Patient education: Primary hyperparathyroidism (Beyond the Basics)

HYPERPARATHYROIDISM OVERVIEW — The parathyroid glands (figure 1) make a hormone called parathyroid hormone (PTH), which helps control the amount of calcium in the blood. In people with primary hyperparathyroidism (PHPT), one or more of the parathyroid glands become overactive and secrete excess amounts of hormone. As a result, the blood calcium rises to a level that is higher than normal; this is called hypercalcemia. Hypercalcemia can cause many short-term and long-term complications.

Primary hyperparathyroidism is different from secondary hyperparathyroidism, which occurs when the parathyroid glands appropriately respond to a reduced blood calcium level. Secondary hyperparathyroidism is characterized biochemically by elevated PTH levels and normal or low blood calcium levels. In this situation, the low calcium level is caused by another condition, such as kidney failure or poor calcium absorption from the intestines. In these situations, the parathyroid glands are responding appropriately and are not diseased.

This article discusses the causes, symptoms, diagnosis, and treatment of primary hyperparathyroidism.

WHAT ARE THE PARATHYROID GLANDS? — Four parathyroid glands are located in the neck, two on each side (figure 1). Rarely, a person has five or six parathyroid glands in the neck, and occasionally one or more parathyroid glands located within the chest cavity. The parathyroid glands secrete a hormone called parathyroid hormone (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; this raises the blood calcium level back to normal by pulling calcium out of bone and reducing calcium excretion by the kidneys. 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.

PRIMARY HYPERPARATHYROIDISM CAUSES — Primary hyperparathyroidism (PHPT) can be caused by several conditions, including:

●A noncancerous tumor (adenoma) due to overgrowth of normal cells in only one of the parathyroid glands. This is the most common cause, occurring in approximately 85 percent of cases.

●Enlargement of more than one parathyroid gland due to an overgrowth of normal cells in these glands, called hyperplasia. This occurs in approximately 15 percent of all cases.

●Parathyroid cancer; this is extremely rare and is due to abnormal (cancerous) overgrowth of cells usually in only one gland. This accounts for less than 1 percent of all cases.

PHPT can occur at any age but is more common in females who have been through menopause (and no longer have monthly periods). At younger ages (eg, below 40 years), PHPT is more likely to be caused by a rare familial (inherited) hyperparathyroidism syndrome, which usually causes several of the parathyroid glands rather than a single gland to become enlarged. In some types of familial hyperparathyroidism, abnormalities are possible in other endocrine glands, including the pituitary, thyroid, pancreas, or adrenal glands.

PHPT has been reported in people who have had past radiation to the head and neck (eg, to treat childhood cancer, to treat certain benign conditions, or after nuclear power plant accidents). People who have been exposed to radiation are more likely to have thyroid nodules (growths on the thyroid gland) as well as PHPT. If thyroid nodules are also present, they may impact the interpretation of some tests and the choice of treatment of PHPT.

PRIMARY HYPERPARATHYROIDISM SYMPTOMS — Approximately 80 percent of people with primary hyperparathyroidism (PHPT) have few or no obvious symptoms. In these people, PHPT is typically diagnosed after an elevated calcium is detected when a blood test is done for some other reason. Most often, the calcium level is only mildly elevated or is elevated intermittently. People with both longstanding vitamin D deficiency and PHPT often have more symptoms.

There are sometimes nonspecific 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 parathyroid hormone (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 education: Kidney stones in adults (Beyond the Basics)".)

●Bone disease – As calcium is reabsorbed from bone, bone density may decrease. As a result, the risk of bone fractures may increase in some people.

●Rheumatologic symptoms – Gout or hardening (calcification) of cartilage in the wrists or knees can rarely occur. (See "Patient education: Gout (Beyond the Basics)".)

●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 PHPT experience another illness, like a viral infection that causes vomiting or diarrhea, which leads to excessive fluid loss or severely limits fluid intake.

During parathyroid crisis, blood PTH and calcium levels rise sharply to very high levels, 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.

PRIMARY HYPERPARATHYROIDISM DIAGNOSIS

Blood tests — Primary hyperparathyroidism (PHPT) is diagnosed based upon levels of blood calcium and parathyroid hormone (PTH). In most people with PHPT, 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 be low when calcium is elevated, a normal or minimally elevated PTH is considered abnormal and usually indicates PHPT. Very rarely, this picture is seen in a person with a genetic condition called familial hypocalciuric hypercalcemia (FHH) in which the elevation in blood calcium is lifelong.

Skeletal assessment: Bone density testing — Bone density testing is usually recommended for people with PHPT. This test can help determine if the bones have become weakened as a result of high PTH levels drawing calcium out of the skeleton. Dual-energy x-ray absorptiometry (DXA) testing is the most commonly used method for measuring bone density. Bone density is usually lowest at the forearm in people with PHPT. This test is described in detail separately. (See "Patient education: Bone density testing (Beyond the Basics)".)

In addition, because of the possibility of asymptomatic vertebral (spine) fractures in people with PHPT, a plain X-ray of the spine or a vertebral fracture assessment of the DXA image to identify the presence of such fractures is sometimes recommended.

Kidney assessment — Hypercalcemia may adversely affect kidney function. Measurement of 24-hour urinary calcium excretion (to assess risk of kidney stones) and serum creatinine (a test of kidney function) is routinely performed in people with asymptomatic PHPT in order to assess the risk of kidney complications (when urine calcium is high or kidney function is impaired) and thus determine subsequent management.

In some people, an abdominal X-ray, an ultrasound, or computed tomography (CT) of the kidneys is obtained to detect silent kidney stones, which, if present, also determine subsequent treatment. (See "Patient education: Kidney stones in adults (Beyond the Basics)".)

PRIMARY HYPERPARATHYROIDISM TREATMENT

Surgical treatment — Surgery is recommended for people with symptoms and is the only way to cure primary hyperparathyroidism (PHPT). Surgery is also often recommended for people with moderately elevated blood calcium levels, impaired kidney function, low bone density, high urine calcium levels, or silent kidney stones or fractures.

In addition, surgery is recommended for people younger than 50 years old or if periodic follow-up would be difficult (eg, if a person lives far from a health care provider or often travels to places where it is difficult to find medical care).

Surgery should be performed by an experienced endocrine surgeon.

Traditional surgery — The surgery is usually done while the person is under anesthesia. An incision is made in the lower neck measuring 2.5 to 10 cm (1 to 5 inches). Usually, at least one abnormal-appearing gland is removed while the normal-appearing glands are left in place.

Minimally invasive surgery — Several kinds of minimally invasive surgery can be performed in cases where one abnormal parathyroid gland has been located by a preoperative imaging study. This most frequently will be a nuclear medicine scan, or an ultrasound, depending on local hospital expertise.

The surgery can be performed under local nerve block and is a good alternative for people who are at high risk for general anesthesia. During the surgery, a small incision (1 to 4 cm or 0.4 to 1.8 inches) is made in the neck and the abnormal tissue is removed. The blood level of parathyroid hormone (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 with traditional surgery is that it requires a smaller incision and less time under anesthesia. This type of procedure is only available for people with certain characteristics, and it requires an experienced surgeon and medical center.

Effectiveness of surgery — With an experienced endocrine surgeon, surgical treatment is effective in curing PHPT in approximately 95 percent of people. 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. Other possible complications include bleeding and/or temporary or permanent hoarseness. In some centers, parathyroid surgery is a day procedure and does not require overnight hospitalization. In other centers, the person is hospitalized for a short time after surgery, usually for one day.

Occasionally, some abnormal parathyroid tissue goes undetected and is not removed during the first operation. In this case, high calcium levels and symptoms of PHPT persist after surgery. Imaging studies are required to locate the abnormal parathyroid tissue. In some people, 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. If another operation is needed, it is best to have two imaging tests to locate the diseased gland(s).

Follow-up care after surgery — In the initial period after surgery, it is important to have adequate calcium intake, and many physicians recommend using calcium supplements. 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 six months after surgery and then 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. (See 'Skeletal assessment: Bone density testing' above and 'Treating bone loss' below.)

Nonsurgical treatment — Nonsurgical treatment may be recommended for people who have no symptoms and whose blood calcium is only mildly elevated, provided they do not have low bone density, asymptomatic vertebral fractures, impaired renal function, or silent kidney stones. 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 two years, depending upon your situation. (See "Primary hyperparathyroidism: Management".)

General measures — People with PHPT who do not have symptoms are advised to:

●Avoid certain medications if possible, including lithium (a mood stabilizer used to treat bipolar illness) and thiazide diuretics (used to treat high blood pressure). These drugs may further increase blood calcium levels. Do not stop or change any of your medications without talking with a health care provider first; they will work with you to figure out the best plan for your situation.

●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 plenty of fluid each day. This may help to minimize the risk of kidney stones.

●Maintain a moderate calcium intake (approximately 1000 mg of elemental calcium/day) (table 1 and table 2), preferably from dairy products or calcium-fortified foods, although low doses of calcium supplements can be used if necessary. Lower calcium intake will stimulate more PTH secretion while higher calcium intake may worsen high calcium levels. (See "Patient education: Calcium and vitamin D for bone health (Beyond the Basics)".)

●Consume a moderate amount of vitamin D (400 to 600 international units, or 10 to 15 micrograms, daily) (table 3). Vitamin D deficiency can stimulate PTH secretion and bone resorption and should be avoided. (See "Patient education: Vitamin D deficiency (Beyond the Basics)".)

Treating bone loss — Medications that inhibit bone breakdown may be prescribed if you have evidence of decreased bone density (osteoporosis). These medications can protect the bones from the bone thinning effects of excess PTH but will not normalize the calcium levels in the blood. The treatment of osteoporosis is discussed in more detail separately. (See "Patient education: Osteoporosis prevention and treatment (Beyond the Basics)".)

WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Primary hyperparathyroidism (The Basics)
Patient education: Osteoporosis (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Kidney stones in adults (Beyond the Basics)
Patient education: Gout (Beyond the Basics)
Patient education: Bone density testing (Beyond the Basics)
Patient education: Calcium and vitamin D for bone health (Beyond the Basics)
Patient education: Vitamin D deficiency (Beyond the Basics)
Patient education: Osteoporosis prevention and treatment (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Primary hyperparathyroidism: Clinical manifestations
Primary hyperparathyroidism: Diagnosis, differential diagnosis, and evaluation
Primary hyperparathyroidism: Management
Management of secondary hyperparathyroidism in adult nondialysis patients with chronic kidney disease
Management of secondary hyperparathyroidism in adult patients on dialysis
Primary hyperparathyroidism: Pathogenesis and etiology
Preoperative localization for parathyroid surgery in patients with primary hyperparathyroidism
Management of hyperphosphatemia in adults with chronic kidney disease
Parathyroid exploration for primary hyperparathyroidism

The following organizations also provide reliable health information.

●National Institutes of Health

(www.niddk.nih.gov/health-information/endocrine-diseases/primary-hyperparathyroidism)

●The National Library of Medicine

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

●The Hormone Foundation

(www.hormone.org)

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