Medullary Thyroid Cancer
Disease Details
Family Health Simplified
- Description
- Medullary thyroid cancer is a rare type of thyroid cancer that arises from the parafollicular cells (C cells) which produce the hormone calcitonin.
- Type
- Medullary thyroid cancer (MTC) is a type of thyroid cancer that arises from the parafollicular C cells of the thyroid gland. It can occur sporadically or be inherited. The inherited form of MTC is typically transmitted in an autosomal dominant pattern and is often associated with multiple endocrine neoplasia type 2 (MEN2), including MEN2A and MEN2B syndromes.
- Signs And Symptoms
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The major clinical symptom of metastatic medullary thyroid carcinoma is diarrhea; occasionally a patient will have flushing episodes. Both occur particularly with liver metastasis, and either symptom may be the first manifestation of the disease. The flushing that occurs in medullary thyroid carcinoma is indistinguishable from that associated with carcinoid syndrome. In MTC, the flushing, diarrhea, and itching (pruritus) are all caused by elevated levels of calcitonin gene products (calcitonin or calcitonin gene-related peptide). By comparison, the flushing and diarrhea observed in carcinoid syndrome is caused by elevated levels of circulating serotonin.
Medullary thyroid carcinoma may also produce a thyroid nodule and enlarged cervical lymph nodes.Sites of spread of medullary thyroid carcinoma include local lymph nodes in the neck, lymph nodes in the central portion of the chest (mediastinum), liver, lung, and bone. Spread to other sites such as skin or brain occurs but is uncommon. - Prognosis
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Depending on source, the overall 5-year survival rate for medullary thyroid cancer is 80%, 83% or 86%, and the 10-year survival rate is 75%.By overall cancer staging into stages I to IV, the 5-year survival rate is 100% at stage I, 98% at stage II, 81% at stage III and 28% at stage IV. The prognosis of MTC is poorer than that of follicular and papillary thyroid cancer when it has metastasized (spread) beyond the thyroid gland.
The prognostic value of measuring calcitonin and carcinoembryonic antigen (CEA) concentrations in the blood was studied in 65 MTC patients who had abnormal calcitonin levels after surgery (total thyroidectomy and lymph node dissection). The prognosis correlated with the rate at which the postoperative calcitonin concentration doubles, termed the calcitonin doubling time (CDT), rather than the pre- or postoperative absolute calcitonin level:
CDT less than 6 months: 3 patients out of 12 (25%) survived 5 years. 1 patient out of 12 (8%) survived 10 years. All died within 6 months to 13.3 years.
CDT between 6 months and 2 years: 11 patients out of 12 (92%) survived 5 years. 3 patients out of 8 (37%) survived 10 years. 4 patients out of 12 (25%) survived to the end of the study.
CDT more than 2 years: 41 patients out of 41 (100%) were alive at the end of the study. These included 1 patient whose calcitonin was stable, and 11 patients who had decreasing calcitonin levels.The calcitonin doubling time was a better predictor of MTC survival than CEA but following both tests is recommended. - Onset
- Medullary thyroid cancer typically has an onset in adulthood, often between the ages of 40 and 60. It can also occur in younger individuals if associated with genetic conditions such as Multiple Endocrine Neoplasia type 2 (MEN2).
- Prevalence
- The prevalence of medullary thyroid cancer (MTC), a rare type of thyroid cancer, is about 1-2% of all thyroid cancer cases.
- Epidemiology
- Medullary thyroid cancer (MTC) represents approximately 3-4% of all thyroid cancers. It can occur sporadically or as part of genetic syndromes such as Multiple Endocrine Neoplasia type 2 (MEN 2). Sporadic cases account for about 75-80% of MTC cases, while hereditary forms make up the remaining 20-25%. The median age of diagnosis for sporadic MTC is around 50 years, whereas hereditary forms often present earlier, sometimes in adolescence or young adulthood. There is no clear gender predilection, as MTC affects both males and females equally.
- Intractability
- Medullary thyroid cancer (MTC) can be challenging to treat, particularly if it has metastasized beyond the thyroid gland or is part of a genetic syndrome like Multiple Endocrine Neoplasia type 2 (MEN 2). Early-stage MTC may be managed effectively with surgery, but advanced cases often require a multimodal approach, including surgery, radiation, and potentially targeted therapies. Despite advances, complete remission can be difficult to achieve in metastatic MTC, making it a relatively intractable condition in advanced stages.
- Disease Severity
- Disease Severity: Medullary thyroid cancer (MTC) can vary in severity based on its stage at diagnosis and whether it has metastasized. Early-stage MTC confined to the thyroid gland typically has a better prognosis and may be curable with surgery. Advanced stages that involve spread to lymph nodes or distant organs have a more serious prognosis and may require additional treatments such as radiation or targeted therapy. Genetic factors, particularly mutations in the RET proto-oncogene, can also influence the severity and progression of the disease. Regular follow-up and monitoring are crucial for managing the disease effectively.
- Healthcare Professionals
- Disease Ontology ID - DOID:3973
- Pathophysiology
- Medullary thyroid cancer (MTC) is a rare type of thyroid cancer originating from the parafollicular C cells of the thyroid gland, which produce the hormone calcitonin. The pathophysiology of MTC involves mutations in the RET proto-oncogene, which lead to uncontrolled cellular proliferation and tumor formation. These mutations can be sporadic or inherited in an autosomal dominant pattern, as seen in familial cases and multiple endocrine neoplasia type 2 (MEN2). Elevated levels of calcitonin serve as a biomarker for the disease, and mutated RET proteins result in activation of signaling pathways promoting cell growth and survival.
- Carrier Status
- Carrier status is not typically a concern for medullary thyroid cancer (MTC). However, familial MTC can be part of multiple endocrine neoplasia type 2 (MEN2), which is caused by mutations in the RET gene. Individuals with a RET gene mutation have a high risk of developing MTC and can pass this mutation to their offspring. Genetic testing for RET mutations can determine carrier status in families with a history of MEN2.
- Mechanism
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Medullary thyroid cancer (MTC) arises from the parafollicular C-cells of the thyroid gland.
**Mechanism:**
MTC typically results from mutations in the RET proto-oncogene. These mutations lead to the activation of the RET receptor tyrosine kinase, promoting uncontrolled cellular growth and proliferation of C-cells.
**Molecular mechanisms:**
1. **RET Proto-Oncogene Mutations:** Most cases of hereditary MTC are associated with germline mutations in the RET proto-oncogene, while sporadic cases often involve somatic RET mutations.
2. **MAPK Pathway Activation:** RET mutations activate downstream signaling pathways, notably the MAPK pathway (Mitogen-Activated Protein Kinase), leading to cell division and tumorigenesis.
3. **PI3K/AKT Pathway Activation:** Another pathway influenced by RET mutations is the PI3K/AKT pathway, which promotes survival and growth of cancer cells.
4. **Transcriptional Regulation:** Mutant RET influences transcription factors that regulate genes involved in cell cycle progression and apoptosis, contributing to neoplastic transformation of C-cells.
Additionally, understanding these mechanisms has paved the way for targeted therapies, like tyrosine kinase inhibitors, which specifically inhibit RET kinase activity. - Treatment
- Surgery and radiation therapy have been the major treatments for medullary thyroid carcinoma. A plasma level of metanephrines should be checked before surgical thyroidectomy takes place to evaluate for the presence of pheochromocytoma since 25% of people found to have medullary thyroid cancer have the inherited form from the MEN2A syndrome. Undiagnosed pheochromocytoma leads to a very high intraoperative risk of hypertensive crisis and, potentially, death.
- Compassionate Use Treatment
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Medullary thyroid cancer (MTC) may sometimes be treated with compassionate use or off-label and experimental treatments when standard therapies are not effective. These options may include:
1. **Targeted Therapies**:
- Vandetanib and cabozantinib are approved targeted therapies for advanced MTC. Experimental or off-label use of other tyrosine kinase inhibitors (TKIs) may be considered, such as lenvatinib or sorafenib.
2. **Immunotherapy**:
- Drugs like pembrolizumab or nivolumab, although primarily used for other cancers, are being investigated for potential effectiveness against MTC.
3. **Experimental Agents**:
- Clinical trials may offer access to new drugs or combinations of drugs currently being studied for efficacy against MTC.
4. **RET Inhibitors**:
- Selpercatinib and pralsetinib are specifically designed to target RET mutations and are indicated for MTC with such genetic alterations.
Patients seeking compassionate use or experimental treatments should discuss these options with their healthcare provider, who may also have access to ongoing clinical trials or expanded access programs. - Lifestyle Recommendations
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For Medullary Thyroid Cancer (MTC), here are some lifestyle recommendations:
1. **Follow Medical Advice**: Regularly see your healthcare provider and stick to the treatment plan, which may include surgery, medications, or other therapies.
2. **Healthy Diet**: Consume a balanced diet rich in fruits, vegetables, whole grains, and lean proteins. Limit processed foods, sugar, and unhealthy fats.
3. **Regular Exercise**: Engage in regular physical activity, such as walking, swimming, or yoga, to maintain overall health and improve energy levels.
4. **Avoid Smoking and Limit Alcohol**: Smoking can worsen treatment outcomes, and excessive alcohol intake can affect overall health.
5. **Manage Stress**: Practice stress-reducing activities like meditation, deep-breathing exercises, or hobbies you enjoy.
6. **Stay Informed**: Keep up-to-date with new information and treatments related to MTC and discuss these with your healthcare provider.
7. **Support System**: Seek support from family, friends, or support groups to help you cope with the disease.
Remember to regularly consult with your healthcare provider for personalized advice tailored to your specific condition. - Medication
- Medications used for medullary thyroid cancer (MTC) include targeted therapies such as vandetanib and cabozantinib. These medications inhibit specific pathways involved in cancer cell growth and are used particularly in cases where the cancer is advanced or metastatic.
- Repurposable Drugs
- There are no widely recognized repurposable drugs specifically approved for medullary thyroid cancer treatment at this time. However, some targeted therapies such as vandetanib and cabozantinib, which are tyrosine kinase inhibitors, have shown efficacy in treating advanced cases of medullary thyroid cancer. Ongoing research and clinical trials may identify additional repurposable drugs in the future.
- Metabolites
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Medullary thyroid cancer (MTC) is known to produce certain metabolites that can be used as tumor markers. The key metabolites and markers for MTC include:
1. **Calcitonin:** Elevated levels are highly indicative of MTC.
2. **Carcinoembryonic Antigen (CEA):** Often elevated in MTC patients and used for monitoring disease progression.
Other potential metabolites and diagnostic markers can include chromogranin A, although Calcitonin and CEA are the primary and most clinically relevant ones. - Nutraceuticals
- For medullary thyroid cancer, the role of nutraceuticals is not well established. There is limited scientific evidence supporting the use of dietary supplements or nutraceuticals specifically for the treatment or management of medullary thyroid cancer. It is important to prioritize conventional treatments, such as surgery, radiotherapy, and systemic therapies, and discuss any complementary approaches with a healthcare professional.
- Peptides
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Medullary thyroid cancer (MTC) is a type of thyroid cancer originating from the parafollicular cells (C cells), which produce the hormone calcitonin. Significant peptides related to MTC include:
1. **Calcitonin**: Elevated levels of this peptide hormone are a hallmark of MTC, as C cells normally produce it.
2. **Carcinoembryonic Antigen (CEA)**: Another marker often elevated in MTC, aiding in diagnosis and monitoring.
3. **Procalcitonin**: Increased levels can be associated with MTC.
However, "nan" does not appear to relate directly to MTC or its typical markers within this context.