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 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
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.
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
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
- Medullary thyroid cancer. American Thyroid Association. Accessed July 1, 2021.
- Calcitonin. You and Your Hormones. Accessed July 1, 2021.
- Medullary thyroid cancer overview. Clayman Thyroid Center. Updated October 21, 2018. Accessed July 1, 2021.
- Somnay YR, Schneider D, Mazeh H. Thyroid: medullary carcinoma. Atlas Genet Cytogenet Oncol Haematol. 2013;17(4):291-296. doi:10.4267/2042/48876
- 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
- Graves CE, Gosnell JE. Medullary thyroid carcinoma in children. Semin Pediatr Surg. 2020;29(3):150921. doi:10.1016/j.sempedsurg.2020.150921
- 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
- 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.