Parathyroid carcinoma

Other Names: Parathyroid cancer

Parathyroid carcinoma (PRTC) is a very rare, slow-growing, clinically serious endocrine tumor that generally develops in mid-adulthood. PRTC presents as a palpable painless mass in the neck and causes severe hypercalcemia and related symptoms, non-specific gastrointestinal manifestations, as well as renal and bone complications related to primary hyperparathyroidism (nephrolithiasis, impaired renal function, osteoporosis, bone pain, and pathologic fractures, etc.). Some PRTCs are however non-functioning tumors.

Parathyroid cancer is a rare cancer that usually affects people in their forties or fifties and occurs in one of the four parathyroid glands. The parathyroid glands are located in the neck and secrete parathyroid hormone, which enhances the release of calcium into the blood.

Cause

Mutations in the CDC73 gene are found in up to 70 percent of cases of parathyroid cancer. In approximately one-third of affected individuals with changes in this gene, the mutation is inherited from a parent and is present in all of the body's cells. In people who have parathyroid cancer with CDC73 gene mutations, the cancer is seven times more likely to metastasize than is parathyroid cancer in affected individuals without CDC73 gene mutations. Individuals with CDC73 gene mutations are also at a higher risk of recurrence of the cancer and have a decreased survival rate compared to those without CDC73 gene mutations. Mutations in other genes have also been found in parathyroid cancer, but each of these mutations has been reported in only a small number of individuals.

The CDC73 gene provides instructions for making a protein called parafibromin. This protein is found within the nucleus of cells throughout the body and is likely involved in gene transcription, which is the first step in protein production. Parafibromin functions as a tumor suppressor, which means it keeps cells from growing and dividing too rapidly or in an uncontrolled way. In individuals with a CDC73 gene mutation, either inherited from a parent or acquired during their lifetime, a second mutation in the other copy of the CDC73 gene must occur in parathyroid cells for cancer to develop. Parathyroid cells with two altered copies of the CDC73 gene produce no functional parafibromin. As a result, cells grow and divide unchecked, which can lead to parathyroid cancer. In most cases of parathyroid cancer, these genetic changes are acquired during a person's lifetime and are present only in certain cells in the parathyroid glands. These changes, which are called somatic mutations, are not inherited.

Risk factors

A significantly increased risk of parathyroid cancer is also a feature of certain rare genetic syndromes. Parathyroid cancer occurs in 15 percent of individuals with hyperparathyroidism-jaw tumor syndrome and in 1 percent of individuals with familial isolated hyperparathyroidism. These conditions are both caused by mutations in the CDC73 gene. In rare cases, parathyroid cancer has also been found in people who have a tumor disorder called multiple endocrine neoplasia, which is caused by mutations in other genes.

Non-genetic factors have also been found to contribute to a person's risk of developing parathyroid cancer, including a history of hyperparathyroidism with chronic kidney failure, thyroid cancer, and previous radiation therapy on the neck.

Symptoms

Symptoms of parathyroid cancer are mainly caused by a high level of calcium in the blood (hypercalcemia), and may affect different parts of the body. They include:

• Bone pain
• Constipation
• Fatigue
• Fractures
• Frequent thirst
• Frequent urination
• Kidney stones
• Muscle weakness
• Nausea and vomiting
• Poor appetite

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

100% of people have these symptoms

• Parathyroid carcinoma
• Primary hyperparathyroidism
• 80%-99% of people have these symptoms
• Elevated circulating parathyroid hormone level
• Hypercalciuria(Elevated urine calcium levels)
• Hypophosphatemia(Low blood phosphate level)

30%-79% of people have these symptoms

• Dysphagia(Poor swallowing)
• Fatigue(Tired)
• Fibroma
• Hoarse voice(Hoarseness)
• Infantile hypercalcemia
• Nephrocalcinosis(Too much calcium deposited in kidneys)
• Nephrolithiasis(Kidney stones)
• Osteoporosis
• Polydipsia(Extreme thirst)
• Shortened QT interval
• Uterine leiomyoma
• Weight loss

5%-29% of people have these symptoms

• Bone pain
• Chondrocalcinosis(Calcium deposits in joints)
• Constipation
• Episodic abdominal pain
• Headache(Headaches)
• Mandibular pain9(Lower jaw pain)
• Muscle weakness(Muscular weakness)
• Nausea and vomiting
• Pancreatitis(Pancreatic inflammation)
• Peptic ulcer(Sore in the lining of gastrointestinal tract)
• Renal cyst(Kidney cyst)
• Renal hamartoma

Diagnosis

Parathyroid cancer is very hard to diagnose. Your doctor will perform a physical exam and ask about your medical history. About half of the time, feeling the neck with the hands (palpation) can reveal a cancerous parathyroid tumor. A cancerous parathyroid tumor tends to produce a very high amount of parathyroid hormone (PTH). Tests for this hormone may include:

• Blood calcium
• Blood PTH

Before surgery, you will have a special radioactive scan of the parathyroid glands. The scan is called the sestamibi scan. You may also have a neck ultrasound. These tests are done to confirm which parathyroid gland is abnormal.

Treatment

The following treatments may be used to correct hypercalcemia due to parathyroid cancer:

• A drug called gallium nitrate, which lowers the calcium level in the blood
• A natural hormone called calcitonin that helps control calcium level
• Drugs that stop the breakdown and reabsorption of bones into the body
• Fluids through a vein (IV fluids)

Surgery is the recommended treatment for parathyroid cancer. Sometimes, it is hard to determine whether a parathyroid tumor is cancerous. Your doctor may recommend surgery even without a confirmed diagnosis. Minimally invasive surgery, using smaller cuts, is becoming more common for parathyroid disease.

If tests before the surgery can find the affected gland, surgery may be done on one side of the neck. If it is not possible to find the problem gland before surgery, the surgeon will look at both sides of your neck.

Chemotherapy and radiation do not work well in preventing the cancer from coming back. Radiation can sometimes help reduce the spread of cancer to the bones. Repeated surgeries for cancer that has returned may increase survival rate and reduce the severe effects of hypercalcemia. The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Cinacalcet (Brand name: Sensipar)Treatment of hypercalcemia in patients with parathyroid carcinoma.

Prognosis

Parathyroid cancer is slow growing. Surgery may help extend life even when the cancer spreads.

NIH genetic and rare disease info

• NIH info on Parathyroid carcinoma

Parathyroid carcinoma is a rare disease.

Parathyroid carcinoma Resources
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