• Author: Manish Suneja, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
Updated: Jul 26, 2016

Practice Essentials

The presentations of patients with hypocalcemia vary widely, from asymptomatic to life-threatening situations. Hypocalcemia is frequently encountered in patients who are hospitalized. Depending on the cause, unrecognized or poorly treated hypocalcemic emergencies can lead to significant morbidity or death.

A 70-kg person has approximately 1.2 kg of calcium in the body, more than 99% of which is stored as hydroxyapatite in bones. Less than 1% (5-6 g) of this calcium is located in the intracellular and extracellular compartments, with only 1.3 g located extracellularly. The total calcium concentration in the plasma is 4.5-5.1 mEq/L (9-10.2 mg/dL). Fifty percent of plasma calcium is ionized, 40% is bound to proteins (90% of which binds to albumin), and 10% circulates bound to anions (eg, phosphate, carbonate, citrate, lactate, sulfate).

At a plasma pH of 7.4, each gram of albumin binds 0.8 mg/dL of calcium. This bond is dependent on the carboxyl groups of albumin and is highly dependent on pH. Acute acidemia decreases calcium binding to albumin, whereas alkalemia increases binding, which decreases ionized calcium. Clinical signs and symptoms are observed only with decreases in ionized calcium concentration (normally 4.5-5.5 mg/dL).[1, 2]

Calcium regulation is critical for normal cell function, neural transmission, membrane stability, bone structure, blood coagulation, and intracellular signaling. The essential functions of this divalent cation continue to be elucidated, particularly in head injury/stroke and cardiopulmonary disorders.

Symptomatic patients with classic clinical findings of acute hypocalcemia require immediate resuscitation and evaluation. However, most cases of hypocalcemia are discovered by clinical suspicion and appropriate laboratory testing. (See Presentation and Workup.)

The treatment of hypocalcemia depends on the cause, the severity, the presence of symptoms, and how rapidly the hypocalcemia developed. Most hypocalcemic emergencies are mild and require only supportive treatment and further laboratory evaluation. On occasion, severe hypocalcemia may result in seizures, tetany, refractory hypotension, or arrhythmias that require a more aggressive approach, including intravenous infusions of calcium. (See Treatment and Medication.)

For more information on hypocalcemia, see the Medscape Reference articles Hypocalcemia in Emergency Medicine and Pediatric Hypocalcemia.



Ionized calcium is the necessary plasma fraction for normal physiologic processes. In the neuromuscular system, ionized calcium facilitates nerve conduction, muscle contraction, and muscle relaxation. Calcium is necessary for bone mineralization and is an important cofactor for hormonal secretion in endocrine organs. At the cellular level, calcium is an important regulator of ion transport and membrane integrity.

Calcium turnover is estimated to be 10-20 mEq/day. Approximately 500 mg of calcium is removed from the bones daily and replaced by an equal amount. Normally, the amount of calcium absorbed by the intestines is matched by urinary calcium excretion. Despite these enormous fluxes of calcium, the levels of ionized calcium remain stable because of the rigid control maintained by parathyroid hormone (PTH), vitamin D, and calcitonin through complex feedback loops. These compounds act primarily at bone, renal, and GI sites. Calcium levels are also affected by magnesium and phosphorus.[3]

PTH stimulates osteoclastic bone reabsorption and distal tubular calcium reabsorption and mediates 1,25-dihydroxyvitamin D (1,25[OH]2 D) intestinal calcium absorption.[4] Vitamin D stimulates intestinal absorption of calcium, regulates PTH release by the chief cells, and mediates PTH-stimulated bone reabsorption. Calcitonin lowers calcium by targeting bone, renal, and GI losses.

The parathyroid gland has a remarkable sensitivity to ionized serum calcium changes. These changes are recognized by the calcium-sensing receptor (CaSR), a 7-transmembrane receptor linked to G-protein with a large extracellular amino-terminal region. Binding of calcium to the CaSR induces activation of phospholipase C and inhibition of PTH secretion. On the other hand, a slight decrease in calcium stimulates the chief cells of the parathyroid gland to secrete PTH.

CaSR is crucial in PTH secretion. A loss of CaSR function leads to pathologic states, such as familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. In renal failure, CaSR agonists suppress the progression of hyperparathyroidism and parathyroid gland growth.

Homeostasis is maintained by an extracellular-to-intracellular gradient, which is largely due to abundant high-energy phosphates intracellularly. Intracellular calcium regulates cyclic adenosine monophosphate (cAMP)–mediated messenger systems and most cell organelle functions. Ion pumps control levels. Extracellular calcium levels are maintained at 8.7-10.4 mg/dL. Variations depend on serum pH, protein and anion levels, and calcium-regulating hormone function.

Patients with a decrease in total serum calcium may not have "true" hypocalcemia, which is defined as a decrease in ionized calcium. A reduction in total serum calcium can result from a decrease in albumin secondary to liver disease, nephrotic syndrome, or malnutrition.

Hypocalcemia causes neuromuscular irritability and tetany. Alkalemia induces tetany due to a decrease in ionized calcium, whereas acidemia is protective. This pathophysiology is important in patients with renal failure who have hypocalcemia because rapid correction of acidemia or development of alkalemia may trigger tetany.[5, 6, 7]



The causes of hypocalcemia include the following:

  • Hypoalbuminemia
  • Hypomagnesemia
  • Hyperphosphatemia
  • Multifactorial enhanced protein binding and anion chelation
  • Medication effects
  • Surgical effects
  • PTH deficiency or resistance
  • Vitamin D deficiency or resistance


Hypoalbuminemia is the most common cause of hypocalcemia. Causes include cirrhosis, nephrosis, malnutrition, burns, chronic illness, and sepsis. In patients who are critically ill, low calcium levels can be simply due to hypoalbuminemia, which has no clinical significance because the active fraction (ionized) is not affected. However, to prevent missing a second hypocalcemic disorder, measure the ionized calcium level whenever the albumin level is low.

In a patient with hypocalcemia, measurement of the serum albumin is essential to distinguish true hypocalcemia, which involves a reduction in ionized serum calcium, from factitious hypocalcemia, meaning decreased total, but not ionized, calcium. To correct for hypoalbuminemia, add 0.8 mg/dL to the total serum calcium for each 1.0 g/dL decrease in albumin below 4.0 g/dL.

Parathyroid hormone–related hypocalcemia

Hypoparathyroidism can be hereditary or acquired. The hereditary and acquired varieties share the same symptoms, although hereditary hypoparathyroidism tends to have a gradual onset.[8]

Acquired hypoparathyroidism may result from the following:

  • Neck irradiation/radioiodine therapy [9]
  • Postparathyroidectomy in dialysis patients [10]
  • Inadvertent surgical removal (can be transient or permanent)
  • Infiltrative disease (eg, hemochromatosis, granulomatous disease [sarcoidosis], thalassemia, amyloidosis, or metastatic malignant infiltration

Late-onset hypoparathyroidism can be seen as a part of a complex autoimmune disorder involving ovarian failure and adrenal failure. Mucocutaneous candidiasis, alopecia, vitiligo, and pernicious anemia are associated with this disorder, which is referred to as polyglandular autoimmune disease (PGA I).

Hereditary hypoparathyroidism may be familial or sporadic, and it can occur as an isolated entity or can be associated with other endocrine manifestations. The familial forms include autosomal dominant and autosomal recessive, as well as a sex-linked form of early onset, for which the gene has been located on the long arm of the X chromosome.

Sporadic, late-onset hypoparathyroidism is a feature of several hereditary syndromes. These syndromes, and their associated features, are as follows:

  • DiGeorge syndrome: congenital heart disease, cleft palate/lip, and abnormal facies
  • Kearns-Sayre syndrome: heart block, retinitis pigmentosa, and ophthalmoplegia
  • Kenny-Caffey syndrome: medullary stenosis of the long bones and growth retardation


Pseudohypoparathyroidism is characterized by end-organ resistance to the effects of PTH. PTH binds to the PTH receptor, which, in turn, activates cAMP through guanine nucleotide regulatory proteins (Gs). These proteins consist of alpha, beta, and gamma subunits.

Pseudohypoparathyroidism is classified into types I and II. Type I is further subdivided into Ia, Ib, and Ic.[8]

Type Ia

Type Ia pseudohypoparathyroidism results from a decrease in the Gs-alpha protein. This disorder comprises the biochemical features of pseudohypoparathyroidism along with the following somatic features of Albright hereditary osteodystrophy (AHO):

  • Short stature
  • Mental retardation
  • Obesity
  • Round-shaped face
  • Brachymetacarpia
  • Brachymetatarsia
  • Subcutaneous bone formation

Laboratory findings in AHO include hypocalcemia, hyperphosphatemia (with normal or high PTH levels), and low calcitriol. Vitamin D may be decreased because of inhibition by elevated levels of phosphorus and by decreased PTH stimulation of 25-hydroxyvitamin D 1-alpha-hydroxylase. The low calcitriol levels, in turn, may cause the resistance to the hypercalcemic effects of PTH in the bone.

The defect of the Gs-alpha protein is not confined to the effects of PTH but also affects other hormonal systems (eg, resistance to glucagon, thyroid-stimulating hormone, gonadotropins). The gene for the Gs-alpha protein is located on chromosome 20. Some family members carry the mutation and display the AHO phenotype but do not have pseudohypoparathyroidism. This is termed pseudo-pseudohypoparathyroidism.

Types Ib and Ic

In type Ib pseudohypoparathyroidism, patients do not present with the somatic features of AHO. These patients have normal Gs-alpha protein, with hormonal resistance to PTH—an impaired cAMP response to PTH, suggesting that the defect lies on the receptor. At what level the receptor is affected is not yet clear.

In type Ic pseudohypoparathyroidism, patients present with resistance to multiple hormonal receptors. However, Gs-alpha protein expression is normal.

Type II

In type II pseudohypoparathyroidism, PTH raises cAMP normally but fails to increase levels of serum calcium or urinary phosphate excretion, suggesting that the defect is located downstream of the generation of cAMP. These patients present with hypocalcemia, hypophosphaturia, and elevated immunoreactive PTH (iPTH) levels. These findings also occur in vitamin D deficiency, but in patients with a vitamin D deficiency, all parameters return to normal after vitamin D administration.


Severe hypomagnesemia can lead to hypocalcemia that is resistant to the administration of calcium and vitamin D. The usual cause of hypomagnesemia is loss via the kidneys (eg, osmotic diuresis, drugs) or the gastrointestinal tract (eg, chronic diarrhea, severe pancreatitis, bypass or resection of small bowel). These patients present with low or inappropriately normal PTH levels in the presence of hypocalcemia.

The mechanism of hypocalcemia includes resistance to PTH in the bone and kidneys, as well as a decrease in PTH secretion. Acute magnesium restoration rapidly corrects the PTH level, suggesting the hypomagnesemia affects the release of PTH, rather than its synthesis.

Vitamin D deficiency

Vitamin D is a necessary cofactor for the normal response to PTH, and vitamin D deficiency renders PTH ineffective. Poor nutritional intake, chronic renal insufficiency, or reduced exposure to sunlight may cause vitamin D deficiency.

Current Recommended Dietary Allowances (RDAs) for vitamin D are 600 IU of vitamin D per day for adults for individuals from 1 to 70 years of age and 800 IU per day for those over 70 years.[11] Studies have demonstrated that despite adequate intake, that vitamin D insufficiency can still occur and lead to an increased PTH and subsequent bone turnover. Studies have also shown that dietary intake of vitamin D varies greatly by race and age. In a review of National Health and Nutrition Examination Survey (NHANES) III data from 2001-2006, 32% of African-American women were at risk for vitamin D deficiency—defined as serum 25-hydroxyvitamin D (24[OH]D) levels <30 nmol/L—as compared with only 3% of white women.[12]

An observational study in elderly adults found that 74% of those studied were deficient in vitamin D, defined as 25(OH)D concentrations <32 ng/mL, despite intake of more than 400-600 IU/d, which was the recommended RDA at the time.[13] The authors of this study suggested that elderly individuals may require as much as 1000 IU per day.

Mild hypovitaminosis D may not be trivial. In an elderly population with an increased PTH and osteoporosis, response to alendronate was attenuated. This attenuation was improved when vitamin D was administered.[14, 15]

Impaired absorption

Numerous conditions can impair the absorption of vitamin D. Small bowel diseases, such as celiac disease, gastric bypass (particularly long limb Roux-en-Y gastric bypass), steatorrhea, and pancreatic diseases can all lead to low vitamin D levels.[16]

Pseudovitamin D deficiency rickets

This condition is secondary to an autosomal mutation of the 1-hydroxylase gene. Ultimately, calcidiol is not hydroxylated to calcitriol, and calcium is not absorbed appropriately. This condition is considered a pseudovitamin D deficiency because high doses of vitamin D can overcome the clinical and biochemical findings of this disease.

Hereditary vitamin D resistance rickets

This condition is extremely rare and is caused by a mutation in the vitamin D receptor. Typically, this condition presents within the first 2 years of life.

Hepatic disease

Liver disease with decreased synthetic function can cause vitamin D deficiency from several sources, as follows:

  • Impaired 25-hydroxylation of vitamin D
  • Decreased bile salts with malabsorption of vitamin D
  • Decreased synthesis of vitamin D–binding protein
  • Other factors

Patients with cirrhosis and osteomalacia have low or normal levels of calcitriol, suggesting that other factors may interfere with vitamin D function or are synergistic with malabsorption or decreased sun exposure. These patients require administration of calcidiol or calcitriol for the treatment of hypocalcemia.

Renal failure

Chronic kidney disease leads to a decrease in the conversion of 25-hydroxyvitamin D to its active form 1,25-dihydroxyvitamin D, particularly when the glomerular filtration rate (GFR) falls below 30 mL/min. This results in an increase in PTH. Ultimately, the increased absorption of phosphorus and calcium can lead to calcium-phosphorus mineral deposition in the soft tissues. In the early stages of renal failure, hypocalcemia can occur because of the decrease in calcitriol production and a subsequent decrease in the intestinal absorption of calcium.

Hungry bone syndrome

Surgical correction of primary or secondary hyperparathyroidism may be associated with severe hypocalcemia due to a rapid increase in bone remodeling. Hypocalcemia results if the rate of skeletal mineralization exceeds the rate of osteoclast-mediated bone resorption.

A less severe picture is also observed after correction of thyrotoxicosis, after institution of vitamin D therapy for osteomalacia, and with tumors associated with bone formation (eg, prostate, breast, leukemia). All of these disease states result in hypocalcemia due to mineralization of large amounts of unmineralized osteoid.[17]

Acute pancreatitis

Pancreatitis can be associated with tetany and hypocalcemia. It is caused primarily by precipitation of calcium soaps in the abdominal cavity, but glucagon-stimulated calcitonin release and decreased PTH secretion may play a role.

When the pancreas is damaged, free fatty acids are generated by the action of pancreatic lipase. Insoluble calcium salts are present in the pancreas, and the free fatty acids avidly chelate the salts, resulting in calcium deposition in the retroperitoneum. In addition, hypoalbuminemia may be a part of the clinical picture, resulting in a reduction in total serum calcium. In patients with concomitant alcohol abuse, a poor nutritional intake of calcium and vitamin D, as well as accompanying hypomagnesemia, may predispose these patients to hypocalcemia.[18]


Hyperphosphatemia may be seen in critical illness and in patients who have ingested phosphate-containing enemas. Phosphate binds calcium avidly, causing acute hypocalcemia. Acute hypocalcemia secondary to hyperphosphatemia may also result from renal failure or excess tissue breakdown because of rhabdomyolysis or tumor lysis.

In acute hyperphosphatemia, calcium is deposited mostly in the bone but also in the extraskeletal tissue. In contrast, in chronic hyperphosphatemia, which is nearly always from chronic renal failure, calcium efflux from the bone is inhibited and the calcium absorption is low, because of reduced renal synthesis of 1,25-dihydroxyvitamin D. However, other consequences of renal failure, including a primary impairment in calcitriol synthesis, also contribute to hypocalcemia.


Patients receiving the calcimimetic agent cinacalcet to help control secondary hyperparathyroidism in renal failure may experience hypocalcemia as a result of acute inhibition of PTH release. Clinically significant hypocalcemia occurs in approximately 5% of patients treated with cinacalcet.[19]

Hypocalcemia can also occur in patients treated with some chemotherapeutic drugs. For example, cisplatin can induce hypocalcemia by causing hypomagnesemia, and combination therapy with 5-fluorouracil and leucovorin can cause mild hypocalcemia (65% of patients in one series), possibly by decreasing calcitriol production.[20]

Hypocalcemia may result from the treatment of hypercalcemia with bisphosphonates, particularly zoledronic acid, which is significantly more potent than other bisphosphonates in suppressing the formation and function of osteoclasts. Patients who are affected appear to lack an adequate PTH response to decreasing serum calcium levels.[21]

Hypocalcemia and osteomalacia have been described with prolonged therapy with anticonvulsants (eg, phenytoin, phenobarbital).[22] The mechanisms differ according to the class of anticonvulsants; for example, phenytoin induces cytochrome P450 enzymes and enhances vitamin D catabolism.

Foscarnet is a drug used to treat refractory cytomegalovirus and herpes infections in patients who are immunocompromised, and it complexes ionized calcium and, therefore, lowers ionized calcium concentrations, potentially causing symptomatic hypocalcemia. Therefore, the ionized calcium concentration should be measured at the end of an infusion of foscarnet.

Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor kappaB ligand (RANKL), an osteoclast differentiating factor. It inhibits osteoclast formation, decreases bone resorption, increases bone mineral density (BMD), and reduces the risk of fracture. See the Fracture Index WITH known Bone Mineral Density (BMD) calculator.

In the denosumab trials, all women were supplemented with daily calcium (1000 mg) and vitamin D (400-800 U). A small proportion of women in the denosumab trials had a decrease in the serum calcium level to less than 8.5 mg/dL. However, in patients with conditions that predispose to hypocalcemia, such as chronic kidney disease, malabsorption syndromes, or hypoparathyroidism, symptomatic hypocalcemia may occur. The nadir in serum calcium occurs approximately 10 days after administration. Thus, denosumab should not be given to patients with preexisting hypocalcemia until it is corrected. In addition, patients with conditions predisposing to hypocalcemia (ie, chronic kidney disease and creatinine clearance < 30 mL/min) should be monitored for hypocalcemia.[23]

Symptomatic hypocalcemia during transfusion of citrated blood or plasma is rare, because healthy patients rapidly metabolize citrate in the liver and kidney. However, a clinically important fall in serum ionized calcium concentration can occur if citrate metabolism is impaired due to hepatic or renal failure or if large quantities of citrate are given rapidly, for example, during plasma exchange or massive blood transfusion.

Sodium phosphate preparations, which come in aqueous and tablet forms, are used to cleanse the bowel prior to GI procedures such as colonoscopy. In certain populations, these agents can lead to acute hyperphosphatemia and subsequent hypocalcemia.[24, 25] Risk factors include the following:

  • Renal failure
  • Advanced age
  • Chronic heart failure
  • Hepatic insufficiency
  • Volume depletion
  • Use of angiotensin-converting enzyme (ACE) inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDS)

Some radiographic contrast dyes may contain ethylenediaminetetraacetic acid (EDTA), which chelates calcium in serum, thereby reducing serum ionized calcium concentration, resulting in hypocalcemia. Gadolinium-based contrast material can falsely lower serum calcium levels and should be considered if levels are drawn shortly after magnetic resonance imaging.

Rarely, an excess intake of fluoride can cause hypocalcemia; this effect is presumably mediated by inhibition of bone resorption. Overfluorinated public water supplies and ingestion of fluoride-containing cleaning agents have been associated with low serum calcium levels. In this case, hypocalcemia is thought to be due to excessive rates of skeletal mineralization secondary to formation of calcium difluoride complex.

Proton pump inhibitors (PPIs) and histamine-2 receptor blockers (eg, cimetidine) reduce gastric acid production; this slows fat breakdown, which is necessary to complex calcium for gut absorption. An association with these medicines and an increased risk for hip fractures in elderly patients has been made because of decreased calcium absorption.

Other medication effects that may lead to hypocalcemia are as follows:

  • Calcitonin and bisphosphonates cause chelation and end-organ inhibition
  • Ethylene glycol complexes with calcium
  • Estrogen inhibits bone resorption
  • Aluminum and alcohol suppress PTH

Enhanced protein binding and anion chelation

Protein binding is enhanced by elevated pH and free fatty acid release in high catecholamine states. Anion chelation is seen in high phosphate states (eg, renal failure, rhabdomyolysis, mesenteric ischemia, oral administration of phosphate-containing enemas); high citrate states (eg, massive blood transfusion, radiocontrast dyes); and high bicarbonate, lactate, and oxalate levels.

Hypocalcemia in the ED

Multifactorial causes are probably the most clinically relevant in hypocalcemic emergencies in the emergency department (ED). These include the following:

  • Rhabdomyolysis: increased phosphates from creatine phosphokinase (CPK) and other anions (ie, lactate, bicarbonate) chelate calcium
  • Toxic shock syndrome can cause hypocalcemia
  • High calcitonin levels cause low calcium
  • Malignancy: osteoblastic metastases (eg, breast cancer, prostate cancer) and tumor lysis syndrome may cause hypocalcemia (by differing mechanisms)
  • Infiltrative disease: sarcoidosis, tuberculosis, and hemochromatosis may infiltrate the parathyroids, causing dysfunction
  • Toxicologic causes include hydrofluoric acid burn or ingestion
  • Trauma patients with massive transfusion will have hemostasis impairment as one effect of hypocalcemia [26]

Critical illness and severe sepsis

Acute illness may lead to hypocalcemia for multiple reasons. In one study, the 3 most common factors identified in patients with hypocalcemia associated with acute illness were hypomagnesemia, acute renal failure, and transfusions.

In gram-negative sepsis, there is a reduction in total and ionized serum calcium. The mechanism for this remains unknown, but it appears to be associated with multiple factors, including elevated levels of cytokines (eg, interleukin-6, interleukin-1, TNF-alpha), hypoparathyroidism, and vitamin D deficiency or resistance.

Mortality rates are increased in patients with sepsis and hypocalcemia, compared with patients who are normocalcemic.[27, 28] However, there is no clear evidence that treating critically ill patients with supplemental calcium alters outcomes.[29]

Postsurgical effects

The following surgical procedures may result in hypocalcemia:

  • Parathyroid adenoma resection causes a transient hypocalcemia due to end-organ PTH resistance in the first postoperative day; in addition, vascular/parathyroid injury may occur as an operative mishap
  • Pancreatectomy prevents calcium absorption in the duodenum and the jejunum by eliminating necessary enzymes
  • Bowel resection may cause hypocalcemia by reducing the surface available to absorb fatty acids and calcium


Epidemiologic studies of hypocalcemia versus other electrolyte abnormalities have not been performed. During the last 20 years, laboratory tests have quantified serum and ionized calcium and PTH levels, enabling easier diagnosis. The incidence of ionized hypocalcemia is difficult to quantify. In intensive care patients, reported rates have ranged from 15-88%.[30] A systematic review and meta-analysis of hypocalcemia after thyroidectomy found that the median incidence of transient hypocalcaemia was 27% (range, 19-38%) and that of permanent hypocalcemia was 1% (range, 0-3%).[31]   In a series of 500 postsurgical patients operated on for hyperparathyroidism, 2% had permanent hypocalcemia.[32]

In order of frequency, hypocalcemia occurs in the following settings:

  • Chronic and acute renal failure
  • Vitamin D deficiency
  • Magnesium deficiency
  • Acute pancreatitis
  • Hypoparathyroidism and pseudohypoparathyroidism
  • Infusion of phosphate, citrate, or calcium-free albumin

Death is rare but has been reported. The disease causing hypocalcemia may have greater impact on morbidity than hypocalcemia itself.

Complications of chronic hypocalcemia predominantly are those of bone disease. In addition, severe hypocalcemia may result in cardiovascular collapse, hypotension unresponsive to fluids and vasopressors, and dysrhythmias. Some patients may manifest digitalis insensitivity. Neurologic complications of hypocalcemia include acute seizures or tetany, basal ganglia calcification, parkinsonism, hemiballismus, and choreoathetosis. Although some patients with hypocalcemia may improve with treatment, the calcification typically is not reversible.

The age distribution of hypocalcemia is contingent on the underling disorder. In children, nutritional deficiencies are more frequent; in adults, renal failure predominates. However, the recognition of the high prevalence of vitamin D deficiency, particularly in elderly patients, may change the understanding of hypocalcemia in the general population.

Contributor Information and Disclosures

Manish Suneja, MD Associate Professor, Department of Internal Medicine, Division of Nephrology, University of Iowa Hospitals and Clinics

Manish Suneja, MD is a member of the following medical societies: American College of Physicians, American Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.


Heather A Muster, MD, MS Medical Director, Davita Clinical Research

Heather A Muster, MD, MS is a member of the following medical societies: American College of Physicians, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Minnesota Medical Association, National Kidney Foundation

Disclosure: Nothing to disclose.

Specialty Editor Board

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, International Society of Nephrology, American Society for Biochemistry and Molecular Biology, American Federation for Medical Research, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, Kentucky Medical Association, National Kidney Foundation, Phi Beta Kappa

Disclosure: Received grant/research funds from Dept of Veterans Affairs for research; Received salary from American Society of Nephrology for asn council position; Received salary from University of Louisville for employment; Received salary from University of Louisville Physicians for employment; Received contract payment from American Physician Institute for Advanced Professional Studies, LLC for independent contractor; Received contract payment from Healthcare Quality Strategies, Inc for independent cont.

Chief Editor

Vecihi Batuman, MD, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.


Jeffrey L Arnold, MD, FACEP Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center

Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians

Disclosure: Nothing to disclose.

Christopher B Beach, MD, FACEP, FAAEM Associate Professor and Vice Chair of Emergency Medicine, Department of Emergency Medicine, Associate Professor of Institute for Healthcare Studies, Institute for Patient Safety, Feinberg School of Medicine, Northwestern University

Christopher B Beach, MD, FACEP, FAAEM is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Robin R Hemphill, MD, MPH Associate Professor, Director, Quality and Safety, Department of Emergency Medicine, Emory University

Robin R Hemphill, MD, MPH is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Eleanor Lederer, MD Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa

Disclosure: Dept of Veterans Affairs Grant/research funds Research

James W Lohr, MD Professor, Department of Internal Medicine, Division of Nephrology, Fellowship Program Director, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, and Central Society for Clinical Research

Disclosure: Genzyme Honoraria Speaking and teaching

Alfredo A Pegoraro, MD Consulting Staff, Nephrology Associates

Alfredo A Pegoraro, MD is a member of the following medical societies: American Medical Assocation, American Society of Nephrology, and International Society of Nephrology

Disclosure: Nothing to disclose.

Erik D Schraga, MD Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

  1. Levine BA, Williams RP. Calcium binding to proteins and other large biological anion centers. Academic Press. 1982. II:1.

  2. Pedersen KO. Binding of calcium to serum albumin. I. Stoichiometry and intrinsic association constant at physiological pH, ionic strength, and temperature. Scand J Clin Lab Invest. 1971 Dec. 28(4):459-69. [Medline].

  3. Sarko J. Bone and mineral metabolism. Emerg Med Clin North Am. 2005 Aug. 23(3):703-21, viii. [Medline].

  4. Hofer AM, Brown EM. Extracellular calcium sensing and signalling. Nat Rev Mol Cell Biol. 2003 Jul. 4(7):530-8. [Medline].

  5. Mundy GR, Guise TA. Hormonal control of calcium homeostasis. Clin Chem. 1999 Aug. 45(8 Pt 2):1347-52. [Medline].

  6. Silver J, Yalcindag C, Sela-Brown A, Kilav R, Naveh-Many T. Regulation of the parathyroid hormone gene by vitamin D, calcium and phosphate. Kidney Int Suppl. 1999 Dec. 73:S2-7. [Medline].

  7. Yamamoto M, Kawanobe Y, Takahashi H, Shimazawa E, Kimura S, Ogata E. Vitamin D deficiency and renal calcium transport in the rat. J Clin Invest. 1984 Aug. 74(2):507-13. [Medline].

  8. Shoback D. Clinical practice. Hypoparathyroidism. N Engl J Med. 2008 Jul 24. 359(4):391-403. [Medline].

  9. Burch WM, Posillico JT. Hypoparathyroidism after I-131 therapy with subsequent return of parathyroid function. J Clin Endocrinol Metab. 1983 Aug. 57(2):398-401. [Medline].

  10. Cruz DN, Perazella MA. Biochemical aberrations in a dialysis patient following parathyroidectomy. Am J Kidney Dis. 1997 May. 29(5):759-62. [Medline].

  11. Vitamin D. National Institutes of Health. Available at https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/#h2. February 11, 2016; Accessed: July 21, 2016.

  12. Looker AC, Johnson CL, Lacher DA, Pfeiffer CM, Schleicher RL, Sempos CT. Vitamin D status: United States, 2001-2006. NCHS Data Brief. 2011 Mar. 30(5):1-8. [Medline]. [Full Text].

  13. Linnebur SA, Vondracek SF, Vande Griend JP, Ruscin JM, McDermott MT. Prevalence of vitamin D insufficiency in elderly ambulatory outpatients in Denver, Colorado. Am J Geriatr Pharmacother. 2007 Mar. 5(1):1-8. [Medline].

  14. Barone A, Giusti A, Pioli G, Girasole G, Razzano M, Pizzonia M, et al. Secondary hyperparathyroidism due to hypovitaminosis D affects bone mineral density response to alendronate in elderly women with osteoporosis: a randomized controlled trial. J Am Geriatr Soc. 2007 May. 55(5):752-7. [Medline].

  15. Beckerman P, Silver J. Vitamin D and the parathyroid. Am J Med Sci. 1999 Jun. 317(6):363-9. [Medline].

  16. Johnson JM, Maher JW, DeMaria EJ, Downs RW, Wolfe LG, Kellum JM. The long-term effects of gastric bypass on vitamin D metabolism. Ann Surg. 2006 May. 243(5):701-4; discussion 704-5. [Medline].

  17. Brasier AR, Nussbaum SR. Hungry bone syndrome: clinical and biochemical predictors of its occurrence after parathyroid surgery. Am J Med. 1988 Apr. 84(4):654-60. [Medline].

  18. Dettelbach MA, Deftos LJ, Stewart AF. Intraperitoneal free fatty acids induce severe hypocalcemia in rats: a model for the hypocalcemia of pancreatitis. J Bone Miner Res. 1990 Dec. 5(12):1249-55. [Medline].

  19. Szczech LA. The impact of calcimimetic agents on the use of different classes of phosphate binders: results of recent clinical trials. Kidney International. 2004. 90:S46-48.

  20. Kido Y, Okamura T, Tomikawa M, Yamamoto M, Shiraishi M, Okada Y. Hypocalcemia associated with 5-fluorouracil and low dose leucovorin in patients with advanced colorectal or gastric carcinomas. Cancer. 1996 Oct 15. 78(8):1794-7. [Medline].

  21. Recker RR, Lewiecki EM, Miller PD, Reiffel J. Safety of bisphosphonates in the treatment of osteoporosis. Am J Med. 2009 Feb. 122(2 Suppl):S22-32. [Medline].

  22. Stamp TC, Round JM, Rowe DJ, Haddad JG. Plasma levels and therapeutic effect of 25-hydroxycholecalciferol in epileptic patients taking anticonvulsant drugs. Br Med J. 1972 Oct 7. 4(5831):9-12. [Medline].

  23. McCormick BB, Davis J, Burns KD. Severe hypocalcemia following denosumab injection in a hemodialysis patient. Am J Kidney Dis. 2012 Oct. 60(4):626-8. [Medline].

  24. Dykes C, Cash BD. Key safety issues of bowel preparations for colonoscopy and importance of adequate hydration. Gastroenterol Nurs. 2008 Jan-Feb. 31(1):30-5; quiz 36-7. [Medline].

  25. Niemeijer ND, Rijk MC, van Guldener C. Symptomatic hypocalcemia after sodium phosphate preparation in an adult with asymptomatic hypoparathyroidism. Eur J Gastroenterol Hepatol. 2008 Apr. 20(4):356-8. [Medline].

  26. Lier H, Krep H, Schroeder S, Stuber F. Preconditions of hemostasis in trauma: a review. The influence of acidosis, hypocalcemia, anemia, and hypothermia on functional hemostasis in trauma. J Trauma. 2008 Oct. 65(4):951-60. [Medline].

  27. Desai TK, Carlson RW, Geheb MA. Prevalence and clinical implications of hypocalcemia in acutely ill patients in a medical intensive care setting. Am J Med. 1988 Feb. 84(2):209-14. [Medline].

  28. Zivin JR, Gooley T, Zager RA, Ryan MJ. Hypocalcemia: a pervasive metabolic abnormality in the critically ill. Am J Kidney Dis. 2001 Apr. 37(4):689-98. [Medline].

  29. Forsythe RM, Wessel CB, Billiar TR, Angus DC, Rosengart MR. Parenteral calcium for intensive care unit patients. Cochrane Database Syst Rev. 2008. (4):CD006163. [Medline].

  30. Steele T, Kolamunnage-Dona R, Downey C, Toh CH, Welters I. Assessment and clinical course of hypocalcemia in critical illness. Crit Care. 2013 Jun 4. 17 (3):R106. [Medline].

  31. Edafe O, Antakia R, Laskar N, Uttley L, Balasubramanian SP. Systematic review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia. Br J Surg. 2014 Mar. 101 (4):307-20. [Medline].

  32. Russell CF, Edis AJ. Surgery for primary hyperparathyroidism: experience with 500 consecutive cases and evaluation of the role of surgery in the asymptomatic patient. Br J Surg. 1982 May. 69(5):244-7. [Medline].

  33. Hurley K, Baggs D. Hypocalcemic cardiac failure in the emergency department. J Emerg Med. 2005 Feb. 28(2):155-9. [Medline].

  34. Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ. 2008 Jun 7. 336(7656):1298-302. [Medline].

  35. Kaye M, Somerville PJ, Lowe G, Ketis M, Schneider W. Hypocalcemic tetany and metabolic alkalosis in a dialysis patient: an unusual event. Am J Kidney Dis. 1997 Sep. 30(3):440-4. [Medline].

  36. Eraut D. Idiopathic hypoparathyroidism presenting as dementia. Br Med J. 1974 Mar 9. 1(5905):429-30. [Medline].

  37. Murphy G, Bartle S. Hypocalcemic laryngospasm and tetany in a child with renal dysplasia. Pediatr Emerg Care. 2006 Jul. 22(7):507-9. [Medline].

  38. Soffer D, Licht A, Yaar I, Abramsky O. Paroxysmal choreoathetosis as a presenting symptom in idiopathic hypoparathyroidism. J Neurol Neurosurg Psychiatry. 1977 Jul. 40(7):692-4. [Medline].

  39. Doorenbos CJ, Ozyilmaz A, van Wijnen M. Severe pseudohypocalcemia after gadolinium-enhanced magnetic resonance angiography. N Engl J Med. 2003 Aug 21. 349(8):817-8. [Medline].

  40. Mark PB, Mazonakis E, Shapiro D, Spooner RJ, Stuart C Rodger R. Pseudohypocalcaemia in an elderly patient with advanced renal failure and renovascular disease. Nephrol Dial Transplant. 2005 Jul. 20(7):1499-500. [Medline].

  41. Prince MR, Choyke PL, Knopp MV. More on pseudohypocalcemia and gadolinium-enhanced MRI. N Engl J Med. 2004 Jan 1. 350(1):87-8; author reply 87-8. [Medline].

  42. Zhang Z, Xu X, Ni H, Deng H. Predictive value of ionized calcium in critically ill patients: an analysis of a large clinical database MIMIC II. PLoS One. 2014. 9 (4):e95204. [Medline]. [Full Text].

  43. Aberegg SK. Ionized Calcium in the ICU: Should It Be Measured and Corrected?. Chest. 2016 Mar. 149 (3):846-55. [Medline].

  44. Zhang Z, Chen K, Ni H. Calcium supplementation improves clinical outcome in intensive care unit patients: a propensity score matched analysis of a large clinical database MIMIC-II. Springerplus. 2015. 4:594. [Medline]. [Full Text].

  45. Mannstadt M, Clarke BL, Vokes T, Brandi ML, Ranganath L, Fraser WD, et al. Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study. Lancet Diabetes Endocrinol. 2013 Dec. 1(4):275-83. [Medline].

  46. Jung RT, Davie M, Hunter JO, Chalmers TM. Ultraviolet light: an effective treatment of osteomalacia in malabsorption. Br Med J. 1978 Jun 24. 1(6128):1668-9. [Medline].

  47. Norman JG, Politz DE. Safety of immediate discharge after parathyroidectomy: a prospective study of 3,000 consecutive patients. Endocr Pract. 2007 Mar-Apr. 13(2):105-13. [Medline].

Electrocardiogram (ECG) findings in severe hypocalcemia.
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