Familial medullary thyroid cancer

Familial medullary thyroid cancer is a rare inherited form of thyroid cancer.

Alternative names for familial medullary thyroid cancer


What is familial medullary thyroid cancer?

Medullary thyroid cancer is a rare form of thyroid cancer. The term medullary describes the type of cells in the thyroid gland affected by the cancer. The majority of patients with medullary thyroid cancer (approximately 80%) have no family history of the condition; the remaining 20% of patients inherit the condition from a parent (thus the disease is ‘familial’). Familial medullary thyroid cancer is inherited in a dominant way, which means a patient with the gene for medullary thyroid cancer will have a 50% chance of passing it on to their offspring. 

The inherited form of medullary thyroid cancer is associated with three conditions: multiple endocrine neoplasia type 2a, multiple endocrine neoplasia type 2b and familial medullary thyroid cancer.

What causes familial medullary thyroid cancer?

Familial medullary thyroid cancer is caused by a mutation in a gene called RET proto-oncogene.

Specialised cells called C-cells in the thyroid gland produce a hormone called calcitonin, which is released into the bloodstream where it lowers blood calcium levels. The RET mutation results in increased growth (hyperplasia) of these C-cells in the thyroid gland. C-cell hyperplasia is present in 20–30% of the general population and does not necessarily lead to medullary thyroid cancer. C-cell hyperplasia is only relevant in patients who have been tested or are known to have the RET mutation.

Over time, C-cell hyperplasia undergoes more growth and develops into medullary thyroid cancer. In the absence of other conditions or features associated with multiple endocrine neoplasia syndromes, this condition is now called familial medullary thyroid cancer. All familial medullary thyroid cancer patients with the RET gene mutation will develop medullary thyroid cancer by the age of 40.

What are the signs and symptoms of familial medullary thyroid cancer?

Medullary thyroid cancer may present as either a single nodule felt in the neck or as symptoms of the cancer spreading to other areas of the body (e.g. lymph nodes, lungs or bone).

The commonest symptoms are associated with the nodule in the neck and discomfort felt as a result of the nodule.

Other associated symptoms can include flushing of the skin and diarrhoea, which are as a result of excessive production of the hormone calcitonin as well as other hormones.

How common is familial medullary thyroid cancer?

Medullary thyroid cancer is a rare form of thyroid cancer accounting for 2–3% of all thyroid cancers. Of these, about 25% are familial, making the incidence of familial medullary thyroid cancer less than 1% of all thyroid cancers. Incidence is equal in men and women and, like most thyroid cancers, it presents between 40 and 50 years of age.

How is familial medullary thyroid cancer diagnosed?

The diagnosis is based on history of a thyroid nodule or lump and also specifically on family history for any similar lumps or diagnoses of thyroid cancers in family members. This would provide strong evidence of a genetic link, which is important in further management and diagnosis of familial medullary thyroid cancer.

It may also be necessary to obtain a tissue sample of the nodule to analyse the cells. To do this, a test called a fine needle aspiration of the thyroid nodule or lymph node is required. This involves using a small thin needle to obtain a specimen of the tissue in the lump or nodule; this can be uncomfortable, but not painful. The specimen is then analysed under a microscope to look for certain features associated with medullary thyroid cancer, such as a protein called amyloid and the hormone calcitonin.

A blood test is carried out to measure levels of calcitonin, which are raised in medullary thyroid cancer.

The definitive diagnosis of familial medullary thyroid cancer is made through genetic analysis of the RET oncogene. The presence of this gene signifies a strong chance of the patient developing medullary thyroid cancer.

Further blood and urine tests and sometimes imaging tests need to be performed to rule out signs of multiple endocrine neoplasia type 2 syndromes, which can also cause medullary thyroid cancer. Taking a detailed family history is crucial to make the differential diagnosis between familial medullary thyroid cancer and multiple endocrine neoplasia type 2a or 2b.

If medullary thyroid cancer is diagnosed, computerised tomography (CT) or magnetic resonance imaging (MRI) scans of the neck and body may be carried out. These scans will help identify how much the cancer has spread within the neck and to any areas outside the thyroid gland.

All of these tests can be performed as outpatient investigations.

How is familial medullary thyroid cancer treated?

The main treatment option is surgery, specifically a procedure called total thyroidectomy and central node dissection. This involves complete removal of the thyroid gland and associated lymph glands in the neck. The surgery can be performed either in patients with a confirmed diagnosis of medullary thyroid cancer or in patients with a strong family history of the condition who test positive for the RET gene. In patients with confirmed familial medullary thyroid cancer, this surgery is carried out in advance, usually between 5 and 10 years of age, to prevent medullary thyroid cancer from developing in the future. If a patient who tests positive for the RET gene refuses preventative surgery, they will need regular blood tests to monitor calcitonin levels and scans of the neck to check for growths.

Radiotherapy may be used to relieve symptoms in cases where surgery is not possible or where the cancer has spread. Chemotherapy is not usually used to treat medullary thyroid cancer, but can occasionally be used for widespread disease. In a small number of cases there are no curative treatment options and patients are treated in a palliative manner, that is, to relieve symptoms.

Are there any side-effects to the treatment?

Side-effects depend mainly on the extent of the cancer spread. The main side-effects result from removal of the thyroid gland requiring lifelong thyroxine replacement therapy, and in certain cases the parathyroid glands, requiring vitamin d and calcium supplements.

There are general risks of surgery and anaesthesia, which should be reviewed by the surgeon or anaesthetist. Further rarer side-effects can include damage to a nerve found near the thyroid gland in the neck, which can affect or alter a patient’s voice (causing a hoarse voice). The parathyroid glands are located behind and attached to the thyroid and can be completely removed by the surgery causing hypoparathyroidism. However, in some cases, one of the parathyroid glands can be preserved in the body. If a patient has any questions about these possible side-effects, they should discuss them with their doctor or surgeon.

In a small number of patients the surgery may not remove the entire tumour and there may be some remnant, which would require further treatment.

What are the longer-term implications of familial medullary thyroid cancer?

If the thyroid gland is removed, the patient will need to take thyroid hormone supplement tablets for life to replace the hormone no longer being produced. All thyroid hormone levels will need to be monitored with regular blood tests.

If diagnosed with familial medullary thyroid cancer, it is important to be aware that there is a chance that siblings may also carry the gene mutation and there is a 50% chance of passing the gene onto children. It is therefore important to speak to your doctor for more advice about the genetic testing of any existing or future children.

Last reviewed: Dec 2014