The parathyroid glands are four small, pea-sized endocrine organs typically situated behind the thyroid gland in the neck. Their primary function is to produce and release parathyroid hormone (PTH), which acts as the body’s main regulator of calcium levels in the blood. Parathyroid cancer (parathyroid carcinoma) is a rare, malignant tumor originating from the cells of one of these glands, accounting for less than one percent of all primary hyperparathyroidism cases. The vast majority of parathyroid tumors are benign growths. This malignancy is distinguished by its ability to invade local tissues and potentially spread to distant organs, leading to the uncontrolled overproduction of PTH.
The Core Mechanism: Uncontrolled Hypercalcemia
The defining characteristic of parathyroid cancer is the excessive and unregulated secretion of parathyroid hormone, resulting in a persistent condition called hypercalcemia. PTH’s normal role is to maintain stable calcium levels by stimulating its release from bone and promoting its reabsorption in the kidneys. The malignant parathyroid cells ignore the body’s feedback mechanisms, constantly releasing high levels of the hormone regardless of the existing calcium concentration. This chronic hormonal excess disrupts the body’s mineral balance, leading to sustained, elevated levels of calcium and abnormal phosphorus regulation.
The uncontrolled PTH acts on the skeletal system by accelerating the activity of osteoclasts, the cells responsible for bone breakdown. This process, known as bone resorption, continuously leaches calcium and phosphate from the bone matrix into the circulation, leading to a loss of bone mineral density over time. Prolonged bone demineralization can cause osteopenia or osteoporosis, increasing the risk of pain and pathologic fractures.
In the kidneys, the high calcium concentration can lead to nephrocalcinosis, where calcium deposits form in the kidney tissue, and the subsequent development of calcium-based kidney stones. The renal system’s attempt to excrete the calcium surplus also impairs its ability to concentrate urine, often causing frequent urination and excessive thirst. Sustained hypercalcemia interferes with nerve and muscle function, which can manifest as muscle weakness, fatigue, and various neuropsychiatric issues. The effects of the disease are systemic, with symptom severity correlating to the degree and duration of the elevated calcium levels.
Identifying the Disease: Symptoms and Diagnosis
The symptoms of parathyroid cancer are often vague and can be easily mistaken for other conditions, contributing to difficulty in early diagnosis. These non-specific complaints are largely the result of the underlying hypercalcemia. Symptoms may include profound fatigue, generalized muscle weakness, bone pain, and gastrointestinal issues such as nausea, vomiting, constipation, and decreased appetite. Neurological and psychological effects can involve depression, confusion, and memory problems.
A few symptoms can hint more specifically toward a localized malignancy in the neck, such as a palpable lump or mass, hoarseness, or difficulty swallowing. The diagnostic workup begins with blood tests to measure serum calcium and PTH levels. Suspicion for malignancy is heightened when serum calcium concentration is markedly elevated (often exceeding 14 milligrams per deciliter) and is accompanied by a PTH level that is five to ten times the upper limit of normal. Additional blood work often reveals lower-than-normal phosphorus levels and elevated alkaline phosphatase, reflecting accelerated bone turnover.
The next step involves imaging studies aimed at localizing the tumor and assessing its size and potential spread. An ultrasound of the neck visualizes the parathyroid glands and nearby structures. A Sestamibi scan uses a radioactive tracer absorbed by overactive parathyroid tissue to pinpoint the problematic gland. Computed tomography (CT) and magnetic resonance imaging (MRI) scans are used to check for invasion into surrounding neck tissues and to search for any signs of metastasis.
A definitive diagnosis of parathyroid cancer is rarely made solely based on blood tests and imaging because the tumor cells often appear highly similar to a benign parathyroid adenoma. Final confirmation of malignancy requires a pathological examination of the tissue after the gland has been surgically removed. Therefore, multiple tests are necessary to confirm hyperparathyroidism, localize the source, and rule out other causes of hypercalcemia.
Treatment Approaches
The primary treatment for parathyroid cancer is complete surgical removal of the tumor, a procedure known as en bloc resection. This surgery removes the entire tumor in one piece, along with the affected parathyroid gland, the adjacent ipsilateral thyroid lobe, and any surrounding soft tissue that may be involved. The goal of this extensive excision is to achieve clear surgical margins and prevent the seeding of cancer cells in the neck, which is a major cause of local recurrence. If there is evidence of spread, the surgeon may also remove lymph nodes in the central neck compartment.
If the cancer is not entirely removable or if it recurs, secondary treatments are employed. Radiation therapy is not a standard first-line treatment because parathyroid cancer cells are often resistant to its effects. However, external beam radiation may be used as an adjunctive therapy following surgery, particularly if the tumor invaded nearby tissues or if the surgical margins were not completely clear. It can also be utilized for palliative reasons to manage inoperable local recurrence.
Medical management is focused on controlling life-threatening hypercalcemia when the disease cannot be cured surgically. Calcimimetic agents, such as cinacalcet, manage the hormonal overactivity of the tumor by increasing the sensitivity of calcium-sensing receptors, which reduces PTH secretion and lowers serum calcium levels. Bisphosphonates are also administered to manage hypercalcemia by slowing the rate of bone breakdown. Chemotherapy is rarely utilized, as it has demonstrated limited effectiveness against this specific, slow-growing malignancy.
Prognosis and Long-Term Monitoring
The prognosis for individuals with parathyroid cancer is strongly linked to the success of the initial surgical resection. When the tumor is completely removed with clear margins during the first operation, the outlook is generally favorable, with five-year survival rates ranging between 79 and 93 percent. However, parathyroid cancer has a significant propensity for recurrence, which occurs in a substantial number of patients, sometimes many years after the initial treatment. Recurrence often appears first as a gradual re-elevation of serum calcium and PTH levels.
Due to the possibility of recurrence, long-term surveillance is a necessary component of post-treatment care. Monitoring involves frequent, regular follow-up blood tests to measure both serum calcium and parathyroid hormone concentrations. Initially, this monitoring is intensive, but continues indefinitely, often with checks performed every few months to a year. A sustained rise in either the calcium or PTH levels is the earliest and most reliable indicator that the disease may have returned.
Ongoing assessment of bone health is also performed periodically using bone density scans, given the damage caused by the pre-operative and potential recurrent hypercalcemia. For patients who experience a local recurrence, further surgery is often the preferred treatment option, as it can provide long periods of disease control and relief from the symptoms of hypercalcemia. The primary goal of all long-term monitoring strategies is the prompt detection and management of any recurrent disease.