Patient information: Primary hyperparathyroidism

HYPERPARATHYROIDISM OVERVIEW

Primary hyperparathyroidism is a disorder of one or more of the parathyroid glands (figure 1). The parathyroid gland(s) becomes overactive and secretes excess amounts of parathyroid hormone. As a result, the blood calcium rises to a level that is higher than normal (called hypercalcemia). An elevated calcium level can cause many short-term and long-term complications.

Primary hyperparathyroidism is different from secondary hyperparathyroidism, which occurs when the parathyroid glands overproduce parathyroid hormone in response to low blood levels of calcium; the low calcium level is caused by another condition, such as not being absorbed correctly from the intestines or kidney failure.

This topic discusses the causes, symptoms, diagnosis, and treatment of primary hyperparathyroidism. Secondary hyperparathyroidism is discussed separately. (See "Treatment of hyperphosphatemia in chronic kidney disease".)

WHAT IS THE PARATHYROID GLAND?

Four parathyroid glands are located in the neck, two on each side (figure 1). Rarely, a person has 5 or 6 parathyroid glands in the neck, and occasionally one or more parathyroid glands is located within the chest cavity. These small glands secrete a hormone called parathyroid hormone (or PTH) that helps the body maintain a normal blood calcium level.

When the blood calcium level drops, the normal response is for the parathyroid glands to release PTH to raise the blood calcium level back to normal. The blood calcium level is normally maintained by the kidneys, bones, and indirectly by the intestines. When the blood calcium level rises, less PTH is released by the parathyroid glands, causing the kidneys to retain less calcium. These actions help keep the body's calcium level within a normal range.

HYPERPARATHYROIDISM CAUSES

Hyperparathyroidism can be caused by several conditions, including:

• A non-cancerous tumor (an adenoma) in one of the parathyroid glands; this is the most common cause.
• Enlargement of one or more of the parathyroid glands due to an overgrowth of normal cells, called hyperplasia.
• Parathyroid cancer; this is rare and accounts for less than 1 percent of all cases.

Hyperparathyroidism can occur at any age, but is more common in older postmenopausal women. At young ages, hyperparathyroidism is often caused by a familial hyperparathyroidism syndrome, which usually causes several of the parathyroid gland to enlarge rather than a single gland to become enlarged. In familial hyperparathyroidism, there is also a possibility of abnormalities of other endocrine glands, including the pituitary, thyroid, pancreas, or adrenal glands.

HYPERPARATHYROIDISM SYMPTOMS

About 80 percent of people with hyperparathyroidism have few or no symptoms. In these people, hyperparathyroidism is typically detected when a blood test is done for some other reason. Most often, the calcium level is only mildly elevated or is elevated intermittently. (See "Clinical manifestations of primary hyperparathyroidism".)

However, there are sometimes non-specific symptoms that might be related to the elevated calcium level, including:

• Joint aches
• Fatigue
• Weakness
• Loss of appetite
• Mild depression
• Difficulty concentrating

Symptoms become more noticeable as the PTH and blood calcium levels rise. At higher levels of PTH and blood calcium, there may be a significant loss of appetite, nausea, constipation, excessive thirst, or frequent urination. In addition, a person may develop:

• Impaired kidney function — The elevated calcium level can affect the kidney's ability to filter blood.
• Kidney stones — As calcium levels rise, the kidneys excrete more calcium into the urine, which can cause kidney stones to develop. (See "Patient information: Kidney stones in adults".)

• Bone disease — As calcium is reabsorbed from bone, bone density may decrease. As a result, the risk of bone fractures may increase in some patients.
• Rheumatologic symptoms — Gout or hardening (calcification) of cartilage in the wrists or knees can sometimes occur. (See "Patient information: Gout".)

• Imbalances in other chemicals — Some people develop a decreased blood phosphate level and a slightly increased magnesium level.

Parathyroid crisis — Parathyroid crisis is a rare condition that sometimes occurs when people with hyperparathyroidism experience another illness, like vomiting or diarrhea, which causes excessive fluid loss or severely limits the amount of fluid they can consume.

During parathyroid crisis, blood PTH and calcium levels rise sharply, causing severe symptoms of hypercalcemia. Most notably, there is a significant change in thinking and alertness, ranging from confusion to coma. Some people also experience severe abdominal pain, nausea, vomiting, stomach ulcers, and pancreatitis (inflammation of the pancreas).

Parathyroid crisis must be treated quickly by replacing lost body fluids and removing the overactive parathyroid tissue.

HYPERPARATHYROIDISM DIAGNOSIS

Blood tests — Hyperparathyroidism is diagnosed based upon levels of blood calcium and parathyroid hormone. In most people with hyperparathyroidism, both levels are higher than normal. Occasionally, a person may have an elevated calcium level and a normal or minimally elevated PTH level. Since PTH should normally be low when calcium is elevated, a minimally elevated PTH is considered abnormal and indicates hyperparathyroidism. (See "Diagnosis and differential diagnosis of primary hyperparathyroidism".)

Bone density testing — Bone density testing is usually recommended for people with hyperparathyroidism. This test can help determine if the bones have become weakened as a result of abnormal blood calcium levels. Dual x-ray absorptiometry (DXA) testing is the most commonly used method for measuring bone density. This test is described in detail separately. (See "Patient information: Bone density testing".)

Kidney stone testing — Testing for "silent" kidney stones is not recommended when you are first diagnosed with hyperparathyroidism. Testing is recommended, however, if you have had a kidney stone previously. Testing usually involves an ultrasound or CT scan of the kidneys. Further testing is not needed after the initial screening unless a person develops signs or symptoms of a stone. (See "Patient information: Kidney stones in adults".)

HYPERPARATHYROIDISM TREATMENT

Non-surgical treatment — Non-surgical treatment may be recommended for people who have no symptoms and whose blood calcium is only mildly elevated. Blood calcium levels should be measured every six months, and tests of kidney function are recommended once per year. Bone density testing is usually recommended every one to three years, depending upon your situation. (See "Management of primary hyperparathyroidism".)

General measures — Patients with hyperparathyroidism who do not have symptoms are advised to:

• Avoid lithium (a mood stabilizer used for bipolar illness) and thiazide diuretics (used to treat high blood pressure) since these drugs may further increase blood calcium levels.
• Avoid excessive loss of body fluids (eg, dehydration), prolonged bed rest or inactivity, and a high calcium diet since these can increase blood calcium levels.
• Minimize bone loss by remaining active.
• Drink an adequate amount of fluid throughout the day. This may help to minimize the risk of kidney stones.
• Maintain a moderate calcium intake (about 1000 mg/day, (table 1 and table 2). Lower calcium intake will stimulate more PTH secretion while higher calcium intake may worsen high calcium levels. (See "Patient information: Calcium and vitamin D for bone health".)

• Consume a moderate amount of vitamin D (400 to 600 IU daily, (table 3). Vitamin D deficiency can stimulate PTH secretion and bone resorption and should be avoided. (See "Patient information: Vitamin D deficiency".)

Treat bone loss — Medications that inhibit bone resorption may be prescribed if you have evidence of decreased bone density (osteopenia or osteoporosis). These medications can protect the bones from the bone thinning effects of excess parathyroid hormone but will not normalize the calcium levels in the blood.

A full discussion of treatments for osteoporosis is available separately. (See "Patient information: Osteoporosis prevention and treatment".)

Trials are currently ongoing to evaluate the safety and efficacy of drugs that decrease parathyroid hormone levels; this could reverse all the effects of hyperparathyroidism, including elevations in serum calcium levels.

Surgical treatment — Surgery is often recommended for people whose blood calcium is moderately elevated. Surgery is also recommended for people who are excreting a significant amount of calcium through their urine and for people with signs of impaired kidney function or decreased bone density. (See "Preoperative localization and surgical therapy of primary hyperparathyroidism".)

It is also recommended if the person is less than 50 years old or if periodic follow-up would be difficult (eg, if a person lived a great distance from a healthcare provider or travels to places where it is difficult to find medical care).

Traditional surgery — The surgery is usually performed while the person is under anesthesia. An incision is made in the lower neck measuring 5 to 10 cm (2 to 5 inches). All four parathyroid glands are examined; usually, at least one abnormal-appearing gland is removed while the normal-appearing glands are left in place.

Minimally invasive surgery — Minimally invasive surgery can be performed in cases where one abnormal parathyroid gland has been located by a pre-operative imaging study.

The surgery can be performed under local nerve block, and is an alternative when one abnormal gland has been localized pre-operatively. This procedure is also a good alternative for patients who are at high-risk for general anesthesia. During the surgery, a small incision (2 to 4 cm or 0.8 to 1.8 inches) is made in the neck and the abnormal tissue is removed. The patient's blood level of PTH is tested before and immediately after removal to confirm that the PTH level drops significantly after the abnormal tissue is removed.

The advantage of minimally invasive surgery compared to traditional surgery is that it requires a smaller incision, less time under anesthesia, and a shorter hospital stay. This procedure is only available for people with certain characteristics and it requires an experienced surgeon and medical center. (See "Preoperative localization and surgical therapy of primary hyperparathyroidism".)

Effectiveness of surgery — With an experienced endocrine surgeon, surgical treatment is effective in curing hyperparathyroidism in about 95 percent of patients. The complication rate associated with surgery is very low.

Complications could include temporary or permanent damage to the other parathyroid glands resulting in low calcium levels and/or temporary or permanent hoarseness. Patients are hospitalized for a short time after surgery, usually for less than two days.

Occasionally, some abnormal parathyroid tissue goes undetected and is not removed during the first operation. In this case, high calcium levels and symptoms of hyperparathyroidism persist after surgery. Imaging studies are required to locate the abnormal parathyroid tissue. In some patients, parathyroid glands may be present in unusual locations, such as in the chest or in other regions of the neck. A second surgical procedure is usually required to remove remaining abnormal tissue.

Follow up care after surgery — Six to eight weeks after surgery, most clinicians recommend a blood test to measure the blood level of calcium and PTH. These tests are then repeated once per year to ensure that they remain normal and that abnormal tissue has not regrown. A bone density test may be recommended one year after surgery to guide treatment of bone loss (osteopenia or osteoporosis) (see 'Bone density testing' above.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Kidney stones in adults
Patient information: Gout
Patient information: Bone density testing
Patient information: Calcium and vitamin D for bone health
Patient information: Vitamin D deficiency
Patient information: Osteoporosis prevention and treatment

Professional Level Information:
Clinical manifestations of primary hyperparathyroidism
Diagnosis and differential diagnosis of primary hyperparathyroidism
Management of primary hyperparathyroidism
Management of secondary hyperparathyroidism and mineral metabolism abnormalities in adult predialysis patients with chronic kidney disease
Management of secondary hyperparathyroidism and mineral metabolism abnormalities in dialysis patients
Pathogenesis and etiology of primary hyperparathyroidism
Preoperative localization and surgical therapy of primary hyperparathyroidism
Treatment of hyperphosphatemia in chronic kidney disease

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Institutes of Health

      (www.niddk.nih.gov/health/endo/pubs/hyper/hyper.htm)

• The National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• The Hormone Foundation

      (www.hormone.org)

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