Medullary Thyroid Carcinoma (MTC)

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Medullary thyroid cancer (MTC) is a type of thyroid cancer that affects thyroid gland cells called the parafollicular C cells.1 These cells are responsible for making the hormone calcitonin, which plays a role in regulating calcium phosphate levels in the blood.2

Medullary thyroid cancer produces no or very few symptoms because the mass may be small and surrounded by normal thyroid tissue.3 In some cases, it can present as a lump or nodule in the neck, which may be discovered during a routine neck examination by a doctor or on imaging tests such as computed tomography (CT) or positron emission tomography (PET) scans performed for other reasons.1  

Symptoms Caused by the Nodule

The nodule that forms in the front of the neck due to medullary thyroid carcinoma can cause a number of symptoms. These can include pain, hoarseness, and difficulty swallowing.1

Pain

The growth of the nodule can press on the nerves in the neck and cause neck pain. This can also extend to the jaw or ears in some cases. 

Hoarseness

If cancer spreads to the vocal cords, it can cause hoarseness. 

Other Symptoms Caused by the Nodule

Other symptoms caused by the nodule include coughing, dyspnea, and dysphagia due to the tumor pushing against the trachea or esophagus.4

Other Symptoms of Medullary Thyroid Cancer

Medullary thyroid cancer can also cause symptoms that are not a direct result of the nodule developing in the neck. These include severe diarrhea, flushing, bone pain, weight loss, and fatigue.4

Severe Diarrhea and Flushing

High levels of calcitonin caused by medullary thyroid carcinoma can lead to severe diarrhea and flushing similar to those seen in carcinoid patients due to high levels of calcitonin.4 However, this is usually very rare, and the mechanism is not well understood. It is thought that it could be related to disordered intestinal motility and/or increased secretion of salt and water, especially in the ileum, due to high levels of the prostaglandins E2 and F2-α.5

Bone Pain

If cancer has spread and formed bone lesions, it can cause bone pain.4 

Weight Loss and Fatigue

Other symptoms of medullary thyroid cancer include weight loss and fatigue, which are common in all types of cancer, especially in advanced stages. The exact reason for this is not known.4

Symptoms in Children

Medullary thyroid cancer occurs sporadically in 75% of cases. In the remaining cases, it can be caused by a germline mutation in the RET proto-oncogene.1 Almost all medullary thyroid cancer cases (95%) in children are hereditary. They are part of multiple endocrine neoplasia (MEN) syndromes MEN 2A and 2B. Symptoms include gastrointestinal problems and musculoskeletal complaints.6

Gastrointestinal Symptoms of Medullary Thyroid Cancer in Children

The gastrointestinal symptoms of medullary thyroid cancer in children include feeding difficulty, which can be caused by the nodule in the thyroid itself, and constipation or diarrhea due to aberrant levels of calcitonin.6

Musculoskeletal Symptoms of Medullary Thyroid Cancer in Children

The musculoskeletal symptoms of medullary thyroid cancer in children include pes cavus, spine abnormalities, and bone pain due to the presence of bone lesions.6 

A study that analyzed 79 children with either MEN1 or MEN2 found that calcitonin levels higher than 40 pg/mL were associated with an increased risk of medullary thyroid cancer and that almost half of children who had a thyroidectomy were beyond the age recommended by the American Thyroid Association (ATA) 2009 guidelines. Their calcium levels were below normal, and half of them required treatment for hypocalcemia.7

Hyperparathyroidism is another symptom of familial medullary thyroid cancer, with 30% of patients with MEN2A developing hyperparathyroidism at a mean age of 33.7 years.8

Medullary Thyroid Cancer Symptoms and Treatment

Because medullary thyroid carcinoma produces no symptoms in most cases, there are no symptomatic treatments available. If cancer is in its early stages and has not spread to other parts of the body, a total thyroidectomy can be used to treat it. If cancer has spread to the lymph nodes, these can also be removed surgically in some cases. Following a total thyroidectomy, patients need to be treated with thyroid hormone therapy for the rest of their lives.1

Two chemotherapy agents, vandetanib and cabozantinib, have been approved by the US Food and Drug Administration (FDA) for the treatment of medullary thyroid carcinoma, and they can be used to slow the progression of the disease or partially reverse its growth. However, they are unlikely to be efficient if cancer has spread widely to the bones, lungs, brain, and liver. In such cases, it is unlikely to be cured.1

References

  1. Medullary thyroid cancer. American Thyroid Association. Accessed July 1, 2021.
  2. Calcitonin. You and Your Hormones. Accessed July 1, 2021.
  3. Medullary thyroid cancer overview. Clayman Thyroid Center. Updated October 21, 2018. Accessed July 1, 2021.
  4. Somnay YR, Schneider D, Mazeh H. Thyroid: medullary carcinoma. Atlas Genet Cytogenet Oncol Haematol. 2013;17(4):291-296. doi:10.4267/2042/48876
  5. Gupta S, Tibbs CJ, Farthing MJG, Pollok RCG. Chronic diarrhoea–all in the bowel? J R Soc Med. 2007;100(8):379-381. doi:10.1177/014107680710000815
  6. Graves CE, Gosnell JE. Medullary thyroid carcinoma in children. Semin Pediatr Surg. 2020;29(3):150921. doi:10.1016/j.sempedsurg.2020.150921
  7. Prete FP, Abdel-Aziz T, Morkane C, Brain C, Kurzawinski TR; MEN2 in Children UK Collaborative Group. Prophylactic thyroidectomy in children with multiple endocrine neoplasia type 2. Br J Surg. 2018;105(10):1319-1327. doi:10.1002/bjs.10856
  8. Wells SA Jr. Advances in the management of MEN2: from improved surgical and medical treatment to novel kinase inhibitors. Endocr Relat Cancer. 2018;25(2):T1-T13. doi:10.1530/ERC-17-0325

Reviewed by Debjyoti Talukdar, MD, on 7/1/2021.