A thyroid nodule is a localized “lump” within the thyroid gland. A thyroid nodule can be single (called a “solitary nodule”) or multiple (called a “multinodular goitre”). Both solitary nodules and multinodular goitres are common, especially in women, and their prevalence increases with patient age. The majority of patients with thyroid nodule(s) do not have any symptoms, and often the thyroid nodule is discovered by accident. When a thyroid nodule is discovered, it requires further workup, which is described below.

Types of Thyroid Nodules
Thyroid nodules may be one of the following:

1. A fluid-containing cyst (these are always benign);
2. benign thyroid nodule (ie. it is not cancer)
3. malignant thyroid nodule (ie. it is cancer)

Clinical Features
Most patients with thyroid nodules are asymptomatic. They do not feel any pain or pressure in their neck, and they do not have any other symptoms. Often the thyroid nodule is found by their doctors when they have routine medical checkups or undergo medical imaging for other conditions. As nodules enlarge, they may get so big that they push on surrounding structures like the trachea or esophagus, causing “mass effect” symptoms like breathing or swallowing difficulty. This typically happens only in very large nodules > 4 cm.

Risk factors for thyroid cancer include a history of radiation therapy to the head and neck, or a family history of thyroid cancer in 2 or more first degree relatives.

On neck exam, thyroid nodules are usually firm, smooth, and can usually be felt by an experienced medical practitioner if they are > 2 cm in size. Smaller nodules are usually only detectable by ultrasound. Malignant thyroid nodules may feel hard, don’t move up and down as well when the patient swallows, and can be associated with enlarged lymph nodes in the neck if the tumour has spread. However, physical examination alone cannot tell the difference between benign and malignant nodules.

Most patients with thyroid nodules have a normal functioning thyroid gland, reflected as a normal TSH level.

Investigations
When a thyroid nodule is discovered, there are several tests that should be done to determine what type of nodule it is including:

1. 1. TSH blood test: a low (“suppressed”) TSH suggests that the thyroid nodule or the entire thyroid gland may be making excess thyroid hormone. If the TSH is suppressed, your doctor will need to do further testing to determine the cause. These tests may include a thyroid scan or thyroid uptake, and/or additional blood work. If the TSH is normal, it is reassuring that the thyroid gland is still working properly and making the right amount of thyroid hormone.
   2. High quality neck ultrasound: neck ultrasounds should describe all thyroid nodules seen including nodule size and appearance. They should then translate the appearance of a nodule into a “score” which estimates the risk of cancer in that nodule. There are two nodule risk systems in use in Canada, and which system is used in your report depends on where you had your neck ultrasound done. Both systems work well. The ATA scoring system rates nodules as low, intermediate, or high risk of cancer. The TIRADS score system rates nodules as TIRADS 1 to 5; the higher the number the greater the risk of cancer.
   3. Fine needle aspiration biopsy: the risk score and size of a thyroid nodule determines whether or not it should be biopsied. When a nodule is biopsied, cells and fluid are removed from the thyroid gland and examined by a pathologist. The result of a thyroid biopsy can be benign (not cancer), malignant (cancer), indeterminate (the pathologist is not sure if it’s cancer or not), or nondiagnostic (the biopsy did not yield a good sample and it needs to be redone).
   4. Molecular testing: if a thyroid biopsy comes back indeterminate, the sample may be sent for molecular testing. Depending on the type of molecular test used at your centre, a molecular test may help to “rule in” or “rule out” thyroid cancer. For example, a BRAFV600E mutation is the most common mutation seen in papillary thyroid cancer and is never seen in benign nodules. As such, if a BRAFV600E mutation was found in your nodule, this would rule in thyroid cancer.

Management
Management of thyroid nodules depends on the nature of the nodule.

Nodules that are making excess thyroid hormone (“hot nodules”) may require treatment with radioactive iodine or surgery to bring the thyroid hormone levels back to normal.

Nodules that are not making excess thyroid hormone (“cold nodules”) need to be evaluated for their risk of thyroid cancer and whether or not they cause “mass effect” symptoms due to their size. Management of cold nodules may include monitoring with TSH and neck US, thyroid biopsy, molecular testing, or thyroid surgery.

Treatment with levothyroxine is only indicated in the setting of hypothyroidism as diagnosed by an increased TSH level. Although tried in the past, levothyroxine does not help to shrink nodules, and nodules that are causing mass effect symptoms like swallowing or breathing difficulties need to be treated with surgery.

Irradiation of the Thyroid and Neck Region
In the 1940’s and early 1950’s, many children were given X-ray treatment for a variety of benign conditions of the thymus, adenoids, tonsils, and skin. It was later realized that this irradiation affected the thyroid gland. In some studies up to 25% of such people eventually developed thyroid nodules, one third of whom developed thyroid cancer.
Thyroid nodules which appear following irradiation should be investigated by clinical examination, thyroid ultrasound and biopsy just like other nodules. However if there is a suspicion of malignancy, the thyroid nodule should be removed and the rest of the gland examined carefully for the presence of thyroid cancer.
What about people who received irradiation but who do not have a nodule? It is important that such people be carefully examined because of the high likelihood of a nodule developing.

Multinodular Goitre
When there is more than one nodule in a thyroid gland, causing the overall gland size to be larger than normal, it is termed a “multinodular goitre”.

In general, the workup and management of a multinodular goitre is the same as that of a solitary nodule, including evaluation of thyroid function, estimating the risk of thyroid cancer in each nodule, and determining if mass effect symptoms are present.

Multinodular goitres can have multiple nodules that are making excess thyroid hormone resulting in hyperthyroidism. These are termed “toxic multinodular goitre”. Toxic multinodular goitres can be treated with radioactive iodine or surgery.

If a multinodular goitre gets so big that it pushes on surrounding neck structures causing symptoms like swallowing difficulties or shortness of breath, then surgery is the preferred treatment approach.

Updated in May 2024 by Sana Ghaznavi, MD, FRCPC, Clinical Assistant Professor, Division of Endocrinology & Metabolism, at the University of Calgary, from the original text written by: Irving B. Rosen, MD., FRCS(C), FACS, and Paul G. Walfish CM, MD, FRCP(C), FACP, FRSM.