Thyroid Nodules

Thyroid nodules and thyroid cancer. Finding the needle in the haystack.

Thyroid nodules are masses or cysts located within the thyroid gland. They are very common, and about 1 person in 20 will have a palpable mass in the thyroid. Nonpalpable thyroid nodules are more common, and on average 1 in 5 or 20% of the population will have a thyroid nodule or nodules visible on ultrasound examination. As we age, the incidence increases, and roughly half of persons over 60 years of age have one or more thyroid nodules. Over the last 20 years there has been a significant increase in the number of patients having imaging of the neck. Carotid ultrasound, neck CT, MRI, and PET scans can all detect nodules in the thyroid that are nonpalpable and completely asymptomatic. This creates a lot of anxiety among patients, and need to evaluate the nodules to exclude the possibility of thyroid cancer.

The great majority of thyroid nodules are benign, however about 5% of persons with a thyroid nodule harbor thyroid cancer. Identifying the cancerous nodules among the large number of benign nodules had been compared to the analogy of finding the needle in the haystack. This is an exaggeration, but it is important to point out a large majority of thyroid nodules will turn out to be benign. There is currently no single diagnostic test that can definitively exclude the presence of cancer, short of surgical excision, but a proper diagnostic evaluation can select those at high risk for cancer that require surgery, identify frankly cancerous nodules, and identify low risk tumors that can be observed.

Symptoms

Most thyroid nodules are asymptomatic. They are generally discovered on examination by your doctor, or you may notice a lump in your neck when looking in a mirror. The lump may also be palpable, or visible by others. Rarely, the lump may be painful, causing pain in the neck or jaw. If the mass is large, it may be visible to others, cause difficulty swallowing, or produce difficulty breathing by pressing on and compressing the airway.

Causes of thyroid nodules:
Thyroid nodules can be classified into a number of benign and malignant (cancer) types.

Benign nodules:
Multinodular goiter
Hashimoto’s Thyroiditis
Cysts (colloid, simple, or hemorrhagic)
Follicular adenomas
Hurthle-cell adenomas

Malignant:
Papillary carcinoma
Follicular carcinoma
Medullary carcinoma
Anaplastic carcinoma
Primary lymphoma of thyroid
Metastases to thyroid (breast, renal, others)

Why benign thyroid nodules form in the first place is not well established. There are several risk factors associated with increased risk of benign thyroid nodules. Alcohol consumption and smoking are associated with development of thyroid enlargement or goiters (See figure XX of large goiter). Uterine fibroids may be associated with an increased likelihood of thyroid nodules. There is also some evidence that statins and oral contraceptive use may decrease likelihood of developing thyroid nodules. A subset of multinodular goiters is familial. In one form of familial goiter, an abnormality has been linked to markers on chromosome 14q, but no specific gene has been identified. A number of point mutations in several oncogenes and tumor suppressor genes have been identified in follicular adenomas.

A number of oncogene abnormalities and gene rearrangements have been identified in papillary and thyroid carcinomas. Medullary carcinoma is associated with mutations in the RET proto-oncogene.

Risk factors for cancer:

Although the risk of a thyroid nodule being cancerous is low, proper evaluation is required. Several factors are associated with a higher likelihood of cancer in a nodule.

Age: The risk of cancer in a child with a nodule is roughly twice that of an adult. The risk of cancer is elevated in the >60 and under 30 age groups compared to the 30-60 year age group.

Gender: The likelihood of a nodule being malignant is twice as high in males.

Prior radiation therapy: Prior radiation therapy to the head and neck region increases the risk for thyroid nodularity and thyroid cancer.

Family history: Some thyroid cancers are associated with familial syndromes, such as Gardner’s Syndrome and Multiple Endocrine Neoplastic syndromes (MEN).

Diagnosis and evaluation

History and Physical Examination

When a nodule is discovered, evaluation starts with a history and physical examination by a physician with expertise in managing thyroid diseases. In addition to a general medical history, your doctor will ask about symptoms related to an overactive or underactive gland, family history of thyroid disorders, prior radiation therapy, medications, and symptoms related to the mass in your neck.

Physical examination will document whether the nodule is palpable, its size and consistency, and mobility. It is important to examine the entire neck, and also to evaluate the voice ox to ensure both vocal cords are mobile.

Laboratory

The first diagnostic test is obtaining TSH level. This test will determine if the nodule is associated with hyperthyroidism or hypothyroidism, and will guide subsequent diagnostic studies. The vast majority of patients will have normal thyroid function (euthyroid).

Ultrasound

The next diagnostic study performed is ultrasonography. (See photo of ultrasound showing nodule) This will either be done in the clinician’s office, or in a radiology suite. It is important to document the size and ultrasound characteristics of all significant nodules. In addition, it is important to examine the entire neck (not just the thyroid) to exclude other pathology, and identify thyroid tumor in a lymph node in the neck.

Fine Needle Aspiration

Fine needle aspiration (FNA) of thyroid nodules has become the standard diagnostic test to evaluate thyroid nodules. Accurate interpretation requires obtaining an adequate specimen, and having an experienced cytopathologist. In expert hands, thyroid FNA has accuracy of determining a nodule is not cancer about 95% of the time, and when a cancer is identified on FNA it is about 99% accurate.

FNA can be performed by palpation to guide the needle, or using ultrasound guidance. Ultrasound guided FNA has the advantage of visualizing the needle entering the mass, and for difficult to palpate lesions, it is more accurate than palpation guided FNA. Furthermore for lesions with cystic and solid components, ultrasound helps guide the needle to the solid portions of the mass which increases diagnostic accuracy.

Thyroid cysts are generally the result of degeneration in a nodule in thyroid goiter or a colloid nodule. Aspiration of the cyst may make it disappear, and provided examination of the cyst contents reveals a benign lesion, these can be observed for recurrence. Thyroid goiters, colloid nodules, and adenomatous nodules are benign macrofollicular lesions. FNA shows significant colloid material, which predicts a benign nature of the nodule.

If there is primarily thyroid follicular cells on the FNA, the cytopathologist may report “follicular neoplasm” on the cytopathology report. This is a nonspecific diagnosis, and can represent a benign follicular adenoma, or a follicular carcinoma. Unfortunately, FNA cannot distinguish between these two entities, and surgical excision is required for diagnosis.

FNA is very accurate for determining presence of papillary thyroid cancer, which has a distinctive cytological appearance. As mentioned earlier, follicular carcinoma cannot be definitively diagnosed on FNA. Medullary thyroid carcinoma is an uncommon form of thyroid cancer that has a distinctive cytological appearance. Finally, anaplastic carcinoma is a rapidly growing form of thyroid cancer with very irregular poorly differentiated cells that has a very distinctive appearance on FNA.

In summary, FNA results can be classified into benign (50-60%) of studies, cancerous (5%), suspicious (10%), or nondiagnostic. A nondiagnostic study results from inadequate tissue on FNA for interpretation. The likelihood of having a nondiagnostic FNA can be decreased by performing FNA with ultrasound guidance, and by having adequacy of the aspirations evaluated by a cytotechnologist before the test is completed.

Thyroid scan

Radioiodine thyroid scans are not commonly performed in the evaluation of thyroid nodules. However, when a patient with a thyroid nodule has low TSH, indicating hyperthyroidism, a radionuclide scan is indicated. It can demonstrate Grave’s disease, and identify autonomously functioning nodules. If the nodule is autonomously functioning and therefore “hot”, surgical removal is not indicated as cancer in these nodules is extremely rare. However, if the nodule is “cold”, FNA is indicated to characterize the nodule.

Treatment

Management of thyroid nodules is guided by results of the diagnostic studies. Your physician will discuss treatment options with you and provide the opportunity to ask questions about choices in your treatment. For clearly benign lesions, observation with follow up examination and ultrasound may be recommended. For lesions that are symptomatic, surgery may be recommended to relieve symptoms. Suspicious lesions will often require thyroid lobectomy to obtain diagnostic material. In general, thyroid malignancy will require total thyroidectomy. In addition, dissection of lymph nodes may be indicated. A number of variables affect treatment recommendations, and a clear discussion with your physician is required to carefully explain the options and reasons for the recommendations.

Before your appointment

In order to prepare for your appointment, it is helpful to have information about your medical history. Notes from referring physicians, copies of laboratory and diagnostic reports, and CD or DVD disks containing images of diagnostic studies will prevent delays in completing the diagnostic evaluation. Write down any symptoms you are having, even if you think they may not be directly related to your thyroid nodule. Also, now is a good time to query family members about family history of thyroid goiters, nodules, or cancer. Please bring a list of your medications. Ultrasound may be performed at your visit, and we encourage having loose fitting shirt/collar that can be opened to expose the entire neck and avoid getting gel on clothing. Finally, it helps to write down a list of questions you will want to ask the doctor.

Additional resources for patients

American Thyroid Association (ATA): http://thyroid.org/patients/brochures.html
Up To Date: http://www.uptodate.com/contents/patient-information-thyroid-nodules-the...
National Cancer Institute: http://www.cancer.gov/cancertopics/types/thyroid