What are the common causes of hypocalcemia (low calcium levels in the blood) in different patient populations, including pediatric, adult, and geriatric individuals?

Common 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 disorders of vitamin D metabolism. 1

Primary Etiologic Categories

Hypocalcemia results from either PTH-mediated or non-PTH-mediated mechanisms 1:

PTH-Mediated Causes (Low or Inappropriately Normal PTH)

Post-Surgical Hypoparathyroidism:

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

Primary Hypoparathyroidism (25% of cases):

• Autoimmune destruction of parathyroid glands 1
• Genetic abnormalities, particularly 22q11.2 deletion syndrome with 80% lifetime prevalence of hypocalcemia 1, 2
• Infiltrative disorders of the parathyroids 1

Magnesium Deficiency:

• Impairs PTH secretion and creates end-organ PTH resistance 1, 2
• Hypocalcemia will not resolve until magnesium levels are corrected 2
• Present in 28% of hypocalcemic patients 3
• Commonly precipitated by alcohol consumption 1, 2

Non-PTH-Mediated Causes (Elevated PTH)

Vitamin D Deficiency and Disorders:

• Impaired production of 1,25-dihydroxyvitamin D reduces intestinal calcium absorption 2
• Decreased vitamin D activation in kidney disease reduces duodenal and jejunal calcium absorption 1
• Malabsorption syndromes affecting vitamin D absorption 4

Chronic Kidney Disease:

• Phosphate retention leads to decreased ionized calcium, stimulating compensatory PTH release 1, 2
• Reduced vitamin D activation in diseased kidneys decreases intestinal calcium absorption 1
• Impaired passive intestinal calcium absorption 1

Medication-Induced Hypocalcemia:

• Bisphosphonates and denosumab: Can cause severe hypocalcemia, particularly in patients with vitamin D deficiency or renal impairment 1; denosumab directly suppresses bone resorption, increasing risk especially when creatinine clearance <30 mL/min 2
• Loop diuretics: Induce hypocalcemia through increased urinary calcium excretion 1, 2
• Calcium channel blockers: May reduce calcium levels by affecting calcium homeostasis 1
• Antiepileptics, aminoglycosides, and proton pump inhibitors: Associated with hypocalcemia in everyday clinical practice 5
• Cisplatin: Commonly associated with hypocalcemia 5

Post-Parathyroidectomy Hungry Bone Syndrome:

• Rapid bone remineralization after correction of hyperparathyroid bone disease 1
• Causes severe, prolonged hypocalcemia requiring aggressive calcium replacement 3

Citrate-Induced Hypocalcemia:

• Occurs during massive blood transfusion as citrate in blood products chelates calcium 1, 2
• Each unit of blood products contains approximately 3g of citrate that binds calcium 3
• Ionized calcium below 0.9 mmol/L predicts mortality better than fibrinogen, acidosis, or platelet count 2
• Citrate metabolism impaired by hypoperfusion, hypothermia, and hepatic insufficiency 2

Precipitating Factors and High-Risk Situations

Biological Stressors:

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

Dietary and Lifestyle Factors:

• Decreased oral calcium intake 1
• Alcohol consumption worsens hypocalcemia 1, 2
• Carbonated beverages, especially colas, may exacerbate hypocalcemia 1, 2

Special Population Considerations

Pediatric Populations:

• Williams syndrome: Idiopathic infantile hypercalcemia in first 2 years, but lifelong abnormalities of calcium metabolism may persist 6
• 22q11.2 deletion syndrome: 80% lifetime prevalence of hypocalcemia, can emerge at any age despite apparent childhood resolution 1, 2

Critically Ill Patients:

• Hypocalcemia is common in ICU settings 7
• Diagnosis complicated by hypoalbuminemia and acid-base disorders affecting total calcium concentration 7
• Measurement of ionized calcium is critical for determining true calcium status 7

Critical Diagnostic Pitfalls

Always measure pH-corrected ionized calcium (most accurate) rather than total calcium alone, as a 0.1 unit increase in pH decreases ionized calcium by approximately 0.05 mmol/L 1, 2

Check magnesium levels in all hypocalcemic patients—magnesium deficiency must be corrected first, as calcium supplementation will be ineffective without adequate magnesium 1, 2

Check PTH levels to distinguish between PTH-mediated (low/normal PTH) and non-PTH-mediated (elevated PTH) causes 1, 2

Evaluate vitamin D status (25-OH vitamin D levels) in all patients with hypocalcemia 1, 2

Assess renal function (creatinine) to evaluate for chronic kidney disease 1