Parathyroid cancer is an exceptionally rare malignancy that begins in the parathyroid glands. These small endocrine glands, typically four in number, are usually situated behind the thyroid gland in the lower front of the neck. Parathyroid carcinoma develops when malignant cells form within the tissue of one of these glands. With fewer than 100 new cases diagnosed annually in the United States, this condition is significantly less common than benign parathyroid tumors.
The Role of Parathyroid Glands and Hypercalcemia
The function of the parathyroid glands is to maintain a tightly controlled balance of calcium and phosphorus in the body. They achieve this by producing parathyroid hormone, or PTH, which acts on the bones, kidneys, and intestines to regulate mineral levels. Normally, if calcium levels in the bloodstream drop, the parathyroid glands release more PTH; conversely, they reduce PTH production if calcium levels become too high.
Parathyroid cancer disrupts this delicate system by causing an uncontrolled and excessive production of PTH. This leads directly to the defining biochemical feature of the disease: severe hypercalcemia, or abnormally high calcium levels in the blood. In patients with parathyroid carcinoma, both the PTH and serum calcium levels are often drastically elevated. The overabundance of PTH forces calcium out of the bones and increases its reabsorption in the kidneys, leading to mineral overload in the blood.
Recognizing the Signs and Symptoms
The physical manifestations of parathyroid cancer are primarily a consequence of the severe hypercalcemia it causes. The symptoms can be subtle and non-specific initially, which sometimes delays diagnosis. However, the systemic impact of high blood calcium is often severe enough to prompt a medical visit.
A historical framework for understanding these symptoms uses the mnemonic “stones, bones, groans, and psychic moans.” “Stones” refers to renal complications, such as kidney stones or excessive urination and thirst. The term “bones” highlights skeletal issues, including bone pain, bone loss, and an increased risk of fractures.
Gastrointestinal problems fall under “groans,” which can involve constipation, nausea, vomiting, or abdominal discomfort. “Psychic moans” describes the neurological and psychological effects of high calcium, manifesting as fatigue, muscle weakness, depression, or confusion. Less frequently, the cancer may grow large enough to cause local symptoms in the neck, such as a palpable lump, a hoarse voice, or difficulty swallowing.
Diagnostic Procedures and Staging
The diagnostic process begins when blood tests reveal significantly high levels of both calcium and parathyroid hormone. A PTH level that is five to ten times above the normal range, coupled with severe hypercalcemia, strongly suggests the presence of carcinoma. Blood chemistry tests may also show elevated alkaline phosphatase, an enzyme indicating increased bone turnover.
Imaging studies are necessary to pinpoint the location of the tumor and assess the extent of local invasion. An ultrasound of the neck is often the initial imaging modality to visualize the parathyroid glands and their relationship to the thyroid. More specialized scans, such as a Sestamibi scan, involve injecting a radioactive tracer that is preferentially absorbed by overactive parathyroid tissue, helping to localize the abnormal gland.
Computed tomography (CT) or magnetic resonance imaging (MRI) scans are used to evaluate local spread and check for enlarged lymph nodes or distant metastases in the chest or abdomen. The definitive diagnosis of parathyroid cancer, however, requires surgical pathology, as it cannot be made solely through blood tests or imaging. Pathologists examine the tissue for specific features of malignancy, such as invasion into the surrounding capsule or blood vessels, usually after the tumor has been surgically removed. The disease is generally described as localized, metastatic, or recurrent, rather than using a standardized staging system.
Management and Treatment Options
Surgery represents the only effective treatment for parathyroid carcinoma and provides the best opportunity for a cure. When parathyroid cancer is suspected, the recommended procedure is an en bloc resection. This aggressive surgical approach involves removing the cancerous parathyroid gland along with the surrounding tissues, which often includes the thyroid lobe on the same side, adjacent fat, and muscle. The goal of this extensive removal is to achieve clear surgical margins and minimize the risk of the cancer returning in the neck.
Controlling the severe hypercalcemia is another major part of management, particularly before and after surgery. Medications known as calcimimetics, such as Cinacalcet, can be used to manage calcium levels by making the parathyroid glands less sensitive to calcium, thereby decreasing PTH secretion. Supportive care for hypercalcemia also includes intravenous hydration and the use of bisphosphonates.
For patients with advanced or recurrent disease, other therapies may be considered. External beam radiation therapy can be used after surgery, particularly if the surgical margins contained cancer cells, or to manage symptoms from tumors that cannot be fully removed. Chemotherapy is not a standard first-line treatment, as its effectiveness against parathyroid carcinoma is limited, but it may be used in cases of widespread or rapidly progressing disease.