Medullary Thyroid Carcinoma (MTC)


Medullary thyroid cancer (MTC) involves thyroid neoplasm, which originates from neuroendocrine-derived parafollicular or calcitonin secreting C cells. Patients diagnosed with MTC demonstrate a wide range of symptoms like diarrhea, flushing, bone pain, or weight loss.¹ The recommended guidelines for  MTC diagnosis involve fine needle aspiration (FNA) of suspicious nodules, measurement of carcinoembryonic antigen (CEA) and serum calcitonin, and germline RET genetic testing. Based on recommended guidelines, an initial diagnosis of MTC based on a suspicious thyroid nodule² can be differentiated with the following:

Anaplastic Thyroid Carcinoma

Anaplastic Thyroid Carcinoma (ATC) causes high mortality up to 40% due to its aggressive nature. It accounts for only 2% of all thyroid cancers. The 5-year survival rate of ATC is less than 10% as most of the patients live for only a couple of months after initial diagnosis. A suspicious thyroid nodule can be diagnosed with fine-needle aspiration biopsy (FNAB) which can lead to either benign, malignant, suspicious, or nondiagnostic thyroid nodule. Patients suffering from ATC have a rapidly growing neck mass, which typically metastases to the lung. Lung metastasis acts as one of the relevant diagnostic criteria for ATC.³

De Quervain Thyroiditis

De Quervain Thyroiditis involves inflammation of the thyroid gland, which can lead to a variation of the thyroid function. It can be painful or painless depending upon the etiology of the disease. Patients diagnosed with De Quervain Thyroiditis suffer from the viral infection involving echovirus, and coxsackievirus (group A & B). Studies show that it is also associated with mumps, measles, influenza, and other viruses. Diagnosis of De Quervain Thyroiditis includes physical findings, such as neck pain, tenderness, etc., along with lab testing of erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), free thyroxine (T4), and thyroid-stimulating hormone levels (TSH). Patients typically present with elevated ESR and CRP levels with mild leukocytosis.⁴

Follicular Thyroid Carcinoma

Follicular Thyroid Carcinoma (FTC) accounts for 95% of all thyroid cancer cases.⁵ Diagnosis of FTC involves surgical excision of the suspected thyroid nodule with complete microscopic analysis. The following thyroid blood test is conducted – TSH, T3, T4, thyroglobulin antibody along with radiological scans like ultrasound, PET/CT, MRI scan. Thyroid surgery with lobectomy or total thyroidectomy is recommended for patients suffering from FTC.⁶

Goiter

Goiter diagnosis involves a physical examination of the neck as an enlarged thyroid gland can be palpated to feel the presence of nodules. A goiter is associated with elevated thyroid hormones in the blood with low TSH. A thyroid scan can be conducted using a radioactive isotope that is injected through the vein. It offers information about the nature and size of the thyroid. Apart from that, a fine needle aspiration biopsy can be conducted to evaluate the tissue extracted from the thyroid gland.⁷

Graves Disease

The clinical diagnosis of Graves disease includes the combination of hyperthyroidism, goiter, and protruding of eyes. The characteristic features and manifestation of the disease are hard to escape. The diagnosis of Graves Disease doesn’t solely depend upon thyrotoxicosis. Ophthalmopathy or pretibial myxedema are also part of the clinical features of the disease. Patients can exhibit a wide array of symptoms, such as prominence or puffiness of eyelids, polyuria, weakness, tremors, nervousness, irritability, insomnia, etc. During the physical examination, a patient might demonstrate tachypnea on exertion, thyroid thrill, and bruit, lymphadenopathy, restlessness, tremor, hypermetric reflexes, etc.⁸

Hyperthyroidism and Thyrotoxicosis

Thyrotoxicosis can lead to an increase in circulating thyroid hormones (T3 and/or T4) causing hyperthyroidism with life-threatening underlying complications like congestive heart failure (CHF), thromboembolic disease, cardiovascular collapse, altered mental status, etc. Most of the patients will present with symptoms like weight loss, fatigue, heat intolerance, palpitations, etc. Untreated or undiagnosed thyrotoxicosis can lead to thyroid storm which can precipitate cardiac and impaired liver function. Appropriate medical therapy with lab studies and imaging is often warranted.⁹

Intestinal Carcinoid Tumor

Intestinal carcinoid tumors can affect the inner linings of the gastrointestinal tract. They don’t exhibit signs and symptoms at an early stage. Carcinoid syndrome can occur when the tumor spreads to the liver and other parts of the body. Examination of the blood and urine can diagnose intestinal or gastrointestinal carcinoid tumors. Patients with a family history of neurofibromatosis type 1 (NF1) or multiple endocrine neoplasia type 1 (MEN1) syndrome are more susceptible to it.¹º

Medullary Thyroid Carcinoma

Patients diagnosed with medullary thyroid carcinoma are detected with a lump in the neck. Cancer typically spreads to the lymph nodes which can be tender or painful. 75% of patients diagnosed with medullary thyroid carcinoma have a genetic inheritance. Studies show that patients diagnosed with medullary thyroid carcinoma usually have RET mutations in their genes. They have a 50% chance of passing it to the next generation. Genetic counseling along with lab testing studies of TSH, Free T4, Calcitonin, CEA, Serum metanephrines, PTH, and Ca need to be conducted along with ultrasound of the neck and fine-needle aspiration of lateral neck lymph nodes.¹¹

Papillary Thyroid Carcinoma

Most patients diagnosed with papillary thyroid carcinoma are found incidentally as a lump within their thyroid gland. It accounts for 85% of all thyroid cancers and women are 3 times more susceptible than men. It is the 5th most common cancer for women in the US. Blood testing of TSH, T3, and T4, Thyroglobulin Antibody is required along with ultrasound-guided fine-needle aspiration (FNA).¹²

Thyroid Lymphoma

Patients diagnosed with primary thyroid lymphoma present with firm and enlarged thyroid glands. It can cause puffiness or swelling of the eyes as it presses on the veins which drain blood from the brain. It can also cause hypothyroidism due to decreased production of thyroid hormones. Patients diagnosed with thyroid lymphoma may present with symptoms like cold or dry skin, constipation, feeling tired or slow, etc. Fine needle aspiration (FNA) of the thyroid gland and/or the lymph nodes is recommended.¹³

Benign Thyroid Nodule 

Thyroid nodules can be diagnosed with physical examination wherein an asymptomatic patient is asked to imitate swallowing while the nodule moves up and down within the thyroid gland. A thyroid nodule can cause hypo or hyperthyroidism. It is important to rule out cancer using fine-needle aspiration biopsy. A thyroid scan can help differentiate between hot nodules which produce excess thyroid hormone and cold nodules, which take up less of the isotope. Hot nodules are usually benign while cold nodules can be cancerous or non-cancerous.¹⁴

Toxic Nodular Goiter 

It involves a rounded mass with an enlarged thyroid gland, which produces too much thyroid hormone. Patients exhibit symptoms like heat intolerance, muscle cramps, frequent bowel movement, restlessness, increased appetite, weight loss, etc. Physical diagnosis reveals rapid heart rate, with single or multiple nodules in the thyroid gland. It can lead to elevated serum T3 and T4, and decreased TSH.¹⁵

Multiple Endocrine Neoplasia Type 2 (MEN2)

MEN2 is a genetic condition that is associated with mutations in the RET gene. Altered genes can increase the risk of developing thyroid cancer. Inheritance of the gene can lead to the development of medullary thyroid cancer, especially among children. RET gene testing is recommended for children with risk of MEN2 subtypes.¹⁶

References

  1. Kebebew, E., Clark, O.H. Medullary thyroid cancer. Current Treatment Options in Oncology. 1, 359–367 (2000). https://doi.org/10.1007/s11864-000-0052-7
  2. Thomas CM, Asa SL, Ezzat S, Sawka AM, Goldstein D. Diagnosis and pathologic characteristics of medullary thyroid carcinoma-review of current guidelines. Current Oncology. 2019;26(5):338-344. doi:10.3747/co.26.5539
  3. Anaplastic thyroid carcinoma. Medscape. Accessed July 2, 2021.
  4. Tabassom A, Edens MA. De quervain thyroiditis. [Updated 2020 Jul 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526066/
  5. Follicular thyroid carcinoma. Medscape. Accessed July 2, 2021.
  6. Diagnosis of follicular thyroid cancer. ClaymanThyroid Center. Accessed July 4, 2021.
  7. Goiter – diagnosis and treatment. Mayo Clinic. Accessed July 2, 2021
  8. DeGroot LJ. Diagnosis and treatment of graves’ disease. [Updated 2016 Nov 2]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK285548/
  9. Blick C, Nguyen M, Jialal I. Thyrotoxicosis. [Updated 2020 Dec 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482216/
  10. Gastrointestinal carcinoid tumors treatment (adult) (PDQ®)–patient version. National Cancer Institute. Accessed July 2, 2021.
  11. Medullary thyroid carcinoma diagnosis. Clayman Thyroid Center. Accessed July 2, 2021.
  12. Diagnosis of papillary thyroid cancer. Clayman Thyroid Center. Accessed July 2, 2021.
  13. Primary thyroid lymphoma. American Thyroid Association. Accessed July 2, 2021.
  14. Thyroid nodules – diagnosis and treatment. Mayo Clinic. Accessed July 2, 2021.
  15. Toxic nodular goiter. UCLA Health. Accessed July 2, 2021.
  16. Multiple endocrine neoplasia type 2. American Society of Clinical Oncology. Accessed July 2, 2021.

Article reviewed by Kyle Habet, MD, on July 1, 2021.

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