Skip to Content



James L. Lewis III

, MD, Brookwood Baptist Health and Saint Vincent’s Ascension Health, Birmingham

Last full review/revision Apr 2020| Content last modified Apr 2020

Hypocalcemia is a total serum calcium concentration < 8.8 mg/dL (< 2.20 mmol/L) in the presence of normal plasma protein concentrations or a serum ionized calcium concentration < 4.7 mg/dL (< 1.17 mmol/L). Causes include hypoparathyroidism, vitamin D deficiency, and renal disease. Manifestations include paresthesias, tetany, and, when severe, seizures, encephalopathy, and heart failure. Diagnosis involves measurement of serum calcium with adjustment for serum albumin concentration. Treatment is administration of calcium, sometimes with vitamin D.

(See also Overview of Disorders of Calcium Concentration and Hypocalcemia in neonates.)

Etiology of Hypocalcemia

Hypocalcemia has a number of causes, including

  • Hypoparathyroidism
  • Pseudohypoparathyroidism
  • Vitamin D deficiency and dependency
  • Renal disease


Hypoparathyroidism is characterized by hypocalcemia and hyperphosphatemia and often causes chronic tetany. Hypoparathyroidism results from deficient parathyroid hormone (PTH), which can occur in autoimmune disorders or after the accidental removal of or damage to several parathyroid glands during thyroidectomy. Transient hypoparathyroidism is common after subtotal thyroidectomy, but permanent hypoparathyroidism occurs after < 3% of such thyroidectomies done by experienced surgeons. Manifestations of hypocalcemia usually begin about 24 to 48 hours postoperatively but may occur after months or years. PTH deficiency is more common after radical thyroidectomy for cancer or as the result of surgery on the parathyroid glands (subtotal or total parathyroidectomy). Risk factors for severe hypocalcemia after subtotal parathyroidectomy include

  • Severe preoperative hypercalcemia
  • Removal of a large adenoma
  • Elevated alkaline phosphatase
  • Chronic kidney disease

Idiopathic hypoparathyroidism is an uncommon sporadic or inherited condition in which the parathyroid glands are absent or atrophied. It manifests in childhood. The parathyroid glands are occasionally absent and thymic aplasia and abnormalities of the arteries arising from the brachial arches (DiGeorge syndrome) are present. Other inherited forms include polyglandular autoimmune failure syndrome, autoimmune hypoparathyroidism associated with mucocutaneous candidiasis, and X-linked recessive idiopathic hypoparathyroidism.


Pseudohypoparathyroidism is an uncommon group of disorders characterized not by hormone deficiency but by target organ resistance to PTH. Complex genetic transmission of these disorders occurs.

Type Ia pseudohypoparathyroidism (Albright hereditary osteodystrophy) is caused by a mutation in the stimulatory Gs-alpha1 protein of the adenylyl cyclase complex (GNAS1). The result is failure of normal renal phosphaturic response or increase in urinary cAMP (cyclic adenosine monophosphate) to PTH. Patients are usually hypocalcemic and hyperphosphatemic. Secondary hyperparathyroidism and hyperparathyroid bone disease can occur. Associated abnormalities include short stature, round facies, intellectual disability with calcification of the basal ganglia, shortened metacarpal and metatarsal bones, mild hypothyroidism, and other subtle endocrine abnormalities. Because only the maternal allele for GNAS1 is expressed in the kidneys, patients whose abnormal gene is paternal, although they have many of the somatic features of the disease, do not have hypocalcemia, hyperphosphatemia, or secondary hyperparathyroidism; this condition is sometimes described as pseudopseudohypoparathyroidism.

Type Ib pseudohypoparathyroidism is less well known. Affected patients have hypocalcemia, hyperphosphatemia, and secondary hyperparathyroidism but do not have the other associated abnormalities.

Type II pseudohypoparathyroidism is even less common than type I. In affected patients, exogenous PTH raises the urinary cAMP normally but does not raise serum calcium or urinary phosphate. An intracellular resistance to cAMP has been proposed.

Vitamin D deficiency and dependency

Vitamin D deficiency and dependency are discussed in full elsewhere.

Vitamin D is ingested in foods naturally high in vitamin D or fortified with it. It is also formed in the skin in response to sunlight (ultraviolet light). Vitamin D deficiency may result from inadequate dietary intake or decreased absorption due to hepatobiliary disease or intestinal malabsorption. It can also result from alterations in vitamin D metabolism as occur with certain drugs (eg, phenytoin, phenobarbital, rifampin) or from decreased formation in the skin due to lack of exposure to sunlight. Aging also decreases skin synthetic capacity.

Decreased skin synthesis is an important cause of acquired vitamin D deficiency among people who spend a great deal of time indoors, who live in high northern or southern latitudes, and who wear clothing that covers them completely or frequently use sunblocking agents. Accordingly, subclinical vitamin D deficiency is fairly common, especially during winter months in temperate climates among the elderly. The institutionalized elderly are at particular risk because of decreased skin synthetic capacity, undernutrition, and lack of sun exposure. In fact, most people with deficiency have both decreased skin synthesis and dietary deficiency. However, most clinicians feel that the significant dangers of skin cancer outweigh the as yet unproven risk of moderately low vitamin D levels so increasing sun exposure or doing without sunblocks is not recommended; vitamin D supplements are readily available for patients with concerns.

Vitamin D–dependency results from the inability to convert vitamin D to its active form or decreased responsiveness of end-organs to adequate levels of active vitamin.

  • Type I vitamin D–dependent rickets (pseudovitamin D–deficiency rickets) is an autosomal recessive disorder involving a mutation in the gene encoding the 1-alpha-hydroxylase enzyme. Normally expressed in the kidney, 1-alpha-hydroxylase is needed to convert inactive vitamin D to the active form calcitriol.
  • In type II vitamin D–dependent rickets, target organs cannot respond to calcitriol. Vitamin D deficiency, hypocalcemia, and severe hypophosphatemia occur. Muscle weakness, pain, and typical bone deformities can occur.

Renal disease

Renal tubular disease, including acquired proximal renal tubular acidosis due to nephrotoxins (eg, heavy metals, cadmium in particular) and distal renal tubular acidosis, can cause severe hypocalcemia due to abnormal renal loss of calcium and decreased renal conversion of vitamin D to active 1,25(OH)2D.

Renal failure can result in diminished formation of 1,25(OH)2D due to

  • Direct renal cell damage
  • Suppression of 1-alpha-hydroxylase (needed for the vitamin D conversion) by hyperphosphatemia

Other causes

Other causes of hypocalcemia include

  • Magnesium depletion (can cause relative parathyroid hormone deficiency and end-organ resistance to PTH action, usually when serum magnesium concentrations are < 1.0 mg/dL [< 0.5 mmol/L]; magnesium repletion increases PTH concentrations and improves renal calcium conservation)
  • Acute pancreatitis (when lipolytic products released from the inflamed pancreas chelate calcium)
  • Hypoproteinemia (reduces the protein-bound fraction of serum calcium; hypocalcemia due to diminished protein binding is asymptomatic—because ionized calcium is unchanged, this entity has been termed factitious hypocalcemia)
  • Hungry bone syndrome (persistent hypocalcemia and hypophosphatemia occurring after surgical or medical correction of moderate to severe hyperparathyroidism in patients in whom serum calcium concentrations had been supported by high bone turnover induced by greatly elevated PTH—hungry bone syndrome has been described after parathyroidectomy, after renal transplantation, and rarely in patients with end-stage renal disease treated with calcimimetics)
  • Septic shock due to suppression of PTH release and decreased conversion of 25(OH)D to 1,25(OH)2D
  • Hyperphosphatemia (causes hypocalcemia by poorly understood mechanisms; patients with renal failure and subsequent phosphate retention are particularly prone)
  • Drugs including anticonvulsants (eg, phenytoin, phenobarbital) and rifampin, which alter vitamin D metabolism, and drugs generally used to treat hypercalcemia
  • Transfusion of > 10 units of citrate-anticoagulated blood
  • Use of radiocontrast agents containing the divalent ion-chelating agent ethylenediaminetetraacetate (EDTA—can decrease the concentration of bioavailable ionized calcium while total serum calcium concentrations remain unchanged)
  • Infusion of gadolinium (may spuriously lower calcium concentration)

Although excessive secretion of calcitonin might be expected to cause hypocalcemia, calcitonin actually has only a minor effect on serum calcium. For example, low serum calcium concentrations rarely occur in patients with large amounts of circulating calcitonin due to medullary carcinoma of the thyroid.

Symptoms and Signs of Hypocalcemia

Hypocalcemia is frequently asymptomatic.

The presence of hypoparathyroidism may be suggested by the clinical manifestations of the underlying disorder (eg, short stature, round facies, intellectual disability, basal ganglia calcification in type Ia pseudohypoparathyroidism; vitiligo with autoimmune hypoparathyroidism).

Major clinical manifestations of hypocalcemia are due to disturbances in cellular membrane potential, resulting in neuromuscular irritability.

Neurologic manifestations

Muscle cramps involving the back and legs are common.

Insidious hypocalcemia may cause mild, diffuse encephalopathy and should be suspected in patients with unexplained dementia, depression, or psychosis.

Papilledema occasionally occurs.

Severe hypocalcemia with serum calcium < 7 mg/dL (< 1.75 mmol/L) may cause hyperreflexia, tetany, laryngospasm, or generalized seizures.

Tetany characteristically results from severe hypocalcemia but can result from reduction in the ionized fraction of serum calcium without marked hypocalcemia, as occurs in severe alkalosis. Tetany is characterized by the following:

  • Sensory symptoms consisting of paresthesias of the lips, tongue, fingers, and feet
  • Carpopedal spasm, which may be prolonged and painful
  • Generalized muscle aching
  • Spasm of facial musculature

Tetany may be overt with spontaneous symptoms or latent and requiring provocative tests to elicit. Latent tetany generally occurs at less severely decreased serum calcium concentrations: 7 to 8 mg/dL (1.75 to 2.20 mmol/L).

Chvostek and Trousseau signs are easily elicited at the bedside to identify latent tetany.

Chvostek sign is an involuntary twitching of the facial muscles elicited by a light tapping of the facial nerve just anterior to the exterior auditory meatus. It is present in ≤ 10% of healthy people and in most people with acute hypocalcemia but is often absent in chronic hypocalcemia.

Trousseau sign is the precipitation of carpal spasm by reduction of the blood supply to the hand with a tourniquet or blood pressure cuff inflated to 20 mm Hg above systolic blood pressure applied to the forearm for 3 minutes. Trousseau sign also occurs in alkalosis, hypomagnesemia, hypokalemia, and hyperkalemia and in about 6% of people with no identifiable electrolyte disturbance.

Other manifestations

Many other abnormalities may occur in patients with chronic hypocalcemia, such as dry and scaly skin, brittle nails, and coarse hair. Candida infections occasionally occur in hypocalcemia but most commonly occur in patients with idiopathic hypoparathyroidism. Cataracts occasionally occur with long-standing hypocalcemia and are not reversible by correction of serum calcium.

Diagnosis of Hypocalcemia

  • Estimation or measurement of ionized calcium (the physiologically active form of calcium)
  • Sometimes further testing, including measurement of magnesium, PTH, phosphate, alkaline phosphatase, and vitamin D concentrations in blood and cAMP and phosphate concentrations in urine

Hypocalcemia may be suspected in patients with characteristic neurologic manifestations or cardiac arrhythmias but is often found incidentally. Hypocalcemia is diagnosed by a total serum calcium concentration < 8.8 mg/dL (< 2.2 mmol/L). However, because low plasma protein can lower total, but not ionized, serum calcium, ionized calcium should be estimated based on albumin concentration.

Suspicion of low ionized calcium mandates its direct measurement, despite normal total serum calcium. A serum ionized calcium concentration < 4.7 mg/dL (< 1.17 mmol/L) is low.

Hypocalcemic patients should undergo measurement of renal function (eg, BUN, creatinine), serum phosphate, magnesium, and alkaline phosphatase.

When no etiology (eg, alkalosis, renal failure, drugs, or massive blood transfusion) is obvious, further testing is needed (see table Typical Laboratory Test Results in Some Disorders Causing Hypocalcemia).

Additional testing begins with serum concentrations of magnesium, phosphate, parathyroid hormone, alkaline phosphatase, and occasionally vitamin D levels, both 25(OH)D and 1,25(OH)2D. Urinary phosphate and cAMP concentrations are measured when pseudohypoparathyroidism is suspected.

PTH concentration should be measured as an assay of the intact molecule. Because hypocalcemia is the major stimulus for PTH secretion, PTH normally should be elevated in response to hypocalcemia. Thus,

  • Low or even low-normal PTH concentrations are inappropriate and suggest hypoparathyroidism.
  • An undetectable PTH concentration suggests idiopathic hypoparathyroidism.
  • A high PTH concentration suggests pseudohypoparathyroidism or an abnormality of vitamin D metabolism.

Hypoparathyroidism is further characterized by high serum phosphate and normal alkaline phosphatase.

In type I pseudohypoparathyroidism, despite the presence of a high concentration of circulating PTH, urinary cAMP and urinary phosphate are absent. Provocative testing by injection of parathyroid extract or recombinant human PTH fails to raise serum or urinary cAMP. Patients with type Ia pseudohypoparathyroidism frequently also have skeletal abnormalities, including short stature and shortened 1st, 4th, and 5th metacarpals. Patients with type Ib disease have renal manifestations without skeletal abnormalities.

In vitamin D deficiency, osteomalacia or rickets may be present, usually with typical skeletal abnormalities on x-ray. Diagnosis of vitamin D deficiency and dependency and measurement of vitamin D concentrations are discussed elsewhere.

Typical Laboratory Test Results in Some Disorders Causing Hypocalcemia



Surgical hypoparathyroidism

Low or low-normal PTH

Normal or high serum PO4

Low urinary PO4

Normal serum alkaline phosphatase

Idiopathic hypoparathyroidism

Undetectable PTH

High serum PO4

Low urinary PO4

Normal serum alkaline phosphatase

Type Ia pseudohypoparathyroidism (Albright hereditary osteodystrophy)

High PTH

High serum PO4

No urinary cAMP or increase in PO4 excretion even after injection of parathyroid extract or PTH

Skeletal and other abnormalities

Type Ib pseudohypoparathyroidism

High PTH

High serum PO4

No urinary cAMP or increase in PO4 excretion even after injection of parathyroid extract or PTH

No skeletal abnormalities

Type II pseudohypoparathyroidism

High PTH

High serum PO4

No urinary cAMP or PO4

Injection of PTH increases urinary cAMP but not urinary PO4

Normal or high vitamin D concentrations

Vitamin D deficiency

High PTH

Low serum PO4

High alkaline phosphatase

Low 25(OH)D*

Type I hereditary vitamin D–dependent rickets

High PTH

Low serum PO4

High alkaline phosphatase

X-ray evidence of rickets

Normal serum 25(OH)D

Low serum 1,25(OH)2D

Type II hereditary vitamin D–dependent rickets

High PTH

Low serum PO4

High alkaline phosphatase

X-ray evidence of rickets

Normal or high serum 25(OH)D

Normal or high 1,25(OH)2D

* Measurement of serum 25(OH)D and 1,25(OH)2D may help distinguish vitamin D deficiency from vitamin D–dependent states.

1,25(OH)2D = 1,25-dihydroxycholecalciferol or calcitriol; 25(OH)D = inactive vitamin D; cAMP = cyclic adenosine monophosphate; PO4 = phosphate; PTH = parathyroid hormone.

Severe hypocalcemia can affect the ECG. It typically shows prolongation of the QTc and ST intervals. Changes in repolarization, such as T-wave peaking or inversion, also occur. ECG may show arrhythmia or heart block occasionally in patients with severe hypocalcemia. However, evaluation of isolated hypocalcemia does not mandate ECG testing.

Estimation of ionized calcium concentration

Ionized calcium concentration can be estimated from routine laboratory tests, usually with reasonable accuracy.

In hypoalbuminemia, measured serum calcium is often low, mainly reflecting a low concentration of protein-bound calcium, while ionized calcium can be normal. Measured total serum calcium decreases or increases by about 0.8 mg/dL (0.2 mmol/L) for every 1 g/dL decrease or increase in albumin. Thus, an albumin concentration of 2.0 g/dL (20 g/L) (normal, 4.0 g/dL [40 g/L]) should itself reduce measured serum calcium by 1.6 mg/dL (0.4 mmol/L).

Similarly, increases in serum proteins, as occur in multiple myeloma, can raise total serum calcium. Acidosis increases ionized calcium by decreasing protein binding, whereas alkalosis decreases ionized calcium.

Treatment of Hypocalcemia

  • IV calcium gluconate for tetany
  • Oral calcium for postoperative hypoparathyroidism
  • Oral calcium and vitamin D for chronic hypocalcemia


For tetany, calcium gluconate 10 mL of 10% solution IV over 10 minutes is given. Response can be dramatic but may last for only a few hours. Repeated boluses or a continuous infusion with 20 to 30 mL of 10% calcium gluconate in 1 L of 5% dextrose in water (D/W) over the next 12 to 24 hours may be needed. Infusions of calcium are hazardous in patients receiving digoxin and should be given slowly and with continuous ECG monitoring after checking for (and correcting) hypokalemia.

When tetany is associated with hypomagnesemia, it may respond transiently to calcium or potassium administration but is permanently relieved only by repletion of magnesium, typically given as a 10% magnesium sulfate solution (1 g/10 mL) IV, followed by oral magnesium salts (eg, magnesium gluconate 500 to 1000 mg orally 3 times a day).

Pearls & Pitfalls

  • Infusions of calcium are hazardous in patients receiving digoxin and should be given slowly and with continuous ECG monitoring after checking for (and correcting) hypokalemia.

Transient hypoparathyroidism

In transient hypoparathyroidism after thyroidectomy or partial parathyroidectomy, supplemental oral calcium may be sufficient: 1 to 2 g of elemental calcium/day may be given as calcium gluconate (90 mg elemental calcium/1 g) or calcium carbonate (400 mg elemental calcium/1 g).

Subtotal parathyroidectomy may cause hypocalcemia that is particularly severe and prolonged, particularly in patients with chronic kidney disease or in patients from whom a large tumor was removed. Prolonged parenteral administration of calcium may be necessary postoperatively; supplementation with as much as 1 g/day of elemental calcium (eg, 111 mL/day of calcium gluconate, which contains 90 mg elemental calcium/10 mL) may be required for 5 to 10 days before oral calcium and vitamin D are sufficient. Elevated serum alkaline phosphatase in such patients may be a sign of rapid uptake of calcium into bone. The need for large amounts of parenteral calcium usually does not fall until the alkaline phosphatase concentration begins to decrease.

Chronic hypocalcemia

In chronic hypocalcemia, oral calcium and occasionally vitamin D supplements are usually sufficient: 1 to 2 g of elemental calcium/day may be given as calcium gluconate or calcium carbonate. In patients without renal failure or hypoparathyroidism, vitamin D is given as a standard oral supplement (eg, vitamin D3, cholecalciferol 20 mcg [800 IU] once/day). Vitamin D therapy is not effective unless adequate dietary or supplemental calcium and phosphate are also supplied.

For patients with renal failure, calcitriol or another vitamin D analog that does not require renal metabolic alteration (eg, alfacalcidiol, dihydrotachysterol) should be used. Patients with hypoparathyroidism also have difficulty converting cholecalciferol to its active form and also usually require calcitriol, usually 0.5 to 2 mcg orally once a day. Pseudohypoparathyroidism can occasionally be managed with oral calcium supplementation alone, but calcitriol at the above dose may be needed. Dihydrotachysterol is usually given orally at 0.8 to 2.4 mg once a day for a few days, followed by 0.2 to 1.0 mg once a day. Alfacalcidiol is not available in the US.

Use of vitamin D analogs can be complicated by vitamin D toxicity, with severe symptomatic hypercalcemia. Serum calcium concentration should be monitored weekly at first and then at 1- to 3-month intervals after calcium concentrations have stabilized. The maintenance dose of calcitriol or its analog, dihydrotachysterol, usually decreases with time.

Hypoparathyroidism that does not respond adequately to calcium and vitamin D supplementation may require treatment with recombinant parathyroid hormone (rhPTH 1-84), which also may decrease the risk of long-term hypoparathyroidism complications (eg, hypercalciuria, decreased bone strength), and lower the doses of calcium and vitamin D needed. Dosing of rhPTH 1-84 begins with 50 mcg subcutaneously once a day along with a decrease in vitamin D dosing by 50%. Serum calcium and phosphate are monitored closely, and the dose of rhPTH 1-84 is increased or decreased at intervals of several weeks as needed up to a maximum of 100 mcg once a day or down to 25 mcg once a day. Although rhPTH 1-34 also has been shown to be effective in treating chronic hypoparathyroidism, it is not approved for this use in the US.

Key Points

  • Causes of hypocalcemia include hypoparathyroidism, pseudohypoparathyroidism, vitamin D deficiency, and renal failure.
  • Mild hypocalcemia may be asymptomatic or cause muscle cramps.
  • Severe hypocalcemia (serum calcium < 7 mg/dL [< 1.75 mmol/L]) may cause hyperreflexia, tetany (paresthesias of the lips, tongue, fingers, and feet, carpopedal and/or facial spasms, muscle aches), or generalized seizures.
  • Diagnose by estimation or measurement of ionized (not total) serum calcium.
  • Typically, measure serum concentrations of magnesium, phosphate, parathyroid hormone, alkaline phosphatase, and occasionally vitamin D levels.
  • Give IV calcium gluconate to patients with tetany; treat others with oral calcium supplements.

Drugs Mentioned In This Article

Drug Name Select Trade
magnesium sulfate No US brand name
calcitriol ROCALTROL
phenytoin DILANTIN
digoxin LANOXIN

Copyright © 2022 Merck & Co., Inc., known as MSD outside of the US, Kenilworth, New Jersey, USA. All rights reserved. Merck Manual Disclaimer