Hypocalcaemia

• Hypocalcaemia is a serum calcium level below the reference range: total calcium under 2.20 mmol/L (8.8 mg/dL) when albumin is normal, or ionised (free) calcium under 1.17 mmol/L (4.7 mg/dL). ^{[8] [1]}
• The commonest cause is damage to, or removal of, the parathyroid glands during neck surgery; vitamin D deficiency, chronic kidney disease, and low magnesium are the other major groups.
• The hallmark is neuromuscular irritability: perioral tingling, carpopedal spasm, positive Chvostek or Trousseau signs, tetany, seizures and, when severe, laryngospasm and arrhythmia with a prolonged QT interval on the ECG.
• Blood tests that separate the causes are parathyroid hormone, phosphate, magnesium, vitamin D and kidney function; parathyroid hormone is inappropriately low in hypoparathyroidism and raised in most other causes.
• Severe or symptomatic disease gets intravenous calcium gluconate with cardiac monitoring; chronic disease gets oral calcium plus vitamin D, magnesium repletion, and treatment of the underlying cause.

By the end of this page you should be able to:

1. Define hypocalcaemia, correct total calcium for albumin, and state the ionised calcium threshold.
2. List the major causes grouped by parathyroid hormone and phosphate, and predict the laboratory pattern for each.
3. Elicit and interpret Chvostek and Trousseau signs, tetany and the ECG changes.
4. Work through a first-line investigation panel and interpret the parathyroid hormone result.
5. Manage acute symptomatic hypocalcaemia, including doses, safety and magnesium repletion, and outline chronic therapy.
6. Describe low-resource adjustments for diagnosis and long-term care.

Calcium in blood exists in three forms: roughly 40 to 45% is bound to plasma proteins (mainly albumin), about 5 to 15% is bound to small anions such as phosphate and citrate, and roughly 40 to 50% is free and ionised, which is the fraction that muscle, nerve and heart actually respond to.^[1] This explains two common traps. First, a low total calcium can be an artefact of low albumin: when albumin is low, the bound fraction falls while the ionised level stays normal, producing asymptomatic "factitious" hypocalcaemia.^[8] Second, ionised calcium is pH dependent: alkalosis increases protein binding and can precipitate tetany even when total calcium is near normal.^[8]

Albumin correction. Because so much calcium is albumin bound, total calcium should be corrected before the diagnosis is made. A widely quoted correction is a fall of about 0.8 mg/dL (0.2 mmol/L) in measured total calcium for every 1 g/dL fall in albumin, referenced to an albumin of 4 g/dL (40 g/L).^[8] Another standard reference gives a slightly different factor of 0.25 mmol/L per 1 g/dL fall in albumin.^[1] Guidelines and laboratories therefore differ; use your local formula and, when the result is unexpected or the patient is unwell, measure ionised calcium directly.

Normal ranges (from a standard reference) are roughly 2.1 to 2.6 mmol/L (8.5 to 10.5 mg/dL) for total calcium and 1.16 to 1.31 mmol/L (4.65 to 5.25 mg/dL) for ionised calcium; laboratory ranges differ slightly.^[1]

Low extracellular calcium lowers the threshold for excitation of nerve and muscle membranes, so cells depolarise more easily and neuromuscular irritability rises before any structural damage occurs.^[8] Parathyroid hormone (PTH, released by the parathyroid glands) and active vitamin D (calcitriol) are the main regulators: PTH releases calcium from bone, increases renal calcium reabsorption and drives calcitriol synthesis; calcitriol increases intestinal absorption of calcium and phosphate; FGF23 and the calcium-sensing receptor fine-tune both.^[1] When the parathyroid glands fail, or when target organs resist PTH, phosphate tends to rise; when vitamin D is deficient or bone is being rebuilt rapidly, phosphate tends to fall.

Disorders causing hypocalcaemia divide broadly into parathyroid-hormone (PTH) mediated and non-PTH mediated disease. Postsurgical hypoparathyroidism is the most frequent single cause; a broader search for non-PTH causes is needed so that treatment addresses the real problem rather than the number alone.^[2]

Several conditions reduce ionised calcium directly even when total calcium is normal: massive transfusion of citrate-anticoagulated blood (more than 10 units), sepsis, and rhabdomyolysis with hyperphosphataemia. Hypoproteinaemia lowers total calcium only. Low magnesium deserves special attention because it impairs both PTH secretion and PTH action, and refeeding magnesium often corrects the calcium.^[8]

Acute pancreatitis. Lipolytic products released from the inflamed pancreas chelate calcium, which is why hypocalcaemia appears in severe pancreatitis.^[8]

Hungry bone syndrome is persistent hypocalcaemia with hypophosphataemia after correction of moderate to severe hyperparathyroidism, when serum calcium had been supported by high bone turnover driven by very high PTH. It has been described after parathyroidectomy, after renal transplantation, and rarely in end-stage renal disease treated with calcimimetics.^[8] Alkaline phosphatase is often high and prolonged parenteral calcium may be needed (see Management).

Hypomagnesaemia deserves its own line. It usually causes hypocalcaemia only when serum magnesium is under 1.0 mg/dL (0.5 mmol/L).^[8] At these levels PTH secretion is blunted and the target organs resist PTH; magnesium repletion corrects both.

Drug-induced disease. Medications used to treat hypercalcaemia (bisphosphonates, denosumab, calcitonin and cinacalcet), certain antivirals (foscarnet) and drugs that alter vitamin D metabolism (phenytoin, phenobarbital, rifampin) can all lower serum calcium. Over-treatment is a particular risk in people with chronic kidney disease, vitamin D deficiency or high bone turnover. Denosumab can produce severe, protracted hypocalcaemia: a published case following a single 60 mg injection reported an adjusted calcium of 1.33 mmol/L and a parathyroid hormone of 34.6 pmol/L, with positive Chvostek and Trousseau signs, a prolonged QT interval, and the need for repeated 10 mL boluses of 10% calcium gluconate plus continuous infusion.^[9]

Medication monitoring. After starting denosumab, calcium, phosphate and magnesium should be checked within 14 days, especially in the presence of vitamin D deficiency, chronic kidney disease or prior bariatric surgery.^[9]

Hypocalcaemia is frequently asymptomatic, particularly when mild. The major manifestations follow disturbed membrane potential and neuromuscular irritability.^[8]

• Tingling of the lips, tongue, fingers and toes, often the first symptom.
• Muscle cramps in the back and legs, facial muscle spasm.
• Palpitations when the QT interval is affected.
• Symptoms of the underlying cause (weight loss and bone pain in malignancy, steatorrhoea, neck scars, hand abnormalities in pseudohypoparathyroidism).

• Tetany. Overt tetany has carpopedal spasm that may be prolonged and painful, facial muscle spasm, and generalised muscle aching. Latent tetany occurs at milder degrees, with serum calcium between 1.75 and 2.20 mmol/L (7 to 8 mg/dL).^[8]
• Chvostek sign: tapping the facial nerve just in front of the ear produces twitching of the facial muscles. It is found in most patients with acute hypocalcaemia but in no more than 10% of healthy people, and it is often absent in chronic hypocalcaemia.^[8]
• Trousseau sign: inflating a blood pressure cuff 20 mm Hg above systolic pressure for 3 minutes precipitates carpal spasm. It also occurs in alkalosis, hypomagnesaemia, hypo- and hyperkalaemia, and in a small minority of people without electrolyte disturbance (reported figures range from about 1% to 6%).^[8]
• Severe disease (serum calcium under 1.75 mmol/L, 7 mg/dL) may cause hyperreflexia, laryngospasm or generalised seizures.^[8]
• Chronic changes: dry scaly skin, brittle nails, coarse hair, cataracts, and Candida infections in idiopathic hypoparathyroidism.^[8]

Severe hypocalcaemia typically produces prolongation of the QTc and ST intervals, with T-wave peaking or inversion; occasionally arrhythmia or heart block occurs. An isolated mild to moderate hypocalcaemia does not by itself require an ECG.^[8] A prolonged QT in someone with tetany or seizures is a useful bedside clue.

Before treating a "low calcium" result, consider whether the low value is real and dangerous. Hypoproteinaemia and alkalosis lower total or ionised calcium without true deficiency. Sepsis, pancreatitis, rhabdomyolysis and rhabdomyolysis-related hyperphosphataemia are systemic emergencies that can produce genuine hypocalcaemia and should be managed on their own. Chvostek and Trousseau signs are not specific and can occur in alkalosis and hypomagnesaemia. Parathyroid hormone, phosphate and magnesium separate most of these.

First-line panel: ionised calcium if available (otherwise estimate it from total calcium and albumin), magnesium, phosphate, alkaline phosphatase, creatinine and estimated kidney function, intact parathyroid hormone, and 25-hydroxyvitamin D. Add 1,25-dihydroxyvitamin D and urinary phosphate and cyclic AMP when pseudohypoparathyroidism is suspected.^[8]

Interpreting parathyroid hormone: because hypocalcaemia is the main stimulus for PTH release, PTH should be raised in response. A low or even low-normal value is inappropriate and points to hypoparathyroidism; an undetectable value suggests idiopathic hypoparathyroidism. A high value suggests pseudohypoparathyroidism or a disorder of vitamin D metabolism. High phosphate plus normal alkaline phosphatase favours hypoparathyroidism.^[8]

Hungry bone syndrome shows persistent hypocalcaemia and hypophosphataemia with a high alkaline phosphatase after parathyroidectomy.^[8]

Hypocalcaemia is confirmed on a low ionised calcium, or a corrected total calcium below the reference range, with compatible symptoms or risk. Severity matters more than the label:

• Mild to moderate: total calcium 1.75 to 2.20 mmol/L (7 to 8 mg/dL), often latent tetany.
• Severe: under 1.75 mmol/L (7 mg/dL), which may cause hyperreflexia, tetany, laryngospasm or generalised seizures.^[8]
• Critical: laryngospasm, seizures, arrhythmia or haemodynamic compromise, irrespective of the exact number.

For tetany, give calcium gluconate 10 mL of 10% solution intravenously over 10 minutes. The response can be dramatic but may last only a few hours. Repeated boluses, or a continuous infusion of 20 to 30 mL of 10% calcium gluconate in 1 L of 5% dextrose in water over 12 to 24 hours, may be needed.^[8]

• Give intravenous calcium with continuous ECG monitoring in tetany, convulsions, markedly prolonged QT, arrhythmia, or a very low calcium; or any patient in whom cardiac function matters.
• Calcium infusions are hazardous in patients receiving digoxin: give them slowly, with continuous ECG monitoring, after checking for and correcting hypokalaemia.^[8]
• Replete magnesium at the same time if it is low: 10% magnesium sulphate (1 g per 10 mL) intravenously, followed by oral magnesium salts (magnesium gluconate 500 to 1000 mg orally three times a day). Tetany with hypomagnesaemia responds only transiently to calcium or potassium and is permanently relieved by magnesium repletion.^[8]
• Check and correct potassium, renal function, and the acid-base state.
• If the patient is acutely ill, treat the underlying cause (sepsis, pancreatitis, rhabdomyolysis) and keep the calcium above the level at which symptoms start rather than chasing a normal number. In critical care, treating mild or moderate hypocalcaemia can worsen outcomes, particularly in sepsis; reserve intravenous repletion for severe hypocalcaemia or clear clinical indication.^[3]

Supplemental oral calcium is often sufficient: 1 to 2 g of elemental calcium a day, as calcium gluconate (90 mg elemental calcium per 1 g) or calcium carbonate (400 mg elemental calcium per 1 g). After subtotal parathyroidectomy the fall can be severe and prolonged, especially with chronic kidney disease or removal of a large adenoma; as much as 1 g of elemental calcium a day intravenously (111 mL of 10% calcium gluconate, which contains 90 mg of elemental calcium per 10 mL) may be needed for 5 to 10 days before oral therapy and vitamin D suffice. A rising alkaline phosphatase at this stage signals rapid uptake of calcium into bone.^[8]

Oral calcium and, when needed, vitamin D are the backbone: 1 to 2 g of elemental calcium a day as calcium gluconate or calcium carbonate. In people without renal failure or hypoparathyroidism, give vitamin D as a standard supplement, for example cholecalciferol (vitamin D3) 20 micrograms (800 IU) once daily. Vitamin D therapy works only if adequate calcium and phosphate are also supplied.^[8]

• Hypoparathyroidism. These patients convert cholecalciferol poorly to its active form, so they usually need calcitriol 0.5 to 2 micrograms orally once daily.^[4][8] If calcium still cannot be maintained, hypoparathyroidism unresponsive to calcium and vitamin D can be treated with a parathyroid hormone analogue: recombinant human parathyroid hormone (rhPTH(1-84)) has been withdrawn from manufacture since 2024 and palopegteriparatide is now used in its place. These agents correct serum calcium and markedly reduce daily calcium and active vitamin D requirements, but they are costly and candidates must be selected carefully. Parathyroid hormone analogues are used for a limited course (about 2 years for rhPTH(1-84)) with close monitoring of calcium and kidney function, and long-acting preparations are expected to change chronic management further.^[2][4][8]
• Chronic kidney disease. Use an active vitamin D analogue that does not depend on renal 1-alpha-hydroxylation (calcitriol, alfacalcidiol or dihydrotachysterol) plus phosphate control; cinacalcet is an option when secondary hyperparathyroidism persists. Avoid aluminium-containing phosphate binders.^[8]
• Pseudohypoparathyroidism. Often managed with oral calcium alone, but calcitriol at the dose above may be needed when calcium cannot be maintained.^[8]
• Dihydrotachysterol may be used at 0.8 to 2.4 mg orally once daily for a few days, then 0.2 to 1.0 mg once daily.^[8]
• Hungry bone syndrome. Prolonged intravenous calcium may be required until alkaline phosphatase falls; expect to give large doses.^[8]
• Drug-induced disease. Stop or reduce the offending agent when possible; hypocalcaemia from denosumab can take weeks to months to settle, needing sustained calcitriol (up to about 1.5 micrograms twice daily) and calcium (for example calcium carbonate 1 g three times daily) before doses can be tapered.^[9]
• Monitoring. Vitamin D analogues can cause hypercalcaemia and hypercalciuria. In hypocalcaemia with renal failure, recheck calcium weekly at first and every 1 to 3 months once stable. ^[8]

• Neuromuscular emergencies: tetany, laryngospasm, generalised seizures.
• Cardiac: arrhythmia, heart block, and, with severe disease, heart failure.
• Tissue calcification from over-treatment: renal stones, nephrocalcinosis, basal ganglia and other soft-tissue deposits.
• Endocrine and metabolic consequences of chronic hypoparathyroidism: candidiasis, cataracts, dry skin and hair; poor growth and enamel defects in children.^[6][8]
• Recombinant PTH is monitored because of osteosarcoma risk in animals and because of calcium and renal effects; it is given for 2 years with monitoring.^[8]

Outcome depends on the cause. Postsurgical hypoparathyroidism is often transient; idiopathic and autoimmune disease usually require lifelong replacement. When the cause is identified and treated (vitamin D deficiency, magnesium depletion, drug-induced disease), recovery is expected. The main avoidable harm is over-treatment with calcium and vitamin D, which can produce hypercalcaemia, hypercalciuria, renal impairment and nephrocalcinosis.^[6][8]

• Estimate rather than measure. When ionised calcium is unavailable, correct total calcium for albumin with your local factor and treat on the clinical picture. In the absence of calcium measurement, perioral tingling, carpopedal spasm, Chvostek sign and a prolonged QT interval on an ECG are valued clues.
• Prioritise the dangerous cases. Laryngospasm, seizures, arrhythmia or a suspected very low calcium warrant parenteral calcium while arranging referral; do not delay treatment for tests.
• Work with what is available. Magnesium, phosphate, creatinine and (where possible) parathyroid hormone change management; vitamin D assays are often unavailable, so a therapeutic trial of cholecalciferol plus calcium and repletion of magnesium is reasonable when vitamin D deficiency is plausible.
• Chronic care. Calcium carbonate and (where available) vitamin D or cholecalciferol are cheap and effective. Where calcitriol is unavailable, patients with hypoparathyroidism can be maintained on calcium and cholecalciferol with careful monitoring, accepting less stable control. Some patients need very large calcium doses for years.
• Nutrition and sunlight. Daily sunlight exposure, calcium-containing foods and repletion of magnesium address root causes cheaply, and follow-up of parathyroid function after neck surgery avoids missed hypoparathyroidism.
• Referral. Seek specialist or surgical opinion for intractable or severe disease, for patients needing active vitamin D or recombinant PTH, and for evidence of organ damage (renal stones, basal ganglia calcification, cataracts).

Hypomagnesaemia, hyperphosphataemia, vitamin D deficiency, chronic kidney disease with mineral and bone disorder, hypercalcaemia, acute pancreatitis, hypoparathyroidism, pseudohypoparathyroidism, hungry bone syndrome.

• Hypocalcaemia is total calcium under 2.20 mmol/L with normal albumin, or ionised calcium under 1.17 mmol/L; roughly 40 to 50% of plasma calcium is free and biologically active.
• Always correct total calcium for albumin, and prefer ionised calcium in ill patients; guidelines differ on whether the correction factor is 0.2 or 0.25 mmol/L per 1 g/dL of albumin.
• The commonest cause is postsurgical hypoparathyroidism; the other major groups are vitamin D deficiency, chronic kidney disease and low magnesium.
• PTH is inappropriately low in hypoparathyroidism and raised in most other causes; phosphate is high in hypoparathyroidism, CKD and pseudohypoparathyroidism, and low in vitamin D deficiency.
• Neuromuscular irritability produces tingling, cramps, tetany, Chvostek and Trousseau signs, seizures and laryngospasm; serum calcium under 1.75 mmol/L marks severe disease.
• Severe hypocalcaemia prolongs the QTc and ST intervals on the ECG; a prolonged QT in someone with tetany or seizures is a useful clue.
• Chvostek and Trousseau signs are suggestive, not diagnostic, and Trousseau occurs in several other electrolyte disorders and in a small minority of healthy people.
• Acute symptomatic disease: calcium gluconate 10 mL of 10% intravenously over 10 minutes, with ECG monitoring; repeat boluses or a 20 to 30 mL infusion in 5% dextrose over 12 to 24 hours may be needed. ^[8]
• Hypomagnesaemia under 1.0 mg/dL (0.5 mmol/L) causes functional hypoparathyroidism and is corrected with 10% magnesium sulphate intravenously then oral magnesium.
• Chronic disease: 1 to 2 g of elemental calcium a day plus vitamin D; hypoparathyroidism usually needs calcitriol 0.5 to 2 micrograms daily, and a parathyroid hormone analogue for refractory cases (rhPTH(1-84) has been withdrawn since 2024).
• Drug-induced hypocalcaemia (bisphosphonates, denosumab, and others) can be severe and prolonged and needs sustained replacement.
• Treat the cause; in chronic kidney disease and drug-induced disease monitor for hypercalcaemia and hypercalciuria from over-treatment.