Serum
mmol/L
Lab Tests Online
Not adjusted for Albumin:
up to 29 days: 2.00 – 2.70 mmol/L
Adjusted for Albumin:
29 days to 16 years: 2.20 – 2.70 mmol/L
16 years and above: 2.05 – 2.55 mmol/L
Plasma calcium exists in the blood in three forms; 50% is ionized, 40-45% is protein bound, and 5-10% is complexed to anions such as bicarbonate, citrate, sulphate, phosphate, and lactate. Plasma ionized calcium is the biologically active moiety. Total calcium levels are maintained between 2.1 and 2.55 mmol/l
Parathyroid hormone and vitamin D regulate normal plasma calcium levels by their actions on kidney, intestine, and bone ion transport.
The main causes of hypercalcaemia are primary hyperparathyroidism, malignant disease, and chronic renal failure. The differential diagnosis of hypercalcaemia depends on the clinical setting. Overall, primary hyperparathyroidism and malignancy account for 80 – 90% of hypercalcaemia cases. However, primary hyperparathyroidism is the cause of ~60% of ambulatory cases and of ~25% of inpatient cases, whereas malignancy causes ~35% of ambulatory cases and 65% of inpatient cases.
Malignancies can raise serum calcium levels by either direct bone destruction or secretion of calcaemic factors. Patients with squamous cell carcinoma of the lung, metastatic breast cancer, multiple myeloma, and renal cell carcinoma are most prone to hypercalcaemia. These tumors may produce PTH related protein (PTH-rp) which binds to PTH receptors, but is not detected by standard intact PTH immunoassays. Specific assays for PTH-RP are NOT currently available in the UK.
The prevalence of hyperparathyroidism in the general population is 1 to 2 cases per 1000 people, but is more frequent in the elderly and in women. The most common pathological lesion is a single parathyroid adenoma (85% of cases) or chief cell hyperplasia (10%). Parathyroid carcinoma occurs in 1 to 3% of cases. Hyperparathyroidism also occurs in multiple endocrine neoplasia type 1 and 2A. Patients identified by laboratory screening are commonly asymptomatic. Presentation with kidney stones is unusual today, but 5% of patients with kidney stone disease have primary hyperparathyroidism. Finding an elevated PTH level in a patient with hypercalcaemia makes the diagnosis.
| Mental | Neurological & Skeletal | GI & Urological |
| Fatigue | Reduced muscle tone | Nausea |
| Obtundation | Muscle weakness | Vomiting |
| Apathy | Myalgia | Polyuria |
| Lethargy | Pain | Polydipsia |
| Confusion | Deep tendon reflexes | Dehydration |
| Disorientation | Anorexia | |
| Coma | Constipation |
Evaluation of hypercalcaemia usually begins with measurement of total calcium. If total calcium is markedly elevated, an ionized calcium level is usually not needed The patient’s history may indicate the cause, such as; immobilization for more than a week, drug therapy, hyperthyroidism, adrenal insufficiency, or familial hypocalciuric hypercalcaemia. If time permits, total calcium levels should be repeated two more times to rule out a transient cause of hypercalcaemia before undertaking a complete work-up. If hypercalcaemia is still evident, serum albumin and total protein should be determined. Calcium levels should be corrected for elevated albumin levels (see below). If total protein is high, but albumin is normal or low, a monoclonal gammopathy should be ruled out by serum protein electrophoresis. Serum chloride, phosphorus and intact PTH are also useful in diagnosing the most frequent causes of hypercalcaemia; malignancy and hyperparathyroidism. Serum chloride is mildly elevated in primary hyperparathyroidism.
Hypocalcaemia most commonly results from PTH deficiency or failure to produce 1,25 dihydroxy vitamin D. The most common causes of hypoparathyroidism are parathyroid or thyroid surgery and parathyroid infiltration by cancer, sarcoid, amyloid or hemochromatosis. Acute illnesses such as pancreatitis, hepatic failure, sepsis, and various medications can also cause hypocalcaemia. The normal response to a fall in the plasma ionized calcium level is increased PTH secretion and 1,25 dihyroxy vitamin D synthesis, leading to increased calcium absorption from the intestine and increased resorption from bone and kidneys.
Some drugs are associated with hypocalcaemia. Gentamicin and cisplatin cause renal magnesium loss, which leads to hypocalcaemia. Heparin therapy releases fatty acids that bind calcium ions and cause transient hypocalcaemia. Anticonvulsants such as dilantin and phenobarbital induce the microsomal oxidase pathway which accelerates inactivation of vitamin D. Loop diuretics such as furosemide enhance renal calcium excretion. Phosphate salts bind up calcium ions causing hypocalcaemia.
The laboratory evaluation of a low total plasma calcium level should include measurement of magnesium, and phosphorus levels. Low ionized calcium rules out artefactual causes of hypocalcaemia, such as hypoalbuminemia (only available on ITU blood gas analyser). Abnormally high or low magnesium levels should be excluded because they can inhibit PTH secretion. A low serum phosphorus level is consistent with vitamin D deficiency, while a high level suggests chronic renal failure or pseudohypoparathyroidism. Measurement of intact PTH levels helps to differentiate between conditions caused by PTH and vitamin D defects. The demonstration of an inappropriately low intact PTH level in the presence of hypocalcaemia is consistent with the diagnosis of hypoparathyroidism. Serum 25-hydroxyvitamin D levels can be measured to confirm vitamin D deficiency.
Total calcium levels are effected by changes in plasma protein concentrations. Most of the protein bound fraction of calcium is bound to albumin.
The RDE use the formula for corrected calcium is:
N.B. Albumin units is in g/L
Two of the four approved gadolinium based magnetic resonance (MR) imaging contrast agents, gadodiamide (Omniscan) and gadoversetamide (OptiMARK), have recently been shown to interfere with calcium measurements on some chemistry analyzers, resulting in falsely low values. Patients with normal renal function may have spuriously low calcium measurements up to 24 hours after administration of these contrast agents, but patients with renal insufficiency may be affected for up to 4.5 days.
Sera from patients receiving EDTA (treatment of hypercalcaemia) are unsuitable for analysis.
1 day
Local test
Can be added on to an existing request up to 4 days following sample receipt
Specimen Labelling Procedure
8210
