Hypocalcemia

Causes

Low PTH

• Hypoparathyroidism
  • DiGeorge syndrome
• Hypomagnesemia (impairs secretion, action of PTH)
• Renal PO₄³⁻ wasting with hypercalciuria (hereditary hypophosphatemic rickets with hypercalciuria)
• Autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED) syndrome
  • Destroys multiple endocrine glands, including parathyroid

High PTH

• Vitamin D deficiency/resistance
• Nutritional
  • Kidney disease
  • Liver disease
• Pseudohypoparathyroidism
• Hungry bone syndrome
• Inadequate intake

Neonatal hypocalcemia

• Prematurity
• Intrauterine growth restriction
• Infant of diabetic mother

Artifact

• Hypoalbuminemia
  • Calcium is highly albumin bound, but only the unbound calcium is physiologically active.
    • If hypoalbuminemia is also present, there may be proportionally more unbound (ionized) calcium; therefore, the ionized calcium should be measured
    • Some will “correct” the calcium for the albumin level (for each 1 g/dL below normal albumin level, add 0.8 mg/dL to the serum calcium), but evidence does not support this practice [PMID 34197298]
• Ionized calcium (iCa) is more reliable
  • Not confounded by albumin level
• Calcium is bound by citrate
  • Citrate-bound calcium is included in total serum calcium level but will result in a lower iCa level
  • If iCa low, ensure not being drawn from line with blood products running in the line (e.g., in secondary lumen)
• Lab error, specimen handling issues

Signs and symptoms

• Characteristically presents with neuromuscular irritability, but can be highly variable
• Weakness
• Paresthesias
• Perioral numbness
• Carpopedal spasms
• Tetany
• Seizures
• Steatorrhea
• Prolonged QT interval
• Rickets
• Poor nail growth
• Papilledema
• Calcifications of basal ganglia

Evaluation

• Labs:
  • Albumin
  • Ionized calcium (iCa)
  • Parathyroid hormone (PTH)
  • Phosphorus
  • Magnesium
  • 25-OH vitamin D
  • 1,25-OH₂ vitamin D
  • Urine calcium/creatinine (UCa/Cr) ratio

Treatment

• Treat underlying cause
• Give calcium
  • Mild-moderate hypocalcemia: oral calcium repletion
  • Severe hypocalcemia: IV calcium
    • Can cause cardiac arrest if administered too rapidly
    • Ideally administered centrally as extravasation can cause tissue necrosis
      • Calcium gluconate safer than calcium chloride for peripheral IV infusion
• Give vitamin D if indicated
• Replace magnesium if hypomagnesemic
• Be aware that calcium and/or vitamin D can cause hypercalciuria