Hyperparathyroidism

Definition

Parathyroid glands are four pea-sized glands located just behind the thyroid gland in the front of the neck. The function of parathyroid glands is to produce a hormone called parathyroid hormone (parathormone), which helps regulate calcium and phosphorous in the body. Hyperparathyroidism is the overproduction of this hormone.

Description

Thyroid glands and parathyroid glands, despite their similar name and proximity, are entirely separate, and each produces hormones with different functions. Hyperparathyroidism may be primary or secondary. It most often occurs in those over age 30, and most commonly in patients 50 to 60 years old. It rarely occurs in children or the elderly. Women are affected by the disease up to three times more often than men. It is estimated that 28 of every 100,000 people in the United States will develop hyperparathyroidism each year.

Normally, parathyroid glands produce the parathormone as calcium levels drop and lower to meet the demands of a growing skeleton, pregnancy, or lactation. However, when one or more parathyroid glands malfunctions, it can lead to overproduction of the hormone and elevated calcium level in the blood. Therefore, a common result of hyperparathyroidism is hypercalcemia, or an abnormally high level of calcium in the blood. Primary hyperparathyroidism occurs as a malfunction of one of the glands, usually as a result of a benign tumor, called adenoma. Secondary hyperparathyroidism occurs as the result of a metabolic abnormality outside the parathyroid glands, which causes a resistance to the function of the parathyroid hormones. Primary hyperparathyroidism is one of the most common endocrine disorders, led only by diabetes and hyperthyroidism.

— Teresa Norris

(medicine) Condition caused by increased functioning of the parathyroid glands.

Definition

Hyperparathyroidism is the overproduction by the parathyroid glands of a hormone called parathyroid hormone (parathormone). Parathyroid glands are four pea-sized glands located just behind the thyroid gland in the front of the neck. Parathyroid hormone (parathormone) helps regulate the levels of calcium and phosphorus in the body.

Description

Thyroid glands and parathyroid glands, despite their similar names and proximity, are entirely separate, and each produces hormones with different functions.

Hyperparathyroidism may be primary or secondary. It most often occurs in patients over age 30, and most commonly in patients 50 to 60 years old. It rarely occurs in children or the elderly. Women are affected by the disease up to three times more often than men. It is estimated that 28 of every 100,000 people in the United States will develop hyperparathyroidism each year.

Normally, parathyroid glands produce the parathormone as calcium levels drop and lower to meet the demands of a growing skeleton, pregnancy, or lactation. However, when one or more parathyroid glands malfunction, it can lead to overproduction of the hormone and elevated calcium level in the blood. Therefore, a common result of hyperparathyroidism is hypercalcemia, or an abnormally high level of calcium in the blood.

Primary hyperparathyroidism occurs as a malfunction of one of the glands, usually as a result of a benign tumor called an adenoma. Secondary hyperparathyroidism occurs as the result of an abnormality outside the parathyroid glands related to the body's metabolism, or chemical changes in living cells that help provide the body's energy. These changes cause a resistance to the function of the parathyroid hormones. Primary hyperparathyroidism is one of the most common endocrine disorders, led only by diabetes and hyperthyroidism.

Causes & Symptoms

Often, there are no obvious symptoms to give rise to suspicion of hyperparathyroidism, and it is first diagnosed when a patient is discovered to be hypercalcemic during a routine blood chemistry profile. Patients may believe they have been feeling fine, but realize improvements in sleep, irritability, and memory following treatment. When symptoms are present, they may include development of gastric ulcers or pancreatitis because high calcium levels can cause inflammation and pain in the linings of the stomach and pancreas.

Most of the symptoms of hyperparathyroidism are those present as a result of hypercalcemia, such as kidney stones, osteoporosis, or bone degradation resulting from the bones giving up calcium. Muscle weakness, central nervous system disturbances such as depression, psychomotor and personality disturbances, and even coma can occur. Patients also may experience heartburn, nausea, constipation, or abdominal pain. In secondary hyperparathyroidism, patients may show such signs of calcium imbalance as deformities of the long bones. Symptoms of the underlying disease also may be present.

Most commonly, hyperparathyroidism occurs as the result of a single adenoma, or benign tumor, in one of the parathyroid glands. About 90 percent of all cases of hyperparathyroidism are caused by an adenoma. The tumors seldom are cancerous. They will grow to a much larger size than the parathyroid glands, often to the size of a walnut. Genetic disorders or multiple endocrine tumors also can cause a parathyroid gland to enlarge and oversecrete hormone. In 10 percent or fewer of patients with primary hyperparathyroidism, there is enlargement of all four parathyroid glands. This condition is called parathyroid hyperplasia.

Diagnosis

Diagnosis of hyperparathyroidism most often is made when a blood test (radioimmunoassay) reveals high levels of parathyroid hormone and calcium. A blood test that specifically measures the amount of parathyroid hormone has made diagnosis simpler. Hypercalcemia is mild or intermittent in some patients, but persistent hypercalcemia is an excellent indicator of primary hyperparathyroidism. Dual energy x-ray absorptiometry (DEXA or DXA), a tool used to diagnose and measure osteoporosis, may be used once the diagnosis is made to show reduction in bone mass for primary hyperparathryroidism patients. Once a diagnosis of hyperparathyroidism is reached, the physician will probably order further tests to evaluate complications. For example, abdominal radiographs might reveal kidney stones.

For secondary hyperparathyroidism, normal or slightly decreased calcium levels in the blood and variable phosphorous levels may be visible. A patient history of familial kidney disease or convulsive disorders may suggest a diagnosis of secondary hyperparathyroidism. Other tests may reveal a disease or disorder that is causing the secondary hyperparathyroidism.

Treatment

Nutritional Therapy

Limiting intake of soft drinks can help to prevent hyperparathyroidism. Soda drinks contain high levels of phosphorus. High phosphorus intake can cause hypocalcemia that leads to secondary hyperparathyroidism. In patients with hyperparathyroidism, forcing fluids and reducing intake of calcium-rich foods can help decrease calcium levels prior to surgery or if surgery is not necessary. These patients should not take any supplements that contain calcium without a doctor's approval.

Allopathic Treatment

Hyperparathyroidism cases will usually be referred to an endocrinologist, who is a physician specializing in hormonal problems, or a nephrologist, who specializes in kidney and mineral disorders.

Patients with mild cases of hyperparathyroidism may not need immediate treatment if they have only slight elevations in blood calcium level and normal kidneys and bones. These patients should be regularly checked, probably as often as every six months, by physical examination and measurement of kidney function and calcium levels. A bone densitometry—a test to diagnose and monitor osteoporosis or thinning of bones—measurement should be performed every one or two years. After several years with no worsened symptoms, the length of time between tests may be increased.

Patients with more advanced hyperparathyroidism usually will have all or half of the affected parathyroid gland or glands surgically removed. This surgery is relatively safe and effective. The primary risks are those associated with general anesthesia. There are some instances in which the surgery can be performed with the patient under regional, or cervical (neck) block, anesthesia. Often such studies as ultrasonography—a test with high-frequency sound waves (ultrasound) that are bounced off tissues and echoes are converted to pictures called sonograms—prior to surgery help pinpoint the affected areas.

Treatment of secondary hyperparathyroidism involves removing or treating the underlying cause. In 2004, a new drug therapy was shown to lower parathyroid levels and improve calcium and phosphorus function in patients receiving dialysis (a blood-purifying treatment often performed on people with kidney diseases) who had uncontrolled secondary hyperparathyroidism. The drug, called cinacalcet, was approved by the U.S. Food and Drug Administration for people who have chronic kidney disease with secondary hyperparathyroidism.

Expected Results

Removal of the enlarged parathyroid gland or glands (parathyroidectomy) cures the disease 95 percent of the time. Relief of bone pain may occur in as few as three days. In 2004, a study showed that parathyroidectomy improved depression in patients with hyperparathyroidism. As many as 54 percent of patients who had the procedure no longer needed antidepressant medications after having the surgery. In up to five percent of patients undergoing surgery, chronically low calcium levels may result, and these patients will require calcium supplements or vitamin D treatment.

Damage to the kidneys as a result of hyperparathyroidism is often irreversible. Prognosis is generally good; however, complications of hyperparathyroidism such as osteoporosis, bone fractures, kidney stones, peptic ulcers, pancreatitis, and nervous system difficulties may worsen prognosis.

Prevention

Secondary hyperparathyroidism may be prevented by early treatment of the disease causing it. Early recognition and treatment of hyperparathyroidism may prevent hypercalcemia. Since the cause of primary hyperparathyroidism, the adenoma which causes parathyroid enlargement, is largely unknown, there are no prescribed prevention methods.

Resources

Books

Murray, Michael T. "Calcium." In Encyclopedia of Nutritional Supplements: The Essential Guide for Improving Your Health Naturally. Rocklin, CA: Prima Publishing, 1996.

Trattler, Ross. Better Health Through Natural Healing. New York, NY: McGraw-Hill Book Company, 985.

Periodicals

Allerheiligen, David A., Joe Schoeber, Robert E. Houston, Virginia K. Mohl, and Karen M. Wildman. "Hyperparathyroidism." American Family Physician 58 (April 15, 1998): 1795–1803.

"Parathyroidectomy Improves Depression in Patients with Hyperparathyroidism." Drug Week (April 23, 2003): 161.

"Positive New Data for Amgen's Sensipar for Secondary Hyperparathyroidism." Pharma Marketletter (April 12, 2004).

Taniegra, Edna D. "Hyperparathyroidism." American Family Physician (January 15, 2004): 333.

Organizations

Osteoporosis and Related Bone Diseases-National Resource-Center. 1150 17th S. NW, Ste. 500, Washington, DC 20036. (800) 624-BONE.

The Paget Foundation. 200 Varick Street, Suite 1004, New York, NY 10014-4810. (800) 23-PAGET.

Other

"Endocrine disorder and endocrine surgery." Endocrine Web. .

[Article by: Mai Tran; Teresa G. Odle]

Abnormally increased activity of the parathyroid gland. Primary hyperparathyroidism is associated with either neoplasia (chiefly adenomas) or hyperplasia.
An excess of parathyroid hormone leads to resorption of bone, increased resorption of calcium and increased excretion of phosphorus by the renal tubules, and increased absorption of calcium by the gastrointestinal mucosa. It may result in kidney stones and calcium deposits in the renal tubules; in generalized decalcification of bone (osteoporosis), resulting in pain and tenderness of bones and spontaneous fractures; and in hypercalcemia, leading to muscular weakness and gastrointestinal signs.
Secondary hyperparathyroidism develops as a compensatory mechanism when the serum calcium level is persistently below normal or serum phosphorus is elevated, as in chronic renal disease, insufficient calcium or excessive phosphorus in the diet, vitamin D deficiency, low-level soluble oxalate intoxication in horses, and intestinal malabsorption syndromes causing insufficient absorption of calcium and vitamin D.
See also pseudohyperparathyroidism.

• nutritional secondary h. — a disease of horses, pigs, goats, dogs, cats, and rarely cattle. It is most commonly caused by an excessive dietary intake of phosphorus in the absence of adequate calcium, which in horses is likely to be the result of a diet mainly of grain and in dogs and cats one predominantly of meat, but it may also result from other dietary causes of secondary hyperparathyroidism. In most species there is swelling of the maxillae and mandibles which is most marked in horses, loosening of teeth, shifting lameness, and particularly in dogs and cats, weight-bearing skeletal deformities (angel wings) and folding or compression fractures. Called also miller's disease, bran disease, bighead, Siamese cat disease, paper-bone disease.
• renal secondary h. — caused by chronic renal dysfunction, mostly in dogs, sometimes in cats, in which there is a secondary hyperparathyroidism, caused by the retention of phosphates. There is demineralization of bones, particularly the maxillae and mandibles, with loosening of teeth and facial swelling. Clinical signs are often overshadowed by the effects of the renal failure. Called also rubber jaw, renal rickets, renal osteitis fibrosa.

Hyperparathyroidism
Classification & external resources

Thyroid and parathyroid.
ICD-10	E21.
ICD-9	252.0
DiseasesDB	20710
eMedicine	emerg/265
MeSH	D006961

Hyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone (PTH). The parathyroid hormone monitors calcium and phosphorus levels and helps to maintain these levels. Overactivity of one or more of the parathyroid glands causes high calcium levels (hypercalcemia) and low levels of phosphorus in the blood [2]. Hyperparathyroidism was first described and treated in the 1930s by Fuller Albright of Massachusetts General Hospital, working at the Mallinckrodt General Clinical Research Center. The oldest known case was found in a cadaver from a Early Neolithic cemetery in southwest Germany.^[1]

Classification

Primary hyperparathyroidism

Main article: Primary hyperparathyroidism

Primary hyperparathyroidism results from a hyperfunction of the parathyroid glands themselves. There is oversecretion of PTH due to adenoma, hyperplasia or, rarely, carcinoma of the parathyroid glands.

Secondary hyperparathyroidism

Main article: Secondary hyperparathyroidism

Secondary hyperparathyroidism is the reaction of the parathyroid glands to a hypocalcemia caused by other than a parathyroid pathology, e.g. chronic renal failure.

Tertiary hyperparathyroidism

Main article: Tertiary hyperparathyroidism

Tertiary hyperparathyroidism is a state of excessive secretion of parathyroid hormone (PTH) after a long period of secondary hyperparathyroidism and resulting in hypercalcemia.

Symptoms and signs

Asymptomatic hyperparathyroidism

Many patients presenting with hyperparathyroidism will have no signs or symptoms, with diagnosis being made on further investigation after a coincidental finding of hypercalcemia. It is, however, reported that many patients will report that they feel better after treatment for hyperparathyroidism.^{[citation needed]}

Symptomatic hyperparathyroidism

Of those patients that do present with symptoms, they are commonly associated with the effects of an increased level of calcium. Since calcium is involved in trans-synaptic communication within our nervous system, high blood calcium levels have a direct effect on the nervous system. Thus, most of the symptoms of parathyroid disease are "neurological" in origin. The most common symptom is fatigue and tiredness. Other very common symptoms are lack of energy, memory problems, depression, problems with concentration, and problems sleeping. Other manifestations of hyperparathyroidism usually involve the kidney (stones) and the skeletal system (bone pain due to the development of osteoporosis).

Almost all patients will have symptoms if their calcium is high and the right questions are asked.^{[citation needed]} Removing the parathyroid tumor which is causing the excess parathyroid hormone will eliminate the symptoms in most patients within several days or weeks. Often it is life-changing when the parathyroid tumor is removed.

The symptoms of hyperparathyroidism can be remembered by the rhyme "moans, groans, stones, bones, and psychiatric overtones":

• "moans" (complaints of not feeling well)
• "groans" (abdominal pain, gastroesophageal reflux)
• "stones" (kidney)
• "bones" (bone pain)
• "psychiatric overtones" (lethargy, fatigue, depression, memory problems).

Other symptoms include: headaches, gastroesophageal reflux, decreased sex drive, thinning hair, hypertension, and heart palpitations which are often due to bouts of atrial fibrillation.^{[citation needed]} Additional symptoms reported consist of an increase of thirst and urination as a result of calcium excretion in the urine, stomach ulcers, nausea, and a loss of appetite [3].

Osteoporosis

Unfortunately, medicines are usually not useful for treating the osteoporosis associated with hyperparathyroidism until the parathyroid tumor is removed. Osteoporosis associated with hyperparathyroidism is caused by the high parathyroid hormone that is secreted by the overactive parathyroid gland(s). This excess parathyroid hormone (PTH) acts directly on the bones to remove calcium from the bones. Thus, the high calcium in the blood comes from the bones. Removing the offending parathyroid gland will usually cause a significant improvement in the osteoporosis, often reversing this process back to normal bone density over several years.

Laboratory tests

Serum calcium

In cases of primary, tertiary and quintary hyperparathyroidism increased PTH consequently leads to increased serum calcium (hypercalcemia) due to:

1. increased bone resorption, allowing flow of calcium from bone to blood
2. reduced renal clearance of calcium
3. increased intestinal calcium absorption

By contrast, in secondary and quartary hyperparathyroidism effectiveness of PTHis reduced.

Serum phosphorus

In primary hyperparathyroidism, serum phosphorus levels are abnormally low as a result of decreased renal tubular phosphorus reabsorption. This contrasts with secondary hyperparathyroidism, in which serum phosphorus levels are generally elevated because of renal disease.

Alkaline phosphatase

Alkaline phosphatase levels are elevated in all types of hyperparathyroidism.

Etiology

Primary hyperparathyroidism

Main article: Primary hyperparathyroidism

• The most common cause is a benign parathyroid adenoma that loses its sensitivity to circulating calcium levels. Usually, only one of the four parathyroid glands is affected.
• A less common cause is from multiple endocrine neoplasia (MEN).

Secondary hyperparathyroidism

Main article: Secondary hyperparathyroidism

Secondary hyperparathyroidism is due to resistance to the actions of PTH, usually due to chronic renal failure. The bone disease in secondary parathyroidism along with renal failure is termed renal osteodystrophy.

Tertiary hyperparathyroidism

Main article: Tertiary hyperparathyroidism

Tertiary hyperparathyroidism, quartary and quintary hyperparathyroidism are rare forms that are caused by long lasting disorders of the calcium feedback control system. When the hyperparathyroidism can not be corrected by medication one calls it tertiary hyperparathyroidism.

Diagnosis

The gold standard of diagnosis is the PTH immunoassay. Once an elevated PTH has been confirmed, goal of diagnosis is to determine whether the hyperparathyroidism is primary or secondary in origin by obtaining a serum calcium level:

PTH	serum calcium	likely type
high	high	primary hyperparathyroidism
high	low or normal	secondary hyperparathyroidism

Tertiary hyperparathyroidism has a high PTH and a high serum calcium. It is differentiated from primary hyperparathyroidism by a history of chronic kidney failure and secondary hyperparathyroidism.

Treatment/Monitoring

Endocrinologists diagnose diseases affecting glands and should be consulted for hyperparathyroidism. Treatment is first and foremost directed at hypercalcemia, if symptomatic patients are sent for surgery to remove the parathyroid tumor (parathyroid adenoma). (see hypercalcemia) Most experts now believe that almost all patients with hyperparathyroidism should be evaluated for surgery. Watching and waiting has been falling out of vogue since it is being realized that the disease will rarely stay the same. It will almost always progress as the tumor grows.

• (see primary hyperparathyroidism)
• (see secondary hyperparathyroidism)

However, if surgery is not available, the following should be monitored:

• Calcium level: Ask the doctor to monitor your calcium levels via urine tests. The results can be used to provide information regarding kidney functionality as well as how much calcium is being excreted in your urine.

• Bone density: Doctors can determine if you're essentially shrinking by performing bone mineral density tests. These tests can be used to assess the risk of osteoporosis. Some of the different types of tests include dual energy X-ray absorptiometry (DEXA) which measures the density of bones in the hip, wrist, and spine and ultrasounds.

• Check for Kidney Stones: Abdominal X-rays can be used to check for kidney stones.

Prevention

If you choose to monitor symptoms, some recommendations for prevention include [2]:

• Exercise, specifically weight and strength training are beneficial. This helps in the process of decreasing bone loss and building stronger bones.

• Vitamin D - Adequate amounts of vitamin D aid in calcium absorption. Sources of vitamin D come from the foods you eat, sunlight, and from vitamin supplemants.

• Stay hydrated - drinking lots of fluids can aid in preventing the formation of kidney stones.

• No smoking - Besides known negative affects of smoking such as cancer, smoking aids in bone loss

References

 1.  Lawrence Kim, MD, Director of Surgical Endocrinology; Chief of Surgery Central Ark. VA, Department of Surgery, Associate Professor of Surgery, University of Arkansas Hospital, 2005.  http://www.emedicine.com/med/topic3200.htm
 2.  Mayo Clinic:  http://www.mayoclinic.com/health/hyperparathyroidism/DS00396
 3.  Hyperparathyroidism:  www.hyperparathyroidism.com 

1. ^ Zink AR, Panzer S, Fesq-Martin M, Burger-Heinrich E, Wahl J, Nerlich AG (2005). "Evidence for a 7000-year-old case of primary hyperparathyroidism". JAMA 293 (1): 40-2. DOI:10.1001/jama.293.1.40-c. PMID 15632333. 

See also

• Hypoparathyroidism
• Multiple endocrine neoplasia

External links

• Description of parathyroid disease and treatment in detail at www.parathyroid.com
• Section on parathyroid disease at endocrineweb.com
• Overview at Mayo Clinic
• Overview at Endocrine and Metabolic Diseases Information Service

Endocrine pathology: endocrine diseases (E00-35, 240-259)
Thyroid	Hypothyroidism (Iodine deficiency, Cretinism, Congenital hypothyroidism, Goitre, Myxedema) - Hyperthyroidism (Graves disease, Toxic multinodular goitre, Teratoma with thyroid tissue or Struma ovarii) - Thyroiditis (De Quervain's thyroiditis, Hashimoto's thyroiditis, Riedel's thyroiditis) - Euthyroid sick syndrome
Pancreas	Diabetes mellitus (type 1, type 2, coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy) - Hypoglycemia - Hyperinsulinism - Zollinger-Ellison syndrome
Parathyroid	Hypoparathyroidism (Pseudohypoparathyroidism) - Hyperparathyroidism (Primary, Secondary, Tertiary)
Pituitary	Hyperpituitarism (Acromegaly, Hyperprolactinaemia, SIADH) - Hypopituitarism (Simmonds' disease/Sheehan's syndrome, Kallmann syndrome, Growth hormone deficiency, Diabetes insipidus)
Adrenal	Cushing's syndrome (Nelson's syndrome, Pseudo-Cushing's syndrome) - CAH (due to 21-hydroxylase deficiency) - Hyperaldosteronism (Conn syndrome, Bartter syndrome) - Adrenal insufficiency (Addison's disease) - Hypoaldosteronism
Gonads	Polycystic ovary syndrome - 5-alpha-reductase deficiency - Hypogonadism - Delayed puberty - Precocious puberty
Other	Autoimmune polyendocrine syndrome - Carcinoid syndrome - Laron syndrome - Multiple endocrine neoplasia (1, 2) - Psychogenic dwarfism - Androgen insensitivity syndrome - Progeria

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