What are the common causes of hypocalcemia?

Causes of Hypocalcemia

Hypoparathyroidism is the single most frequent cause of hypocalcemia, with post-surgical hypoparathyroidism accounting for 75% of all hypoparathyroidism cases, followed by vitamin D deficiency and magnesium deficiency. 1

PTH-Mediated Causes

Post-Surgical Hypoparathyroidism

• Represents 75% of all hypoparathyroidism cases and occurs after anterior neck surgery including thyroidectomy or parathyroidectomy 2, 1
• Can develop immediately post-operatively or emerge years after surgery 1

Primary Hypoparathyroidism

• Accounts for 25% of hypoparathyroidism cases and includes autoimmune destruction of parathyroid glands, genetic abnormalities, and infiltrative disorders 2, 1
• 22q11.2 deletion syndrome has an 80% lifetime prevalence of hypocalcemia due to underlying parathyroid dysfunction, and can emerge at any age despite apparent childhood resolution 2, 1

Non-PTH-Mediated Causes

Magnesium Deficiency

• Present in 28% of hypocalcemic patients and impairs PTH secretion while creating end-organ PTH resistance 1
• Commonly precipitated by alcohol consumption 1, 3
• Critical pitfall: Calcium supplementation will be ineffective without adequate magnesium correction 1, 3
• Patients can have magnesium deficiency despite normal serum concentrations since less than 1% of total body magnesium is in extracellular fluids 3

Vitamin D Deficiency and Disorders

• Impairs production of 1,25-dihydroxyvitamin D, reducing intestinal calcium absorption 1
• Particularly associated with chronic kidney disease 1

Chronic Kidney Disease

• Phosphate retention leads to decreased ionized calcium, which stimulates compensatory PTH release 2, 1
• Reduced vitamin D activation in diseased kidneys decreases duodenal and jejunal calcium absorption 2
• Impaired passive intestinal calcium absorption can be partially compensated by increasing calcium intake 2

Medication-Induced Hypocalcemia

Specific Medications

• Bisphosphonates and denosumab can cause severe hypocalcemia, particularly in patients with vitamin D deficiency or renal impairment 2, 1
• Loop diuretics induce hypocalcemia through increased urinary calcium excretion 2
• Calcium channel blockers may potentially reduce calcium levels by affecting calcium homeostasis 2

Post-Parathyroidectomy Hungry Bone Syndrome

• Rapid bone remineralization after correction of hyperparathyroid bone disease 2

Citrate-Induced Hypocalcemia

• Occurs during massive transfusion as citrate in blood products chelates calcium 2
• Hypocalcemia below 0.9 mmol/L during massive transfusion predicts mortality and transfusion requirements better than fibrinogen, acidosis, or platelet count 2

Precipitating Factors and High-Risk Situations

Biological Stressors

• Surgery, fractures, injuries, childbirth, acute illness, and fever can unmask or worsen hypocalcemia 2, 1
• Perioperative periods, puberty, and pregnancy are particularly high-risk times 2, 1

Dietary and Lifestyle Factors

• Decreased oral calcium intake 2, 1
• Alcohol consumption can worsen hypocalcemia and precipitate hypomagnesemia 2, 1
• Carbonated beverages, especially colas, may worsen hypocalcemia 2, 1

Critical Illness-Associated Hypocalcemia

• Hypocalcemia occurs in up to 88% of critically ill patients and correlates with severity of illness (Acute Physiology and Chronic Health Evaluation II score) and patient mortality 4
• The frequency does not depend on specific ICU setting or presence of sepsis, but rather on overall illness severity 4
• Associated with hypomagnesemia, number of blood transfusions, and presence of acute renal failure 4

Essential Diagnostic Considerations

Key Laboratory Pitfalls

• Measure pH-corrected ionized calcium as the most accurate diagnostic test, since a 0.1 unit increase in pH decreases ionized calcium by approximately 0.05 mmol/L 2, 1
• Check magnesium levels in all hypocalcemic patients, as magnesium deficiency must be corrected first before calcium supplementation will be effective 1, 3
• Evaluate PTH levels to distinguish between PTH-mediated and non-PTH-mediated causes 2, 1
• Assess vitamin D status (25-hydroxyvitamin D levels) 1
• Check renal function (creatinine) to evaluate for chronic kidney disease 2, 1