Parathyroid cancer

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Parathyroid cancer is a rare cancer that usually affects people in their forties or fifties and occurs in one of the four parathyroid glands. The parathyroid glands are located in the neck and secrete parathyroid hormone, which enhances the release of calcium into the blood.

In about 90 percent of cases, the early signs of parathyroid cancer are high levels of parathyroid hormone (hyperparathyroidism) and calcium (hypercalcemia) in the blood. In these cases, the cancer is described as hormonally functional because the parathyroid glands are producing excess hormone.

Many individuals with hormonally functional parathyroid cancer develop hypercalcemic crisis, in which calcium levels in the blood are very high. Neurological problems can develop, including changes in mood and depression. About 30 percent of individuals with hypercalcemia due to parathyroid cancer develop kidney and skeletal problems. These problems include increased urine production (polyuria), deposits of calcium in the kidneys (nephrocalcinosis) leading to the formation of kidney stones (nephrolithiasis), bone pain, bone loss, and increased bone fractures. Abdominal pain, inflammation of the pancreas (pancreatitis), sores (ulcers) in the lining of the digestive tract, nausea, vomiting, weight loss, and fatigue are also common.

About 10 percent of cases of parathyroid cancer are described as hormonally nonfunctional. In these cases, levels of parathyroid hormone and calcium are normal. The signs and symptoms of hormonally nonfunctional parathyroid cancer are related to the tumor obstructing nearby structures in the neck. These problems include difficulty swallowing (dysphagia) and speaking (dysarthria), a hoarse voice, shortness of breath (dyspnea), or vocal cord paralysis.

Up to 85 percent of individuals with parathyroid survive at least 5 years after they are diagnosed. The disease recurs in approximately half of individuals. If cancer does recur, it will commonly be within 3 years of the original diagnosis and up to 78 percent of people with recurrent cancer survive at least 5 years. Hormonally nonfunctional parathyroid cancer has a lower survival rate because it is often found at a later stage, as it does not have early signs such as increased calcium and parathyroid hormone levels.

In hormonally functional parathyroid cancer, death is usually caused by organ failure (usually kidney failure) due to prolonged hypercalcemia and not directly due to the tumor. In hormonally nonfunctional parathyroid cancer, the cause of death is typically related to the tumor itself, such as its impact on the function of nearby structures or its spread to other tissues (metastasis).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Cancers occur when genetic mutations build up in critical genes, specifically those that control cell growth and division (proliferation) or the repair of damaged DNA. These changes allow cells to grow and divide uncontrollably to form a tumor. In most cases of parathyroid cancer, these genetic changes are acquired during a person's lifetime and are present only in certain cells in the parathyroid glands. These changes, which are called somatic mutations, are not inherited. Somatic mutations in many different genes have been found in parathyroid cancer cells. Less commonly, genetic changes present in all of the body's cells increase the risk of developing parathyroid cancer. These genetic changes, which are classified as germline mutations, are usually inherited from a parent. In people with germline mutations, changes in other genes, together with non-genetic factors, also influence whether a person will develop parathyroid cancer.

Mutations in the CDC73 gene are found in up to 70 percent of cases of parathyroid cancer. In approximately one-third of affected individuals with changes in this gene, the mutation is inherited from a parent and is present in all of the body's cells. In people who have parathyroid cancer with CDC73 gene mutations, the cancer is seven times more likely to metastasize than is parathyroid cancer in affected individuals without CDC73 gene mutations. Individuals with CDC73 gene mutations are also at a higher risk of recurrence of the cancer and have a decreased survival rate compared to those without CDC73 gene mutations. Mutations in other genes have also been found in parathyroid cancer, but each of these mutations has been reported in only a small number of individuals.

The CDC73 gene provides instructions for making a protein called parafibromin. This protein is found within the nucleus of cells throughout the body and is likely involved in gene transcription, which is the first step in protein production. Parafibromin functions as a tumor suppressor, which means it keeps cells from growing and dividing too rapidly or in an uncontrolled way. In individuals with a CDC73 gene mutation, either inherited from a parent or acquired during their lifetime, a second mutation in the other copy of the CDC73 gene must occur in parathyroid cells for cancer to develop. Parathyroid cells with two altered copies of the CDC73 gene produce no functional parafibromin. As a result, cells grow and divide unchecked, which can lead to parathyroid cancer.

A significantly increased risk of parathyroid cancer is also a feature of certain rare genetic syndromes. Parathyroid cancer occurs in 15 percent of individuals with hyperparathyroidism-jaw tumor syndrome and in 1 percent of individuals with familial isolated hyperparathyroidism. These conditions are both caused by mutations in the CDC73 gene. In rare cases, parathyroid cancer has also been found in people who have a tumor disorder called multiple endocrine neoplasia, which is caused by mutations in other genes.

Non-genetic factors have also been found to contribute to a person's risk of developing parathyroid cancer, including a history of hyperparathyroidism with chronic kidney failure, thyroid cancer, and previous radiation therapy on the neck.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Most cases of parathyroid cancer are not caused by inherited genetic factors. These cancers are associated with somatic mutations that are acquired during a person's lifetime, and they do not cluster in families.

A predisposition to parathyroid cancer caused by a germline mutation is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing a tumor. It is important to note that people inherit an increased likelihood of developing cancer, not the disease itself. Not all people who inherit a cancer-predisposing gene mutation will ultimately develop cancer.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Parathyroid cancer is one of the rarest types of cancer. It accounts for 0.005 percent of all cancers, with about 1,000 cases reported in the medical literature.

Which doctor should you see?

The suggested department for discussing Parathyroid cancer is Oncology, with a oncologist and relevant organ specialist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics; Relevant organ specialist / Surgical Oncology as indicated.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Has the exact tumour type been confirmed, and is staging relevant?
• What is the goal of each proposed treatment option?
• How will side effects, daily function and supportive care be addressed?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Parathyroid cancer. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.