Introduction
Hypocalcemia is defined when the level of calcium in your blood (not your bones) is too low. It is not as common as hypercalcemia, but it can be life-threatening if not promptly diagnosed and treated.
The main factors that regulate calcium levels in the body are parathyroid hormone (PTH), vitamin D, and calcitonin.
About 99% of the body’s calcium is stored in bones, and the remaining 1% is found in blood, muscle, and other tissues.
Of that 1 %, about 45% of the body’s calcium is bound to plasma albumin, another 15% is bound to phosphate and citrate and the balance 40% is in the free state.
The total serum calcium concentration ranges between 8.5 to 10.5 mg/dL (2.12 to 2.62 mmol/L). Any level below this range is considered hypocalcemia.
Since most of the body’s calcium is bound to plasma albumin, a diagnosis of hypocalcemia should be made after checking both calcium and albumin levels.
Total calcium concentration falls by about 0.8 mg/dL (0.25 mmol/L) for every drop of 1 g/dL (10 g/L) of the serum albumin concentration.
Causes of hypocalcemia
In neonates, hypocalcemia is more likely to develop in infants born to mothers with diabetes or preeclampsia during pregnancy. Hypocalcemia may also occur in infants born to mothers with hyperparathyroidism.
Since many complex factors are involved with maintaining normal levels of calcium in your blood and body, various health conditions can cause hypocalcemia.
Parathyroid hormone (PTH) deficiency
Parathyroid glands are four small glands, which secrete the parathyroid hormone that regulates the calcium in our bodies. They are located in the neck behind the thyroid
Low PTH secretion can be due to the damage of the parathyroid glands caused either by surgery or autoimmune diseases. It can also be due to abnormal secretion of PTH or abnormal development of the parathyroid gland. PTH deficiency (hypoparathyroidism) can be due to :
- Neck surgery. This is the most common cause of hypoparathyroidism. It can develop due to accidental surgical damage to or removal of the parathyroid glands. The surgery on the neck could be indicated for abnormal conditions of the thyroid gland, or for treating cancer in the neck.
- Autoimmune disease. In some cases, the immune system attacks parathyroid tissues, which then stop producing their hormone.
- Hereditary hypoparathyroidism. PTH deficiency can also be due to the congenital absence of the parathyroid glands or the glands may not be functioning properly.
- Low levels of magnesium in the blood can affect the function of the parathyroid glands because normal magnesium levels are required for normal production and release of parathyroid hormone.
- Extensive cancer radiation treatment of the face or neck can cause damage to the parathyroid glands resulting in PTH deficiency.
Vitamin D deficiency
Vitamin D is necessary for the proper absorption of calcium. Therefore, vitamin D deficiency can result in calcium deficiency.
Kidney failure
Hypocalcemia in chronic renal failure is due to impaired phosphate excretion leading to an increased level of phosphorus in your blood and decreased conversion of 25 hydroxyvitamin D to 1,25-dihydroxy vitamin D.
Other causes of hypocalcemia include:
- Hypomagnesemia: Your parathyroid glands need magnesium to produce and release parathyroid hormone, so when your magnesium is too low (hypomagnesemia), PTH production suffers, and blood calcium levels also fall.
- Pancreatitis: Approximately 15% to 88% of people who have acute pancreatitis develop hypocalcemia.
- Pseudohypocalcemia: Serum calcium binds to proteins (notably albumin) in the blood, and therefore low albumin levels can give a false low total serum calcium level.
- Certain drugs can cause a fall in calcium levels.
- Bisphosphonates and denosumab can cause severe hypocalcemia.
- Cinacalcet is a calcimimetic agent that can decrease PTH secretion. It is used in the treatment of hyperparathyroidism. The resulting decrease in PTH secretion can cause hypocalcemia.
- Cisplatin, a chemotherapeutic drug, can also cause hypocalcemia by inducing hypomagnesemia.
- Foscarnet forms complexes with ionized calcium, thereby reducing levels of ionized calcium.
- Rifampin used in treatment of tuberculosis can induce hypocalcemia
- Massive blood transfusion: Iionized calcium binds to citrate, which is used as an anticoagulant in the stored blood. This can cause an acute fall in ionized calcium levels.
- Bone metastasis, due to prostate cancer, can cause hypocalcemia, which can be severe. This is due to the increased calcium uptake into the bones from increased bone formation.
- Family history of hypocalcemia
- Low-calcium diet
- Lack of sun exposure
Symptoms of hypocalcemia
Symptoms of hypocalcemia include:
- Seizures
- Tetany
- Paresthesias: tingling or pricking usually around the mouth or in the extremities.
- Psychiatric symptoms such as anxiety and depression can sometimes be seen in some cases of hypocalcemia.
- Carpopedal spasm (Trousseau’s sign) characterized by the appearance of a carpopedal spasm, which involves flexion of the wrist, thumb, and metacarpophalangeal joints when a sphygmomanometer is inflated above systolic blood pressure for three minutes.
- Chvostek’s sign: This is another manifestation of hypocalcemia due to heightened neuromuscular excitability. Tapping of the facial nerve in front of the ear causes contraction of the ipsilateral facial muscles.
Chronic hypocalcemia may produce the following dermatologic symptoms:
Severe hypocalcemia of less than 7 mg/dl can cause complications such as seizures or life-threatening arrhythmias.
Diagnosis
Testing for the ionized calcium level must be performed rapidly with whole blood.
- Hypocalcemia is defined as a total serum calcium concentration < 8.8 mg/dL (< 2.20 mmol/L) in the presence of normal plasma protein (albumin) concentrations or when serum ionized calcium concentration fall below 4.7 mg/dL (< 1.17 mmol/L). If hypoalbuminemia is present, it should be corrected adding 0.8 mg/dl to the total serum calcium for each 1 g/dl decrease in albumin below 4 g/dl.
- An ECG should be obtained to look for QTc prolongation, which is directly proportional to the degree of hypocalcaemia.
- To diagnose the cause of hypocalcemia: Once hypocalcemia is confirmed, further testing should be done to determine the cause of hypocalcemia. That includes checking
- electrolytes such as serum magnesium and phosphorus levels,
- PTH levels
- vitamin D levels.
- serum lipase should be checked in suspected pancreatitis.
Imaging studies of the bones may reveal osteomalacia, rickets, or even metastasis.
Treatment
Treatment of hypocalcemia depends on the severity of symptoms and the cause of hypocalcemia. Calcium supplements form the main stay of treatment. Management of hypocalcemia can be divided into different categories:
- Intravenous (IV) calcium is recommended for use in patients with severe symptoms and hypocalcemic-specific ECG changes. Calcium gluconate 1 to 2 g or 1 g of calcium chloride is given intravenously over 10 to 20 minutes. This may be followed by a slow infusion if hypocalcemia persists.
- If the symptoms are mild, oral calcium carbonate or calcium citrate can be given. Totally, the aim is to give 1500 to 2000 mg elemental calcium per day that can be divided into 2 to 3 doses. Calcium carbonate should be avoided in patients taking proton pump inhibitors as it needs an acidic medium to be absorbed.
- Vitamin D supplementation is often recommended with calcium preparations for better absorption of calcium.
- Disease-specific treatment:
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- Postsurgical hypoparathyroidism: Hypocalcemia due to surgical hypoparathyroidism is treated prophylactically with calcium. Calcium levels should be monitored closely and then may be tapered off.
- Hypomagnesemia if present should be treated first as hypocalcemia will be difficult to correct without correcting serum magnesium.
- Vitamin D deficiency if present should be corrected first before treating hypocalcemia.
- Chronic kidney failure causes hypocalcemia due to vitamin D deficiency. This is treated by giving its active metabolite, calcitriol. Patients with significant vitamin D deficiency should be given ergocalciferol 50,000 units weekly for 8 to 12 weeks followed by cholecalciferol at lower doses of 1000 to 5000 units daily.
The overall prognosis of hypocalcemia is good as it is easy to treat.
