Calcium 3.0 - ICN INDIA

Calcium 3.0

7 min read

By: Dr. Ameya Tripathi, Bureau Chief-ICN U.P.

Hypocalcemia-Part 1

LUCKNOW: Low calcium level in our body can lead to different problems. As discussed earlier we know that calcium is very important for our day to day functions. But when its level fall below the optimum level its known as deficiency of calcium. This calcium deficiency is known as “Hypocalcemia”. Hypocalcaemia is a potentially life threatening biochemical abnormality that carries risks for serious errors in diagnosis and treatment. Hypocalcaemia is low calcium levels in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dl, 4.3–5.2 mEq/L) with levels less than 2.1 mmol/l defined as hypocalcemia. Mildly low levels that develop slowly often have no symptoms. Otherwise symptoms may include numbness, muscle spasms, seizures, confusion, or cardiac arrest. Hypocalcaemia presents in primary and secondary care; it has a prevalence of 18% in all patients in hospital and 85% in the intensive care unit. The most common cause of hypocalcaemia in primary care is vitamin D deficiency, which—depending on population demographics—may have a prevalence as high as 50%. Hypocalcaemia may be an asymptomatic laboratory finding or a life threatening metabolic disturbance. Acute hypocalcaemia can result in severe symptoms that require rapid admission to hospital and correction. Common causes include hypoparathyroidism and vitamin D deficiency. Others causes include kidney failure, pancreatitis, calcium channel blocker overdose, rhabdomyolysis, tumor lysis syndrome, and medications such as bisphosphonates. Diagnosis should generally be confirmed with a corrected calcium or ionized calcium level. Specific changes may be seen on an electrocardiogram


Hypocalcemia most commonly results when too much calcium is lost in urine or when not enough calcium is moved from bones into the blood. Causes of hypocalcemia include the following:

  • Vitamin D inadequacy or vitamin D resistance
  • Hypoparathyroidism following surgery
  • Hypoparathyroidism owing to autoimmune disease or genetic causes
  • Renal disease or end-stage liver disease causing vitamin D inadequacy
  • Pseudohypoparathyroidism or pseudopseudohypoparathyroidism
  • Metastatic or heavy metal (copper, iron) infiltration of the parathyroid gland
  • Hypomagnesemia or hypermagnesemia
  • Sclerotic metastases
  • Hungry bone syndrome postparathyroidectomy
  • Infusion of phosphate or citrated blood transfusions
  • Critical illness
  • Drugs (eg, high-dose intravenous bisphosphonates)
  • Fanconi syndrome
  • Past radiation of parathyroid glands


Hypoparathyroidism is characterized by hypocalcemia and hyperphosphatemia and often causes chronic tetany. Hypoparathyroidism results from deficient parathyroid hormone (PTH), which can occur in autoimmune disorders or after the accidental removal of or damage to several parathyroid glands during thyroidectomy. Transient hypoparathyroidism is common after subtotal thyroidectomy, but permanent hypoparathyroidism occurs after < 3% of such thyroidectomies done by experienced surgeons. Manifestations of hypocalcemia usually begin about 24 to 48 hours postoperatively but may occur after months or years. PTH deficiency is more common after radical thyroidectomy for cancer or as the result of surgery on the parathyroid glands (subtotal or total parathyroidectomy). Risk factors for severe hypocalcemia after subtotal parathyroidectomy include

Severe preoperative hypercalcemia

Removal of a large adenoma

Elevated alkaline phosphatase

Chronic kidney disease

Idiopathic hypoparathyroidism is an uncommon sporadic or inherited condition in which the parathyroid glands are absent or atrophied. It manifests in childhood. The parathyroid glands are occasionally absent and thymic aplasia and abnormalities of the arteries arising from the brachial arches (DiGeorge syndrome) are present. Other inherited forms include polyglandular autoimmune failure syndrome, autoimmune hypoparathyroidism associated with mucocutaneous candidiasis, and X-linked recessive idiopathic hypoparathyroidism.

Pseudo hypoparathyroidism

Pseudo hypoparathyroidism is an uncommon group of disorders characterized not by hormone deficiency but by target organ resistance to PTH. Complex genetic transmission of these disorders occurs.

  • Type Ia pseudo hypoparathyroidism (Albright hereditary osteodystrophy) is caused by a mutation in the stimulatory Gs-alpha1 protein of the adenylyl cyclase complex (GNAS1). The result is failure of normal renal phosphaturic response or increase in urinary cAMP to PTH. Patients are usually hypocalcemic and hyperphosphatemic. Secondary hyperparathyroidism and hyperparathyroid bone disease can occur. Associated abnormalities include short stature, round facies, intellectual disability with calcification of the basal ganglia, shortened metacarpal and metatarsal bones, mild hypothyroidism, and other subtle endocrine abnormalities. Because only the maternal allele for GNAS1 is expressed in the kidneys, patients whose abnormal gene is paternal, although they have many of the somatic features of the disease, do not have hypocalcemia, hyperphosphatemia, or secondary hyperparathyroidism; this condition is sometimes described as pseudo hypoparathyroidism.
  • Type Ib pseudo hypoparathyroidism is less well known. Affected patients have hypocalcemia, hyperphosphatemia, and secondary hyperparathyroidism but do not have the other associated abnormalities.
  • Type II pseudo hypoparathyroidism is even less common than type I. In affected patients, exogenous PTH raises the urinary cAMP normally but does not raise serum calcium or urinary phosphate. An intracellular resistance to cAMP has been proposed.

Vitamin D deficiency and dependency

Vitamin D deficiency and dependency will be discussed in detail in different article however let’s take a quick glance on them

  • Vitamin D is ingested in foods naturally high in vitamin D or fortified with it. It is also formed in the skin in response to sunlight (UV light). Vitamin D deficiency may result from inadequate dietary intake or decreased absorption due to hepatobiliary disease or intestinal malabsorption. It can also result from alterations in vitamin D metabolism as occur with certain drugs (eg, phenytoin, phenobarbital, rifampin) or from decreased formation in the skin due to lack of exposure to sunlight. Aging also decreases skin synthetic capacity.
  • Decreased skin synthesis is an important cause of acquired vitamin D deficiency among people who spend a great deal of time indoors, who live in high northern or southern latitudes, and who wear clothing that covers them completely or frequently use sunblocking agents. Accordingly, subclinical vitamin D deficiency is fairly common, especially during winter months in temperate climates among the elderly. The institutionalized elderly are at particular risk because of decreased skin synthetic capacity, undernutrition, and lack of sun exposure. In fact, most people with deficiency have both decreased skin synthesis and dietary deficiency. However, most clinicians feel that the significant dangers of skin cancer outweigh the as yet unproven risk of moderately low vitamin D levels so increasing sun exposure or doing without sunblocks is not recommended; vitamin D supplements are readily available for patients with concerns.
  • Vitamin D–dependency results from the inability to convert vitamin D to its active form or decreased responsiveness of end-organs to adequate levels of active vitamin.
  • Type I vitamin D–dependent rickets (pseudovitamin D–deficiency rickets) is an autosomal recessive disorder involving a mutation in the gene encoding the 1-alpha-hydroxylase enzyme. Normally expressed in the kidney, 1-alpha-hydroxylase is needed to convert inactive vitamin D to the active form calcitriol.
  • In type II vitamin D–dependent rickets, target organs cannot respond to calcitriol. Vitamin D deficiency, hypocalcemia, and severe hypophosphatemia occur. Muscle weakness, pain, and typical bone deformities can occur.

Renal disease

  • Renal tubular disease, including acquired proximal renal tubular acidosis due to nephrotoxins (eg, heavy metals, cadmium in particular) and distal renal tubular acidosis, can cause severe hypocalcemia due to abnormal renal loss of calcium and decreased renal conversion of vitamin D to active 1,25(OH)2D.
  • Renal failure can result in diminished formation of 1,25(OH)2D due to
  • Direct renal cell damage
  • Suppression of 1-alpha-hydroxylase (needed for the vitamin D conversion) by hyperphosphatemia
  • Other causes
  • Other causes of hypocalcemia include

Magnesium depletion –(can cause relative parathyroid hormone deficiency and end-organ resistance to PTH action, usually when serum magnesium concentrations are < 1.0 mg/dL [< 0.5 mmol/L]; magnesium repletion increases PTH concentrations and improves renal calcium conservation)

  • Acute pancreatitis (when lipolytic products released from the inflamed pancreas chelate calcium)
  • Hyperproteinemia (reduces the protein-bound fraction of serum calcium; hypocalcemia due to diminished protein binding is asymptomatic—because ionized calcium is unchanged, this entity has been termed factitious hypocalcemia)
  • Hungry bone syndrome (persistent hypocalcemia and hypophosphatemia occurring after surgical or medical correction of moderate to severe hyperparathyroidism in patients in whom serum calcium concentrations had been supported by high bone turnover induced by greatly elevated PTH—hungry bone syndrome has been described after parathyroidectomy, after renal transplantation, and rarely in patients with end-stage renal disease treated with calcimimetics)
  • Septic shock due to suppression of PTH release and decreased conversion of 25(OH)D to 1,25(OH)2D

Hyperphosphatemia –(causes hypocalcemia by poorly understood mechanisms; patients with renal failure and subsequent phosphate retention are particularly prone)

  • Drugs including anticonvulsants (e.g., phenytoin, phenobarbital) and rifampin, which alter vitamin D metabolism, and drugs generally used to treat hypercalcemia
  • Transfusion of > 10 units of citrate-anticoagulated blood
  • Use of radiocontrast agents containing the divalent ion-chelating agent ethylene diamine tetra acetate (EDTA—can decrease the concentration of bioavailable ionized calcium while total serum calcium concentrations remain unchanged)
  • Infusion of gadolinium (may spuriously lower calcium concentration)
  • Although excessive secretion of calcitonin might be expected to cause hypocalcemia, calcitonin actually has only a minor effect on serum calcium. For example, low serum calcium concentrations rarely occur in patients with large amounts of circulating calcitonin due to medullary carcinoma of the thyroid.

Neonatal hypocalcemia– this is an abnormal clinical and laboratory hypocalcemia condition that is frequently observed in infants. This is a very important and vast topic and I will cover it in a separate article.

In this part we discussed the causes of hypocalcemia. There are plethora of causes and we tried to bring in as many as we can. In the second part we will discuss the physiological changes and management of hypocalcemia.

Stay tuned for part 2 of hypocalcemia.

Still if you have some more points about hypocalcemia to add .Please  free to share with me on my email id or . the article will be updated ASAP. thanks for your cooperation.

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