Hypocalcaemia

The normal range for total serum calcium is 2.25-2.5 mmol/l (normal range is quoted for guide only - ranges vary between laboratories).

Derangements above (hypercalcaemia) and below (hypocalcaemia) this level interfere with the normal function of most body cells but nerve and muscle cells in particular.
In the hypocalcaemic state, about 40% of plasma calcium is bound to albumin. It is the unbound, ionised fraction of calcium that is important physiologically and the level for serum calcium is usually reported as both an uncorrected and corrected (where adjustment is made for changes in albumin levels).

Adjusting calcium level for albumin

• Approximate "correction": add 0.1 mmol/l to calcium concentration for every 4 g/l that albumin is below 40 g/l and a similar subtraction for raised albumin.
• This does not replace measurement of ionised calcium concentration.
• Special care should be taken where the measured albumin concentration is less than about 20 g/L because of the known inaccuracy of albumin measurement at low levels.
• Other factors affect calcium binding. For example, plasma proteins in myeloma.

Symptoms

Symptoms generally correlate with the magnitude and rapidity of the fall in serum calcium: mild hypocalcaemia (2.00-2.12 mmol/l) can be asymptomatic whereas acute symptoms of neuromuscular irritability can develop in the more severe form(<1.9 mmol/l):

• Paraesthesia (usually fingers, toes and around mouth)
• Tetany
• Carpopedal spasm (wrist flexion and fingers drawn together)
• Muscle cramps

Signs

• Chvostek's sign (tapping over facial nerve causes facial muscles to twitch) Note: this may be present in some normocalcaemic individuals.
• Trousseau's sign (carpopedal spasm after inflating a BP cuff on the upper arm)
• Seizures
• Prolonged QT interval which may progress to VF or heart block
• Laryngospasm
• Bronchospasm

With prolonged hypocalcaemia

• Sub-capsular cataract
• Papilloedema
• Abnormal teeth
• Ectopic calcification (for example, in basal ganglia may cause extrapyramidal neurological symptoms)
• Dementia and confusion

Causes of true hypocalcaemia fall into two main classes:

With low PTH levels (hypoparathyroidism)

• Parathyroid agenesis- alone or along with other abnormalities e.g. Di George syndrome
• Parathyroid destruction- due to surgery, radiotherapy, infiltration by metastases or systemic disease (e.g. amyloidosis, sarcoidosis)
• Autoimmune
• Reduced parathyroid secretion - due to gene defects, hypomagnesaemia, neonatal hypocalcaemia (may be due to maternal hypercalcaemia), hungry bone disease (after parathyroidectomy), mutation in calcium-sensing receptor.

With high PTH levels (secondary hyperparathyroidism)

• Vitamin D deficiency- due to nutritional lack, malabsorption, liver disease, receptor defects
• Vitamin D resistance (rickets)- renal tubular dysfunction (Fanconi's syndrome) or receptor defect
• PTH resistance - pseudohypoparathyroidism, hypomagnesaemia

Important other causes

• Hyperventilation
• Drugs- calcium chelators (citrate in blood transfusion); bone resorption inhibitors (bisphosphonates, calcitonin, plicamycin); drugs affecting vitamin D (phenytoin, ketoconazole), foscarnet
• Acute pancreatitis
• Acute rhabdomyolysis - usually in relation to crush injuries
• Malignancy - tumour lysis(following chemotherapy) or osteoblastic metastases (most common in prostate and breast cancers)
• Toxic shock syndrome

Commonest causes are hypoparathyroidism (frequently following surgery), vitamin D deficiency or abnormal metabolism, renal failure, hypomagnesaemia.
Hypocalcemia is extremely common in patients in hospital and correlates with the severity of their illness.³

• Hypoalbuminaemia - correct for albumin
• Consider drug therapy, malignancy, acute pancreatitis and rhabdomyolysis

• Is the patient really hypocalcaemic? (Ideally take fasting blood specimens, uncuffed -remove tourniquet after needle in vein, but before taking blood sample). Ensure use an adjusted calcium value
• Exclude renal failure (check U&Es), acute pancreatitis (check amylase), rhabdomyloysis (check serum CK)
• Estimate serum magnesium
• Estimate serum PTH
• Evaluate Vitamin D metabolism

Always assess the patient clinically. Patients vary: some may be symptomatic within the normal reference range since there are narrow individual ranges within the normal reference range.

Acute hypocalcaemia

• Treat where symptomatic (seizures, tetany) or at high risk of complications with a serum calcium <1.90 mmol/l
• Give calcium gluconate IV 10 ml (2.25 mmol) of calcium gluconate 10% by slow injection. Repeat as necessary or follow with infusion of calcium gluconate 10% infusion - 40 ml (9 mmol)/24 hours.⁴
• Calcium glubionate is an oral preparation providing 23 mg elemental calcium/mg. It is readily absorbed and well tolerated so is used as a supplement for infants and adults without good IV access.¹
• Monitor serum calcium concentrations regularly to judge response.
• If likely to be persistent, give vitamin D by mouth.
• If hypomagnesemic, necessary to correct magnesium level before the hypocalcaemia will resolve.

Persistent hypocalcaemia

• Initially supplementary calcium (10-20 mmol calcium bd-qds) and vitamin D but calcium may be discontinued once stabilised.
• Calcitriol (oral 1,25(OH)₂D₃) is more expensive than the parent Vitamin D compounds, Vitamin D₂(ergocalciferol) and Vitamin D₃, but is used first line in patients with renal impairment because it does not require hydroxylation by the kidney for activation. Usual dose is 0.5-1.0 μg daily.
• Monitor patient's serum and urine concentration initially at 1-2 weekly intervals, and once stabilised 3-6 monthly intervals and whenever nausea or vomiting are present. In some hypoparathyroid individuals, calcium levels may remain permanently unstable and it is important that the maintenance dose is regularly monitored.and adjusted.

• To avoid hypocalcaemia in patients on TPN, ensure magnesium and calcium levels are checked at least weekly and more frequently if acutely unwell.
• Giving 1,25 (OH)₂D₃ and calcium for several days before elective subtotal parathyroidectomy may prevent extreme hypocalcaemia.