A parathyroid adenoma is a non-cancerous growth that develops on one of the parathyroid glands. This abnormal growth causes the affected gland to produce an excessive amount of parathyroid hormone (PTH), leading to a condition known as primary hyperparathyroidism. The overproduction of PTH disrupts the body’s calcium balance, resulting in elevated calcium levels in the bloodstream. This imbalance can contribute to various health issues, including kidney stones and weakened bones.
Understanding the Parathyroid Glands
The parathyroid glands are four small, pea-sized endocrine glands located in the neck, behind the thyroid gland. These glands play a central role in maintaining calcium and phosphorus levels within the blood. They achieve this by releasing parathyroid hormone (PTH).
PTH works to increase blood calcium by stimulating its release from bones, enhancing its absorption from food in the intestines, and promoting its conservation by the kidneys. Maintaining balanced calcium levels is important for proper nerve and muscle function, as well as for strong bones.
Genetic and Hereditary Predispositions
Most parathyroid adenomas occur sporadically but are linked to genetic changes that develop during a person’s lifetime. These acquired genetic alterations, known as somatic mutations, contribute to the formation of the adenoma. Genetic factors are more commonly identified as the cause when the diagnosis occurs at a younger age.
Several inherited syndromes significantly increase the risk of developing parathyroid adenomas. Multiple Endocrine Neoplasia Type 1 (MEN1) is the most frequent familial cause of primary hyperparathyroidism. This syndrome involves a predisposition to tumors in the parathyroid glands, pituitary gland, and pancreas, stemming from germline mutations in the MEN1 gene.
Another inherited condition is Multiple Endocrine Neoplasia Type 2A (MEN2A), which involves overactivity of the parathyroid glands along with tumors in the adrenal or thyroid glands. Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT) is a hereditary disorder, often characterized by parathyroid overactivity and benign tumors in the jaw. This syndrome is associated with mutations in the CDC73 gene, which provides instructions for the parafibromin protein, a tumor suppressor.
Familial Isolated Hyperparathyroidism (FIHP) is another inherited form where primary hyperparathyroidism occurs without other syndromic features. FIHP can be caused by mutations in the MEN1, CDC73, or CASR genes. The CASR gene provides instructions for the calcium-sensing receptor protein, which helps regulate calcium levels and PTH production. These inherited mutations can predispose cells to uncontrolled growth, accelerating the development of an adenoma.
Environmental and Acquired Risk Factors
Beyond genetic predispositions, several environmental exposures and acquired medical conditions can increase the likelihood of developing a parathyroid adenoma. One recognized risk factor is radiation exposure, particularly to the head and neck area. This can occur from past medical treatments, such as radiation therapy for conditions like acne or thyroid disorders.
Long-term use of lithium, a medication often prescribed for bipolar disorder, is another factor associated with an increased risk of parathyroid adenomas. Lithium therapy can influence calcium metabolism, potentially leading to an overactive parathyroid gland. Additionally, conditions that chronically stimulate the parathyroid glands can sometimes lead to adenoma formation.
Severe vitamin D deficiency or chronic kidney disease can cause the parathyroid glands to work harder to maintain calcium balance. This sustained overactivity can sometimes lead to adenoma formation. Environmental chemicals, including certain persistent organic pollutants, have also been detected in human parathyroid tumors, suggesting a potential link.
The Cellular Development of Adenomas
A parathyroid adenoma originates from the uncontrolled proliferation of a single, abnormal parathyroid cell. This cellular malfunction often stems from genetic mutations. These mutations can affect genes responsible for regulating cell growth and division, such as the MEN1 gene, which normally produces a tumor suppressor protein called menin.
When these genes are mutated, the affected cell may disregard the normal signals that control its growth, leading to an expansion of this abnormal cell population. This unchecked growth results in the formation of a benign tumor, the adenoma. These mutations can also impact genes involved in hormone production or the calcium-sensing receptor (CASR). The altered function of the CASR can lead to the adenoma overproducing parathyroid hormone (PTH) independently of the body’s calcium needs, thus elevating blood calcium levels.