What is Parathyroid Cancer?
Parathyroid cancer is a rare type of cancer that starts in the parathyroid glands. These are small glands located behind your thyroid, which is in the front part of your neck. The size and weight of these glands can differ, but they generally weigh about 60 mg and are 5 mm long, 3 mm wide, and 1 mm thick. They are usually yellow-brown in color. There are usually four of these glands, two at the top and two at the bottom, but the location of these glands can change based on how they developed in the body.
The parathyroid glands have some notable neighbors in the body. The upper parathyroid glands are often found near the cricothyroid junction, which is just above where the recurrent laryngeal nerve (a nerve in the neck responsible for the sensation of the larynx) crosses paths with the inferior thyroid artery (the main blood supply to the thyroid). These upper parathyroids are closely related to the back part of the top of the thyroid. However, the lower parathyroid glands have a less predictable location. More than half are located near the bottom of the thyroid, but they can also be found in the part of the chest behind the breastbone, along the thyrothymic ligament (a tissue that connects the thyroid to the thymus).
The main blood supply for each parathyroid gland usually comes from the inferior thyroid artery. However, in about 20% of cases, it may come from the superior thyroid artery. The veins that carry blood out of the parathyroids follow the same routes as these arteries, ultimately draining into a big vein in your neck called the internal jugular vein. The lymph fluid from the parathyroid glands goes to the deep cervical and pretracheal lymph nodes, much like the lymph fluid from the thyroid gland itself.
The main job of the parathyroid is carried out by its chief cells, which produce parathyroid hormone. This hormone plays a critical role in controlling calcium levels in the body. Another type of cell, known as oxyphil cells, are also found in the parathyroids. The specific job of these cells isn’t known, but they tend to be packed with mitochondria, the energy factories of the cell.
Parathyroid cancer, like all cancers, is caused by uncontrolled growth of cells in the gland, in this case, the parathyroid cells. Most parathyroid cancers produce parathyroid hormone, which can lead to high levels of calcium in the blood. This cancer can develop in any of the parathyroid glands and doesn’t seem to favor any specific ones. The most significant sign of parathyroid cancer is being found to have very high levels of parathyroid hormone in the blood, much higher than seen in non-cancerous parathyroid conditions.
What Causes Parathyroid Cancer?
Most parathyroid cancers tend to develop without a known cause and occur randomly. However, there’s a known link between these cancers and two medical conditions: Multiple Endocrine Neoplasia (MEN) syndrome types I and IIa, and hyperparathyroidism-jaw tumor syndrome (HPT-JT).
Parathyroid cancer is a rare cause of primary hyperparathyroidism, a condition where the parathyroid glands produce too much parathyroid hormone. It only accounts for around 0.1% to 5% of cases. It’s not clear whether parathyroid cancer starts as non-cancerous parathyroid lesions, but some researchers believe that it might develop when the parathyroid cells start growing excessively. However, this possibility of it turning cancerous is still a theory.
Parathyroid cancer is known to be related to alterations in a specific gene called HRPT2 (CDC73), which normally helps prevent cells from growing uncontrollably. This gene is found on the chromosome 1 and its product is a protein named parafibromin, which helps to control cell proliferation or growth.
This mutation of HRPT2 is found in people with hyperparathyroidism-jaw tumor syndrome and parathyroid cancer that happens without any known reason.
When it comes to hyperparathyroidism-jaw tumor syndrome, patients usually develop benign (non-cancerous) tumors in the jaw, cysts, and tumors in the kidneys. These individuals are at an increased risk of developing parathyroid cancer. Research shows that 15% of people with hyperparathyroidism-jaw tumor syndrome develop parathyroid cancer.
As for the MEN syndromes, these have been thoroughly discussed in other StatPearls articles which can be consulted for more detail on MEN I and MEN IIa.
Risk Factors and Frequency for Parathyroid Cancer
Parathyroid carcinoma is an extremely rare type of cancer. It affects about 1.25 out of every 10 million people. In the United States, it is found in less than 1% of all people suffering from hyperparathyroidism. The number of reported cases are only in the hundreds. It commonly appears in people aged 44 to 54 and affects both men and women equally.
- Parathyroid carcinoma is a very rare cancer with a condition rate of 1.25 cases per 10 million people.
- It represents less than 1% of all hyperparathyroidism cases in the United States.
- The number of reported cases is only in the hundreds.
- The average age of onset is between 44 to 54 years.
- It affects both males and females equally.
Signs and Symptoms of Parathyroid Cancer
It’s essential to thoroughly examine the head and neck. Around half of people with parathyroid carcinoma, a type of cancer, show signs of a noticeable lump in the middle of their neck. This symptom comes along with other signs related to high levels of calcium and parathyroid hormone in the body, such as kidney stones, irregular heartbeats, and weakened bones (osteoporosis). If a neck lump is found alongside these symptoms, it could indicate parathyroid carcinoma. As part of the check-up, the doctor will ask detailed questions about your medical history, particularly about any hormone-related conditions or cancers in your family to look out for hidden genetic syndromes. It’s also important to tell the doctor if you’ve ever had radiation treatment to your head or neck, as there have been rare cases of parathyroid carcinoma linked to this.
Physical assessment includes a detailed examination of your mouth, jaw, and neck. The doctor will feel the sides and the middle of your neck for any lumps or swollen lymph nodes and will inspect your thyroid gland, both when you’re at rest and while you’re swallowing. They’ll also take note of the sound and strength of your voice, and if there’s any hint of weakness, they might use a special flexible camera (called a laryngoscope or stroboscope) to closely examine how your vocal cords are working.
Testing for Parathyroid Cancer
When doctors want to check for parathyroid cancer, they will often perform the same laboratory tests as they would for primary hyperparathyroidism. This includes checking the levels of parathyroid hormone and calcium in your body. If these levels are exceptionally high (even running into the thousands of pg/mL), it could indicate parathyroid cancer, which typically causes these levels to be much higher than in the case of primary hyperparathyroidism. For example, if your parathyroid hormone levels are three times higher than the normal range, this could raise suspicion for cancer. If these levels are ten times higher, there is an 84% chance that it is parathyroid cancer.
In addition to these laboratory tests, doctors might use imaging tests to get a better look at the potential tumor and how far it might have spread. A computed tomography (CT) scan is typically the first choice to evaluate a newly found lump in the neck, which could reveal a mass near the thyroid and whether it has spread to the thyroid. This test also helps to check the rest of the neck for potential spread of disease. Even though its reliability for parathyroid cancer isn’t firmly established, doctors may use a positron-emission tomography (PET) scan to help with staging and checking for metastasis, which is the spread of cancer from the initial site to other parts of the body.
Other imaging tests like Sestamibi scans can detect overactive parathyroid glands, but they aren’t helpful in specifically identifying cancer. Similarly, ultrasound can be used to help describe parathyroid tumors, but it too can’t definitively diagnose parathyroid cancer. Having said this, recent studies suggest some ultrasound characteristics might assist in the diagnosis of parathyroid malignancy. Doctors might also perform X-rays of your hand and skull to check for osteoporosis, but these tests are very general and not specific for parathyroid cancer, so they aren’t typically recommended for screening.
Using ultrasound to guide a needle into the lump (a procedure known as fine-needle aspiration) has also been tried, but doctors are not sure if it is effective in differentiating between benign (non-cancerous) hyperactive parathyroid and malignant (cancerous) parathyroid.
Treatment Options for Parathyroid Cancer
The best treatment for parathyroid carcinoma, a type of cancer that affects the parathyroid glands, is usually an operation. This procedure generally includes removal of the affected parathyroid gland and the adjacent portion of the thyroid gland. If doctors strongly suspect that a patient has parathyroid carcinoma before surgery, they aim to remove the cancerous gland, the nearby part of the thyroid, and any surrounding tissues that appear to be affected by the disease.
If, after the surgery, further examination confirms that some cancer was left behind, another operation may be necessary to clean out these remaining cancer cells. However, the second operation can be complicated, potentially requiring removal of parts of the windpipe and food pipe, and sometimes even a nerve connected to the larynx (voice box), known as the recurrent laryngeal nerve. The patient and their surgeon must be prepared for this possibility and the reconstructive procedures that would be needed afterward.
If the cancer is too widespread and cannot be completely removed through surgery, doctors switch to a different approach that aims to ease the patient’s symptoms and control their high calcium levels, a common condition with parathyroid cancer. However, the prognosis for patients in this situation is generally not very positive. Treatment in such cases usually consists of hydration (fluids given directly into a vein) and medications called bisphosphonates, which help lower calcium levels. If the calcium levels don’t respond to bisphosphonates, doctors may try a drug called cinacalcet.
If the cancer comes back in the same area or shows up in nearby regions, the recommended treatment is another operation to remove the recurring cancer. This surgery provides relief from high calcium levels, but whether it can lead to a long-term cure isn’t yet clear. If the cancer has spread to the lungs or liver, surgery in these areas can be performed for symptom relief, but it’s currently unknown if such operations can prolong survival.
What else can Parathyroid Cancer be?
Parathyroid cancer gives similar signs as primary hyperparathyroidism, both showing high levels of parathyroid hormone and serum calcium in the body. There are also certain illnesses that can mimic these symptoms with high calcium levels, but these differ in that they show high levels of a specific substance related to the parathyroid hormone. Additionally, lumps in the thyroid may be mistaken for parathyroid cancers, as both conditions can lead to the feeling of a lumpy mass in the neck.
When working out what might be causing these symptoms, doctors consider several possibilities:
- Parathyroid adenoma (a noncancerous tumor in the parathyroid glands)
- Parathyroid hyperplasia (enlargement of the parathyroid glands)
- Paraneoplastic syndrome (related to lung or head and neck cancers)
- Thyroid nodule (a small abnormal lump in the thyroid gland)
- Primary thyroid cancer
- Brown’s tumor (a type of bone lesion)
What to expect with Parathyroid Cancer
The outlook for patients with parathyroid carcinoma, a type of cancer that occurs in the parathyroid glands, largely depends on whether the cancer has spread to nearby areas or other parts of the body. In roughly one-third of cases, the cancer is well-defined and hasn’t spread, making total surgical removal with clear margins around the tumor likely and providing a very positive outlook.
However, in another third of cases, the disease tends to come back after a long period without the disease. In such situations, another surgery usually results in getting rid of the disease. Unfortunately in the remaining third of the cases, the disease takes a quick and severe course, leading to the death of the patient.
Recovery from Parathyroid Cancer
After an operation, it is important to keep a close eye on the patient’s calcium levels in their blood. If these levels are low, they may need to take extra calcium. If the patient had very high calcium levels in their blood before the operation, they could potentially develop a condition called ‘hungry bone syndrome’ after having surgery on their parathyroid glands. This would mean they need to have calcium delivered straight into their bloodstream.
It’s also vital to continually check the patient’s PTH (Parathyroid Hormone) and calcium levels after the operation. If these levels start to increase, it could mean that the patient needs more tests as this could be a sign of continuous or metastatic disease (cancer that has spread from the initial site to other parts of the body).
Preventing Parathyroid Cancer
If you have family members with a condition known as hyperparathyroidism-jaw tumor syndrome, it’s important for you to have regular check-ups with your doctor that include routine physical exams and blood tests. Also, it’s advised to consult with medical genetic specialists. This condition tends to run in families, so it’s useful to understand your genetic risks.
Similarly, if through these checks you are found to have a condition known as MEN syndrome, you will need further examinations that involve hormone and genetic tests. This syndrome affects the production of certain hormones, so these further tests can provide important information about your health.
Parathyroid carcinoma, a type of cancer that affects the parathyroid glands, is quite rare. However, if you have an unusual growth on your neck and your tests show very high levels of the parathyroid hormone and a condition called hypercalcemia (high levels of calcium in your blood), your doctor may suspect this type of cancer. Being aware of these symptoms can help in early detection and better treatment.
