Sporadic MTC presents with a unilateral tumor, which is in contrast to the bilateral and multiple MTC masses found in MEN2 cases. Another notable characteristic regarding hereditary forms is that MTC is the initial presenting disease in the MEN2 syndromes.

With regards to the clinical picture, patients with MTC typically complain of a lump at the base of the neck that often appears during swallowing. Furthermore, larger tumors may cause manifestations such as hoarseness, dysphagia, and dyspnea. Additionally, there are consequences of elevated serum calcitonin levels since this in turn will increase the intestinal secretion of electrolytes, which results in diarrhea. Flushing is another feature of raised calcitonin values.

Metastasis of MTC involves distant sites such as the liver, lung, mediastinum, bone, and lymph nodes. Hence, systemic disease may cause weight loss, lethargy, jaundice, abdominal pain, and bone pain.

In rare cases, paraneoplastic syndromes such as Cushing or carcinoid syndrome may develop. These present with their own constellation of symptoms.

Physical exam

A remarkable finding on examination is a prominent thyroid nodule at the base of the neck. Furthermore, locally advanced disease will be evidenced by palpable cervical lymph nodes.

• Cervical Lymphadenopathy

  The children had near-normal calcitonin levels, and none had sonographic evidence of suspicious thyroid nodules or cervical lymphadenopathy. [ncbi.nlm.nih.gov]

  Palpable cervical lymphadenopathy signifies disease that has progressed locally. Icterus, and rarely, bone tenderness may occur in patients with systemic metastases. [reference.medscape.com]

  She also had a large multinodular goiter involving both lobes of thyroid with retrosternal extension and left lateral cervical lymphadenopathy ( Figure 2 ). She has proximal myopathy with grade 4 power in bilateral lower limbs. [omicsonline.org]

  Neck ultrasonography is particularly useful in sporadic cases as these typically manifest with a thyroid mass and/or cervical lymphadenopathy. Ultrasound also provides guidance during the FNA procedure. [symptoma.com]

• Thyroid Nodule

  Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. [reference.medscape.com]

  BACKGROUND: To prospectively evaluate the role of procalcitonin (PCT) in screening of patients with thyroid nodules for medullary thyroid carcinoma (MTC). [ncbi.nlm.nih.gov]

  Isolated thyroid nodule At presentation, most of the time, patients have an isolated thyroid nodule [2], and the diagnosis needs fine needle biopsy with elevated serum calcitonin. [intechopen.com]

  Task Force on thyroid nodules and differentiated thyroid cancer. [current-oncology.com]

• Pain

  A 53-year-old white woman presented with increasing fatigue, loss of appetite, and severe epigastric pain radiating to her back. [ncbi.nlm.nih.gov]

  Learning points When patients present with neck pains, a thorough, focused physical exam should be performed. [casereports.bmj.com]

  These may include: a large mass in the neck pain in the neck, jaw, or ear choking sensations People with cancer that has spread to the nerves that control the vocal cords may also experience hoarseness or changes in their voice. [medicalnewstoday.com]

  Neck pain. Pain in the front of the neck may be related to the growth of a thyroid tumor. This pain can also extend to the ears. Hoarseness. The nerve that controls your vocal cords runs alongside the trachea near the thyroid. [healthline.com]

• Goiter

  Clinical examples of amyloid deposition in parathyroid glands are exceedingly rare and usually present as an incidental finding in a patient with amyloid goiter. [ncbi.nlm.nih.gov]

  Some symptoms may include hoarseness, enlarged thyroid (goiter), and cough. Common symptoms reported by people with medullary thyroid cancer Reports may be affected by other conditions and/or medication side effects. [patientslikeme.com]

  Figure 2: Goiter. On investigation, She was biochemically Euthyroid with TSH value of 4.85mIU/L. Fine needle aspiration cytology was suggestive of Medullary carcinoma thyroid with serum calcitonin value more than 20000pg/ml. [omicsonline.org]

  (plunging) (substernal) E04.9 ICD-10-CM Diagnosis Code E04.9 Nontoxic goiter, unspecified 2016 2017 2018 2019 Billable/Specific Code Applicable To Goiter NOS Nodular goiter (nontoxic) NOS cancerous C73 malignant C73 Hurthle cell adenocarcinoma C73 carcinoma [icd10data.com]

• Lymphadenopathy

  The children had near-normal calcitonin levels, and none had sonographic evidence of suspicious thyroid nodules or cervical lymphadenopathy. [ncbi.nlm.nih.gov]

  Neither imaging modalities showed associated lymphadenopathy. The diagnosis of a neuroendocirne thyroid tumour was made and ultrasound guided fine-needle aspiration cytology of the thyroid mass was performed. [endocrine-abstracts.org]

  Palpable cervical lymphadenopathy signifies disease that has progressed locally. Icterus, and rarely, bone tenderness may occur in patients with systemic metastases. [reference.medscape.com]

  Because preoperative neck ultrasound is highly sensitive for detecting lateral lymphadenopathy, an ipsilateral lateral lymphadenectomy can be added when the ultrasound or physical exam suggests the presence of lateral lymphadenopathy. [theoncologist.onlinelibrary.wiley.com]

• Fatigue

  A 53-year-old white woman presented with increasing fatigue, loss of appetite, and severe epigastric pain radiating to her back. [ncbi.nlm.nih.gov]

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: January 31, 2019 [patientslikeme.com]

  The causes of fatigue during cancer are complex and not well understood. Weight loss. Unusual weight loss is a symptom of advanced medullary thyroid cancer that has spread beyond the thyroid into other organs. [healthline.com]

  Of patients on cabozantinib, 69% reported grade 3 or 4 adverse events mainly diarrhoea, palmar-plantar erythrodysesthesia and fatigue. [touchendocrinology.com]

  Despite the diagnosis and struggling with fatigue and constant trips to the bathroom, Emmy said she remained positive and was almost relieved to have a diagnosis after two years of stress. [express.co.uk]

• Hoarseness

  These may include: a large mass in the neck pain in the neck, jaw, or ear choking sensations People with cancer that has spread to the nerves that control the vocal cords may also experience hoarseness or changes in their voice. [medicalnewstoday.com]

  The noticeable signs and symptoms like hoarseness, difficulty swallowing, or throat lumps often don’t appear until the tumor has advanced. [healthline.com]

  As a result, symptoms may include: Swelling of the neck Hoarseness Breathing problems due to narrowing of airways Cough Cough with blood Diarrhea due to high calcitonin level Your health care provider will perform a physical exam and ask about your symptoms [nlm.nih.gov]

  Some symptoms may include hoarseness, enlarged thyroid (goiter), and cough. Common symptoms reported by people with medullary thyroid cancer Reports may be affected by other conditions and/or medication side effects. [patientslikeme.com]

• Dyspnea

  Shortness of breath (dyspnea). Similar to trouble swallowing, if a thyroid tumor is large enough, it can push against the windpipe and interfere with breathing. [healthline.com]

  Furthermore, larger tumors may cause manifestations such as hoarseness, dysphagia, and dyspnea. [symptoma.com]

  The thyroid nodule is associated with clinical symptoms, such as dysphagia, hoarseness, dyspnea and coughing. Laryngoscopy usually reveals vocal cord dysfunction resulting from involvement of the recurrent laryngeal nerve. [doi.org]

• Diarrhea

  The patient's symptoms of diarrhea, coughing, and shortness of breath disappeared. CT reexaminations for efficacy assessment at 1, 2, and 3 months after the treatment indicated partial remission. [ncbi.nlm.nih.gov]

  Our patient’s main presenting symptom was diarrhea, in which case MTC is not high on a differential. [hindawi.com]

  In MTC, the flushing, diarrhea, and itching (pruritus) are all caused by elevated levels of calcitonin gene products (calcitonin or calcitonin gene-related peptide).[4] Alternatively, the flushing and diarrhea observed in carcinoid syndrome is caused [en.wikipedia.org]

• Dysphagia

  Of the final two probands, one had an incidental 1.5 mm MTC and C-cell hyperplasia uncovered after surgery for papillary thyroid carcinoma, and one had two foci of MTC (largest dimension 2.3 cm) detected after surgery for dysphagia. [ncbi.nlm.nih.gov]

  He denied any dysphagia, respiratory difficulties or changes in voice. Thyroid stimulating hormone was normal at 1.18 mIU/ml. [casereports.bmj.com]

  There may also be a swelling in the neck (a goitre) which may cause difficulty with swallowing (dysphagia). Individuals may indeed be asymptomatic or may present with skin changes such as lichen amyloidosis. [endocrinesurgeon.co.uk]

  Trouble swallowing (dysphagia). If a thyroid tumor becomes large enough, it can press on the esophagus and make swallowing difficult. Shortness of breath (dyspnea). [healthline.com]

  […] however, one or more of the following symptoms may be observed: Patients may describe a lump at the base of the neck, which may interfere with or become more prominent during swallowing Patients with locally advanced disease may present with hoarseness, dysphagia [reference.medscape.com]

• Dysphagia

  Of the final two probands, one had an incidental 1.5 mm MTC and C-cell hyperplasia uncovered after surgery for papillary thyroid carcinoma, and one had two foci of MTC (largest dimension 2.3 cm) detected after surgery for dysphagia. [ncbi.nlm.nih.gov]

  He denied any dysphagia, respiratory difficulties or changes in voice. Thyroid stimulating hormone was normal at 1.18 mIU/ml. [casereports.bmj.com]

  There may also be a swelling in the neck (a goitre) which may cause difficulty with swallowing (dysphagia). Individuals may indeed be asymptomatic or may present with skin changes such as lichen amyloidosis. [endocrinesurgeon.co.uk]

  Trouble swallowing (dysphagia). If a thyroid tumor becomes large enough, it can press on the esophagus and make swallowing difficult. Shortness of breath (dyspnea). [healthline.com]

  […] however, one or more of the following symptoms may be observed: Patients may describe a lump at the base of the neck, which may interfere with or become more prominent during swallowing Patients with locally advanced disease may present with hoarseness, dysphagia [reference.medscape.com]

• Abdominal Pain

  We present a 55-year-old man with abdominal pain associated with well-differentiated NET liver metastases and incidental medullary thyroid carcinoma demonstrated on a Ga-DOTATATE PET/CT. [ncbi.nlm.nih.gov]

  Once it spreads, symptoms may include: Weight loss Lethargy Jaundice Abdominal pain Bone pain On the physical exam, the physician will feel a thyroid nodule at the base of the neck. [symptoma.com]

  Abdominal pain, jaundice, and rarely, bone tenderness may occur in patients with systemic metastases. [reference.medscape.com]

  A 91 years-old man was admitted to Emergency Department reporting abdominal pain and vomit. [giornalechirurgia.it]

  In the healthy controls and MTC patients, several transitory side effects were observed during the pentagastrin test: a feeling of substernal tightness in 38 of 40 cases, nausea in 34 of 40 cases, abdominal pain in 29 of 40 cases, tachycardia in 26 of [clinchem.aaccjnls.org]

• Jaundice

  Once it spreads, symptoms may include: Weight loss Lethargy Jaundice Abdominal pain Bone pain On the physical exam, the physician will feel a thyroid nodule at the base of the neck. [symptoma.com]

  Abdominal pain, jaundice, and rarely, bone tenderness may occur in patients with systemic metastases. [reference.medscape.com]

• Flushing

  During assessment he commented that over the same period he had also had intermittent sweats, flushing and redness of the face especially after eating and taking red wine. [endocrine-abstracts.org]

  In MTC, the flushing, diarrhea, and itching (pruritus) are all caused by elevated levels of calcitonin gene products (calcitonin or calcitonin gene-related peptide).[4] Alternatively, the flushing and diarrhea observed in carcinoid syndrome is caused [en.wikipedia.org]

• Bone Pain

  Bone pain. People with medullary thyroid cancer may have bone pain if the cancer has spread to form bone lesions. Lethargy. Many people with advanced cancer may feel physically, emotionally, or mentally tired. [healthline.com]

  Metastasis of MTC involves distant sites such as the liver, lung, mediastinum, bone, and lymph nodes. Hence, systemic disease may cause weight loss, lethargy, jaundice, abdominal pain, and bone pain. [symptoma.com]

  Abdominal pain, jaundice, and rarely, bone tenderness may occur in patients with systemic metastases. [reference.medscape.com]

  You may also have any of the following: Bone pain. Flushed (red) skin. Hoarse (rough) voice. Increased fat on your neck, collar area, and back with puffiness of your face. Trouble swallowing. Diarrhea (loose, watery bowel movements). [drugs.com]

  Distant metastatic sites of MTC may include lung, liver, and bones, and more rarely to the brain and skin. Disseminated disease may cause symptoms of weight loss, lethargy, and bone pain. [atlasgeneticsoncology.org]

• Neck Mass

  Our patient presented with neck mass for 1 year with an outside laboratory report of neoplastic lesion. His serum calcitonin levels were normal, but serum carcinoembryonic antigen (CEA) levels were high. [ncbi.nlm.nih.gov]

  […] cells is removed from the suspicious neck mass and sent for evaluation Blood work: Calcitonin and other chemistry tests can be obtained to evaluate the clinical picture as a whole Imaging: Ultrasound of the neck will help provide details of the tumor. [symptoma.com]

  Most MTC patients will present with neck mass and may complain of hoarseness, dysphagia, and/or difficulty swallowing and breathing. MTC patients often present with metastasis to cervical and paratracheal lymph nodes. [atlasgeneticsoncology.org]

  Diagnosis Most patients diagnosed with sporadic MTC present with a palpable neck mass. MTC tends to present in the fifth or sixth decade of life and there is a slight female preponderance. Sporadic MTC is usually unifocal. [theoncologist.onlinelibrary.wiley.com]

• Lethargy

  Lethargy. Many people with advanced cancer may feel physically, emotionally, or mentally tired. The causes of fatigue during cancer are complex and not well understood. Weight loss. [healthline.com]

  Once it spreads, symptoms may include: Weight loss Lethargy Jaundice Abdominal pain Bone pain On the physical exam, the physician will feel a thyroid nodule at the base of the neck. [symptoma.com]

  […] various paraneoplastic syndromes, including Cushing or carcinoid syndrome Diarrhea may occur from increased intestinal electrolyte secretion secondary to high plasma calcitonin levels Distant metastases (eg, lung, liver, bone) may result in weight loss, lethargy [reference.medscape.com]

  Disseminated disease may cause symptoms of weight loss, lethargy, and bone pain. MTC patients often present with diarrhea due to an increased secretion of an intestinal electrolyte which occurs secondary to high plasma calcitonin levels. [atlasgeneticsoncology.org]

• Irritability

  “I thought it was irritable bowel syndrome. I left it, and left it, as you do. I didn’t want to be a hypochondriac. They told me I was stressed. [express.co.uk]

  With the higher doses of thyroid hormone replacements, children may experience mild symptoms of hyperthyroidism, including: Anxiousness, irritability and/or nervousness Poor, restless sleep Increased activity (fidgetiness, hyperactivity, restlessness) [chop.edu]

  In children and adolescents, cervical adenopathy is very common, usually due to an upper respiratory infection, minor head and neck trauma, or irritation. [clinicaladvisor.com]

  Not uncommonly, on direct questioning, patients will have suffered from irritable bowel symptoms for years. [touchendocrinology.com]

When a patient presents clinically with symptoms suggestive of thyroid cancer, the assessment should include a thorough personal and family history, a physical exam with emphasis on the thyroid gland and lymph nodes, as well as the pertinent studies. Preoperative investigations aim to determine if the tumor is local or metastatic, which will guide the management and treatment of these patients. Additionally, testing will help identify those with RET mutation carrier status and patients with MEN2 [1]. The latter will be discussed in the prevention chapter.

Laboratory tests

Patients with suspicious cases of MTC will undergo FNA of the new nodule. Immunohistochemical staining for calcitonin, chromogranin A, or carcinoembryonic antigen (CEA) can provide accuracy and verification of the disease [10].

With regards to tumor markers, CEA is present in more than half of patients with MTC. Moreover, a CEA level greater than 30ng/mL is associated with poor prognosis despite surgery [11] and a level above 100ng/mL indicates metastasis.

According to the American Thyroid Association (ATA), there is no preference for or against screening with calcitonin. However, levels above 100 pg/mL should raise suspicion for MTC [7] [12].

Imaging

Ultrasonography is the initial imaging technique used in the evaluation of patients with FNA findings suggestive of MTC or elevated calcitonin levels. This modality is very beneficial in the diagnosis and treatment of thyroid nodules as it provides information about the mass and detects other existing lesions or lymph nodes. Neck ultrasonography is particularly useful in sporadic cases as these typically manifest with a thyroid mass and/or cervical lymphadenopathy [10]. Ultrasound also provides guidance during the FNA procedure.

If advanced disease is suspected, the neck and chest will be surveyed with computed tomography (CT) or magnetic resonance imaging (MRI) in order to identify lymph nodal and mediastinal metastasis. Furthermore, the liver is imaged with three-phase CT with contrast or MRI with contrast enhancement in cases with lymph node involvement or if preoperative calcitonin is above 400pg/mL [7].

Other

Patients should be screened for other MEN2B diseases such as pheochromocytoma, since this disease may impact anesthesia used in surgery.

• ACTH Increased

  As described in other cases of CS caused by MTC, a marked ACTH increase after desmopressin stimulation was observed before vandetanib therapy. [ncbi.nlm.nih.gov]

The treatment and management of patients with MTC is best provided by a multidisciplinary care of a team consisting of a head and neck surgeon, oncologist, endocrinologist, general physician or pediatrician, and other specialists as needed. Generally, the therapy depends on whether the disease is local or advanced.

Surgery

When cancer confined to the thyroid gland, total thyroidectomy is the treatment of choice. This seeks to control the disease and to preserve the functions of speaking and swallowing. Additionally, at least 75% of MTC patients have palpable lymph nodes and therefore routine central neck dissection is recommended [13]. The prognosis is very promising in localized cases.

Radiation therapy

Locally relapsing cancer can be treated with external radiation therapy although it has not been shown to increase survival [14].

Targeted therapy

Drugs that target the genetic defects of MTC can be used in metastatic disease and palliative care. One promising agent, vandetanib, inhibits the RET kinase, as well as the vascular endothelial growth-factor receptor (VEGFR) and epidermal growth-factor receptor (EGFR).

This treatment has demonstrated progression-free survival (PFS) [15]. However, vandetanib is associated with adverse effects such as QT prolongation, hypertension, rash, and diarrhea.

Other

Note that the other components of MEN2 syndromes will require management.

The prognosis of MTC is good overall with a 10-year survival rate of 75% to 85%. Furthermore, localized tumors are associated with an approximately 96% 10-year survival rate [8]. Patients with distant metastases have a poor outcome as their 10-year survival percentage is 40% [8].

Almost half of MTC patients will experience recurrence. A sensitive biomarker for residual tumor or tumor recurrence is the calcitonin level. If it is greater than 100pg/mL, this is suggestive of residual neck tumor or metastasis. A value above 1000pg/mL is indicative of liver disease [8] [9].

MTC develops sporadically in approximately 75% of MTC cases [2]. In the remaining patients, it occurs as part of a hereditary syndrome such as MEN 2 syndromes, which are transmitted through an autosomal dominant trait. There are 3 subtypes of MEN 2 syndromes: MEN 2A, MEN 2B, and familial MTC (FMTC). The first two are characterized by a constellation of diseases.

The RET proto-oncogene plays a key role in all patients with MEN2A, MEN2B and FMTC. Similarly, it is central in almost half of all cases with sporadic MTCs [3] [4] [5]. The RET proto-oncogene, located on chromosome 10, codes for a tyrosine kinase transmembrane receptor which is found on cells of neural crest origin such as thyroid parafollicular cells (C cells), parathyroid cells, and others as well.

In MEN2A, the mutations of RET are of the missense type, while the genetic defects of MEN2B occur as a result of a specific mutation on exon 16 and the resultant structural abnormality of RET protein. In FMTC, the RET gene is characterized by germ-line mutations [4] [5].

MTC comprises 1% to 2% thyroid malignancies in the United States [1]. This number was previously reported as 3% to 5% but the decrease in incidence observed has been attributed to the relative rise in the incidence of papillary thyroid carcinoma (PTC).

The median age at diagnosis for individuals with MTC is 52 years with a range that spans ages 40 to 65 [6]. Note that patients with MEN 2 syndrome present a decade earlier compared to those with sporadic MTC [7]. The patient demographics demonstrate a slight preference for females [6].

The RET proto-oncogene codes for a receptor tyrosine kinase, which plays a role in signaling pathways that regulate cell growth, proliferation, differentiation, migration, and survival. A mutation in RET causes a disruption in these mechanisms. All hereditary forms of MTC manifest from these RET mutations.

MTC emerges from the parafollicular C cells of the thyroid gland, which produce numerous hormones including calcitonin, corticotropin, serotonin, melanin, vasoactive intestinal peptide, carcinoembryonic antigen (CEA) and prostaglandins. In rare cases, the release of these hormones and peptides can result in the development of paraneoplastic syndromes.

MEN 2 syndromes

MEN2A is composed of MTC, pheochromocytoma, and primary hyperparathyroidism while MEN2B is comprised of MTC, pheochromocytoma, ganglioneuromatosis, and marfanoid habitus. The onset of MTC occurs earlier in these diseases in contrast to sporadic form.

Pathology

On gross inspection, the tumor is colored white or gray; it is also firm on palpation. Furthermore, the histologic evaluation reveals a nested pattern of uniform cells with stromal amyloid deposits. Hereditary forms of MTC are characterized by “C-cell hyperplasia," which describes a specific quantity of C cells. Since these cells release various chemicals, immunohistochemical stains can be used to diagnose MTC.

According to the ATA, all patients with MTC should undergo genetic testing. Additionally, first-degree family members of patients with hereditary MTC should be offered genetic testing for RET mutations as well as parents of children affected with MEN2B [1]. The ATA has a list of other groups who should also be screened.

Very importantly, the clinician should understand the implications of genetic detection of RET mutation. Since children with MEN2B and RET mutations usually manifest with an aggressive and an early onset MTC, the ATA recommends prophylactic thyroidectomy for these individuals [1].

Genetic counseling is paramount for all RET mutation carriers of childbearing age, especially for individuals with MEN2B. They should be offered testing prior to conception or antenatally. Those who decline genetic testing should be educated about the tests available to the child, especially prior to the age of 5 [1].

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine cancer that comprises 1% to 2% of thyroid cancers in the United States [1]. It occurs spontaneously, or as a component of the multiple endocrine neoplasia 2 syndrome (MEN2). The latter accounts for at least 25% of all cases of MTC. A mutation in the RET (REarranged during Transfection) gene is implicated in all hereditary cases and almost 50% of sporadic MTC.

The clinical presentation of this disease features a solitary neck nodule that is typically bothersome during swallowing. Patients may develop a hoarse voice, difficulty in swallowing, and difficulty breathing. Other manifestations may arise if there are metastases to the liver, lung, and bone.

The diagnosis is achieved through a detailed personal and family history, a physical and neck exam, and pertinent studies. Fine needle aspiration (FNA) of the new mass is obtained and analyzed for characteristic findings of MTC. Additionally, calcitonin levels are measured in cases that are suspicious for MTC. Moreover, imaging tools such as ultrasonography are instrumental in diagnosis and management of MTC. Other imaging techniques are warranted if metastatic disease is indicated.

The mainstay of therapy is the surgical resection of the entire thyroid. In patients with metastasis, chemotherapy is used. Radiation therapy does not play a significant role in the primary treatment of individuals with MTC but is used to treat locally recurrent disease.

Other crucial elements in the management of MTC are genetic counseling and testing. These approaches are essential in all individuals with MTC as well first-degree relatives of patients with RET mutations. Experts recommend prophylactic thyroidectomy in children with specific mutations that are associated with aggressive forms of MTC.

What is Medullary Thyroid Cancer (MTC)?

This is a rare type of thyroid cancer. It develops from the parafollicular cells of the thyroid gland, which produces various hormones such as calcitonin. This hormone helps regulate the levels of calcium in the body.

What are the causes?

This type of thyroid cancer can occur spontaneously or it can develop as part of an inherited syndrome. In all inherited cases and almost half of spontaneous cases, the disease is caused by a mutation (change) in the RET gene. The mutation causes the uncontrollable growth and increase of cells. Note that all patients with RET mutations will develop MTC.

In the hereditary forms, the mutations are inherited in an autosomal dominant pattern. This means that the patient inherits one good copy and one bad copy of the gene. In other words, a child of an affected parent has a 50% probability of inheriting the disease.

In the hereditary form known as MEN 2 syndrome, MTC develops along with other specific diseases.

What are the signs and symptoms?

Patients with MTC may complain of:

• Lump at the base of the neck especially notable during swallowing
• Hoarse voice
• Difficulty swallowing
• Difficulty breathing
• Possibly diarrhea (due to increased secretion of electrolytes from intestines)

It can spread to the liver, lung, bone, and lymph nodes. Once it spreads, symptoms may include:

• Weight loss
• Lethargy
• Jaundice
• Abdominal pain
• Bone pain

On the physical exam, the physician will feel a thyroid nodule at the base of the neck. If the cancer has spread locally, the neck lymph nodes will be enlarged.

How is it diagnosed?

In patients suspected to have MTC, the clinician will obtain a detailed personal and family history, perform a careful exam especially of the neck and lymph nodes, and perform important tests such as:

• Fine needle aspiration (FNA) in which a sample of cells is removed from the suspicious neck mass and sent for evaluation
• Blood work: Calcitonin and other chemistry tests can be obtained to evaluate the clinical picture as a whole
• Imaging: Ultrasound of the neck will help provide details of the tumor. CT scan or MRI provide benefit in cases where spread of the cancer is suspected.

How is it treated?

The only effective therapy for MTC is the surgical resection of the tumor. This is referred to as total thyroidectomy. For patients with disease that spread to other locations, chemotherapy is used.

Can it be prevented?

Children with RET mutations will usually have their thyroid gland removed before the cancer develops. This is called prophylactic thyroidectomy. Fortunately, once the thyroid is removed, they do not typically have a risk for relapse.

Note that genetic counseling is important for all individuals with RET mutations of childbearing age. Also, relatives of individuals with hereditary forms of MTC should also be offered genetic counseling and testing, especially in young children who may be eligible for prophylactic thyroidectomy.

What is the prognosis?

The prognosis is generally good if the cancer has not spread.

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