Medullary Thyroid Carcinoma

Overview

• Neuroendocrine tumor arising from parafollicular C-cells of the thyroid (not follicular cells).
• Produces calcitonin (tumor marker) and sometimes carcinoembryonic antigen (CEA).
• Accounts for ~3–4% of thyroid cancers.
• Can be sporadic (~75%) or hereditary (~25%) as part of Multiple Endocrine Neoplasia (MEN) type 2A, 2B, or FMTC (germline RET mutations).

Key Clinical Features

• Neck mass, cervical lymphadenopathy
• Elevated calcitonin & CEA
• May secrete hormones → flushing, diarrhea (due to calcitonin, VIP, or serotonin)
• Aggressive course, often with early lymph node and liver metastasis

Diagnosis

• Serum calcitonin & CEA (biomarkers for disease burden and progression)
• Genetic testing for RET mutations (mandatory for patients and relatives)
• Ultrasound of thyroid and neck nodes
• No role for radioactive iodine (tumor is not iodine-avid)

Management

1. Surgery (curative if localized)
   • Total thyroidectomy + central neck dissection
   • In hereditary cases: prophylactic thyroidectomy in RET-positive children (timing depends on RET mutation risk group).
2. Systemic Therapy (advanced/metastatic, unresectable disease):
   • First-line TKIs:
     • Vandetanib (Caprelsa®) – RET, VEGFR, EGFR inhibitor
     • Cabozantinib (Cometriq®) – RET, VEGFR, MET inhibitor
   • Selective RET inhibitors (preferred if RET mutation present):
     • Selpercatinib (Retevmo®)
     • Pralsetinib (Gavreto®)
   • Both RET-selective inhibitors show higher response rates and better tolerability than older multikinase TKIs.
3. Symptom management
   • Control diarrhea (loperamide, somatostatin analogs if severe and calcitonin-mediated)
   • Supportive care for hypertension, rash, QT prolongation with TKIs

Prognosis

• Depends on stage and presence of metastasis
• 10-year survival:
  • Localized: >90%
  • Distant metastasis: ~40%
• Persistent elevation of calcitonin or CEA post-surgery → suggests residual or recurrent disease

Key Pharmacist Points

• Radioactive iodine and levothyroxine suppression therapy are NOT effective (C-cells don’t uptake iodine or respond to TSH).
• Monitor calcitonin & CEA regularly for disease progression.
• TKI therapy requires monitoring for hypertension, diarrhea, QT prolongation (vandetanib), hand-foot syndrome (cabozantinib), and drug–drug interactions.
• Encourage genetic counseling for patients and families with hereditary forms.