Parathyroid cancer is a condition that arises when one of the four parathyroid glands in the neck becomes cancerous. People with parathyroid cancer develop hyperparathyroidism (or overactive parathyroid functioning) and will present with severe hypercalcemia (high blood calcium levels).

Parathyroid cancer is extremely rare. Fewer than 100 people are diagnosed with this type of cancer in the United States each year, and less than 0.5% of people who have hyperparathyroidism develop parathyroid cancer.

Parathyroid cancer is more common among people in their 40s and 50s but can develop at any age. Men and women are diagnosed equally. Treatment typically involves surgical removal of the affected parathyroid gland and any involved surrounding tissues to restore blood calcium to normal levels.

Parathyroid cancer occurs when one of the four pea-sized parathyroid glands (located behind the thyroid gland, which is in the lower neck) develops a tumor. It is a very uncommon condition; a growth on a parathyroid gland, if it does occur, is usually a benign (noncancerous) adenoma (tumor).

The parathyroid glands produce parathyroid hormone (PTH), which performs essential functions. It helps the body to keep adequate calcium levels, a necessity for maintaining bone, muscle, and nerve health. It aids the digestive system in absorbing the proper amount of calcium from food sources. The hormone prevents the kidneys from excreting too much calcium in the urine. And when the parathyroid glands detect low blood-calcium levels, they produce enough PTH to signal the bones to release calcium into the bloodstream.

When a person has parathyroid cancer, a tumor that grows within one of the parathyroid glands causes the gland to produce too much PTH, disrupting its calcium regulation role, as well as raising the body’s calcium levels. Excess calcium tends to be more pronounced in someone with parathyroid cancer compared to primary hyperparathyroidism caused by a noncancerous tumor.

Doctors don’t know what causes parathyroid cancer, but it often occurs in people who have certain genetic mutations.

As many as 70% of people with parathyroid cancer have mutations in the CDC73 gene. This gene typically mutates during a person’s lifetime; only about one-third of people with parathyroid cancer have inherited a CDC73 gene mutation from a parent.

Other gene mutations may also be affiliated with parathyroid cancer.

People who have parathyroid cancer may experience symptoms related to hypercalcemia and hyperparathyroidism that include:

• Bone pain
• Fractures
• Fatigue
• Mood changes
• Depression
• Excessive thirst
• Frequent urination
• Kidney stones
• Constipation
• Ulcers in the digestive tract
• Abdominal pain
• Inflammation of the pancreas
• Muscle weakness
• A lump in the neck
• Poor appetite
• Nausea
• Vomiting
• Unexpected weight loss
• Difficulty swallowing
• Difficulty speaking
• Hoarseness
• Vocal cord paralysis
• Shortness of breath

It can be difficult to diagnose parathyroid cancer because it’s uncommon and its symptoms are similar to hyperparathyroidism caused by an adenoma. Doctors may suspect parathyroid cancer by learning about a patient’s health history, performing a physical examination, and reviewing diagnostic tests.

You should tell your doctors if you have ever had radiation therapy to treat a head or neck cancer (such as thyroid cancer), if you’ve been diagnosed with hyperparathyroidism, or if you have had kidney stones or broken bones.

During a physical exam, doctors may check if your bones are sore or sensitive to the touch. In some cases, there may be a palpable lump in the neck, which may be a sign of parathyroid cancer.

The following tests may be used to evaluate patients for parathyroid cancer:

• Blood tests to check your calcium and albumin levels, as well as your PTH levels
• Urine tests to assess the level of calcium in your urine
• Ultrasound to look for abnormalities in the parathyroid; other imaging tests, such as CT scan or MRI, may also be used
• A 4-D CT scan, a special type of CT scan, to look for a large mass behind the thyroid gland that could be suggestive of parathyroid cancer
• Surgery to remove the parathyroid gland, which is performed instead of a biopsy. The affected parathyroid gland would be removed, in addition to any surrounding tissue that appears to be invaded by the tumor.

Parathyroid cancer is treated by surgically removing the affected parathyroid gland and any involved surrounding tissues. A patient’s prognosis improves when the entire parathyroid cancer is removed at the initial surgery.

Outside of surgery, no other therapies are effective in curing parathyroid cancer.

If the parathyroid cancer is unable to be cured with surgery, managing the elevated levels of calcium in your blood is the priority. To control blood calcium levels, you may be prescribed:

• Bisphosphonates
• Calcitonin
• Cinacalcet
• Denosumab
• Gallium nitrate

Monitoring is crucial after surgery. Blood tests to check calcium and PTH levels may be recommended every 3 months for 3 years, then every 6 months for 5 years, then annually for the rest of your life. An annual neck ultrasound may also be recommended to look for growths on the parathyroid glands.

About 85% of people with parathyroid cancer survive 5 years or more after diagnosis. Roughly half of those treated will relapse, often within the first 3 years. About 78% of people whose parathyroid cancer returns will survive 5 or more years after a subsequent diagnosis.

Cancer is also more likely to spread to distant body parts among people with the CDC73 gene mutation. Having the CDC73 gene mutation also increases the risk of recurrence.

“Yale is unique in that we have a multidisciplinary team of endocrinologists, endocrine and head and neck surgeons, specialized radiologists and pathologists, medical and radiation oncologists, and nurses who are experts in endocrine cancers, including parathyroid cancers,” says Yale Medicine medical oncologist Hari Deshpande, MD. “They meet weekly at a multidisciplinary tumor board and discuss new cases. As a result, patients receive multispecialty care at an Endocrine Oncology Center of Excellence.”