Hypoparathyroidism is decreased function of the

parathyroid gland Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes par ...

s with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing

cramp A cramp is a sudden, involuntary, painful skeletal muscle contraction or overshortening associated with electrical activity. While generally temporary and non-damaging, they can cause significant pain and a paralysis-like immobility of the aff ...

ing and twitching of muscles or tetany (involuntary muscle contraction), and several other symptoms. It is a very rare disease. The condition can be inherited, but it is also encountered after

thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...

or parathyroid gland surgery, and it can be caused by immune system-related damage as well as a number of rarer causes. The diagnosis is made with

blood test A blood test is a medical laboratory, laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose ...

s, and other investigations such as

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

depending on the results. The primary treatment of hypoparathyroidism is calcium and vitamin D supplementation. Calcium replacement or

vitamin D Vitamin D is a group of structurally related, fat-soluble compounds responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most important compo ...

can ameliorate the symptoms but can increase the risk of

kidney stone Kidney stone disease (known as nephrolithiasis, renal calculus disease, or urolithiasis) is a crystallopathy and occurs when there are too many minerals in the urine and not enough liquid or hydration. This imbalance causes tiny pieces of cr ...

s and

chronic kidney disease Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

. Additionally, medications such as recombinant human parathyroid hormone or teriparatide may be given by injection to replace the missing hormone.

Signs and symptoms

The main symptoms of hypoparathyroidism are the result of the low blood calcium level, which interferes with normal

muscle contraction Muscle contraction is the activation of Tension (physics), tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in musc ...

and nerve conduction. As a result, people with hypoparathyroidism can experience

paresthesia Paresthesia is a sensation of the skin that may feel like numbness (''hypoesthesia''), tingling, pricking, chilling, or burning. It can be temporary or Chronic condition, chronic and has many possible underlying causes. Paresthesia is usually p ...

, an unpleasant tingling sensation around the mouth and in the hands and feet, as well as muscle cramps and severe spasms known as " tetany" that affect the hands and feet. Many also report a number of subjective symptoms such as

fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

bone pain Bone pain (also known medically by several other names) is pain coming from a bone, and is caused by damaging stimuli. It occurs as a result of a wide range of diseases or physical conditions or both, and may severely impair the quality of life. ...

and

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

. Crampy

abdominal pain Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Since the abdomen contains most of the body's vital organs, it can be an indicator of a wide variety of diseases. Given th ...

may occur.

Physical examination In a physical examination, medical examination, clinical examination, or medical checkup, a medical practitioner examines a patient for any possible medical signs or symptoms of a Disease, medical condition. It generally consists of a series of ...

of someone with

hypocalcemia Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), while levels less than 2.1 ...

may show tetany, but it is also possible to provoke tetany of the facial muscles by tapping on the

facial nerve The facial nerve, also known as the seventh cranial nerve, cranial nerve VII, or simply CN VII, is a cranial nerve that emerges from the pons of the brainstem, controls the muscles of facial expression, and functions in the conveyance of ta ...

(a phenomenon known as Chvostek's sign) or by using the cuff of a

sphygmomanometer A sphygmomanometer ( ), also known as a blood pressure monitor, blood pressure machine, or blood pressure gauge, is a device used to measure blood pressure, composed of an inflatable cuff to collapse and then release the artery under the cuff i ...

to temporarily obstruct the blood flow to the arm (a phenomenon known as Trousseau's sign of latent tetany). A number of medical emergencies can arise in people with low calcium levels. These are

seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

, severe irregularities in the normal heart beat (specifically prolongation of the QT interval), as well as spasm of the upper part of the airways or the smaller airways known as the bronchi (both potentially causing

respiratory failure Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a r ...

Related conditions

Causes

Hypoparathyroidism can have the following causes: * Removal of, or trauma to, the parathyroid glands due to anterior neck surgery (including

surgery) ( thyroidectomy), parathyroid surgery (parathyroidectomy). This is the most common cause of hypoparathyroidism, with 78% of cases of hypoparathyroidism arising due to a complication of anterior neck surgery. Although

surgeon In medicine, a surgeon is a medical doctor who performs surgery. Even though there are different traditions in different times and places, a modern surgeon is a licensed physician and received the same medical training as physicians before spec ...

s generally make attempts to spare normal parathyroid glands at surgery, inadvertent injury to the glands or their blood supply is still common. When this happens, the parathyroids may cease functioning. This is usually temporary but occasionally long term (permanent). Hypoparathyroidism may occur as a complication in up to 8% of anterior neck surgeries with 75% of those resolving by 6 months, and 25% of those having permanent hypoparathyroidism. * Kenny–Caffey syndrome *

Autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an " autoimmune disease" ...

invasion and destruction is the most common non-surgical cause. It can occur as part of autoimmune polyendocrine syndromes. * Hemochromatosis can lead to iron accumulation and consequent dysfunction of a number of endocrine organs, including the parathyroids. * Absence or dysfunction of the parathyroid glands is one of the components of chromosome 22q11 microdeletion syndrome (other names: DiGeorge syndrome, Schprintzen syndrome, velocardiofacial syndrome). * Magnesium deficiency * A defect in the calcium receptor leads to a rare congenital form of the disease * Idiopathic (of unknown cause) * Occasionally due to other hereditary causes (e.g. Barakat syndrome (HDR syndrome) a genetic development disorder resulting in hypoparathyroidism, sensorineural deafness, and kidney disease)

Mechanism

The parathyroid glands are so named because they are usually located behind the

thyroid gland The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...

in the neck. They arise during

fetal development Prenatal development () involves the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal deve ...

from structures known as the third and fourth pharyngeal pouch. The glands, usually four in number, contain the parathyroid chief cells that sense the level of

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

in the blood through the calcium-sensing receptor and secrete parathyroid hormone.

Magnesium Magnesium is a chemical element; it has Symbol (chemistry), symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 ...

is required for PTH secretion. Under normal circumstances, the parathyroid glands secrete PTH to maintain a calcium level within normal limits, as calcium is required for adequate muscle and nerve function (including the

autonomic nervous system The autonomic nervous system (ANS), sometimes called the visceral nervous system and formerly the vegetative nervous system, is a division of the nervous system that operates viscera, internal organs, smooth muscle and glands. The autonomic nervo ...

). PTH acts on several organs to regulate calcium levels and phosphorus levels. PTH acts on the kidneys to increase calcium reabsorption into the blood, and to inhibit phosphorus reabsorption (which causes phosphorus to be lost in the urine). It increases calcium and phosphorus absorption in the bowel indirectly by stimulating the kidneys to produce vitamin D which then acts on the gut. PTH also causes increase

bone resorption Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. The osteoclasts are multi-nuclea ...

which leads to the releases calcium and phosphorus into the blood.

Diagnosis

Diagnosis is by measurement of

serum albumin Serum albumin, often referred to simply as blood albumin, is an albumin (a type of globular protein) found in vertebrate blood. Human serum albumin is encoded by the ''ALB'' gene. Other mammalian forms, such as bovine serum albumin, are chem ...

(for correction) and PTH in

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...

. If necessary, measuring cAMP (cyclic AMP) in the urine after an intravenous dose of PTH can help in the distinction between hypoparathyroidism and other causes. Differential diagnoses are: * Pseudohypoparathyroidism (normal PTH levels but tissue insensitivity to the hormone, associated with

intellectual disability Intellectual disability (ID), also known as general learning disability (in the United Kingdom), and formerly mental retardation (in the United States), Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010).Archive is a generalized neurodevelopmental ...

and skeletal deformities) and pseudopseudohypoparathyroidism. * Vitamin D deficiency or hereditary insensitivity to this vitamin (X-linked dominant). *

Malabsorption Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a varie ...

Kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an Inflammation, inflammatory kidney disease and has several types according to the location of the inflammation. Infla ...

* Medication:

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

diuretic A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics ...

s, some

antiepileptic Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatmen ...

s. Other tests include ECG for abnormal heart rhythms, and measurement of blood magnesium levels.

Treatment

Severe hypocalcaemia, a potentially life-threatening condition, is treated as soon as possible with

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

(e.g. as calcium gluconate). Calcium gluconate can be given via a peripheral IV, however other calcium formulations require infusion via a central venous catheter as the calcium can irritate peripheral veins and cause

phlebitis Phlebitis (or venitis) is inflammation of a vein, usually in the legs. It most commonly occurs in superficial veins. Phlebitis often occurs in conjunction with thrombosis (clotting inside blood vessels) and is then called thrombophlebitis or ...

. Precautions are taken to prevent seizures or larynx spasms. The heart is monitored for abnormal rhythms during IV treatment as calcium may affect cardiac conduction. When the life-threatening attack has been controlled, the person is then transitioned to long term therapy with oral or

subcutaneous injection Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus (medicine), bolus into the subcutis, the layer of skin directly below the dermis and ...

medications. Long-term treatment of hypoparathyroidism is with

analogs (such as

calcitriol Calcitriol is a hormone and the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the exp ...

or alfacalcidol), vitamin D supplementation and calcium supplementation. Potential risks of treatment for hypoparathyroidism include

hypercalcemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range for total calcium is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L def ...

and hypercalciuria (elevated calcium in the urine) which may lead to kidney calcification ( nephrocalcinosis) and

. Calcium levels in the blood and urine (along with other electrolytes) must be monitored during long-term treatment of hypoparathyroidism and blood calcium levels are intentionally kept at the lower limits of normal, or mildly low, specifically to avoid hypercalciuria, kidney calcification and kidney damage. Recombinant human parathyroid hormone and teriparatide (which consists of the first

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

34 amino acids of parathyroid hormone, the bioactive portion of the hormone)(PTH 1-34) may be used as a second line therapy in those that have not responded to conventional therapy. Both medication may be given via subcutaneous injections, but the use of pump delivery of synthetic PTH 1-34 provides the closest approach to physiologic PTH replacement therapy. Recombinant human parathyroid hormone and teriparatide are also associated with a risk of hypercalcemia, hypercalciuria with associated kidney calcification and kidney damage. If these medications are discontinued, they should be tapered and calcium levels should be closely monitored as the transient PTH depletion after stopping the medications can lead to bone leaching of calcium as a compensatory mechanism to increase calcium levels. A 2019 systematic review has highlighted that because of the research gap in recent rigorous studies, there is a lack of high-quality evidence for the use of vitamin D, calcium, or recombinant parathyroid hormone in the management of both temporary and long-term hypoparathyroidism following thyroidectomy. Kidney ultrasound may be considered periodically to assess for any nephrocalcinosis for those on long term therapy for hypoparathyroidism.

References

External links

{{Authority control Parathyroid disorders Endocrine-related cutaneous conditions Rare diseases