Patients with solitary thyroid nodules associated with suppressed TSH levels, with overt or subclinical hyperthyroidism, do not require routine FNAB. In such cases, the patient may be referred to an endocrinologist to discuss iodine-131 treatment versus surgical intervention. REFERENCESSection 7 of 7
Article Last Updated: Sep 20, 2007 |
