Patient education: Primary hyperparathyroidism (Beyond the Basics)
- Ghada El-Hajj Fuleihan, MD, MPH
Ghada El-Hajj Fuleihan, MD, MPH
- Professor of Medicine
- American University of Beirut Medical Center, Lebanon
- Shonni J Silverberg, MD
Shonni J Silverberg, MD
- Professor of Medicine
- Columbia University College of Physicians and Surgeons
Primary hyperparathyroidism (PHPT) 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 (PTH). 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 PTH 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. In this setting, the parathyroid glands are responding appropriately and are not diseased/abnormal.
This topic discusses the causes, symptoms, diagnosis, and treatment of primary hyperparathyroidism. Secondary hyperparathyroidism is discussed separately. (See "Management 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 five or six parathyroid glands in the neck, and occasionally one or more parathyroid glands located within the chest cavity. These small 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 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.
PRIMARY HYPERPARATHYROIDISM CAUSES
Primary hyperparathyroidism (PHPT) can be caused by several conditions, including:
●A noncancerous tumor (an 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 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 older postmenopausal women. At young ages, PHPT is often caused by a familial hyperparathyroidism syndrome, which usually causes several of the parathyroid glands 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.
PHPT has been reported in patients with a history of irradiation to the head and neck (eg, for the treatment of childhood malignancy, for the treatment of benign conditions, or after nuclear power plant accidents). The clinical presentation of radiation-related PHPT is usually similar to that of PHPT that is not related to radiation exposure. However, radiation-exposed patients are more likely to have concurrent thyroid tumors.
PRIMARY HYPERPARATHYROIDISM SYMPTOMS
Approximately 80 percent of people with primary hyperparathyroidism (PHPT) have few or no 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. (See "Primary hyperparathyroidism: Clinical manifestations".)
However, there are sometimes nonspecific symptoms that might be related to the elevated calcium level, including:
●Loss of appetite
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 patients.
●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 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 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 normally be low when calcium is elevated, a minimally elevated PTH is considered abnormal and indicates PHPT. (See "Primary hyperparathyroidism: Diagnosis, differential diagnosis, and evaluation".)
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 abnormal blood calcium levels. Dual-energy x-ray absorptiometry (DXA) testing is the most commonly used method for measuring bone density. Bone density is lowest at the forearm in patients 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 fractures in patients with PHPT, a plain x-ray of the spine or a vertebral fracture assessment of 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) are routinely performed in patients with asymptomatic PHPT in order to assess the risk of renal complications (when urine calcium is high or kidney function is impaired) and thus determine subsequent management.
In some patients, an abdominal x-ray or 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
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 three years, depending upon your situation. (See "Primary hyperparathyroidism: Management".)
General measures — Patients with primary hyperparathyroidism (PHPT) 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. Discontinuation of such drugs should only be performed under medical supervision.
●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 (approximately 1000 mg of elemental calcium/day) (table 1 and table 2). Lower calcium intake will stimulate more parathyroid hormone (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 daily) (table 3). Vitamin D deficiency can stimulate PTH secretion and bone resorption and should be avoided. Higher doses may be prescribed to patients with low vitamin D levels. (See "Patient education: Vitamin D deficiency (Beyond the Basics)".)
Treat bone loss — Medications that inhibit bone resorption 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. A full discussion of treatments for osteoporosis is available separately. (See "Patient education: Osteoporosis prevention and treatment (Beyond the Basics)".)
Surgical treatment — Surgery is recommended for people with symptoms. It is often also recommended for people with moderately elevated blood calcium levels, impaired kidney function, low bone density, high urine calcium levels, and silent kidney stones or fractures. (See "Primary hyperparathyroidism: Management", section on 'Candidates for surgery'.)
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 health care 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 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 patients 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 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 with traditional surgery is that it requires a smaller incision, less time under anesthesia, and a shorter hospital stay. This type of procedure is only available for people with certain characteristics, and it requires an experienced surgeon and medical center. (See "Preoperative localization for parathyroid surgery in patients with primary hyperparathyroidism" and "Parathyroid exploration for primary hyperparathyroidism", section on 'Intraoperative parathyroid hormone monitoring'.)
Effectiveness of surgery — With an experienced endocrine surgeon, surgical treatment is effective in curing PHPT in approximately 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, bleeding, 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 PHPT 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 — 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 'Treat bone loss' above.)
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.
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 dialysis patients
Pathogenesis and etiology of primary hyperparathyroidism
Preoperative localization for parathyroid surgery in patients with primary hyperparathyroidism
Management of hyperphosphatemia in chronic kidney disease
Parathyroid exploration for primary hyperparathyroidism
The following organizations also provide reliable health information.
●National Institutes of Health
●The National Library of Medicine
●The Hormone Foundation
- Bilezikian JP, Brandi ML, Eastell R, et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab 2014; 99:3561.
- Eastell R, Brandi ML, Costa AG, et al. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab 2014; 99:3570.
- Silverberg SJ, Clarke BL, Peacock M, et al. Current issues in the presentation of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab 2014; 99:3580.
- Udelsman R, Åkerström G, Biagini C, et al. The surgical management of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab 2014; 99:3595.
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.