Medullary thyroid cancer

Disease Description (Causes and Symptoms)

• Definition and pathophysiology: Medullary thyroid carcinoma (MTC) is a rare thyroid cancer that arises from the C cells (parafollicular cells) of the thyroid and secretes calcitonin. Some cases are caused by somatic (acquired) RET gene mutations, and approximately 20–30% are hereditary (RET germline mutations, familial MTC, or MEN2 syndrome). The tumor commonly causes local invasion and lymph node metastasis, and as it progresses, it may metastasize to distant sites such as the lungs, liver, and bones.
• Main causes: Activating RET gene mutations (hereditary and sporadic), and other molecular alterations (in some cases).
• Main symptoms:
  • A lump in the neck (palpable) or a foreign-body sensation
  • Voice changes (recurrent laryngeal nerve involvement)
  • Difficulty swallowing or breathing (when the tumor is large or has invaded surrounding structures)
  • Diarrhea, flushing, and other systemic symptoms caused by the secretion of calcitonin or other peptides (in some patients)
  • Often asymptomatic in the early stages

Treatment Methods

• Primary and standard treatment after diagnosis
  • Surgery: The definitive treatment is surgery, usually total thyroidectomy + central (central compartment) neck lymph node dissection. If lymph node metastasis is confirmed or suspected, lateral neck lymph node dissection is performed.
  • Radioactive iodine therapy: Medullary thyroid carcinoma absorbs little to no radioactive iodine and therefore does not respond to it (not used).
• Management according to genetic predisposition
  • RET genetic testing is recommended for all patients with MTC (to determine whether it is hereditary and to screen family members).
  • If a pathogenic RET variant is identified, genetic testing for family members is recommended. In the case of some high-risk variants, prophylactic total thyroidectomy may be considered depending on the age and mutation type.
• Drug treatment for advanced or refractory disease
  • Targeted therapy: Selective RET inhibitors (such as selpercatinib and pralsetinib) may be effective for advanced/metastatic MTC with a confirmed RET mutation.
  • Multitarget tyrosine kinase inhibitors (e.g., vandetanib and cabozantinib) are approved treatment options for advanced/metastatic MTC.
  • Other systemic treatments (chemotherapy and clinical trials) may be considered depending on the patient's condition and molecular markers.
• Follow-up and supportive treatment
  • Thyroid hormone replacement therapy after surgery (lifelong)
  • Regular measurement of blood calcitonin and CEA (tumor marker) to monitor for recurrence or residual disease
  • Monitoring for metastasis with imaging tests (neck ultrasound, CT, PET/CT, etc.)
• Precautions (complications and self-care)
  • Surgical complications: Voice changes (voice impairment) due to laryngeal nerve injury, and hypocalcemia (weakness, tingling, etc.) due to parathyroid injury
  • Take thyroid hormone medication on an empty stomach (in the morning, preferably 30 minutes before a meal) and maintain a time interval from other medications and supplements (such as iron, calcium, and antacids)
  • Targeted therapy for advanced disease may cause side effects (fatigue, hypertension, gastrointestinal symptoms, abnormal liver function, etc.), requiring regular monitoring
  • If the disease is hereditary, family screening and genetic counseling are recommended

Checklist Before an Outpatient Visit (Including Items to Bring and Example Questions)

• Items to bring
  • A list of currently taken medications and supplements (including doses and administration times)
  • Copies or records of previous test results (ultrasound, FNA report, CT/MRI, blood test results, etc.)
  • Family history information (thyroid cancer, thyroid surgery, endocrine diseases, and history related to MEN)
  • A record of symptom changes (changes in neck size, pain, voice changes, swallowing/breathing problems, diarrhea, etc.)
• Items to check before the outpatient visit
  • Recent weight changes, fatigue, tingling or numbness in the hands and feet, and muscle cramps (symptoms of hypocalcemia)
  • If you have recently undergone imaging, bring the images or records if possible
• Prepared questions to ask the doctor during the outpatient visit (examples)
  • Whether surgery is necessary and how urgent it is, and the extent of surgery (total thyroidectomy + whether lymph node dissection is needed)
  • Whether RET genetic testing is needed and whether testing for family members is recommended

Examples of General Questions to Ask the Doctor

• What is the standard treatment for this disease, and what treatment strategy is recommended in my case?
• What complications can be expected after surgery, and how can they be prevented and managed?
• How often and with which tests will recurrence be monitored after surgery (frequency of calcitonin/CEA testing, imaging tests, etc.)?
• When should genetic testing (RET) be performed? What tests and procedures are recommended for family members?
• What medications (targeted therapies) can be used for advanced disease, and what are their efficacy and major side effects?
• What are the specific instructions for taking thyroid hormone medication (timing and interval from food and medications)?

Examples of Disease-Specific Questions (1–2)

• What criteria based on my pathology results or blood calcitonin/CEA levels indicate a cured state after surgery (normal range or criteria for a sharp decline)?
• A pathogenic variant was found on my RET genetic test. When and how should my children or siblings undergo genetic testing, and might they be advised to have prophylactic surgery?

(If necessary, discuss additional tests and treatment options, as well as genetic counseling and a family screening plan, with your treating doctor.)