Özge’s background is in research; she holds a MSc. in Molecular Genetics from the University of Leicester and a PhD. in Developmental Biology from the University of London. Özge worked as a bench scientist for six years in the field of neuroscience before embarking on a career in science communication. She worked as the research communication officer at MDUK, a UK-based charity that supports people living with muscle-wasting conditions, and then a research columnist and the managing editor of resource pages at BioNews Services before joining Rare Disease Advisor.
Medullary thyroid cancer (MTC) is a type of thyroid cancer that affects the parafollicular C cells of the thyroid gland, which make the calcitonin hormone. Around 25% of MTC cases are inherited and these patients have a mutation in the RET proto-oncogene.1
The diagnostic workup for MTC starts with a medical history and physical examination. This is followed by blood tests to check the function of the thyroid and imaging tests, such as ultrasound. If the imaging tests are indicative of MTC, a fine needle aspiration biopsy is performed.
Following a diagnosis of MTC, patients should have a blood test to see whether they have a mutation in the RET proto-oncogene. If so, other family members should also be genetically tested to reach an early diagnosis and curative surgery before cancer develops.1
Medical History and Physical Examination
During a medical history, the age of the patient, hoarseness, any family history of thyroid cancer, and any history of radiation exposure to the head, neck, or chest should be assessed. Individuals younger than 20 and older than 70 are at a higher risk of medullary thyroid cancer.2
During the physical examination, any hard nodules and enlarged lymph nodes should be assessed.2
Following a medical history and physical examination, a blood test should be performed to check for levels of thyroid-stimulating hormone (TSH). TSH levels are usually normal in the case of thyroid cancer.3
Calcitonin and carcinoembryonic antigen measurements in the blood can confirm a diagnosis of MTC.1 In patients with the disease, levels of calcitonin are higher than 500 pg/mL.4 The higher the calcitonin levels, the more pervasive the disease. High levels of carcinoembryonic antigen may also be a sign of a more aggressive form of the disease.2
An ultrasound can reveal the size of the thyroid and features of any nodules such as size, number, calcification status, echotexture, borders, shape, and whether they are solid or cystic.
Microcalcifications, hypoechoic nodules, hypervascularity, irregular borders, and enlarged lymph nodes are usually indicative of thyroid cancer.2
Other imaging tests such as a CT scan, magnetic resonance imaging (MRI), and positron emission tomography (PET), can help determine whether cancer has spread and identify other areas that might be affected.3
Radioiodine scans are not used for the diagnosis of MTC because parafollicular C cells do not absorb iodine.3
Fine Needle Aspiration Biopsy (FNAB)
Fine needle aspiration biopsy is indicated for nodules larger than 1 cm in diameter. If the patient has a family history of thyroid cancer, has been exposed to radiation, or has suspicious ultrasound findings, nodules that are larger than 0.5 cm in diameter should also be biopsied.
The FNAB results can indicate benign disease in which case an ultrasound and physical exam should be repeated after six months. They can also indicate a malignant disease, where a total thyroidectomy is indicated.
In some cases, a definite diagnosis cannot be reached based on the cytological findings of the biopsy. In such cases, a partial or total thyroidectomy may be indicated.
In 5 to 10% of cases, the biopsy can be inconclusive, i.e. not enough cells have been removed to reach a diagnosis. In such cases, the biopsy may be repeated. Following two or more non-conclusive biopsies a patient may receive a partial or total thyroidectomy especially in case of high risk based on other findings.2
RET Proto-oncogene Mutation Analysis
Following a diagnosis of MTC, a blood test should be performed to see whether the disease is familial or sporadic. In 25% of cases, patients with MTC have a mutation in the RET proto-oncogene.1
The RET proto-oncogene encodes for a transmembrane receptor of the tyrosine kinase family. Specific RET mutations are associated with the aggressiveness of the disease and determine the suitability of a thyroidectomy. The clinical features of the disease will dictate the order of mutation testing. If there are no clinical features, mutations in exons 10 and 11 of the RET gene are tested first. If there are no mutations in these exons, exons 13 to 16 are then tested.4
Family members of a patient with familial MTC should also be tested for any mutations in the RET proto-oncogene and offered the necessary treatment, as well as genetic counseling to guide and educate family members of patients with MTC and to discuss the diagnosis, its implications, and interpretation of genetic test results.2
- Medullary Thyroid Cancer. American Thyroid Association. Accessed June 29, 2021.
- Medullary Thyroid Cancer. Columbia Thyroid Center. Accessed June 29, 2021.
- Tests for Thyroid Cancer. American Cancer Society. May 12, 2020. Accessed June 29, 2021.
- Thomas CM, Asa SL, Ezzat S, Sawka AM, Goldstein D. Diagnosis and pathologic characteristics of medullary thyroid carcinoma-review of current guidelines. Curr Oncol. 2019;26(5):338-344. doi:10.3747/co.26.5539
Article reviewed by Harshi Dhingra, MD, on July 1, 2021.