Which are the causes of Hyperparathyroidism?

TL;DR: Hyperparathyroidism is primarily caused by an overactive parathyroid gland—usually due to a benign tumor called an adenoma—which leads to the overproduction of parathyroid hormone (PTH) and subsequent calcium imbalance. While most cases are sporadic and have no clear environmental trigger, a small percentage are linked to specific hereditary genetic syndromes that cause multiple endocrine tumors.

What are the primary causes of Hyperparathyroidism?

The underlying cause of Hyperparathyroidism depends on the type, but the most common form, Primary Hyperparathyroidism, is usually caused by a single benign (non-cancerous) tumor known as a parathyroid adenoma. This growth disrupts the body’s "thermostat" for calcium. Think of the parathyroid glands like a furnace: in a healthy body, they turn on and off to keep blood calcium levels steady. In Hyperparathyroidism, the "furnace" is stuck in the "on" position, continuously pumping out parathyroid hormone (PTH) regardless of how much calcium is already in the blood.

Is Hyperparathyroidism hereditary?

While most cases of Hyperparathyroidism occur sporadically in individuals with no family history, approximately 5% to 10% of cases are inherited as part of a genetic syndrome. These syndromes involve mutations in specific genes that regulate cell growth in endocrine tissues. Key genetic associations include:

• MEN1 (Multiple Endocrine Neoplasia type 1): Caused by mutations in the MEN1 gene.


• MEN2A: Associated with mutations in the RET proto-oncogene.


• HPT-JT (Hyperparathyroidism-Jaw Tumor syndrome): Linked to mutations in the CDC73 gene.


• Familial Isolated Hyperparathyroidism (FIHP): A condition where Hyperparathyroidism is the only clinical feature, often without a fully identified genetic cause in every family.

What is the difference between causes and risk factors?

In the context of Hyperparathyroidism, a "cause" is the direct mechanism—such as a tumor on the gland or a genetic mutation—that forces the gland to overproduce hormone. A "risk factor," by contrast, is something that increases the likelihood of developing the condition but does not directly trigger it. Known risk factors include:

• Age: The condition is most common in individuals over age 50.


• Gender: Women are diagnosed with Hyperparathyroidism at a rate two to three times higher than men, especially after menopause.


• Radiation Exposure: Prior radiation therapy to the neck or head, often used to treat unrelated cancers decades earlier, is a documented risk factor.


• Lithium Therapy: Long-term use of lithium, a medication used for bipolar disorder, can sometimes stimulate the parathyroid glands.

What is the current state of research?

Medical researchers are actively working to understand why the parathyroid glands become overactive in the absence of genetic syndromes. Current studies are investigating the role of chronic vitamin D deficiency and mild, long-term stimulation of the glands as potential contributors to the development of Hyperparathyroidism. Furthermore, advancements in molecular genetics are helping clinicians identify which patients might harbor hidden genetic mutations, allowing for better screening of family members who may be at risk.

Next steps

• Consult an endocrinologist to interpret your blood calcium and PTH levels.


• If you have a strong family history of endocrine tumors, ask your doctor about genetic counseling and testing.


• Join our community at DiseaseMaps.org to connect with the 154 members currently sharing their lived experience with Hyperparathyroidism.


• Request a referral to a specialized parathyroid surgeon if imaging confirms an adenoma.

Medical disclaimer: This content is for informational purposes only and does not constitute medical advice, diagnosis, or treatment; always seek the advice of your physician or other qualified health provider with any questions regarding a medical condition.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Hyperparathyroidism overview.


• Orphanet: Rare endocrine diseases database.


• OMIM (Online Mendelian Inheritance in Man): Clinical synopsis for Multiple Endocrine Neoplasia.


• The American Association of Endocrine Surgeons (AAES): Patient education on parathyroid disease.