Medullary thyroid carcinoma



Last Review Date: September 7, 2019


What is it?

The thyroid is a small gland found at the front of your enck, just below the Adam's apple. Thyroid cancer is the unregulated growth of thyroid cells. There are four main types of thyroid cancer; Papillary thyroid cancer, Follicular thyroid cancer, Medullary thyroid cancer and Anaplastic thyroid cancer. The most common is papillary thyroid cancer, which usually grows in one lobe of the thyroid gland (about 70-80% of all cases). Follicular thyroid cancer accounts for about 20% of thyroid cancers. Medullary thyroid cancer (MTC) is less common. This tumour originates from parafollicular C cells which produce calcitonin in the thyroid gland.
MTC is, as the name suggests, a neuroendocrine tumour of the thyroid gland.
Even though thyroid cancer is more common in women than men female, this preponderance is less marked in MTC.

The thyroid gland produces the hormones thyroxine and calcitonin. Thyroxine, while essential to the body, does not play a part in medullary thyroid cancer. Calcitonin is produced by C-cells in the thyroid gland and plays a part in the control of the level of calcium in blood together with other hormones PTH and 1,25 OH vitamin D. It is from these C-cells that MTC arises and calcitonin may be measured to aid diagnosis of the cancer or as a tumour marker to check a person’s response to treatment along with another tumour marker CEA.

Thyroid cancers account for about 1.5 per cent of all cancer cases and of this 1.5 per cent, about 5 per cent of them are of the medullary sub-type. MTC can develop spontaneously (sporadically) or be inherited. The majority of cases of MTC arise sporadically (Up to 75%). Inherited medullary thyroid cancer (23% of cases) is caused by a mutation in the RET gene and is often associated with multiple endocrine neoplasia type 2 (MEN), which is also caused by mutations in the RET gene. 


Signs and symptoms

A number of conditions can cause symptoms similar to thyroid cancer. For example, thyroid nodules or lumps are common and usually not cancerous.
Many people will first recognise a nodule in the middle of their neck that may be painful. People may also notice difficulty swallowing or a change in their voice. In rare cases people may notice diarrhoea and flushing as well as a nodule.

In cases where people have MEN syndrome, doctors may specifically look for early signs of thyroid cancer along with other causes of flushing and diarrhoea.


Tests

A person with a lump in the neck will lead the doctor to suspect a problem with the thyroid gland. The doctor may ask you questions about other possible symptoms that you could be experiencing at the time. They will then feel the area of the neck where the lump is and if they suspect that the thyroid is involved they will order some tests to confirm this. The majority of these nodules are benign thyroid nodules or cysts.

Non-laboratory tests

Ultrasound: Most neck lumps will be investigated with the use of ultrasound. This imaging technique allows doctors to assess the location and characteristics of the lump, which includes size, mass and calcium deposits to help decide whether it is benign or cancer. Ultrasound may also be used to detect whether MTC has spread to local lymph nodes. Other causes of thyroid lumps which  include papillary thyroid cancer and multi nodular goitre, can also be assessed with this technique.

Laboratory tests

Fine needle aspiration: Often a sample of the lump is taken while the doctor is viewing the lump by ultrasound. This small amount of tissue can give an indication of whether or not the lump is cancer and has a high degree of sensitivity especially including special staining methods for diagnosis.

Calcitonin: this is a hormone produced by the C-cells in the thyroid gland. In cases of medullary thyroid cancer it will often be raised. Calcitonin levels, as well as a calcitonin stimulation test may be ordered to confirm MTC.

In addition to aiding diagnosis of MTC, the blood test for this hormone may be used for monitoring treatment and recurrence of MTC. With successful treatment, calcitonin levels will usually fall to very low levels. If, after successful treatment, calcitonin levels begin to rise, then it is likely that there is a recurrence of medullary thyroid cancer.
Calcitonin Stimulation tests- more sensitive than calcitonin measurements alone. This involves collecting a baseline sample, then giving the patient an injection of intravenous calcium or less commonly, pentagastrin, to stimulate calcitonin production. Several more blood samples are then collected over the next few minutes to gauge the effect of the stimulation. Patients with early C-cell hyperplasia and/or MTC will usually have very significant increases in their levels of calcitonin during this test.


Thyroid function tests: These are one of the first tests ordered when a doctor suspects a problem with your thyroid. It includes TSH, FT4 and FT3 and provides information about how your thyroid in functioning.

Carcinoembryonic antigen (CEA)- this antigen is often elevated in people with MTC. Malignant transformed C cells- may produce and secrete (CEA).

Genetic testing: Due to the high percentage of inherited MTC, doctors may advise that a genetic test be performed. The presence of the RET oncogene indicates an inheritable form of the cancer and will guide investigation of family members. 


Treatment

Once medullary thyroid cancer has been confirmed, treatment will often be the surgical removal of the entire thyroid gland. This may then be followed by other modes of treatment to remove any remaining cells. Ultimately the form of treatment for each patient will depend upon the extent of the cancer and will involve a discussion between the patient and their doctor.


Related Pages

On this site

Tests: Calcitonin, CEA, RET oncogene 
Conditions: Thyroid Diseases, MEN 

Elsewhere on the web

Endocrine Web – Medullary thyroid cancer
Medscape Reference – Medullary thyroid cancer


References

Tuttle R. Clinical manifestations, diagnosis, evaluation, and staging of medullary thyroid cancer. (Internet) Up to date (updated august 2012) Accessed via: http://www.uptodate.com.ezproxy.library.uq.edu.au/contents/clinical-manifestations-diagnosis-evaluation-and-staging-of-medullary-thyroid-cancer?

Kumar V, Abbas A, Fausto N, Aster J. Robins and Cotran’s Pathological Basis of Disease 8th Ed. Philadelphia, USA: Saunders Elsevier; 2010. Ch 24

Thyroid Cancer Council Australia

Wilkins R, Cross S, Megson I et al. Oxford Handbook of Medical Sciences. Oxford, England: Oxford University Press; 2006. p 576

Kloos R, Eng C, Evans D et al. Medullary Thyroid Cancer: Management Guidelines of the American Thyroid Association. Thyroid. 2009. Nov 6;19:565-612