Hypocalcaemia

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Calcium stabilises neuronal membranes, supports muscle contraction and shapes cardiac repolarisation. Total calcium changes with albumin, while alkalosis increases protein binding and can lower ionised calcium enough to cause tetany despite a less alarming total result. Begin with tempo, symptoms and context: recent thyroid or parathyroid surgery, CKD, pancreatitis, sepsis, massive transfusion, tumour lysis, rhabdomyolysis, malabsorption, vitamin D deficiency, antiresorptive treatment and medicines such as cinacalcet. Check the neck for a surgical history, examine for neuromuscular irritability and record ECG. Chvostek and Trousseau signs can support the diagnosis but do not replace ionised calcium or clinical severity. In critical illness, use ionised measurement rather than relying on albumin correction formulas.

Emergency calcium relieves membrane instability but will not hold if the cause remains. Society guidance uses 10% calcium gluconate with ECG monitoring for severe or symptomatic adult hypocalcaemia, followed by an infusion titrated to repeated measurements. Concurrently replace magnesium, address alkalosis or citrate load where relevant, and obtain PTH before large replacement when practical. A high PTH indicates an intact compensatory response and directs attention to vitamin D deficiency, renal phosphate retention, malabsorption or rapid skeletal uptake. A low response suggests surgical, autoimmune, infiltrative or genetic hypoparathyroidism. After parathyroidectomy for high-turnover disease, hungry bone syndrome may consume calcium, phosphate and magnesium for days and require substantial specialist replacement. Chronic goals in hypoparathyroidism differ from normal physiology: pursue symptom control and a safe low-normal calcium while avoiding hypercalciuria, nephrolithiasis and renal decline.

Key points

Confirm true hypocalcaemia with albumin-adjusted calcium or ionised calcium; low total calcium from hypoalbuminaemia alone does not require calcium replacement.
Symptoms reflect the ionised fraction and speed of fall, so acute postoperative hypocalcaemia can be severe before total calcium reaches an extreme value.
Paraesthesia, cramps, carpopedal spasm, tetany, laryngospasm, seizure and QT prolongation are important acute discriminators.
Measure magnesium early because profound deficiency impairs both PTH release and action and makes calcium refractory until magnesium is corrected.
PTH should rise when calcium is low; a low or inappropriately normal result points to hypoparathyroidism, while a raised result suggests vitamin D deficiency, CKD or resistance.
After neck surgery, falling PTH can predict hypocalcaemia, but active symptoms and serial calcium determine emergency treatment.
Intravenous calcium chloride contains more elemental calcium but is irritant and generally requires central access; calcium gluconate is preferred peripherally.
Long-term treatment depends on cause: nutritional vitamin D deficiency needs native vitamin D, whereas absent PTH often needs activated vitamin D plus carefully titrated oral calcium.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Reduced PTH effect

Neck surgery, autoimmune or genetic hypoparathyroidism and severe magnesium deficiency reduce PTH secretion or action, limiting renal calcium conservation.

Vitamin D or renal disease

Deficient vitamin D, malabsorption and chronic kidney disease reduce calcium absorption or activation and often provoke a compensatory PTH rise.

Acute sequestration or binding

Pancreatitis, massive transfusion, tumour lysis, rhabdomyolysis, alkalosis and hungry bone physiology can rapidly lower available ionised calcium.

Medicine-related loss

Antiresorptives, calcimimetics and other medicines can reduce calcium entry or increase skeletal uptake, particularly when vitamin D or renal reserve is limited.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Ionised calcium falls
Reduced absorption, impaired PTH action, tissue sequestration or increased protein binding lowers the biologically active extracellular calcium fraction.
2
Membranes become excitable
Low ionised calcium lowers the threshold for neuronal and muscle depolarisation, producing paraesthesia, cramps, tetany and laryngospasm.
3
Cardiac repolarisation lengthens
Reduced calcium availability prolongs ventricular repolarisation and can impair contractility or provoke arrhythmia, especially with concurrent magnesium disturbance.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Neuromuscular irritability

Perioral or acral tingling, cramps, twitching, carpopedal spasm and tetany are characteristic, especially after surgery or during alkalosis.

Airway and neurological danger

Stridor from laryngospasm, seizure, encephalopathy or severe bronchospasm represents organ-threatening hypocalcaemia and needs immediate monitored treatment.

Cardiac manifestation

QT prolongation, heart failure or arrhythmia may occur and is magnified by magnesium disturbance, digoxin exposure or underlying cardiac disease.

Postoperative timing

Symptoms in the first days after thyroid or parathyroid surgery suggest gland injury or hungry bone physiology; delayed cases also occur and need clear discharge safety-netting.

Chronic phenotype

Fatigue, cognitive symptoms, cataracts, basal-ganglia calcification, dental abnormalities or ectopic calcification may accompany longstanding calcium-PTH disorders without dramatic tetany.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Ionised calcium or albumin-adjusted calciumFirst step
Why
Confirm biologically meaningful deficiency and quantify severity in the relevant clinical state.
Interpretation and limitations
Ionised calcium is preferred in critical illness or major acid-base disturbance. An isolated low total value with low albumin and normal ionised calcium is not true hypocalcaemia.
02
ECG
Why
Identify prolonged repolarisation and arrhythmia and monitor intravenous calcium response.
Interpretation and limitations
QT prolongation supports physiological significance; rhythm disturbance mandates monitored treatment, while a normal ECG does not exclude symptomatic neuromuscular disease.
03
Magnesium and phosphate
Why
Detect refractory magnesium deficiency and distinguish PTH deficiency, renal retention and hungry bone uptake.
Interpretation and limitations
Low magnesium can suppress or resist PTH. High phosphate with low PTH supports hypoparathyroidism; low phosphate with high turnover can fit vitamin D deficiency or hungry bone syndrome.
04
PTH sampled with calcium
Why
Determine whether the parathyroid response is appropriate during confirmed hypocalcaemia.
Interpretation and limitations
Low or normal PTH is inappropriate and supports hypoparathyroidism; raised PTH redirects towards secondary drivers or pseudohypoparathyroidism.
05
25-hydroxyvitamin D and renal function
Why
Identify nutritional deficiency, impaired activation and kidney constraints on replacement.
Interpretation and limitations
Low 25-hydroxyvitamin D supports deficiency; advanced CKD changes phosphate and active vitamin D handling and requires a renal-specific plan.
06
Cause-directed acute screen
Why
Identify pancreatitis, sepsis, tumour lysis, rhabdomyolysis, citrate exposure or medicine effects in a rapidly falling calcium.
Interpretation and limitations
Select lipase, creatine kinase, phosphate, urate and transfusion review from the presentation; definitive treatment of the driver determines whether calcium remains stable.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Low albumin

Reduced protein lowers total calcium without equivalent ionised deficiency; direct ionised measurement is more informative in critical illness or protein disturbance.

Respiratory alkalosis

Hyperventilation increases calcium binding to albumin, causing tetany with low ionised calcium despite a less striking total concentration.

Hypomagnesaemia

Low magnesium impairs PTH release and action and causes associated refractory hypokalaemia, making calcium difficult to correct in isolation.

Seizure from another cause

Epilepsy, sodium disturbance or cerebral disease can cause seizure; simultaneous ionised calcium and clinical context show whether hypocalcaemia is causal.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01EmergencyStabilise symptomatic calcium deficiencyFirst stepTetany, seizure, airway symptom, arrhythmia or severe measured hypocalcaemia is present.

1Start ABCDE and continuous ECG, obtain ionised or adjusted calcium, magnesium, phosphate and renal bloods, and summon senior acute support.
2Give 10% calcium gluconate using the current Society or local dilution and bolus protocol, reassessing symptoms and ECG and repeating if necessary.
3Continue with a monitored calcium infusion for ongoing need, replace magnesium and treat the cause, involving endocrinology and critical care according to severity.

02MechanismInterpret the PTH responseTrue hypocalcaemia is confirmed and immediate instability is controlled.

1Review neck surgery, CKD, nutrition, malabsorption, pancreatitis, transfusion and calcium-lowering medicines and inspect serial results.
2Interpret paired PTH, phosphate, magnesium, vitamin D and renal function to separate gland failure, resistance and a compensatory secondary response.
3Choose native versus activated vitamin D and oral calcium according to cause, using specialist renal or endocrine input when PTH is absent or kidney function is advanced.

03After surgeryPrevent delayed deteriorationA patient has undergone thyroid or parathyroid surgery or treatment of severe high-turnover bone disease.

1Use the operation-specific PTH and calcium pathway to stratify risk and ensure symptoms are checked before discharge.
2Provide exact oral calcium or activated vitamin D instructions, interaction advice and urgent contact criteria for tingling, cramp, stridor or confusion.
3Arrange early calcium, phosphate, magnesium and renal testing with a named reviewer, anticipating prolonged hungry bone replacement after very high turnover.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Provides ionised calcium rapidly to stabilise cardiac and neuromuscular membranes while the cause is corrected.

Calcium gluconate 10%

For severe or symptomatic adult hypocalcaemia, Society guidance uses 10–20 mL diluted in 50–100 mL of 5% glucose over about 10 minutes with ECG monitoring, repeated if necessary, then an infusion titrated by specialist protocol.

Extravasation damages tissue, rapid administration can cause arrhythmia, and digoxin exposure needs expert caution. Confirm the preparation and elemental calcium because chloride and gluconate are not equivalent.

Restores PTH secretion and peripheral responsiveness when magnesium deficiency makes hypocalcaemia refractory.

Magnesium replacement

Replace through the current oral or intravenous local regimen selected for severity, symptoms, kidney function and measured deficit, with slower and lower treatment when renal excretion is impaired.

Intravenous magnesium can cause hypotension and toxicity, especially in kidney failure. Recheck magnesium and calcium and do not assume calcium infusion alone will succeed.

Maintains calcium after acute treatment and supports chronic therapy when intake or PTH physiology is insufficient.

Oral calcium salt

Divide the locally selected elemental-calcium regimen across the day and titrate to symptoms, calcium and urinary risk; separate it from levothyroxine, iron and other interacting medicines.

Constipation, nephrolithiasis and hypercalciuria can occur. Product labels list salt rather than elemental calcium, and over-replacement with activated vitamin D can damage kidneys.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Tetany and airway compromise

Neuromuscular irritability can progress from paraesthesia and carpopedal spasm to bronchospasm or laryngospasm that threatens ventilation.

Seizure and encephalopathy

Severe or rapidly falling calcium can cause confusion, seizure and reduced consciousness through widespread neuronal instability.

Cardiac arrhythmia

Prolonged repolarisation and interacting magnesium or potassium abnormalities can produce ventricular arrhythmia, impaired contractility or haemodynamic instability.

Renal harm from chronic treatment

In hypoparathyroidism, excessive calcium and active vitamin D replacement can cause hypercalciuria, stones and declining kidney function.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

During intravenous treatment, repeat ionised or adjusted calcium and ECG at protocol-defined intervals and observe the cannula for extravasation.
Follow magnesium, phosphate, potassium and renal function because correction of one component can expose or perpetuate another deficit.
After antiresorptive therapy or neck surgery, monitor through the expected delayed nadir rather than discharging after one normal sample.
In chronic hypoparathyroidism, track symptoms, serum calcium-phosphate, eGFR and urinary calcium with renal imaging when indicated.
Review adherence, elemental calcium content, vitamin D formulation and medicine spacing before escalating a regimen for apparent failure.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Alkalosis unmasks tetany

Rising pH increases albumin binding and lowers ionised calcium. Hyperventilation can therefore worsen paraesthesia and spasm without a large total-calcium change.

Magnesium controls both sides

Severe magnesium deficiency reduces PTH release and target-organ response. Calcium may remain refractory until magnesium physiology is restored.

Hungry bone consumes phosphate too

After sudden PTH reduction, avid skeletal mineralisation lowers calcium, phosphate and magnesium. The pattern differs from isolated postoperative gland failure.

Total calcium may tell the wrong story

Critical illness and acid-base shifts undermine albumin correction. Ionised measurement directly answers whether excitable tissue is exposed to low calcium.

Chronic goals protect kidneys

Replacing absent PTH to a high-normal serum calcium can drive urine calcium because renal conservation is missing. Symptom control at a safer level is often preferable.

11Common pitfallsFrequent interpretation and management errors.

01
Treating low total calcium caused by hypoalbuminaemia without confirming ionised or adjusted calcium.
02
Giving intravenous calcium without ECG monitoring in symptomatic severe disease.
03
Escalating calcium repeatedly while leaving profound magnesium deficiency untreated.
04
Using calcium chloride through a peripheral vein as though it were interchangeable with gluconate.
05
Discharging a high-risk post-parathyroidectomy patient before the delayed hungry bone nadir.
06
Normalising chronic hypoparathyroid serum calcium without monitoring hypercalciuria and renal function.