Hypoparathyroidism

Hypoparathyroidism

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Hypoparathyroidism is not the name you expected.

Disorder Subdivisions

  • Acquired Hypoparathyroidism
  • Autoimmune Hypoparathyroidism
  • Congenital Hypoparathyroidism
  • Idiopathic Hypoparathyroidism

General Discussion

Hypoparathyroidism is a rare condition in which the parathyroid glands fail to produce sufficient amounts of functional parathyroid hormone. The parathyroid glands are part of the endocrine system, the network of glands that secrete hormones into the bloodstream where they travel to various areas of the body. These hormones regulate the chemical processes (metabolism) that influence the function of various organs and activities within the body. Hormones are involved in numerous vital processes including regulating heart rate, body temperature and blood pressure as well as cell differentiation and growth and also in modulation of several metabolic processes. Parathyroid hormone (along with vitamin D and the hormone calcitonin, which is produced by the thyroid gland) plays a role in regulating the levels of calcium and phosphorus in the blood. Due to a deficiency of parathyroid hormone, individuals may exhibit abnormally low levels of calcium in the blood (hypocalcemia) and high levels of phosphorus.



Hypocalcemia can cause a variety of symptoms including weakness, muscle cramps, excessive nervousness, headaches, and/or uncontrollable twitching and cramping spasms of certain muscles such as those of the hands, feet, arms, and/or face (tetany). The most common cause of hypoparathyroidism is damage to or removal of the parathyroid glands due to surgery for another condition. Hypoparathyroidism can also be caused by an autoimmune process or can occur for unknown reasons (idiopathic) or in association with a number of different underlying disorders.



In extremely rare cases, hypoparathyroidism may occur as a genetic disorder. Such cases can include familial hypoparathyroidism, which may be inherited as an autosomal recessive, autosomal dominant or X-linked recessive trait. NORD has a separate report on familial isolated hypoparathyroidism.

Symptoms

The symptoms of hypoparathyroidism occur due to low levels of calcium in the blood. The severity of the condition can range from mild symptoms such as a tingling or burning sensation in the fingers, toes or around the lips (paresthesias) to severe muscle cramps and tetany, a condition characterized by uncontrollable twitching and cramping spasms of certain muscles such as those of the hands, feet, arms, and/or face. In rare cases, seizures or fits can occur, or the level of consciousness can be depressed.



Additional symptoms that may be associated with hypoparathyroidism include fatigue, weakness, muscle aches, excessive anxiety or nervousness, and headaches. Affected individuals may also have dry, coarse skin, brittle nails, and patchy hair loss such as the thinning of the eyebrows. Some individuals with hypoparathyroidism, especially those with chronic hypoparathyroidism since childhood, may have abnormalities affecting the teeth including the underdevelopment of the hard outer layer of the teeth (enamel hypoplasia), malformation of the roots and an increased risk of cavities (dental caries).



Hoarseness or voice changes, wheezing and difficulty breathing (dyspnea) can also be associated with chronic hypoparathyroidism. Sudden, muscular spasms affecting the larynx (laryngospasm) and the bronchial tubes (bronchospasm) may also occur. Laryngospasm causes closure of the upper end of the trachea and prevents air from reaching the lungs. Bronchospasm can restrict the flow of air into and out of the lungs.



Depression, irritability, confusion, disorientation, mood swings and loss of memory have also been reported in individuals with hypoparathyroidism. In children, chronic hypoparathyroidism can result in stunted growth and slow mental development if it is not treated.



Less often, more serious complications can occur in individuals with hypoparathyroidism especially when hypoparathyroidism goes untreated or persists. Such symptoms include clouding of the lenses of the eyes (cataracts), seizures or convulsions, fainting, abnormal heartbeats (cardiac arrhythmias) and, potentially, signs of congestive heart failure. Some individuals may develop calcium deposits (calcifications) in the brain or the kidneys. If enough calcifications occur in the kidneys, kidney function can become impaired. Individuals with hypoparathyroidism may be prone to developing kidney stones. Increased pressure of cerebrospinal fluid in the skull (intracranial hypertension) can also occur and may cause severe headaches and vision changes.

Causes

Hypoparathyroidism may result from removal of or damage to the parathyroid glands, the absence of or failure to function properly of the parathyroid glands at birth (congenital hypoparathyroidism) or due to or in association with a number of different underlying disorders.



Hypoparathyroidism most often occurs because of the surgical removal of some or all of the parathyroid glands. Surgical damage or removal of parathyroid tissue usually occurs following treatment for another condition, especially hyperparathyroidism (in which there is too much production of parathyroid hormone). Hyperparathyroidism may be treated by the surgical removal of parathyroid tissue. In some cases, such surgery may result in too much parathyroid tissue being removed and, consequently, cause hypoparathyroidism.



Surgery to treat nearby cancer or thyroid disease may also cause hypoparathyroidism, usually through damage to the blood supply for the parathyroid glands. In such cases, hypoparathyroidism may be temporary (transient) depending upon the extent of the damage. Post-surgical hypoparathyroidism is often a temporary (transient) condition, but can become permanent. Post-surgical hypoparathyroidism may occur shortly after surgery or appear months to years later. When hypoparathyroidism occurs due to external factors such as surgery, these cases are sometimes referred to as acquired hypoparathyroidism.



Although very rare, cancer from another tissue can spread to the parathyroid glands and alter their function. In extremely rare cases, hypoparathyroidism is caused by extensive radiation therapy to the neck region as may be done as part of a cancer treatment regimen.



In rare cases, hypoparathyroidism occurs as an autoimmune disorder. Autoimmune disorders are caused when the body's natural defenses (antibodies, lymphocytes, etc.) against invading organisms suddenly begin to attack perfectly healthy tissue for unknown reasons. These cases may be called autoimmune hypoparathyroidism and develop when the body's own immune system mistakenly attacks parathyroid tissue and leads to the loss of the secretion of parathyroid hormone. Autoimmune hypoparathyroidism can occur as part of a larger autoimmune syndrome that damages many organs of the body or as isolated damage to the parathyroid glands.



Congenital hypoparathyroidism refers to infants who are born without parathyroid tissue, the ability to make PTH, or with parathyroid glands that do not function properly. Congenital hypoparathyroidism that occurs during the first few months of life may be temporary (transient) or permanent. In some cases, the cause of hypoparathyroidism is unknown (idiopathic). In some of these cases, hypoparathyroidism may resolve (spontaneously), but most do not resolve and may need treatment.



Congenital hypoparathyroidism may also occur in infants whose mothers have hyperparathyroidism. As opposed to "hypo"-parathyroidism, "hyper"-parathyroidism results in excess calcium in the body. In a pregnant woman, the excess calcium may cross over to the developing fetus and suppress parathyroid hormone production in the parathyroid glands. In a newborn infant, this may result in abnormally low levels of calcium after birth. However, this is only a temporary condition and is not associated with permanent changes in the infant's parathyroid glands. Transient hypoparathyroidism can also occur in preterm infants of women who have diabetes mellitus. This may resolve but should be carefully watched until it does.



Congenital hypoparathyroidism can also refer to cases that occur as an isolated genetic disorder. (For more information these disorders, choose "familial isolated hypoparathyroidism" as your search term in the NORD Rare Disease Database.)



One of the most common causes of hypoparathyroidism is an activating mutation of the extracellular calcium-sensing receptor (CASR) gene. The CASR gene encodes for a protein that is found in the hormone-producing cells of the parathyroid gland. Activating mutations of this gene ultimately lead to suppression of parathyroid hormone secretion and hypoparathyroidism. In many cases, this condition is mild and often detected incidentally. Treatment may not be needed unless symptoms develop. This mutation may be inherited as an autosomal dominant trait, but sporadic cases occur as well.



Another common cause of hypoparathyroidism is abnormally low levels of magnesium (hypomagnesemia) in the blood. This is often called functional hypoparathyroidism because it resolves when magnesium is restored. Magnesium is a mineral that is very important in the function of the parathyroid glands. When magnesium levels are low, it often leads to low levels of calcium in the blood as well. Without proper levels of magnesium, the parathyroid glands fail to function normally. One common cause of low levels of magnesium in the body is chronic alcoholism. Other causes of hypomagnesemia include malnutrition, malabsorption, diabetes, certain kidney disorders and the use of certain medications.



Less often, hypoparathyroidism can be caused by abnormally high levels of magnesium (hypermagnesemia) in the blood. Magnesium can activate certain proteins called calcium-sensing receptors and, consequently, inhibit the secretion of parathyroid hormone. Hypermagnesemia can be occur when magnesium accumulates because of impaired kidney function or when magnesium is given as a therapy as in tocolytic therapy (which is given to women to suppress preterm labor).



Hypoparathyroidism can also develop as part of a larger syndrome such as chromosome 22q11.2 deletion syndrome, Barakat syndrome (hypoparathyroidism - sensorineural deafness - renal disease), Kenney-Caffey disease, Sanjad-Sakati syndrome (hypoparathyroidism - retardation - dysmorphism), autoimmune polyendocrine syndrome type I or lymphedema-hypoparathyroidism syndrome. It can also occur as part of certain mitochondrial disorders such as Kearns-Sayre syndrome or MELAS syndrome. In some cases, hypoparathyroidism may occur in association with Wilson disease (due to copper accumulating in the parathyroid glands) or hemochromatosis (due to iron accumulating in the parathyroid glands). (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)

Affected Populations

Hypoparathyroidism affects males and females in equal numbers. The incidence and prevalence of hypoparathyroidism in the general population are unknown. Hypoparathyroidism can affect individuals of any age.

Standard Therapies

Diagnosis

A diagnosis of hypoparathyroidism is made based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Blood tests can reveal abnormal levels of calcium, phosphorus, magnesium, albumin, creatinine and intact parathyroid hormone. Urine tests can reveal if the body is excreting too much calcium.



In addition, the Food and Drug Administration (FDA) has approved the use of the synthetic parathyroid hormone, teriparatide as a diagnostic agent to distinguish hypoparathyroidism from pseudohypoparathyroidism.



Additional tests may be performed to detect complications that may be associated with hypoparathyroidism. For example, an electrocardiogram, a test that records electrical activity of the heart, can reveal arrhythmias that are sometimes associated with low calcium levels and hypoparathyroidism. An ophthalmologic exam should also be done to check for cataracts.



Molecular genetic testing is available through commercial and academic research laboratories to detect specific gene mutations that cause genetic forms of hypoparathyroidism.



Treatment

The treatment of hypoparathyroidism is directed toward the specific symptoms that are apparent in each individual and the lab tests. Treatment is aimed at raising calcium levels high enough to provide symptom relief without causing abnormally high levels of calcium in the blood (hypercalcemia) or in the urine (hypercalciuria). The specific therapies used may vary depending upon the disease severity, the specific symptoms present, an individual's age and overall health, personal preference and additional factors. Individuals are recommended to see a physician who specializes in diagnosing and treating disorders affecting the endocrine system (endocrinologist) for optimal treatment of hypoparathyroidism and family screening and specialized testing.



The primary therapies for individuals with hypoparathyroidism are calcium and vitamin D supplements, except in individuals whose condition is caused by hypo- or hypermagnesemia. In these cases, hypoparathyroidism is treated by normalizing magnesium levels (e.g., taking magnesium supplements to treat hypomagnesemia).



These are several different types of calcium supplements available. Some brands may work better for certain people. High doses of calcium can cause gastrointestinal side effects such as constipation and should only be taken at the instruction of a physician.



The main supplemental form of vitamin D used for individuals with hypoparathyroidism is calcitriol. Two other synthetic forms of vitamin D that are often used are ergocalciferol and dihydrotachysterol. These forms of vitamin D have a longer duration of action because they are stored in the body. Long-term therapy with vitamin D analogs carries a risk of serious side effects including calcium deposits accumulating in the kidneys (nephrocalcinosis), the development of kidney stones and, ultimately, improper function of the kidneys if blood tests are not carefully monitored.



Some individuals, especially those with severe symptoms, may require immediate relief through intravenous calcium therapy, even if their calcium levels are only mildly reduced. Intravenous means that a substance (e.g., calcium) is delivered into the bloodstream through an injection or infusion directly into a vein.



Some individuals with severe hypoparathyroidism that do not respond to other therapies may be treated with thiazide diuretics. These drugs enhance calcium absorption in the kidneys and can help control or prevent hypercalciuria in individuals taking vitamin D and calcium.



Some individuals with hypoparathyroidism may be encouraged to make dietary changes to help treat their condition. Affected individuals may be encouraged to eat foods high in calcium such as dairy products, breakfast cereals, fortified orange juice and green, leafy vegetables. Affected individuals may also be encouraged to avoid foods high in phosphorus such as carbonated soft drinks, eggs and meat.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Toll-free: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, in the main, contact:

www.centerwatch.com.



Researchers are studying treating individuals with hypoparathyroidism by replacing the missing hormone with man-made (synthetic) versions.



Researchers are studying the use of teriparatide [PTH (1-34)] for the treatment of individuals with hypoparathyroidism. Teriparatide is a recombinant form of parathyroid hormone and has been used for years to treat osteoporosis. Some individuals with hypoparathyroidism have reported an improvement in their symptoms when treated with teriparatide, which is usually given as an injection under the skin (subcutaneously) once or twice a day. Teriparatide has been given to some affected individuals who did not respond to conventional therapies with positive results.



Researchers are also studying a synthetic form of parathyroid hormone [PTH (1-84)] known as NPSP558 for the treatment of individuals with hypoparathyroidism. Initial studies have shown that treatment with NPSP558 significantly reduced the need for calcium and vitamin D supplements in individuals with hypoparathyroidism. More research is necessary to determine the long-term safety and effectiveness of this potential treatment for individuals with hypoparathyroidism.



In studies with synthetic human parathyroid hormone 1-34 (HPTH) for the treatment of individuals with hypoparathyroidism, researchers have found decreased urinary calcium excretion. They may be able to reduce the need for calcium and vitamin D supplements in individuals with hypoparathyroidism. More research is necessary to determine the long-term safety and effectiveness of this potential therapy for individuals with hypoparathyroidism.

References

JOURNAL ARTICLES

Khan MI, Waguespack SG, Hu MI. Medical management of postsurgical hypoparathyroidism. Endocr Pract. 2011;17:18-25.



Rubin MR, Sliney J Jr, McMahon DJ, Silverberg SJ, Bilezikian JP. Therapy of hypoparathyroidism with intact parathyroid hormone. Osteoporos Int. 2010;21:1927-1934.



Winer KK, Sinali N, Reynolds J, et al. Long-term treatment of 12 children with chronic hypoparathyroidism: a randomized trial comparing synthetic human parathyroid hormone 1-34 versus calcitriol and calcium. J Clin Endocrinol Metab. 2010;95:2680-2688.



Brown EM. Anti-parathyroid and anti-calcium sensing receptor antibodies in autoimmune hypoparathyroidism. Endocrinol Metab Clin North Am. 2009;38:437-x.



Shoback D. Hypoparathyroidism. N Engl J Med. 2008;359:391-403.



Winer KK, Sinali N, Peterson D, Sainz B Jr, Culter GB Jr. Effects of once versus twice-daily parathyroid hormone 1-34 therapy in children with hypoparathyroidism. J Clin Endocrinol Metab. 2008;93:3389-3395.



Puig-Domingo M, Diaz G, Nicolau J, et al. Successful treatment of vitamin D unresponsive hypoparathyroidism with multipulse subcutaneous infusion of teriparatide. Eur J Endocrinol. 2008;159:653-657.



Angelopoulos NG, Goula A, Tolis G. Sporadic hypoparathyroidism treated with teriparatide: a case report and literature review. Exp Clin Endocrinol Diabetes. 2007;115:50-54.



FROM THE INTERNET

Gonzalez-Campoy JM. Hypoparathyroidism. Emedicine Journal, June 14 2006. Available at: http://emedicine.medscape.com/article/122207-overview Accessed on: June 1, 2011.



Eunice Kennedy Shriver National Institute of Child Health and Human Development. Hypoparathyroidism. March 22, 2007. Available at: http://www.nichd.nih.gov/health/topics/hypoparathyroidism.cfm Accessed On: June 1, 2011.



Mayo Clinic for Medical Education and Research. Hypoparathyroidism. April 19, 2011. Available at: http://www.mayoclinic.com/health/hypoparathyroidism/DS00952 Accessed On: June 1, 2011.

Resources

Hypoparathyroidism Association, Inc.

PO Box 2258

Idaho Falls, ID 83403

Tel: (866)213-0394

Fax: (205)524-3857

Tel: (866)213-0394

Email: hpth@hypopara.org. hpth@hypopara.org. hpth@hypopara.org. hpth@hypopara.org

Internet: http://www.hypopara.org



NIH/National Institute of Diabetes, Digestive & Kidney Diseases

Office of Communications & Public Liaison

Bldg 31, Rm 9A06

31 Center Drive, MSC 2560

Bethesda, MD 20892-2560

Tel: (301)496-3583

Email: NDDIC@info.niddk.nih.gov

Internet: http://www2.niddk.nih.gov/



Thyroid Foundation of Canada

263 MCG Building

Labrosse Ave

Pointe-Claire

QC, H9R 1A3

Canada

Fax: 5146309815

Tel: 8002678822

Internet: http://www.thyroid.ca



Endocrine Society

8401 Connecticut Ave

Suite 900

Chevy Chase, MD 20815

USA

Tel: (301)941-0200

Fax: (301)941-0259

Tel: (888)363-6274

Email: societyservices@endo-society.org

Internet: http://www.endo-society.org



NIH/National Institute of Child Health and Human Development

31 Center Dr

Building 31, Room 2A32

MSC2425

Bethesda, MD 20892

Fax: (866)760-5947

Tel: (800)370-2943

TDD: (888)320-6942

Email: NICHDInformationResourceCenter@mail.nih.gov

Internet: http://www.nichd.nih.gov/



American Thyroid Association

6066 Leesburg Pike, Suite 550

Falls Church, VA 22041

USA

Tel: (703)998-8890

Fax: (703)998-8893

Email: thyroid@thyroid.org

Internet: http://www.thyroid.org



Hormone Health Network

8401 Connecticut Avenue

Suite 900

Chevy Chase, MD 20815-5817

Fax: (310)941-0259

Tel: (800)467-6663

Email: hormone@endo-society.org

Internet: http://www.hormone.org/



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



For a Complete Report

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