Hypoparathyroidism
Encyclopedia
Hypoparathyroidism is decreased function of the parathyroid gland
s with under production of parathyroid hormone
. This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany
(involunary muscle contraction), and several other symptoms. The condition can be inherited, but it is also encountered after thyroid
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
s, and other investigations such as genetic testing
depending on the results. The treatment of hypoparathyroidism is limited by the fact that there is no artificial form of the hormone that can be administered as replacement
; calcium replacement or vitamin D
can ameliorate the symptoms but can increase the risk of kidney stone
s and chronic kidney disease.
and nerve conduction
. As a result, people with hypoparathyroidism can experience paresthesia
, 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, headache
s, bone pain
and insomnia
. Crampy abdominal pain
may occur. Physical examination
of someone with hypocalcemia may show tetany, but it is also possible to provoke tetany of the facial muscles by tapping on the facial nerve
(a phenomenon known as Chvostek's sign) or by using the cuff of a sphygmomanometer
to temporarily obstruct the blood flow to the arm (a phenomenon known as Trousseau's sign
).
A number of medical emergencies
can arise in people with low calcium levels. These are seizures, severe irregularities in the normal heart beat
, as well as spasm of the upper part of the airways
or the smaller airways known as the bronchi
(both potentially causing respiratory failure
).
In hypoparathyroidism, urinary calcium
excretion is increased. This can lead to kidney stone
s that can cause painful attacks when released into the ureter
s, but also to ongoing kidney damage and chronic kidney disease, the symptoms of which are non-specific but include fatigue, nausea
.
in the neck. They arise during fetal development
from structures known as the third and fourth pharyngeal pouch. The glands, usually four in number, contain the parathyroid chief cell
s that sense the level of calcium
in the blood through the calcium-sensing receptor
and secrete parathyroid hormone. Magnesium
is required for PTH secretion. Under normal circumstances, the parathyroids 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
). PTH acts on several organs to increase calcium levels. It increases calcium absorption in the bowel, while in the kidney it prevents calcium excretion and increases phosphate release and in bone it increases calcium through bone resorption.
, serum albumin
(for correction) and PTH in blood
. PTH degrades rapidly at ambient temperatures and the blood sample therefore has to be transported to the laboratory on ice.
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:
Other tests include ECG for abnormal heart rhythms, and measurement of blood magnesium levels.
(e.g. as calcium gluconate
). Generally, a central venous catheter is recommended, as the calcium can irritate peripheral vein
s and cause phlebitis
. In the event of a life-threatening attack of low calcium levels or tetany (prolonged muscle contractions), calcium is administered by intravenous (IV) infusion. Precautions are taken to prevent seizures or larynx spasms. The heart is monitored for abnormal rhythms until the person is stable. When the life-threatening attack has been controlled, treatment continues with medicine taken by mouth as often as four times a day.
Long-term treatment of hypoparathyroidism is with calcium and vitamin D3 supplementation (D1 is ineffective in the absence of renal conversion). Teriparatide
, a synthetic form of PTH (presently registered for osteoporosis
) might become the treatment of choice for PTH supplementation, although further studies are awaited. Currently, hypoparathyroidism is the only disease of hormone deficiency that does not have a hormone-replacement-therapy available, but research is being conducted to establish recombinant human parathyroid hormone (1-84) (rhPTH[1-84]) as just such a replacement.
Parathyroid gland
The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone. Humans usually have four parathyroid glands, which are usually located on the rear surface of the thyroid gland, or, in rare cases, within the thyroid gland itself or in the chest...
s with under production of parathyroid hormone
Parathyroid hormone
Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...
. This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany
Tetany (medical sign)
Tetany is a medical sign consisting of the involuntary contraction of muscles, which may be caused by disease or other conditions that increase the action potential frequency...
(involunary muscle contraction), and several other symptoms. The condition can be inherited, but it is also encountered after thyroid
Thyroidectomy
A thyroidectomy is an operation that involves the surgical removal of all or part of the thyroid gland. Surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other condition of the thyroid gland...
or parathyroid gland surgery
Parathyroidectomy
Also known as "Parathyroid gland removal", Parathyroidectomy is the surgical removal of one or more parathyroid glands. This procedure is used to remove primary tumors or hyperplasia of the glands, especially when they produce excessive parathyroid hormone. As drugs such as Fosamax do not treat the...
, and it can be caused by immune system-related damage
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
as well as a number of rarer causes. The diagnosis is made with blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s, and other investigations such as genetic testing
Genetic testing
Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...
depending on the results. The treatment of hypoparathyroidism is limited by the fact that there is no artificial form of the hormone that can be administered as replacement
Hormone therapy
Hormone therapy, or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also referred to as hormonal therapy...
; calcium replacement or vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
can ameliorate the symptoms but can increase the risk of kidney stone
Kidney stone
A kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...
s and chronic kidney disease.
Signs and symptoms
The main symptoms of hypoparathyroidism are the result of the low blood calcium level, which interferes with normal muscle contractionMuscle contraction
Muscle fiber generates tension through the action of actin and myosin cross-bridge cycling. While under tension, the muscle may lengthen, shorten, or remain the same...
and nerve conduction
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
. As a result, people with hypoparathyroidism can experience paresthesia
Paresthesia
Paresthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...
, 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, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
s, bone pain
Bone pain
Bone pain is a debilitating form of pain emanating from the bone tissue. It occurs as a result of a wide range of diseases and/or physical conditions and may severely impair the quality of life for patients who suffer from it...
and insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
. Crampy abdominal pain
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
may occur. Physical examination
Physical examination
Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...
of someone with hypocalcemia may show tetany, but it is also possible to provoke tetany of the facial muscles by tapping on the facial nerve
Facial nerve
The facial nerve is the seventh of twelve paired cranial nerves. It emerges from the brainstem between the pons and the medulla, and controls the muscles of facial expression, and functions in the conveyance of taste sensations from the anterior two-thirds of the tongue and oral cavity...
(a phenomenon known as Chvostek's sign) or by using the cuff of a sphygmomanometer
Sphygmomanometer
A sphygmomanometer or blood pressure meter is a device used to measure blood pressure, comprising an inflatable cuff to restrict blood flow, and a mercury or mechanical manometer to measure the pressure. It is always used in conjunction with a means to determine at what pressure blood flow is just...
to temporarily obstruct the blood flow to the arm (a phenomenon known as Trousseau's sign
Trousseau sign of latent tetany
Trousseau sign of latent tetany is a medical sign observed in patients with low calcium. This sign may become positive before other gross manifestations of hypocalcemia such as hyperreflexia and tetany, but is generally believed to be more sensitive than the Chvostek sign for hypocalcemia.To...
).
A number of medical emergencies
Medical emergency
A medical emergency is an injury or illness that is acute and poses an immediate risk to a person's life or long term health. These emergencies may require assistance from another person, who should ideally be suitably qualified to do so, although some of these emergencies can be dealt with by the...
can arise in people with low calcium levels. These are seizures, severe irregularities in the normal heart beat
Cardiac dysrhythmia
Cardiac dysrhythmia is any of a large and heterogeneous group of conditions in which there is abnormal electrical activity in the heart. The heart beat may be too fast or too slow, and may be regular or irregular.Some arrhythmias are life-threatening medical emergencies that can result in cardiac...
, as well as spasm of the upper part of the airways
Laryngospasm
In medicine, laryngospasm is an uncontrolled/involuntary muscular contraction of the laryngeal cords. The condition typically lasts less than 60 seconds, and causes a partial blocking of breathing in, while breathing out remains easier. It may be triggered when the vocal cords or the area of the...
or the smaller airways known as the bronchi
Bronchospasm
Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release of substances from mast cells or basophils under the influence of anaphylatoxins...
(both potentially causing respiratory failure
Respiratory failure
The term respiratory failure, in medicine, is used to describe inadequate gas exchange by the respiratory system, with the result that arterial oxygen and/or carbon dioxide levels cannot be maintained within their normal ranges. A drop in blood oxygenation is known as hypoxemia; a rise in arterial...
).
In hypoparathyroidism, urinary calcium
Urinary calcium
Urinary calcium is calcium in the urine. It is termed -calcuria or -calciuria as a suffix.-Normal amount:In a urinalysis, the normal amount of urinary calcium can be measured in amount per time...
excretion is increased. This can lead to kidney stone
Kidney stone
A kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...
s that can cause painful attacks when released into the ureter
Ureter
In human anatomy, the ureters are muscular tubes that propel urine from the kidneys to the urinary bladder. In the adult, the ureters are usually long and ~3-4 mm in diameter....
s, but also to ongoing kidney damage and chronic kidney disease, the symptoms of which are non-specific but include fatigue, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
.
Causes
Hypoparathyroidism can have a number of divergent causes:- Removal of or trauma to the parathyroid glands in thyroidThyroidThe thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
surgery (thyroidectomyThyroidectomyA thyroidectomy is an operation that involves the surgical removal of all or part of the thyroid gland. Surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other condition of the thyroid gland...
) or other neck surgeries is a recognized cause. It is now uncommon, as surgeonSurgerySurgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
s generally can spare them during procedures after identifying them. In a small percentage of cases, however, they can become traumatized during surgery and/or their blood supply can be compromised. When this happens the parathyroids may cease functioning for a while or stop altogether. - Autoimmune invasion and destruction is the most common non-surgical cause. It can occur as part of autoimmune polyendocrine syndromeAutoimmune polyendocrine syndromeIn medicine, autoimmune polyendocrine syndromes are a heterogeneous group of rare diseases characterised by autoimmune activity against more than one endocrine organs, although non-endocrine organs can be affected....
s. - 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 deficiencyMagnesium deficiency (medicine)Magnesium deficiency refers to an intake of dietary magnesium below minimal levels, which can result in numerous symptoms and diseases. These can generally be remedied by an increase of magnesium in diet or oral supplements...
- DiGeorge syndromeDiGeorge syndrome22q11.2 deletion syndrome, which has several presentations including DiGeorge syndrome , DiGeorge anomaly, velo-cardio-facial syndrome, Shprintzen syndrome, conotruncal anomaly face syndrome, Strong syndrome, congenital thymic aplasia, and thymic hypoplasia is a syndrome caused by the deletion of a...
, a disease in which hypoparathyroidism can occur due to a total absence of the parathyroid glands at birth. Familial hypoparathyroidism occurs with other endocrine diseases, such as adrenal insufficiency, in a syndrome called type I polyglandular autoimmune syndrome (PGA I). - Some very rare diseaseRare diseaseA rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...
s - Idiopathic (of unknown cause), occasionally familial
Mechanism
The parathyroid glands are so named because they are usually located behind the thyroid glandThyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
in the neck. They arise during fetal development
Human embryogenesis
Human embryology is the study of human development during the first eight weeks from gametogenesis pre-conception through fertilization up to and including the 8th week after implantation of the zygote in the uterus...
from structures known as the third and fourth pharyngeal pouch. The glands, usually four in number, contain the parathyroid chief cell
Parathyroid chief cell
Parathyroid chief cells are cells in the parathyroid glands which produce parathyroid hormone....
s that sense the level of calcium
Calcium in biology
Calcium plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization...
in the blood through the calcium-sensing receptor
Calcium-sensing receptor
The calcium-sensing receptor is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone .-Signal transduction:The release of PTH is...
and secrete parathyroid hormone. Magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
is required for PTH secretion. Under normal circumstances, the parathyroids 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
Autonomic nervous system
The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
). PTH acts on several organs to increase calcium levels. It increases calcium absorption in the bowel, while in the kidney it prevents calcium excretion and increases phosphate release and in bone it increases calcium through bone resorption.
Diagnosis
Diagnosis is by measurement of calciumCalcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
, serum albumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
(for correction) and PTH in blood
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
. PTH degrades rapidly at ambient temperatures and the blood sample therefore has to be transported to the laboratory on ice.
If necessary, measuring cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
(cyclic AMP) in the urine after an intravenous dose of PTH can help in the distinction between hypoparathyroidism and other causes.
Differential diagnoses are:
- PseudohypoparathyroidismPseudohypoparathyroidismPseudohypoparathyroidism is a condition associated primarily with resistance to the parathyroid hormone. Patients have a low serum calcium and high phosphate, but the parathyroid hormone level is actually appropriately high...
(normal PTH levels but tissue insensitivity to the hormone, associated with mental retardationMental retardationMental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
and skeletal deformitiesSkeletonThe skeleton is the body part that forms the supporting structure of an organism. There are two different skeletal types: the exoskeleton, which is the stable outer shell of an organism, and the endoskeleton, which forms the support structure inside the body.In a figurative sense, skeleton can...
) and pseudopseudohypoparathyroidismPseudopseudohypoparathyroidismPseudopseudohypoparathyroidism is an inherited disorder, named for its similarity to pseudohypoparathyroidism in presentation...
(sic). - Vitamin D deficiency or hereditary insensitivity to this vitamin (X-linked dominant).
- MalabsorptionMalabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
- Kidney disease
- Medication: steroidSteroidA steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
s, diureticDiureticA diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
s, some antiepileptics.
Other tests include ECG for abnormal heart rhythms, and measurement of blood magnesium levels.
Treatment
Severe hypocalcemia, a potentially life-threatening condition, is treated as soon as possible with intravenous calciumCalcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
(e.g. as calcium gluconate
Calcium gluconate
Calcium gluconate is a mineral supplement.-Hypocalcemia:10% calcium gluconate solution is the form of calcium most widely used in the treatment of hypocalcemia. This form of calcium is superior to calcium lactate, but it only contains 0.93% calcium ion. Calcium gluconate is a salt of calcium and...
). Generally, a central venous catheter is recommended, as the calcium can irritate peripheral vein
Peripheral vein
Peripheral Veins are the veins not in the chest or abdomen . These veins lead deoxygenated blood from the capillaries in the extremities back to the heart....
s and cause phlebitis
Phlebitis
Phlebitis is an inflammation of a vein, usually in the legs.When phlebitis is associated with the formation of blood clots , usually in the deep veins of the legs, the condition is called thrombophlebitis...
. In the event of a life-threatening attack of low calcium levels or tetany (prolonged muscle contractions), calcium is administered by intravenous (IV) infusion. Precautions are taken to prevent seizures or larynx spasms. The heart is monitored for abnormal rhythms until the person is stable. When the life-threatening attack has been controlled, treatment continues with medicine taken by mouth as often as four times a day.
Long-term treatment of hypoparathyroidism is with calcium and vitamin D3 supplementation (D1 is ineffective in the absence of renal conversion). Teriparatide
Teriparatide
Teriparatide is a recombinant form of parathyroid hormone, used in the treatment of some forms of osteoporosis. It is manufactured and marketed by Eli Lilly and Company.-Administration:...
, a synthetic form of PTH (presently registered for osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
) might become the treatment of choice for PTH supplementation, although further studies are awaited. Currently, hypoparathyroidism is the only disease of hormone deficiency that does not have a hormone-replacement-therapy available, but research is being conducted to establish recombinant human parathyroid hormone (1-84) (rhPTH[1-84]) as just such a replacement.
Complications
A number of complications can occur in hypoparathyroidism:- Tetany can lead to a blocked airway, requiring a tracheotomyTracheotomyAmong the oldest described surgical procedures, tracheotomy consists of making an incision on the anterior aspect of the neck and opening a direct airway through an incision in the trachea...
. - Stunted growth, malformed teeth, and slow mental development can occur if hypoparathyroidism develops in childhood.
- Overtreatment with vitamin DVitamin DVitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
and calciumCalciumCalcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
can cause hypercalcemia (high blood calcium) and sometimes interfere with kidney function. - There is an increased risk of pernicious anemiaPernicious anemiaPernicious anemia is one of many types of the larger family of megaloblastic anemias...
, Addison's diseaseAddison's diseaseAddison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...
, cataractCataractA cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light...
development, and Parkinson's diseaseParkinson's diseaseParkinson's disease is a degenerative disorder of the central nervous system...
.