Hypocalcemia is a topic covered in the Washington Manual of Medical Therapeutics.

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General Principles

  • A serum calcium <8.4 mg/dL with a normal serum albumin or an ionized calcium <4.2 mg/dL defines hypocalcemia.
  • Pseudohypocalcemia describes the situation in which the total calcium is reduced because of hypoalbuminemia, but the corrected [Ca2+] (see Calcium, Hypercalcemia, Diagnostic Testing section) and ionized calcium remain within the normal ranges.
  • Effective hypoparathyroidism. Reduced PTH activity can result from decreased PTH release from autoimmune, infiltrative, or iatrogenic (e.g., post-thyroidectomy) destruction of parathyroid tissue. In rare patients, hypoparathyroidism is congenital, as in DiGeorge syndrome or familial hypocalcemia. Release of PTH is also impaired with both hypomagnesemia (<1 mg/dL) and severe hypermagnesemia (>6 mg/dL).
  • Vitamin D deficiency lowers total body calcium but does not usually affect serum calcium levels unless the deficiency is severe because the resultant secondary hyperparathyroidism often corrects serum calcium levels. Significant vitamin D deficiency can occur in the elderly or those with limited sun exposure, advanced liver disease (due to decreased synthesis of precursors), and nephrotic syndrome. Reduced activity in vitamin D activation via 1-α-hydroxylase activity can be seen with vitamin D-dependent rickets and chronic renal insufficiency.
  • Serum calcium levels may also be reduced by profound elevations in serum phosphorus, which binds with the calcium and deposits in various tissues. Calcium can also be bound by citrate (during transfusion of citrate-containing blood products or with continual renal replacement using citrate anticoagulation) as well as by drugs such as foscarnet and fluoroquinolones. Increased binding to albumin can also be seen in the context of alkalemia, which increases the exposure of negatively charged binding sites on albumin.
  • Other. A low serum free calcium level is common in critically ill patients perhaps due to a cytokine-mediated decrease in PTH and calcitriol release with target organ resistance to their effects.

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