What are the causes of hypocalcemia (low calcium levels)?

Causes of Hypocalcemia

Hypocalcemia results from either inadequate parathyroid hormone (PTH) secretion, resistance to PTH or vitamin D, or conditions that impair calcium homeostasis through non-PTH mechanisms. 1

PTH-Mediated Causes

Hypoparathyroidism

• Postsurgical hypoparathyroidism is the most common cause of hypocalcemia, typically occurring after anterior neck surgery including thyroidectomy or parathyroidectomy 2, 3
• Genetic disorders, particularly 22q11.2 deletion syndrome, carry an 80% lifetime prevalence of hypocalcemia due to underlying parathyroid dysfunction 1
• Autoimmune destruction of the parathyroid glands can cause chronic hypoparathyroidism 3
• Congenital absence or underdevelopment of the parathyroid glands represents a rare cause 3
• Infiltrative disorders (hemochromatosis, Wilson's disease, metastatic disease) can destroy parathyroid tissue 3

Magnesium Disorders

• Hypomagnesemia impairs PTH secretion and creates PTH resistance, and hypocalcemia will not resolve until magnesium levels are corrected 1, 4
• Hypermagnesemia can also impair PTH secretion 3
• The normalization of calcium levels requires approximately 4 days after initiating magnesium therapy, even when PTH levels normalize within 24 hours 4

Pseudohypoparathyroidism

• PTH resistance at target organs causes elevated PTH levels with hypocalcemia and hyperphosphatemia 3

Non-PTH-Mediated Causes

Vitamin D Deficiency and Disorders

• Impaired production of 1,25-dihydroxyvitamin D reduces intestinal calcium absorption 1
• Vitamin D deficiency from inadequate sun exposure or dietary intake is a common cause 5
• Malabsorption syndromes (celiac disease, inflammatory bowel disease, chronic pancreatitis) impair vitamin D absorption 5

Chronic Kidney Disease

• Phosphate retention in renal failure leads to decreased ionized calcium, stimulating PTH release and causing secondary hyperparathyroidism 6, 1
• Decreased vitamin D activation in kidney disease compounds the problem by reducing intestinal calcium absorption 6, 1

Medication-Induced Hypocalcemia

• Loop diuretics induce hypocalcemia through increased urinary calcium excretion 1
• Calcium channel blockers may reduce calcium levels by affecting calcium homeostasis 1
• Antipsychotic medications can precipitate hypocalcemia, particularly in vulnerable patients 1
• Bisphosphonates can cause hypocalcemia, especially in patients with multiple myeloma 6
• Citrate in blood transfusions can cause acute hypocalcemia during massive transfusion 6, 1

Acute Pancreatitis

• Calcium sequestration in areas of fat necrosis can cause acute hypocalcemia 5

Tumor Lysis Syndrome

• Rapid cell breakdown releases phosphate, which binds calcium and causes acute hypocalcemia 5

Hungry Bone Syndrome

• Rapid bone remineralization after parathyroidectomy causes severe hypocalcemia 5

Precipitating Factors and High-Risk Situations

Biological Stress

• Surgery, fractures, injuries, childbirth, and infection increase hypocalcemia risk 6, 1
• Perioperative periods represent particularly vulnerable times for calcium decompensation 1
• Fever, ischemia, and hypoxia can trigger hypocalcemic episodes 1
• Acute illness of any type increases vulnerability 1

Life Stages

• Puberty and pregnancy are high-risk periods for hypocalcemia manifestation 6, 1
• Maternal hypocalcemia can result in increased rates of spontaneous abortion, premature and dysfunctional labor, and possibly preeclampsia 7

Dietary and Lifestyle Factors

• Decreased oral calcium intake contributes to hypocalcemia 1
• Alcohol consumption worsens hypocalcemia 6, 1
• Carbonated beverages, especially colas, may exacerbate hypocalcemia 6, 1

Critical Diagnostic Pitfalls

• Always measure pH-corrected ionized calcium (most accurate) rather than total calcium alone 6, 1
• Check magnesium levels in all hypocalcemic patients, as hypomagnesemia must be corrected first 1, 4
• The European Society of Cardiology recommends not administering calcium without first correcting magnesium, as it will be ineffective 4
• Less than 1% of the body's total magnesium is in extracellular fluids, so patients can have magnesium deficiency despite normal serum concentrations 4
• Hypocalcemia can occur at any age in patients with underlying parathyroid dysfunction, even without prior history 1
• Symptoms may be subtle and confused with psychiatric conditions such as anxiety or depression 6, 1