Hypocalcaemia

Hypocalcaemia is a reduced corrected serum calcium, and, as with hypercalcaemia, the corrected value or an ionised calcium must be used rather than the total.

Symptoms depend on both severity and the rate of fall: a calcium that drops abruptly after parathyroidectomy causes tetany at a level that a patient with chronic kidney disease tolerates without complaint.

Causes include hypoparathyroidism (most often post-surgical after thyroid or parathyroid surgery, also autoimmune or infiltrative), vitamin D deficiency, chronic kidney disease, hypomagnesaemia (which both impairs PTH secretion and causes PTH resistance), acute pancreatitis, rhabdomyolysis, tumour lysis syndrome, massive transfusion (citrate chelation), and drugs including bisphosphonates and denosumab.

• Paraesthesia, characteristically perioral and in the fingers and toes, is often the earliest symptom
• Muscle cramps and carpopedal spasm, progressing to tetany in more severe cases
• Chvostek's sign (facial muscle twitching on tapping over the facial nerve) and Trousseau's sign (carpal spasm induced by inflating a blood pressure cuff above systolic for three minutes). Trousseau's is the more specific of the two; Chvostek's is present in a proportion of normocalcaemic people and its absence does not exclude hypocalcaemia
• Laryngospasm and bronchospasm, which are life-threatening
• Seizures, which may occur without other classical features and should prompt a calcium check in any first seizure
• Cardiac: prolonged QT interval, and in severe cases arrhythmia, hypotension and impaired cardiac contractility
• Chronic hypocalcaemia may present more insidiously with cataracts, dental abnormalities, dry skin, brittle nails, and basal ganglia calcification

• Corrected calcium with albumin, or ionised calcium where available, confirmed on repeat
• Magnesium, which must be checked in every case: hypomagnesaemia causes functional hypoparathyroidism and PTH resistance, and calcium will not correct until magnesium is replaced
• PTH: low or inappropriately normal indicates hypoparathyroidism; raised indicates an appropriate secondary response, as in vitamin D deficiency or chronic kidney disease
• Vitamin D (25-hydroxyvitamin D), phosphate, renal function and alkaline phosphatase
• ECG for QT prolongation
• In the post-operative neck surgery patient, hypocalcaemia is anticipated rather than investigated from scratch, and calcium should be monitored routinely
• Consider amylase or lipase if pancreatitis is plausible, and creatine kinase if rhabdomyolysis is suspected

The phosphate level helps orientate the cause: high phosphate with low calcium suggests hypoparathyroidism, chronic kidney disease, tumour lysis or rhabdomyolysis, while low phosphate with low calcium suggests vitamin D deficiency.

Severe or symptomatic hypocalcaemia (tetany, seizures, laryngospasm, QT prolongation, arrhythmia):

• Intravenous calcium gluconate, typically 10–20 mL of 10% solution diluted and given slowly over 10 minutes with cardiac monitoring, repeated as needed, followed by a calcium infusion if hypocalcaemia is likely to persist
• Calcium gluconate is preferred peripherally over calcium chloride, which is more sclerosing and causes tissue necrosis if it extravasates
• Give with caution in digoxin-treated patients, with cardiac monitoring
• Correct magnesium in parallel, not afterwards. This is the commonest reason apparently refractory hypocalcaemia fails to respond

Mild or asymptomatic:

• Oral calcium supplementation, with activated vitamin D (alfacalcidol or calcitriol) where hypoparathyroidism or renal impairment is present, since these patients cannot adequately hydroxylate standard vitamin D
• Plain vitamin D (colecalciferol) where the cause is simple deficiency with intact renal and parathyroid function
• Treat the underlying cause and stop contributing drugs

Post-thyroidectomy or post-parathyroidectomy:

• Anticipate hypocalcaemia, monitor calcium routinely in the first days, and be alert for hungry bone syndrome where preoperative bone turnover was high
• Patients discharged on calcium and activated vitamin D need clear instructions and early recheck, since both under- and over-treatment cause harm

Referral: endocrinology for hypoparathyroidism and for ongoing management of chronic hypocalcaemia; surgical team if post-operative; ICU for laryngospasm or arrhythmia.