Parathyroid cancer is an extremely rare malignancy that develops within one of the four parathyroid glands located in the neck. These tiny endocrine glands, typically about the size of a grain of rice, regulate calcium levels in the bloodstream. The cancer arises from the cells that produce Parathyroid Hormone (PTH), leading to an uncontrolled overproduction of this hormone. Fewer than 100 new cases are diagnosed annually in the United States.
How Parathyroid Cancer Develops
The parathyroid glands are positioned behind the thyroid gland at the base of the neck. Their primary role is to monitor and maintain the body’s calcium balance by releasing PTH in response to low calcium levels. PTH acts on the bones, kidneys, and intestines to increase calcium in the blood. Parathyroid cancer involves the abnormal growth of these cells, causing a massive, sustained release of PTH. This results in dangerously high calcium levels, known as severe hypercalcemia.
While most cases occur sporadically, certain risk factors are associated with the disease. Individuals with inherited genetic syndromes, such as Multiple Endocrine Neoplasia type 1 (MEN1) or Hyperparathyroidism-Jaw Tumor syndrome, have an elevated risk. Prior exposure to radiation in the head or neck area, particularly during childhood, is another recognized risk factor. A mutation in the CDC73 gene, which codes for the tumor suppressor protein parafibromin, is also common.
Recognizing the Signs and Symptoms
The effects of parathyroid cancer are predominantly due to the severe hypercalcemia caused by the excess PTH, rather than the tumor mass itself. Patients often experience a collection of symptoms referred to clinically as “stones, bones, groans, and psychic moans.” The “stones” refer to the formation of painful kidney stones and excessive urination as the kidneys try to excrete the surplus calcium.
“Bones” indicates bone pain and increased risk of fractures, as PTH continuously pulls calcium from the skeletal structure. “Groans” covers abdominal symptoms like nausea, vomiting, and constipation. “Psychic moans” describes neurological effects such as fatigue, generalized weakness, and difficulty concentrating. In about half of all cases, the tumor is large enough to be felt as a firm, fixed mass in the neck, which may sometimes cause hoarseness if it affects the vocal cord nerve.
Confirming the Diagnosis and Determining Extent
Diagnosis begins with blood work measuring serum calcium and Parathyroid Hormone levels. A combination of significantly elevated calcium and extremely high PTH levels, often several times the upper limit of normal, is a strong indicator of malignancy. Imaging studies are then used to locate the tumor, which typically appears as a large mass on a neck ultrasound or a Sestamibi scan. The Sestamibi scan uses a radioactive tracer that is preferentially absorbed by overactive parathyroid tissue.
A definitive diagnosis is often challenging to make before surgery, as the tumor cells can look similar to a benign growth under a microscope. Therefore, fine-needle aspiration (FNA) biopsy is generally avoided pre-operatively due to the risk of tumor cell seeding along the needle track. Malignancy is often confirmed after surgical removal by a pathologist examining the tissue for invasive features. These definitive signs include tumor cells invading the surrounding capsule, penetrating blood vessels (vascular invasion), or growing along nerves (perineural invasion).
Since a standardized staging system is not consistently used for this rare cancer, the extent of the disease is generally described as localized, regional, or metastatic. Localized disease is confined to the neck, while regional disease involves spread to nearby lymph nodes. Metastatic parathyroid cancer is characterized by spread to distant organs (most commonly the lungs, liver, or bones).
Primary Treatment Strategies
Complete surgical removal offers the only chance for a cure and is the primary treatment for parathyroid cancer. The procedure requires an extensive surgery known as en bloc resection. This involves removing the entire affected parathyroid gland, the surrounding tissue capsule, and often the adjacent thyroid lobe on the same side. The goal is to remove the tumor intact without rupturing the capsule, which risks seeding cancer cells and causing recurrence.
Managing the severe hypercalcemia is an immediate priority, often requiring pre-operative treatment with intravenous fluids and medications like bisphosphonates to quickly lower calcium levels. Following surgery, some patients with locally advanced disease or unclear surgical margins may be candidates for adjuvant radiation therapy. Radiation can be used to destroy microscopic cancer cells remaining in the neck area, reducing the risk of local recurrence. For advanced or recurrent disease that cannot be surgically removed, systemic treatments are used, including the drug Cinacalcet to help lower PTH and calcium levels, or chemotherapy for widespread metastatic cancer.
Prognosis and Monitoring for Recurrence
Parathyroid cancer is an aggressive disease, and a significant challenge is its high rate of local recurrence, occurring in up to 50% of patients. Recurrence most commonly happens in the neck within two to five years after the initial surgery. However, recurrence can appear much later due to its slow-growing nature in some cases, making long-term monitoring essential for all patients. The severity of the disease and its impact on survival are often more related to the difficulty of controlling the resulting hypercalcemia than the tumor mass itself.
Long-term follow-up care involves lifelong surveillance with regular blood tests to monitor serum calcium and PTH levels, often scheduled every six months. A rise in these levels is typically the first sign of recurrence, prompting the use of imaging studies like ultrasound or Sestamibi scans to locate the returning cancer. Managing calcium levels can be complex post-surgery, as the remaining parathyroid glands may take time to recover function, requiring temporary calcium and vitamin D supplementation.