What causes hypocalcemia (low calcium levels)?

Causes of Hypocalcemia

Hypocalcemia is primarily caused by hypoparathyroidism, vitamin D deficiency, and chronic kidney disease, with hypoparathyroidism being the most common cause (75% surgical, 25% primary). 1

Major Causes of Hypocalcemia

Parathyroid Hormone (PTH) Related Causes

• Hypoparathyroidism (most common cause of hypocalcemia)
  • Surgical hypoparathyroidism (75% of cases) - typically following thyroid or parathyroid surgery 1
  • Primary hypoparathyroidism (25% of cases) - may be genetic or autoimmune 1
• Genetic disorders with hypoparathyroidism, such as 22q11.2 deletion syndrome (80% lifetime prevalence of hypocalcemia) 2
• PTH resistance syndromes 3

Vitamin D Related Causes

• Vitamin D deficiency (inadequate intake, malabsorption, or insufficient sun exposure) 1
• Vitamin D-dependent rickets (hereditary disorders affecting vitamin D metabolism) 3
• Vitamin D resistance syndromes 3

Mineral Imbalances

• Hypomagnesemia (can impair PTH secretion and action) 4
• Phosphate retention (especially in chronic kidney disease) 2

Kidney-Related Causes

• Chronic kidney disease (CKD) - leads to phosphate retention, vitamin D metabolism impairment, and secondary hyperparathyroidism 2
• Renal tubular disorders that cause calcium wasting 3

Other Causes

• Acute pancreatitis (calcium sequestration) 3
• Massive blood transfusions (citrate binding of calcium) 3
• Tumor lysis syndrome (phosphate release) 3
• Medications (bisphosphonates, denosumab, certain antibiotics, anticonvulsants) 3
• Hungry bone syndrome (following parathyroid surgery) 3

Precipitating Factors

• Biological stress increases risk of hypocalcemia:
  • Surgery, fractures, or injuries 2, 5
  • Infections or acute illness 2, 4
  • Childbirth and pregnancy 2, 4
  • Puberty 4
• Dietary and lifestyle factors:
  • Alcohol consumption can worsen hypocalcemia 2
  • Carbonated beverages, especially colas, may worsen hypocalcemia 2, 5
  • Decreased oral calcium intake 4

Pathophysiological Mechanisms

• In chronic kidney disease, phosphate retention leads to decreased ionized calcium, which stimulates PTH release 2
• Decreased vitamin D activation in kidney disease reduces intestinal calcium absorption 2
• Hypomagnesemia impairs PTH secretion and reduces target organ responsiveness to PTH 4
• Calcium plays a crucial role in neuromuscular function; deficiency leads to increased neuronal excitability 5

Clinical Pearls and Pitfalls

• Hypocalcemia symptoms may be confused with psychiatric conditions, leading to misdiagnosis 2, 4
• Always check magnesium levels when evaluating hypocalcemia, as hypomagnesemia is a common contributor 4
• Monitor calcium levels during vulnerable periods (surgery, acute illness, pregnancy) in at-risk patients 2, 4
• Overcorrection of calcium can lead to hypercalcemia, renal calculi, and renal failure 2, 4
• Thyroid dysfunction, particularly hypothyroidism, may be associated with hypocalcemia and should be evaluated 2, 4

Diagnostic Approach

• Measure pH-corrected ionized calcium (most accurate method) 4
• Check parathyroid hormone (PTH) levels to determine if hypoparathyroidism is present 4
• Assess magnesium levels, as hypomagnesemia can contribute to hypocalcemia 4
• Monitor thyroid function, as hypothyroidism may be associated with hypocalcemia 4
• Check renal function (creatinine) to evaluate for potential kidney disease 4