Parathyroid disease happens when one or more of your four parathyroid glands produce too much or too little parathyroid hormone (PTH), the chemical messenger that controls calcium levels in your blood. The most common form, primary hyperparathyroidism, is caused by a noncancerous growth on a single gland in about 85% of cases. But the full picture is more varied, ranging from surgical damage and kidney disease to inherited gene mutations and vitamin D deficiency.
How the Parathyroid Glands Work
Your parathyroid glands are four tiny structures, each about the size of a grain of rice, sitting behind your thyroid in your neck. Their sole job is to monitor blood calcium and release PTH when levels drop. PTH pulls calcium from your bones, tells your kidneys to hold onto calcium instead of flushing it out, and activates vitamin D so your gut absorbs more calcium from food. When calcium rises back to normal, the glands dial PTH back down.
This feedback loop is tightly regulated. Problems start when a gland can’t sense calcium properly, grows abnormally, gets damaged, or receives faulty signals from somewhere else in the body. Which of those happens determines the type of parathyroid disease you develop.
Primary Hyperparathyroidism: Overactive Glands
Primary hyperparathyroidism is the most common parathyroid disorder. In 85% of patients, the cause is a single adenoma, a benign tumor that forms on one of the four glands and produces PTH on its own, ignoring the normal calcium feedback signal. The remaining cases are split between multiple adenomas (tumors on more than one gland) and four-gland hyperplasia, where all the glands enlarge and overproduce hormone together.
Parathyroid cancer is rare, accounting for less than 1% of all hyperparathyroidism cases. It tends to cause much higher calcium levels than a benign adenoma, which is sometimes what prompts doctors to suspect it.
Women develop primary hyperparathyroidism roughly three times as often as men, and the gap widens after age 50. Rates climb steadily with age in both sexes, peaking in women over 80. The reasons for this gender difference aren’t fully understood, but the drop in estrogen after menopause likely plays a role, since estrogen helps regulate how bones respond to PTH.
Radiation and Other External Triggers
A history of radiation to the head or neck raises the risk of parathyroid adenomas and, rarely, parathyroid cancer. The lag time can be remarkably long. Case reports document parathyroid tumors appearing more than 40 years after radiation exposure. People who received combined chemotherapy and radiation for childhood cancers like Hodgkin lymphoma face an especially elevated risk of secondary tumors in the neck region.
Lithium and Medication Effects
Lithium, a medication used for bipolar disorder, can trigger hyperparathyroidism through a different mechanism. It increases calcium reabsorption in the kidneys and independently stimulates PTH release, essentially raising the calcium level at which the glands decide to stop producing hormone. This shift can persist even after lithium is discontinued, sometimes requiring surgery.
Secondary Hyperparathyroidism: A Response to Another Problem
In secondary hyperparathyroidism, the parathyroid glands themselves are healthy at first. They’re overproducing PTH because something else in the body is keeping calcium chronically low. The most common culprit is chronic kidney disease.
Healthy kidneys convert vitamin D into its active form, which helps your gut absorb calcium. As kidney function declines, active vitamin D drops and phosphorus builds up in the blood. Both changes push calcium levels down, forcing the parathyroid glands to work harder. Over time, the glands enlarge and their internal sensors become less responsive to calcium. Even when calcium is brought back to a normal range, the glands don’t shut off the way they should. Receptors for both calcium and vitamin D get downregulated, meaning the glands need a bigger signal to respond, and the whole system drifts further out of balance.
This form of parathyroid disease affects a significant percentage of people with advanced kidney disease and is one of the reasons kidney patients undergo regular blood monitoring for calcium, phosphorus, and PTH.
Vitamin D Deficiency Without Kidney Disease
You don’t need kidney failure for this mechanism to kick in. Vitamin D deficiency on its own can trigger a compensatory rise in PTH. When blood levels of 25-hydroxyvitamin D fall below 20 ng/mL, the parathyroid glands ramp up hormone production to maintain calcium, accelerating bone loss in the process. This is sometimes called “normocalcemic secondary hyperparathyroidism” because calcium may stay in the normal range while PTH runs high. It’s often missed on routine bloodwork unless a doctor specifically checks PTH alongside calcium and vitamin D.
Tertiary Hyperparathyroidism: Glands That Won’t Reset
Tertiary hyperparathyroidism develops when secondary hyperparathyroidism has been present so long that the parathyroid glands become autonomous. Even after the original trigger is corrected, typically through a kidney transplant, the glands continue overproducing PTH on their own. The cells have proliferated and no longer respond normally to rising calcium levels.
Patients who had very high PTH levels before transplant (above 300 pg/mL) are at the greatest risk. Tertiary hyperparathyroidism is defined by the combination of elevated calcium and elevated PTH persisting at least one year after a successful kidney transplant. When it occurs, surgery to remove the enlarged glands is sometimes the only effective treatment.
Hypoparathyroidism: Too Little Hormone
Hypoparathyroidism, where the glands produce too little PTH, has a very different set of causes. About 75% of cases result from damage during neck surgery, most often thyroid surgery, parathyroid surgery, or procedures for head and neck cancers. The parathyroid glands are so small and so close to the thyroid that they can be accidentally removed, bruised, or have their blood supply cut off during an operation. In many cases the damage is temporary and the glands recover within weeks, but for some patients, hormone production never fully returns.
The remaining cases fall into several categories. Autoimmune hypoparathyroidism occurs when the immune system attacks the parathyroid glands, sometimes as part of a broader autoimmune condition affecting multiple glands. Rare genetic conditions can cause the parathyroid glands to develop abnormally or fail to form at all. DiGeorge syndrome, a chromosomal deletion present from birth, is one of the more recognized causes in children.
Genetic and Inherited Causes
Several inherited syndromes directly affect the parathyroid glands. The most important is Multiple Endocrine Neoplasia type 1, or MEN1, caused by a mutation in the gene that produces a tumor-suppressing protein called menin. Without functioning menin, cells in the parathyroid glands (along with the pituitary and pancreas) can grow and divide unchecked. MEN1 follows an autosomal dominant pattern, meaning a child needs only one copy of the mutated gene from one parent to inherit the condition.
A diagnosis of MEN1 is made when a person has two or more MEN1-related tumors, or one tumor plus a first-degree relative with the condition, or simply carries the gene mutation even without symptoms. Because parathyroid tumors are often the first sign, unexplained hyperparathyroidism in a young person sometimes prompts genetic testing for MEN1.
MEN2A, a related but distinct syndrome, also causes parathyroid overactivity in some patients, though it more commonly affects the thyroid (through medullary thyroid cancer) and the adrenal glands. Familial hypocalciuric hypercalcemia is another inherited condition that mimics hyperparathyroidism. It’s caused by a defective calcium-sensing receptor and is important mainly because it can be mistaken for a parathyroid adenoma, leading to unnecessary surgery.
What Determines Your Risk
Several factors overlap in raising your likelihood of developing parathyroid disease. Being female and over 50 is the strongest demographic predictor for primary hyperparathyroidism. Having chronic kidney disease puts you on a path toward secondary hyperparathyroidism. A family history of MEN1 or other endocrine syndromes warrants proactive screening. Prior radiation to the neck, long-term lithium use, and severe vitamin D deficiency are modifiable or monitorable risk factors that your doctor can assess with straightforward blood tests and a detailed medical history.
Most parathyroid disease is caught through a routine blood test showing abnormal calcium. If your calcium is high, the next step is checking your PTH level. If both are elevated, the diagnosis is usually straightforward. If calcium is low with low PTH, hypoparathyroidism is the likely explanation. The pattern of those two numbers together tells the story of which type of parathyroid disease is at work and, often, points toward its underlying cause.