Hyperparathyroidism

(elevated parathyroid hormone)

What are the parathyroid glands and what is hyperparathyroidism?

Most people have four pea-sized glands, called parathyroid glands, located behind the thyroid gland in the neck. Though their names are similar, the thyroid and parathyroid glands are completely different. The parathyroid glands make parathyroid hormone (PTH), which helps your body keep the right balance of calcium and phosphorous.
If your parathyroid glands make too much or too little hormone, it disrupts this balance. If they secrete extra PTH, you have hyperparathyroidism.

What are the causes of hyperparathyroidism?

The main causes encountered in clinical practice of elevations in parathyroid hormone levels (hyperparathyroidism) are primary hyperparathyroidism (PHPT) (see below), and secondary hyperparathyroidism due to underlying kidney dysfunction and vitamin D deficiency. The parathyroid glands’ function is closely linked to the function of the kidneys. Any condition that affects the function of the kidneys could lead to hyperparathyroidism. Treating the underlying kidney ailment (if possible) normalizes the hyperparathyroidism thus the reason why this is called secondary (tied in to kidney function) hyperparathyroidism. Hyperparathyroidism can also occur in the setting of vitamin D deficiency which is very prevalent today and again dealing with the underlying cause and restoring normal vitamin D levels can restore normal parathyroid hormone levels.

What is primary hyperparathyroidism (PHPT)?

Primary hyperparathyroidism (PHPT) occurs when your parathyroid glands make too much parathyroid hormone (PTH) independent of normal physiologic restraints. Under normal physiologic conditions with normal kidney function and vitamin D levels PTH should only be produced in excess when calcium levels in the bloodstream are low. This increase in PTH then leads to a compensatory restoration of normal calcium levels. In PHPT excess PTH is produced by the parathyroid glands despite normal calcium levels in an autonomous way which then leads to elevation in calcium levels (hypercalcemia, see other section).

What are the symptoms of PHPT?

Most people who have PHPT do not experience any symptoms. Some people may have one or more of the following symptoms:

  • Feeling weak or tired most of the time
  • General aches and pains throughout your body
  • Abdominal pain
  • Frequent heartburn (because the high calcium level in your blood causes your stomach to make too much acid)
  • Nausea
  • Vomiting
  • Loss of appetite
  • Bone and joint pain
  • An increase in bone fractures or breaks
  • Confusion and memory loss
  • Kidney stones
  • Excessive urination
  • High blood pressure

What causes PHPT?

In about 80 percent of people with primary hyperparathyroidism, a benign, or noncancerous, tumor called an adenoma has formed in one of the parathyroid glands. The tumor causes the gland to become overactive. In most other cases, the excess hormone comes from two or more overactive parathyroid glands, a condition called multiple tumors or hyperplasia. Rarely, primary hyperparathyroidism is caused by cancer of a parathyroid gland.

In most cases, health care providers don’t know why adenoma or multiple tumors occur in the parathyroid glands. Most people with primary hyperparathyroidism have no family history of the disorder, but some cases can be linked to an inherited problem. For example, familial multiple endocrine neoplasia type 1 is a rare, inherited syndrome that causes multiple tumors in the parathyroid glands as well as in the pancreas and the pituitary gland. There is also multiple endocrine neoplasia type 2 in which PHPT is also present and it is associated with other clinical manifestations. Another rare genetic disorder, familial hypocalciuric hypercalcemia (FHH), causes a kind of hyperparathyroidism that is atypical, in part because it does not respond to standard parathyroid surgery.

How is PHPT diagnosed?

PHPT is first suspected when hypercalcemia develops along with hyperparathyroidism and both of these labs are confirmed to be abnormal on routine blood testing. A big point of emphasis is that this is a diagnosis that should ONLY be made based on laboratory data. This diagnosis is at times elusive and at other times completely ignored as in many instances bloodstream calcium levels fluctuate between normal to slightly high on repeat confirmatory testing. The most common scenario is for both calcium and PTH levels to both be elevated. Other scenarios that make this diagnosis more challenging are normal calcium levels with elevated parathyroid hormone (PTH) levels and elevated calcium levels with normal parathyroid hormone (PTH) levels. A specialist with expertise in diagnosing this condition is of utmost importance to prevent unnecessary testing and delays in diagnosis.

How is PHPT treated?

Surgery
Surgery to remove the overactive parathyroid gland or glands is the only definitive treatment for the disorder, particularly if the patient has a very high blood calcium level or has had a fracture or a kidney stone. In patients without any symptoms, guidelines are used to identify who might benefit from parathyroid surgery.
A consensus statement recommended the following indications for surgery in asymptomatic primary hyperparathyroidism:

  • Serum calcium: 1.0 mg/dl above upper limit of normal
  • 24-h urinary calcium >400 mg
  • Creatinine clearance reduced by 30% compared with age-matched subjects.
  • Bone mineral density t-score <−2.5 at any site
  • Age <50
  • Patients who prefer the procedure for definitive treatment.

When performed by experienced endocrine surgeons, surgery cures primary hyperparathyroidism in more than 95 percent of operations. Finding an experienced surgeon is critical for optimal outcome. We work very closely with experienced surgeons that operate for this condition.

Surgeons often use imaging tests before surgery to locate the overactive gland to be removed. The most commonly used tests are sestamibi and ultrasound scans. In a sestamibi scan, the patient receives an injection of a small amount of radioactive dye that is absorbed by overactive parathyroid glands. The overactive glands can then be viewed using a special camera. These tests may come back normal (failing to highlight the overactive parathyroid gland(s)) and a common pitfall of less experienced clinicians is to assume the condition is not present. Surgery should still be considered if appropriate criteria is met, because the diagnosis of this condition should ONLY be established by laboratory testing and often times the operators performing these imaging studies are not experienced enough to identify the abnormal glands or the abnormal glands are not sufficiently large enough for detection.

Surgeons use two main strategies to remove the overactive gland or glands:

  • Minimally invasive parathyroidectomy. This type of surgery, which can be done on an outpatient basis, may be used when only one of the parathyroid glands is likely to be overactive. Guided by a tumor-imaging test, the surgeon makes a small incision in the neck to remove the gland. The small incision means that patients typically have less pain and a quicker recovery than with more invasive surgery. Local or general anesthesia may be used for this type of surgery.
  • Standard neck exploration. This type of surgery involves a larger incision that allows the surgeon to access and examine all four parathyroid glands and remove the overactive ones. This type of surgery is more extensive and typically requires a hospital stay of 1 to 2 days. Surgeons use this approach if they plan to inspect more than one gland. General anesthesia is used for this type of surgery.

Almost all people with primary hyperparathyroidism who have symptoms can benefit from surgery. Experts believe that those without symptoms but who meet guidelines for surgery will also benefit from surgery. Surgery can lead to improved bone density and fewer fractures and can reduce the chance of forming kidney stones. Other potential benefits are being studied by researchers.
Surgery for primary hyperparathyroidism has a complication rate of 1–3 percent when performed by experienced endocrine surgeons. Rarely, patients undergoing surgery experience damage to the nerves controlling the vocal cords, which can affect speech. A small number of patients lose all their healthy parathyroid tissue and thus develop chronic low calcium levels, requiring lifelong treatment with calcium and some form of vitamin D. This complication is called hypoparathyroidism. The complication rate is slightly higher for operations on multiple tumors than for a single adenoma because more extensive surgery is needed.

People with primary hyperparathyroidism due to familial hypocalciuric hypercalcemia should not have surgery.
Although surgery is the preferred treatment option in most cases it is not the only option. The very elderly, patients with short life spans, or patients with multiple other significant health problems for which undergoing general anesthesia could pose risks may not be ideal surgical candidates.
Monitoring

Some people who have mild primary hyperparathyroidism may not need immediate or even any surgery and can be safely monitored. People may wish to talk with their health care provider about long-term monitoring if they

  • are symptom-free
  • have only slightly elevated blood calcium levels
  • have normal kidneys and bone density

Long-term monitoring should include periodic clinical evaluations, annual serum calcium measurements, annual serum creatinine measurements to check kidney function, and bone density measurements every 1 to 2 years. Vitamin D deficiency should be corrected if present. Patients who are monitored need not restrict calcium in their diets. If the patient and health care provider choose long-term monitoring, the patient should

  • drink plenty of water
  • exercise regularly
  • avoid certain diuretics, such as thiazides

Either immobilization—the inability to move due to illness or injury—or gastrointestinal illness with vomiting or diarrhea that leads to dehydration can cause blood calcium levels to rise further in someone with primary hyperparathyroidism. People with primary hyperparathyroidism should seek medical attention if they find themselves immobilized or dehydrated due to vomiting or diarrhea.

Medications

Calcimimetics are a new class of medications that decrease parathyroid gland secretion of PTH. The calcimimetic, cinacalcet (Sensipar), has been approved by the U.S. Food and Drug Administration for the management of hypercalcemia associated with primary hyperparathyroidism.

A number of other medications are being studied to learn whether they may be helpful in treating primary hyperparathyroidism. These medications include bisphosphonates and selective estrogen receptor modulators.

Eating, Diet, and Nutrition

Eating, diet, and nutrition have not been shown to play a role in causing or preventing primary hyperparathyroidism.
Vitamin D. Experts suggest correcting vitamin D deficiency in people with primary hyperparathyroidism to achieve a serum level of 25-hydroxy-vitamin D greater than 20 nanograms per deciliter (50 nanomoles per liter).

Calcium. People with primary hyperparathyroidism without symptoms who are being monitored do not need to restrict calcium in their diet. People with low calcium levels due to loss of all parathyroid tissue from surgery will need to take calcium supplements for the rest of their life.