Hypercalcaemia: Everything You Need to Know

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Chapters
0:00 Introduction
1:03 causes of Hypercalcaemia
2:41 symptoms of Hypercalcaemia
3:00 Heart
3:16 bone and muscles
3:29 neurological symptoms
3:38 Diagnosis
4:10 Treatment
Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum.[1][3] The normal range is 2.1-2.6 mmol/L (8.8-10.7 mg/dL, 4.3-5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemia.[1][2][4] Those with a mild increase that has developed slowly typically have no symptoms.[1] In those with greater levels or rapid onset, symptoms may include abdominal pain, bone pain, confusion, depression, weakness, kidney stones or an abnormal heart rhythm including cardiac arrest.[1][2]
Most cases are due to primary hyperparathyroidism or cancer.[1] Other causes include sarcoidosis, tuberculosis, Paget disease, multiple endocrine neoplasia (MEN), vitamin D toxicity, familial hypocalciuric hypercalcaemia and certain medications such as lithium and hydrochlorothiazide.[1][2][3] Diagnosis should generally include either a corrected calcium or ionized calcium level and be confirmed after a week.[1] Specific changes, such as a shortened QT interval and prolonged PR interval, may be seen on an electrocardiogram (ECG).[2]
Treatment may include intravenous fluids, furosemide, calcitonin or pamidronate in addition to treating the underlying cause.[1][2] The evidence for furosemide use, however, is poor.[1] In those with very high levels, hospitalization may be required.[1] Haemodialysis may be used in those who do not respond to other treatments.[1] In those with vitamin D toxicity, steroids may be useful.[1] Hypercalcemia is relatively common.[1] Primary hyperparathyroidism occurs in 1-7 per 1,000 people, and hypercalcaemia occurs in about 2.7% of those with cancer.[1] The neuromuscular symptoms of hypercalcaemia are caused by a negative bathmotropic effect due to the increased interaction of calcium with sodium channels. Since calcium blocks sodium channels and inhibits depolarization of nerve and muscle fibers, increased calcium raises the threshold for depolarization.[5] This results in diminished deep tendon reflexes (hyporeflexia), and skeletal muscle weakness.[6]
Other symptoms include cardiac arrhythmias (especially in those taking digoxin), fatigue, nausea, vomiting (emesis), loss of appetite, abdominal pain, & paralytic ileus. If kidney impairment occurs as a result, manifestations can include increased urination, urination at night, and increased thirst.[6] Psychiatric manifestation can include emotional instability, confusion, delirium, psychosis, and stupor.[6] Calcium deposits known as limbus sign may be visible in the eyes.[7]
Symptoms are more common at high calcium blood values (12.0 mg/dl or 3 mmol/l).[6] Severe hypercalcaemia (above 15-16 mg/dl or 3.75-4 mmol/l) is considered a medical emergency: at these levels, coma and cardiac arrest can result. The high levels of calcium ions decrease the neuron membrane permeability to sodium ions, thus decreasing excitability, which leads to hypotonicity of smooth and striated muscle. This explains the fatigue, muscle weakness, low tone and sluggish reflexes in muscle groups. The sluggish nerves also explain drowsiness, confusion, hallucinations, stupor or coma. In the gut this causes constipation. Hypocalcaemia causes the opposite by the same mechanism.[8]