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Hyperparathyroidism

  • A condition in which the parathyroid glands produce too much parathyroid hormone
  • Symptoms include fatigue, muscle weakness, depression, memory problems, bone pain
  • Treatment includes dietary changes, medication, surgery
  • Involves endocrinology, endocrine surgery

Hyperparathyroidism

Overview

Hyperparathyroidism is a condition in which the parathyroid glands produce too much parathyroid hormone (PTH). This affects calcium levels in the body, which can then impact your blood, bones, and other organs.

Hyperparathyroidism often affects older adults, especially those in their 50s, 60s, and beyond. About 100,000 people are diagnosed with the condition each year in the United States. Women are diagnosed with the condition about three times as often as men.

There are primary, secondary, and tertiary forms of hyperparathyroidism. Each has a different cause. Treatments are available to help people manage the condition—depending on its cause—with lifestyle modifications, medication, or surgery.

What is hyperparathyroidism?

Hyperparathyroidism is a condition that occurs when too much PTH is produced by the parathyroid glands. It’s often a “silent” condition without noticeable symptoms. It is often diagnosed during routine blood tests at annual well visits.

We all have four parathyroid glands, each of which is about the size of a pea. They are located in the neck on the back side of the thyroid gland, at the tops and bottoms of each lobe of the thyroid.

In healthy people, the parathyroid gland produces and releases PTH, which helps to maintain proper levels of calcium in the bones and bloodstream. (Calcium helps the body maintain strong bones and teeth, but it’s also an essential mineral for the nerves, muscles, and heart.)

PTH stimulates the synthesis of calcitriol in the kidneys that, in turn, enables the digestive system to absorb calcium from food sources. The hormone instructs the kidneys to retain calcium instead of releasing it from the body in urine. And when a person’s blood-calcium levels are too low, the parathyroid glands release just enough PTH to instruct the bones to release the proper amount of calcium into the bloodstream to maintain adequate levels.

But in someone with hyperparathyroidism, too much PTH is produced. There are three forms of hyperparathyroidism, each with a different cause.

  • Primary hyperparathyroidism: One or more of the parathyroid glands grows too large and releases too much PTH, which leads to elevated levels of calcium (because of excessive production of calcitriol and release of calcium from the bones).
  • Secondary hyperparathyroidism: Blood-calcium or vitamin D levels are so low—often due to dietary deficiency—they cause the parathyroid glands to release excessive levels of PTH to counteract the deficiency by inducing excessive release of calcium from bone.
  • Tertiary hyperparathyroidism: Chronically reduced calcium and vitamin D deficiency—or reduced calcitriol synthesis due to kidney disease—cause all four parathyroid glands to grow and produce PTH regardless of whether the body needs the hormone, leading to elevated levels of calcium levels (because of excessive release of calcium from the bones).

What causes hyperparathyroidism?

There are different possible causes of hyperparathyroidism, depending on whether the condition is primary, secondary, or tertiary.

  • Primary hyperparathyroidism: The condition is usually due to a benign (non-cancerous) tumor or growth, called an adenoma, arising in one of the four parathyroid glands. The presence of the adenoma causes the parathyroid gland to become overactive, producing more PTH than it should. Doctors aren’t sure why adenomas form in the parathyroid glands.
    
    Sometimes, primary hyperparathyroidism occurs because two or more parathyroid glands have adenomas. In other cases, all four parathyroid glands become enlarged. This condition is also caused by parathyroid hyperplasia.
    
    Uncommon causes of primary hyperparathyroidism include rare genetic conditions like multiple endocrine neoplasia type 1, multiple endocrine neoplasia type 2, or familial hypocalciuric hypercalcemia. Rarely, hyperparathyroidism-jaw tumor syndrome can cause hyperparathyroidism and sometimes parathyroid cancer.
  • Secondary hyperparathyroidism: The condition occurs because of chronically low levels of calcium or vitamin D in the blood, which causes the parathyroid glands to chronically release high levels of PTH. This can also happen when people produce less calcitriol due to chronic kidney disease which is thought to be due to excessive levels of phosphate in the blood and elevations of fibroblast growth factor (FGF23). Blood calcium levels are low, not high and high PTH is appropriate to help normalizing calcium levels.
  • Tertiary hyperparathyroidism: The condition occurs among people who have had secondary hyperparathyroidism for a long time, particularly among people who have had chronic kidney disease for many years. Like in primary hyperparathyroidism, calcium levels are elevated in tertiary hyperparathyroidism.

What are the symptoms of hyperparathyroidism?

Most people with hyperparathyroidism don’t notice any symptoms. Those who do may experience bone pain, muscle weakness, and fatigue.

Some symptoms are also specific to the cause of hyperparathyroidism.

Common symptoms of hyperparathyroidism are:

  • Fatigue
  • Muscle weakness
  • Depression
  • Memory problems or forgetfulness
  • Bone pain
  • Weak, fragile wrist, hip, and back bones that break easily
  • Joint pain due to calcium crystals in the joint fluid
  • Loss of appetite
  • Nausea or vomiting
  • Constipation
  • Confusion
  • Kidney stones
  • Increased urination
  • Increased thirst

People with secondary hyperparathyroidism may additionally have:

  • Low calcium levels
  • Stress fractures in the pelvis and midfeet
  • Spontaneous rupture of a tendon

People with tertiary hyperparathyroidism additionally may have:

  • Kidney disease
  • Calcium deposits in soft tissue and blood vessels
  • Itchiness
  • Changes in mental status

What are the risk factors for hyperparathyroidism?

People who are at increased risk of hyperparathyroidism have, or have had:

  • Radiation therapy treatments to the head or neck
  • Parathyroid adenoma
  • Hyperplasia
  • Parathyroid cancer
  • Kidney stones/kidney failure
  • Chronic kidney disease
  • Kidney transplant
  • Difficulty absorbing nutrients from food
  • Too little calcium in the diet
  • Too much calcium excreted in the urine
  • Vitamin D deficiency/disorders
  • Multiple endocrine neoplasia type 1/2
  • Familial hypocalciuric hypercalcemia
  • Familial hyperparathyroidism
  • Hyperparathyroidism-jaw tumor syndrome

Some medications can increase the risk of hyperparathyroidism, including lithium, loop diuretics, and bisphosphonates.

How is hyperparathyroidism diagnosed?

Hyperparathyroidism is commonly diagnosed during routine blood tests, which check blood-calcium levels. It’s less common for people to be diagnosed with the condition because of symptoms or complications. In those instances, however, doctors will diagnose the condition after learning about a patient’s medical history, performing a physical examination, and giving diagnostic tests.

You should tell your doctor if you have bone pain, muscle weakness, kidney stones, constipation, fatigue, or depression. You should also discuss any medications and dietary supplements you are taking, as well as any history of head and neck cancer (including radiation therapy).

During a physical exam, your sensitivity to bones being touched, which could be a sign of bone pain or tenderness, will be assessed.

There are different tests to check for hyperparathyroidism, including:

  • Blood tests that check the levels of:
    • Calcium
    • PTH
    • Phosporus
    • Creatinine
    • Vitamin D
  • Urine tests, which can check for levels of calcium and creatinine.
  • Imaging tests, including:
    • Ultrasound
    • CT scan
    • MRI

Imaging tests are used more frequently when surgery is needed to pinpoint an adenoma.

How is hyperparathyroidism treated?

Different treatments are available for people with hyperparathyroidism.

Medical Management. Some patients may not need treatment beyond medical management, which includes:

  • Optimize vitamin D and calcium intake with diet
  • Drinking enough fluids to lower the risk of kidney stones
  • Alternatives medications for any drugs you may be taking that raise calcium levels, if applicable
  • Checking blood-calcium levels twice annually
  • Monitoring bone density every year

Surgery. Certain patients may need surgery to remove one or more of the parathyroid glands. Surgery is usually not recommended for people who have primary or tertiary hyperparathyroidism without symptoms. It may be offered to people:

  • Whose blood-calcium levels are higher than the normal range
  • Who excrete too much calcium in the urine
  • Who have osteoporosis, based on bone density test results

Surgery is not needed to treat secondary hyperparathyroidism

Medication. Some people who would benefit from surgery but cannot have the procedure may be prescribed medication, such as cinacalcet, which can lower PTH and calcium levels in the blood. Bisphosphonates, which increase bone density, may also be prescribed.

What is the outlook for people with hyperparathyroidism?

Medical management of asymptomatic hyperparathyroidism is an effective way to help control the condition. When people need surgery to remove one or more parathyroid glands, the procedure is successful in 94% of cases. However, if parathyroid cancer is the cause of hyperparathyroidism, life expectancy can be impacted. About 78% of patients with parathyroid cancer live five or more years.

What makes Yale unique in its treatment of hyperparathyroidism?

“The Yale Bone Center is a regional center for expertise in management of disorders of mineral metabolism, including hyperparathyroidism,” says Yale Medicine endocrinologist Clemens Bergwitz, MD. “Yale offers a team-based approach, with physicians, nurse practitioners, physical therapists, and nutritionists providing state-of-the-art care, incorporating the latest medical and surgical treatments tailored to each patient. In addition, there are ongoing research studies for hypoparathyroidism, hypophosphatemic rickets, and osteogenesis imperfecta to help advance our understanding of both the mechanisms underlying this disease and ways to improve treatment.”