Diagnosis

Thyroid nodules are commonly discovered by a patient at home or by a physician during a routine physical exam. They are also often discovered incidentally on unrelated imaging studies such as a chest CT scan, an MRI of the cervical spine, or a doppler ultrasound study of the carotid arteries.

In general, the standard diagnostic approach for thyroid cancer includes a physical examination to identify a nodule, blood tests, imaging, and possibly a fine-needle biopsy. Patients can expect their doctor to have a discussion with them about the risks, benefits, and alternatives to each of the following approaches.

Physical Exam

To start, a physician will feel (“palpate”) the neck to detect any abnormal swelling, hardness, tenderness, or asymmetry. Vocal cord function and ease of swallowing may also be assessed depending on patient symptoms.

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Blood Tests

Blood tests are used to detect the levels of thyroid hormone circulating in the body. Most thyroid nodules do not produce thyroid hormones. However, some nodules do make excess thyroid hormones, which can cause significant symptoms, and can be detected on a blood test.

Patients often undergo a number of blood tests before and/or after being diagnosed with thyroid cancer. These might include tests to detect thyroid stimulating hormone (TSH), thyroxine (T4),  and certain antibodies that suggest an autoimmune thyroid disease (e.g. Graves’ or Hashimoto’s disease).

  • TSH is a hormone produced by the pituitary gland, which stimulates the thyroid to produce more thyroid hormone. TSH regulates the thyroid gland in order to maintain a hormone balance.
  • Thyroxine, also known as T4, is the main hormone produced by the thyroid gland. It regulates metabolism and other functions throughout the body. 

Thyroid hormone tests (TSH and T4) will help doctors determine the next steps in the workup of a thyroid nodule. Read more about thyroid blood tests.

Imaging

Once a nodule has been identified, the blood tests described above can help doctors determine which imaging studies should be used to further evaluate the nodule. Imaging of the neck will be required to determine the size and location of a thyroid nodule, and is a vital step prior to any treatment decision.

  • Generally, patients with hyperthyroidism (low TSH and elevated T4) will be ordered to have an ultrasound and an I-131 uptake scan. Through the uptake scan, the doctor will determine whether the nodule in question is the cause of thyroid hormone overproduction. Nodules that produce thyroid hormones in excess are called “functional” nodules, and are unlikely to be malignant. Therefore, functional nodules do not need to be biopsied and can be followed with regular ultrasounds. 
  • On the other hand, patients with normal (euthyroidism) or low (hypothyroidism)  thyroid hormone function are more likely to have malignant nodules. Therefore, ultrasound is the study of choice in these cases. If the ultrasound of the nodule shows worrisome characteristics or demonstrates involvement of lymph nodes, a biopsy should be performed. 

For thyroid cancer, the gold standard initial imaging test is an ultrasound. Ultrasounds are always used to evaluate thyroid nodules, and often lymph nodes in the surrounding neck area.  In some cases, a doctor may also recommend more advanced imaging studies such as a CT scan,  MRI, PET/CT, or I-131 uptake scan (as described above). Read more about thyroid ultrasounds.

Biopsy

The best way to determine if a thyroid nodule is cancerous is with a fine needle aspiration (FNA) biopsy to remove a small piece of tissue and examine it under a microscope. This procedure is performed with local numbing medicine under the guidance of an ultrasound, and is essentially risk free. Read more about FNA biopsies.

The majority of thyroid nodules are benign (not cancerous). Only about 5–15% of nodules are found  to be cancerous after a biopsy. Since benign thyroid nodules are very common, not all nodules need to be biopsied, especially if they are very small (< 1 cm). However, nodules that grow or appear “suspicious” on ultrasound should be evaluated further with follow-up ultrasounds and a biopsy.

The Bethesda System

The results of thyroid nodule FNA biopsies are reported using the Bethesda System, which is a 1–6 scale used to predict how likely it is that the biopsied nodule is cancerous. It is important to know that a doctor will not be completely sure about the pathology for the nodule until it has been surgically removed and examined under the microscope. Keep in mind that the Bethesda System is different than cancer staging.

I. Non-diagnostic / Unsatisfactory

This means that the sample of cells taken by the needle was inadequate, so the biopsy cannot provide any useful results. The biopsy should be repeated. 

II. Benign 

This means that no cancer was detected. The risk of the result being inaccurate and the nodule actually being cancerous is 0–3%. 

III. Atypia of Undetermined Significance / Follicular Lesion of Undetermined Significance*

This means that the diagnosis was uncertain, or indeterminate. The cancer risk in this case is 10–30%. A doctor should either repeat the biopsy, order molecular testing, or perform a thyroid lobectomy.

IV. Follicular Neoplasm / Suspicious for a Follicular Neoplasm*

This indicates a 25–40% risk of cancer. Further molecular testing or a thyroid lobectomy is recommended.

V. Suspicious for Malignancy

This indicates a 50–75% risk of cancer. Patients should undergo a thyroid lobectomy or total thyroidectomy in most cases.

VI. Malignant

This confirms a 97–99% risk of cancer. Patients should undergo a thyroid lobectomy or total thyroidectomy in most cases. 

* See section on molecular testing

Molecular Testing

Multiple molecular tests are now available to help better assess the risk of malignancy in certain thyroid nodules that are not well characterized on the basis of cytology alone.  These tests look for genetic mutations in the biopsied cells that can be found in thyroid cancers. Molecular testing is commonly recommended when biopsies return as Bethesda III or IV (see above). There are multiple types of molecular assays available which have been shown to have similar accuracy in detecting possible malignancy. Learn more about molecular testing

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