Hypoparathyroidism

Last updated
Hypoparathyroidism
Specialty Endocrinology
Symptoms hypocalcemia
Medication Recombinant human parathyroid hormone, Palopegteriparatide

Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). 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. It is a very rare disease. 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 primary treatment of hypoparathyroidism is calcium and vitamin D supplementation. Calcium replacement or vitamin D can ameliorate the symptoms but can increase the risk of kidney stones and chronic kidney disease. [1] Additionally, medications such as recombinant human parathyroid hormone or teriparatide may be given by injection to replace the missing hormone. [2]

Contents

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. [3] Many also report a number of subjective symptoms such as fatigue, headaches, bone pain and insomnia. [1] Crampy abdominal pain may occur. [4] 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). [4]

A number of medical emergencies can arise in people with low calcium levels. These are seizures, 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). [1] [5]

ConditionAppearance PTH levels Calcitriol Calcium Phosphates Imprinting
HypoparathyroidismNormalLowLowLowHighNot applicable
Pseudohypoparathyroidism Type 1A Skeletal defects HighLowLowHighGene defect from mother (GNAS1)
Type 1BNormalHighLowLowHighGene defect from mother (GNAS1 and STX16)
Type 2NormalHighLowLowHigh ?
Pseudopseudohypoparathyroidism Skeletal defects NormalNormalNormal [6] Normalgene defect from father

Causes

Hypoparathyroidism can have the following causes: [1]

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 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).

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). [5] It increases calcium and phosphorus absorption in the bowel indirectly by stimulating the kidneys to produce vitamin D which then acts on the gut. [5] PTH also causes increase bone resorption which leads to the releases calcium and phosphorus into the blood. [5]

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.[ citation needed ]

Differential diagnoses are:

Other tests include ECG for abnormal heart rhythms, and measurement of blood magnesium levels.[ citation needed ]

Treatment

Severe hypocalcaemia, a potentially life-threatening condition, is treated as soon as possible with intravenous calcium (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. [5] 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. [5] When the life-threatening attack has been controlled, the person is then transitioned to long term therapy with oral or subcutaneous injection medications. [5]

Long-term treatment of hypoparathyroidism is with vitamin D analogs (such as calcitriol or alfacalcidol), vitamin D supplementation and calcium supplementation. [5] Potential risks of treatment for hypoparathyroidism include hypercalcemia and hypercalciuria (elevated calcium in the urine) which may lead to kidney calcification (nephrocalcinosis) and chronic kidney disease. [5] [8] 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. [5]

Recombinant human parathyroid hormone and teriparatide (which consists of the first N-terminal 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. [5] 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. [9] Recombinant human parathyroid hormone and teriparatide are also associated with a risk of hypercalcemia, hypercalciuria with associated kidney calcification and kidney damage. [5] 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. [5]

A 2019 systematic review has highlighted that 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. [10]

Kidney ultrasound may be considered periodically to assess for any nephrocalcinosis for those on long term therapy for hypoparathyroidism. [5]

See also

Related Research Articles

<span class="mw-page-title-main">Parathyroid gland</span> Endocrine 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 parathyroid hormone in response to low blood calcium, which plays a key role in regulating the amount of calcium in the blood and within the bones.

<span class="mw-page-title-main">Parathyroid hormone</span> Mammalian protein found in humans

Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.

<span class="mw-page-title-main">Calcium metabolism</span> Movement and regulation of calcium ions in and out of the body

Calcium metabolism is the movement and regulation of calcium ions (Ca2+) in (via the gut) and out (via the gut and kidneys) of the body, and between body compartments: the blood plasma, the extracellular and intracellular fluids, and bone. Bone acts as a calcium storage center for deposits and withdrawals as needed by the blood via continual bone remodeling.

<span class="mw-page-title-main">Hypocalcemia</span> Low calcium levels in ones blood serum

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, while levels less than 2.1 mmol/L are defined as hypocalcemic. Mildly low levels that develop slowly often have no symptoms. Otherwise symptoms may include numbness, muscle spasms, seizures, confusion, or in extreme cases cardiac arrest.

Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range 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 defined as hypercalcemia. Those with a mild increase that has developed slowly typically have no symptoms. In those with greater levels or rapid onset, symptoms may include abdominal pain, bone pain, confusion, depression, weakness, kidney stones or an abnormal heart rhythm including cardiac arrest.

Disorders of calcium metabolism occur when the body has too little or too much calcium. The serum level of calcium is closely regulated within a fairly limited range in the human body. In a healthy physiology, extracellular calcium levels are maintained within a tight range through the actions of parathyroid hormone, vitamin D and the calcium sensing receptor. Disorders in calcium metabolism can lead to hypocalcemia, decreased plasma levels of calcium or hypercalcemia, elevated plasma calcium levels.

<span class="mw-page-title-main">Parathyroid chief cell</span>

Parathyroid chief cells are one of the two cell types of the parathyroid glands, along with oxyphil cells. The chief cells are much more prevalent in the parathyroid gland than the oxyphil cells. It is perceived that oxyphil cells may be derived from chief cells at puberty, as they are not present at birth like chief cells.

<span class="mw-page-title-main">Hyperparathyroidism</span> Increase in parathyroid hormone levels in the blood

Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands or as response to external stimuli. Symptoms of hyperparathyroidism are caused by inappropriately normal or elevated blood calcium excreted from the bones and flowing into the blood stream in response to increased production of parathyroid hormone. In healthy people, when blood calcium levels are high, parathyroid hormone levels should be low. With long-standing hyperparathyroidism, the most common symptom is kidney stones. Other symptoms may include bone pain, weakness, depression, confusion, and increased urination. Both primary and secondary may result in osteoporosis.

<span class="mw-page-title-main">Hyperphosphatemia</span> Excess phosphate in the blood

Hyperphosphatemia is an electrolyte disorder in which there is an elevated level of phosphate in the blood. Most people have no symptoms while others develop calcium deposits in the soft tissue. The disorder is often accompanied by low calcium blood levels, which can result in muscle spasms.

<span class="mw-page-title-main">Parathyroidectomy</span> Surgical removal of one or more of the parathyroid glands

Parathyroidectomy is the surgical removal of one or more of the (usually) four parathyroid glands. This procedure is used to remove an adenoma or hyperplasia of these glands when they are producing excessive parathyroid hormone (PTH): hyperparathyroidism. The glands are usually four in number and located adjacent to the posterior surface of the thyroid gland, but their exact location is variable. When an elevated PTH level is found, a sestamibi scan or an ultrasound may be performed in order to confirm the presence and location of abnormal parathyroid tissue.

The Chvostek sign is a clinical sign that someone may have a low blood calcium level. The Chvostek sign is the abnormal twitching of muscles that are activated (innervated) by the facial nerve. When the facial nerve is tapped in front of the ear, the facial muscles on the same side of the face will contract sporadically. The muscles that control the nose, lips and eyebrows are often the ones that will spasm.

<span class="mw-page-title-main">Primary hyperparathyroidism</span> Excess hormone production by the parathyroid gland

Primary hyperparathyroidism is a medical condition where the parathyroid gland produce excess amounts of parathyroid hormone (PTH). The symptoms of the condition relate to the resulting elevated serum calcium (hypercalcemia), which can cause digestive symptoms, kidney stones, psychiatric abnormalities, and bone disease.

<span class="mw-page-title-main">Thyroid disease</span> Medical condition

Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning that it is an endocrine organ. These hormones normally act in the body to regulate energy use, infant development, and childhood development.

<span class="mw-page-title-main">Osteitis fibrosa cystica</span> Medical condition

Osteitis fibrosa cystica is a skeletal disorder resulting in a loss of bone mass, a weakening of the bones as their calcified supporting structures are replaced with fibrous tissue, and the formation of cyst-like brown tumors in and around the bone. Osteitis fibrosis cystica (OFC), also known as osteitis fibrosa, osteodystrophia fibrosa, and von Recklinghausen's disease of bone, is caused by hyperparathyroidism, which is a surplus of parathyroid hormone from over-active parathyroid glands. This surplus stimulates the activity of osteoclasts, cells that break down bone, in a process known as osteoclastic bone resorption. The hyperparathyroidism can be triggered by a parathyroid adenoma, hereditary factors, parathyroid carcinoma, or renal osteodystrophy. Osteoclastic bone resorption releases minerals, including calcium, from the bone into the bloodstream, causing both elevated blood calcium levels, and the structural changes which weaken the bone. The symptoms of the disease are the consequences of both the general softening of the bones and the excess calcium in the blood, and include bone fractures, kidney stones, nausea, moth-eaten appearance in the bones, appetite loss, and weight loss.

<span class="mw-page-title-main">Secondary hyperparathyroidism</span> Medical condition

Secondary hyperparathyroidism is the medical condition of excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia, with resultant hyperplasia of these glands. This disorder is primarily seen in patients with chronic kidney failure. It is sometimes abbreviated "SHPT" in medical literature.

<span class="mw-page-title-main">Milk-alkali syndrome</span> Medical condition

Milk-alkali syndrome (MAS), also referred to as calcium-alkali syndrome, is the third most common cause of hypercalcemia. Milk-alkali syndrome is characterized by elevated blood calcium levels, metabolic alkalosis, and acute kidney injury.

<span class="mw-page-title-main">Jansen's metaphyseal chondrodysplasia</span> Rare genetic disorder involving dwarfism and endocrine symptoms

Jansen's metaphyseal chondrodysplasia (JMC) is a disease that results from ligand-independent activation of the type 1 (PTH1R) of the parathyroid hormone receptor, due to one of three reported mutations.

<span class="mw-page-title-main">Parathyroid disease</span> Medical condition

Many conditions are associated with disorders of the function of the parathyroid gland. Some disorders may be purely anatomical resulting in an enlarged gland which will raise concern. Such benign disorders, such as parathyroid cyst, are not discussed here. Parathyroid diseases can be divided into those causing hyperparathyroidism, and those causing hypoparathyroidism.

A calcimimetic is a pharmaceutical drug that mimics the action of calcium on tissues, by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues. Calcimimetics are used to treat secondary hyperparathyroidism (SHPT).

Recombinant human parathyroid hormone, sold under the brand name Preotact among others, is an artificially manufactured form of the parathyroid hormone used to treat hypoparathyroidism. Recombinant human parathyroid hormone is used in the treatment of osteoporosis in postmenopausal women at high risk of osteoporotic fractures. A significant reduction in the incidence of vertebral fractures has been demonstrated. It is used in combination with calcium and vitamin D supplements.

References

  1. 1 2 3 4 Bilezikian JP, Khan A, Potts JT, Brandi ML, Clarke BL, Shoback D, et al. (October 2011). "Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research". Journal of Bone and Mineral Research. 26 (10): 2317–2337. doi:10.1002/jbmr.483. PMC   3405491 . PMID   21812031.
  2. ↑ Mannstadt, Michael; Clarke, Bart L; Bilezikian, John P; Bone, Henry; Denham, Douglas; Levine, Michael A; Peacock, Munro; Rothman, Jeffrey; Shoback, Dolores M; Warren, Mark L; Watts, Nelson B; Lee, Hak-Myung; Sherry, Nicole; Vokes, Tamara J (1 November 2019). "Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism". The Journal of Clinical Endocrinology & Metabolism. 104 (11): 5136–5147. doi: 10.1210/jc.2019-01010 . hdl: 1805/22077 .
  3. ↑ Shoback D (July 2008). "Clinical practice. Hypoparathyroidism". The New England Journal of Medicine. 359 (4): 391–403. doi:10.1056/NEJMcp0803050. PMID   18650515.
  4. 1 2 Potts Jr JT (2005). "Diseases of the parathyroid gland". In Kasper DL, Braunwald E, Fauci AS, et al. (eds.). Harrison's Principles of Internal Medicine (16th ed.). New York, NY: McGraw-Hill. pp. 2249–68. ISBN   978-0-07-139140-5.
  5. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Gafni, Rachel I.; Collins, Michael T. (2 May 2019). "Hypoparathyroidism". New England Journal of Medicine. 380 (18): 1738–1747. doi:10.1056/NEJMcp1800213.
  6. ↑ 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.
  7. ↑ Maeda, Sergio S.; Fortes, Erika M.; Oliveira, Ulisses M.; Borba, Victoria C. Z.; Lazaretti-Castro, Marise (August 2006). "Hypoparathyroidism and pseudohypoparathyroidism". Arquivos Brasileiros de Endocrinologia & Metabologia. 50: 664–673. doi: 10.1590/S0004-27302006000400012 . ISSN   1677-9487.
  8. ↑ 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
  9. ↑ 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.
  10. ↑ Edafe O, Mech CE, Balasubramanian SP, et al. (Cochrane Metabolic and Endocrine Disorders Group) (May 2019). "Calcium, vitamin D or recombinant parathyroid hormone for managing post-thyroidectomy hypoparathyroidism". The Cochrane Database of Systematic Reviews. 2019 (5): CD012845. doi:10.1002/14651858.CD012845.pub2. PMC   6530809 . PMID   31116878.
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