Hypoparathyroidism

Hypoparathyroidism
Classification and external resources
Specialty	Endocrinology
ICD-10	E20, E89.2, P71.4
ICD-9-CM	252.1
OMIM	146200
DiseasesDB	6490
MedlinePlus	000385
eMedicine	med/1131 emerg/276 ped/1125
Patient UK	Hypoparathyroidism
MeSH	D007011

Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone. This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary 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 tests, 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 stones and chronic kidney disease.^[1]

Signs and symptoms

The main symptoms of hypoparathyroidism are the result of the low blood calcium level, which interferes with normal muscle contraction 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.^[2] Many also report a number of subjective symptoms such as fatigue, headaches, bone pain and insomnia.^[1] Crampy abdominal pain may occur.^[3] 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 of latent tetany).^[3]

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).^[1]

Causes

Hypoparathyroidism can have the following causes:^[1]

• Removal of, or trauma to, the parathyroid glands due to thyroid surgery (thyroidectomy), parathyroid surgery (parathyroidectomy) or other surgical interventions in the central part of the neck (such as operations on the larynx and/or pharynx) is a recognized cause. It is the most common cause of hypoparathyroidism. Although surgeons 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).
• Autoimmune 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
• DiGeorge syndrome, 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 autoimmune polyglandular failure syndrome type 1 (APS-I).
• A defect in the calcium receptor leads to a rare congenital form of the disease
• Idiopathic (of unknown cause), occasionally familial (e.g. Barakat syndrome (HDR syndrome) a genetic development disorder resulting in hypoparathyroidism, sensorineural deafness and renal disease)

Mechanism

The parathyroid glands are so named because they are usually located behind the thyroid gland 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 cells 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.

Diagnosis

Diagnosis is by measurement of calcium, serum albumin (for correction) and PTH in blood.

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 mental retardation and skeletal deformities) and pseudopseudohypoparathyroidism.
• Vitamin D deficiency or hereditary insensitivity to this vitamin (X-linked dominant).
• Malabsorption
• Kidney disease
• Medication: steroids, diuretics, some antiepileptics.

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 calcium (e.g. as calcium gluconate). Generally, a central venous catheter is recommended, as the calcium can irritate peripheral veins 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 vitamin D analogs and calcium supplementation may be ineffective in some due to potential renal damage.^[4] The N-terminal fragment of parathyroid hormone (PTH 1-34) has full biological activity. The use of pump delivery of synthetic PTH 1-34 provides the closest approach to physiologic PTH replacement therapy.^[5] Injections of recombinant human parathyroid hormone are available as treatment in those with low blood calcium levels.^[6]

Related conditions

Condition		Appearance	PTH levels	Calcitriol	Calcium	Phosphates	Imprinting
Hypoparathyroidism		Normal	Low	Low	Low	High	Not applicable
Pseudohypoparathyroidism	Type 1A	Skeletal defects	High	Low	Low	High	Gene defect from mother (GNAS1)
	Type 1B	Normal	High	Low	Low	High	Gene defect from mother (GNAS1 and STX16)
	Type 2	Normal	High	Low	Low	High	?
Pseudopseudohypoparathyroidism		Skeletal defects	Normal	Normal	Normal[7]	Normal	gene defect from father

See also

• Hyperparathyroidism

References

1. Bilezikian JP, Khan A, Potts JT, et al. (October 2011). "Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research". J. Bone Miner. Res. 26 (10): 2317–37. doi:10.1002/jbmr.483. PMC 3405491. PMID 21812031.
2. Shoback D (July 2008). "Hypoparathyroidism". N. Engl. J. Med. 359 (4): 391–403. doi:10.1056/NEJMcp0803050. PMID 18650515.
3. Potts Jr JT (2005). "Diseases of the parathyroid gland". In Kasper DL, Braunwald E, Fauci AS; et al. Harrison's Principles of Internal Medicine (16th ed.). New York, NY: McGraw-Hill. pp. 2249–68. ISBN 0-07-139140-1.
4. Winer KK, Yanovski JA, Cutler GB Jr. Synthetic human parathyroid hormone 1-34 vs calcitriol and calcium in the treatment of hypoparathyroidism: Results of a randomized crossover trial" JAMA 1996;276:631-636
5. Winer KK, Zhang B, Shrader J, et al. Synthetic human parathyroid hormone 1-34 replacement therapy: A randomized crossover trial comparing pump versus injections in the treatment of chronic hypoparathyroidism. J Clin Endocrinol Metab. Nov.2011.
6. "FDA approves Natpara to control low blood calcium levels in patients with hypoparathyroidism". http://www.fda.gov/. Retrieved 30 January 2015. External link in |website= (help)
7. Shahid Hussain; Sharif Aaron Latif; Adrian Hall (1 July 2010). Rapid Review of Radiology. Manson Publishing. pp. 262–. ISBN 978-1-84076-120-7. Retrieved 30 October 2010.