General Principles

• A serum calcium <8.4 mg/dL with a normal serum albumin or an ionized calcium <4.2 mg/dL defines hypocalcemia.
• Effective hypoparathyroidism. Reduced PTH activity can result from decreased PTH release from autoimmune, infiltrative, or iatrogenic (e.g., post-thyroidectomy) destruction of parathyroid tissue. 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 or oxalate, which bind with the calcium and deposit 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.