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Management of a Thyroid Nodule

Jan 2010 – by N. Santoro, MD

Case Presentation: Ms. X is a 58 year old woman who presents for a well woman examination. She has a BP of 130/85 and a BMI of 23 kg/m2. On examination of the neck, a small, firm 1.5 cm nodularity is felt within the thyroid gland.

The prevalence of thyroid nodules varies with the level of iodine sufficiency of the population. About 5% of US women have palpable thyroid nodules, because iodine deficiency is relatively rare. A much higher prevalence of thyroid nodules exists when imaging tests are used. The prevalence of ultrasound detected nodules can be as high as 67%.

The universal concern with a thyroid nodule is the possibility that a cancer is present. Even though most thyroid cancers are well differentiated, slow growing, and have an overall good prognosis, it is incumbent on the clinician to exclude a thyroid cancer when a palpable nodule is present. The most cost-effective way to do so is a matter of some controversy but much consensus.

When is a Nodule Significant Enough to Warrant a Workup?

Nodules over 1cm in size, whether detected by palpation or incidentally by ultrasound merit a diagnostic evaluation. The risk of cancer is identical for a 1cm nodule that can be felt on clinical exam as compared with one that is detected by ultrasound. It may also be appropriate to investigate nodules smaller than 1cm in patients with either a suspicious ultrasound or other characteristics that increase the risk of malignancy (e.g., family history of thyroid cancer).

What Testing Should Be Performed?

A directed clinical history should be performed to screen for risk factors that augment the possibility that the nodule is cancerous. These are summarized in Table 1. On physical examination, fixation of the nodule or lymphadenopathy are worrisome clinical signs (Table 1).

Table 1. Risk Factors for Malignant Thyroid Nodule

  • History
  • Radiation
    • Head and neck irradiation for any reason
    • Whole body irradiation for bone marrow transplant
    • Exposure to Chernobyl radioactive fallout at age <14
  • Family History
    • First-degree relative with thyroid cancer
  • Rapid growth of nodule
  • Hoarseness or dysphagia
  • Physical Examination
  • Vocal cord paralysis
  • Ipsilateral cervical node enlargement
  • Fixation

Laboratory Testing and Management

After initial clinical evaluation, laboratory testing should be performed to ascertain whether the nodule is or is not producing thyroid hormone. The initial evaluation of all thyroid nodules includes a TSH determination. Further steps will depend upon the outcome of this initial test. If the TSH level is low, a radionuclide thyroid scan (99Tch or 123I) can help determine whether or not the nodule is producing thyroid hormone in excess, thereby suppressing serum TSH ('hot' nodule). In the above case, if the palpated nodule can be identified as the same as the functioning (hot or warm) nodule on the scan, tissue sampling need not be done and the nodule can be followed (see below). This is because functioning nodules are unlikely to be malignant, and the radionuclide scan results can allow the clinician to defer a fine needle aspiration. However, such a patient may be hyperthyroid, and may require referral to an Endocrinologist for further management. Note that it is not recommended to perform additional thyroid testing (i.e., T4, T3, or RT3 uptake) as part of the initial workup of a nodule.

If the nodule appears on scan to be 'warm' (evidence of function similar to surrounding thyroid tissue) or 'cold' (nonfunctioning), an ultrasound evaluation is needed.
If the TSH is normal or elevated, then a thyroid ultrasound, and not a radionuclide scan, is the appropriate next step. The advantage of a thyroid ultrasound is that it can confirm the presence of a nodule, and the nodule can be evaluated for its cystic component and its location within the thyroid gland. The more cystic, and the more posterior a nodule, the less accessible it is to an adequate fine needle aspiration. There are also ultrasound features that can be used to help predict the likelihood of malignancy, and thus the need for a biopsy. At the time of the diagnostic ultrasound, an ultrasound-guided fine needle aspiration (FNA) can be performed immediately. These results can then be used to guide further management.

It is important to recognize that multiple nodules (such as might be found in a woman with a multinodular goiter) do not rule out malignancy. Sampling each nodule with an FNA is not practical, but ultrasound features of the nodules can be used to help predict the likelihood for malignancy or target the nodule(s) for biopsy. Hypoechogenicity, microcalcifications and hypervascularity are all potential signs of malignancy.

Additional testing that may be done as part of the initial evaluation include a serum calcitonin level, to rule out medullary carcinoma, but this is controversial as it may not be cost-effective. On the other hand, there maybe superior survival for the rare patient with medullary carcinoma if the diagnosis can be made earlier by use of this test.

Long Term Follow Up

A false-negative rate of 5% has been observed with thyroid FNA. Moreover, the clinical assessment of growth over time when palpation is compared to ultrasound greatly favors the use of serial ultrasound in following up patients with thyroid nodules and benign initial histology. Some clinicians however, may choose to follow easily palpable nodules by clinical examination. If serial ultrasounds are performed to follow a thyroid nodule for interval growth, the recommended interval is every 6-18 months and a worrisome increase in size is in the range of 15-20%. Thyroid suppression is NOT recommended for women with benign thyroid nodules because it is ineffective in shrinking the nodules and may cause osteoporosis and/or heart disease.

Unresolved Questions

While FNA has been proven to be a very cost-effective method for evaluating thyroid nodules, other tests may be less helpful. Serum calcitonin may help diagnose medullary carcinoma earlier but may not be cost-effective. Cytopathologic screening of FNA specimens for molecular markers may assist in the diagnosis and guide management, but the indications are not currently clear and there are no strong recommendations in this area. The role of PET scanning in the event of a non-diagnostic FNA finding is also controversial. Nondiagnostic FNA findings (present in 15-30% of aspirates) mandate close follow-up, but there is no clear consensus about when surgical excision should be performed. Neither clinical patient characteristics nor molecular markers improve the diagnostic accuracy in such cases.

Outcome of the Case

The patient's TSH was normal at 3.1 uU/ml. Ultrasound demonstrated a 50% cystic, anterior lesion corresponding to the palpated nodule. FNA results were benign. The patient was scheduled for a follow up scan in 1 year. Note that in this 58 year old woman, a decision to suppress the nodule with thyroid hormone would be expected to have negative consequences on her bone mineral density.

REFERENCES

Cooper DS, Doherty GM, Haugen B, Kloos RT, Lee S, Mandel S, Mazzaferri EL, McIver B, Sherman SI, Tuttle RM. Management Guidelines for Patients with Thyroid Nodules and Well Differentiated Thyroid Cancer. Thyroid 2006; 16: 4-33.

Cooper DS, Doherty GM, Haugen B, Kloos RT, Lee S, Mandel SJ, Mazzaferri EL, McIver B, Pacni F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM. Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2009; 19: 1-48.

Gharib H, Mazzaferri EL. Thyroxine Suppressive Therapy in Pateints with Nodular Thyroid Disease. Ann Int Med 1998; 128:386-394.