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Disorders of calcium metabolism | |
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Calcium | |
Specialty | Endocrinology |
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. [1] Disorders in calcium metabolism can lead to hypocalcemia, decreased plasma levels of calcium or hypercalcemia, elevated plasma calcium levels.
Hypocalcemia is common and can occur unnoticed with no symptoms or, in severe cases, can have dramatic symptoms and be life-threatening. [1] Hypocalcemia can be parathyroid related or vitamin D related. Parathyroid related hypocalcemia includes post-surgical hypoparathyroidism, inherited hypoparathyroidism, pseudohypoparathyroidism, and pseudo-pseudohypoparathyroidism. [1] Post-surgical hypoparathyroidism is the most common form, and can be temporary (due to suppression of tissue after removal of a malfunctioning gland) or permanent, if all parathyroid tissue has been removed. [1] Inherited hypoparathyroidism is rare and is due to a mutation in the calcium sensing receptor. Pseudohypoparathyroidism is maternally inherited and is categorized by hypocalcemia and hyperphosphatemia. Finally, pseudo-pseudohypoparathyroidism is paternally inherited. Patients display normal parathyroid hormone action in the kidney, but exhibit altered parathyroid hormone action in the bone. [1] Vitamin D related hypocalcemia may be associated with a lack of vitamin D in the diet, a lack of sufficient UV exposure, or disturbances in renal function. Low vitamin D in the body can lead to a lack of calcium absorption and secondary hyperparathyroidism (hypocalcemia and raised parathyroid hormone). [1] Symptoms of hypocalcemia include numbness in fingers and toes, muscle cramps, irritability, impaired mental capacity and muscle twitching. [1]
Hypercalcemia is suspected to occur in approximately 1 in 500 adults in the general adult population. [2] Like hypocalcemia, hypercalcemia can be non-severe and present with no symptoms, or it may be severe, with life-threatening symptoms. Hypercalcemia is most commonly caused by hyperparathyroidism and by malignancy, and less commonly by vitamin D intoxication, familial hypocalciuric hypercalcemia and by sarcoidosis. [2] Hyperparathyroidism occurs most commonly in postmenopausal women. Hyperparathyroidism can be caused by a tumor, or adenoma, in the parathyroid gland or by increased levels of parathyroid hormone due to hypocalcemia. [2] Approximately 10% of individuals with cancer experience hypercalcemia due to malignancy. [2] Hypercalcemia occurs most commonly in breast cancer, lymphoma, prostate cancer, thyroid cancer, lung cancer, myeloma, and colon cancer. [2] It may be caused by secretion of parathyroid hormone-related peptide by the tumor (which has the same action as parathyroid hormone), or may be a result of direct invasion of the bone, causing calcium release. [2] Symptoms of hypercalcemia include anorexia, nausea, vomiting, constipation, abdominal pain, lethargy, depression, confusion, polyuria, polydipsia and generalized aches and pains. [2]
The amount of biologically active calcium varies with the level of serum albumin, a protein to which calcium is bound, and therefore levels of ionized calcium are better measures than a total calcium; however, one can correct a total calcium if the albumin level is known.[ citation needed ]
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.
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.
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.
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, 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. Additionally, medications such as recombinant human parathyroid hormone or teriparatide may be given by injection to replace the missing hormone.
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.
Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, fluid balance, oxygen delivery, acid–base balance and much more. Electrolyte imbalances can develop by consuming too little or too much electrolyte as well as excreting too little or too much electrolyte. Examples of electrolytes include calcium, chloride, magnesium, phosphate, potassium, and sodium.
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.
Cinacalcet, sold under the brand name Sensipar among others, is a medication used to treat primary hyperparathyroidism, tertiary hyperparathyroidism and parathyroid carcinoma. Cinacalcet acts as a calcimimetic by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues.
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.
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.
Pseudohypoparathyroidism is a rare autosomal dominant genetic condition associated primarily with resistance to the parathyroid hormone. Those with the condition have a low serum calcium and high phosphate, but the parathyroid hormone level (PTH) is inappropriately high. Its pathogenesis has been linked to dysfunctional G proteins. Pseudohypoparathyroidism is a very rare disorder, with estimated prevalence between 0.3 and 1.1 cases per 100,000 population depending on geographic location.
Tertiary hyperparathyroidism is a condition involving the overproduction of the hormone, parathyroid hormone, produced by the parathyroid glands. The parathyroid glands are involved in monitoring and regulating blood calcium levels and respond by either producing or ceasing to produce parathyroid hormone.
Paricalcitol (chemically it is 19-nor-1,25-(OH)2-vitamin D2. Marketed by Abbott Laboratories under the trade name Zemplar) is a drug used for the prevention and treatment of secondary hyperparathyroidism (excessive secretion of parathyroid hormone) associated with chronic kidney failure. It is an analog of 1,25-dihydroxyergocalciferol, the active form of vitamin D2 (ergocalciferol).
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.
Familial hypocalciuric hypercalcemia (FHH) is an inherited condition that can cause hypercalcemia, a serum calcium level typically above 10.2 mg/dL; although uncommon. It is also known as familial benign hypocalciuric hypercalcemia (FBHH) where there is usually a family history of hypercalcemia which is mild, a urine calcium to creatinine ratio <0.01, and urine calcium <200 mg/day (hypocalciuria).
Neonatal hypocalcemia is an abnormal clinical and laboratory hypocalcemia condition that is frequently observed in infants. It is commonly presented within the first 72 hours of a newborn's life. Neonatal hypocalcemia can cause seizures in infants requiring a calcium infusion until homeostasis is achieved; allowing for positive clinical outcomes within weeks of treatment.
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.
Palopegteriparatide, sold under the brand name Yorvipath, is a hormone replacement therapy used for the treatment of hypoparathyroidism. It is a transiently pegylated parathyroid hormone. It is a parathyroid hormone analog.