What causes hypocalcemia?

Causes of Hypocalcemia

Hypocalcemia results from either inadequate parathyroid hormone (PTH) secretion, impaired vitamin D metabolism, or conditions that disrupt calcium homeostasis—with hypoparathyroidism and vitamin D deficiency being the most common chronic causes. 1, 2

PTH-Mediated Causes

Hypoparathyroidism is the classic cause of chronic hypocalcemia and accounts for the majority of cases requiring long-term management. 3

• Surgical hypoparathyroidism represents 75% of hypoparathyroidism cases, typically following thyroid or parathyroid surgery 4
• Primary hypoparathyroidism accounts for 25% of cases 4
• Genetic disorders, particularly 22q11.2 deletion syndrome, carry an 80% lifetime prevalence of hypocalcemia due to underlying parathyroid dysfunction 2
• Hypocalcemia in genetic disorders can emerge at any age, even without prior neonatal history 2

Vitamin D-Related Causes

Disorders disrupting vitamin D metabolism lead to chronic hypocalcemia by reducing intestinal calcium absorption. 3

• Vitamin D deficiency is a common and often overlooked cause 4
• Impaired production of 1,25-dihydroxyvitamin D reduces intestinal calcium absorption 2
• Decreased vitamin D activation in kidney disease compounds hypocalcemia by reducing intestinal calcium absorption and leads to secondary hyperparathyroidism 2

Renal Causes

Chronic kidney disease creates hypocalcemia through multiple mechanisms. 1

• Phosphate retention in renal failure leads to decreased ionized calcium, which stimulates PTH release 2
• Decreased vitamin D activation further reduces intestinal calcium absorption 2
• This dual mechanism leads to secondary hyperparathyroidism 2

Magnesium Deficiency

Hypomagnesemia is a critical and often missed cause that must be identified and corrected first. 2

• Magnesium deficiency impairs PTH secretion and creates PTH resistance 2
• Hypocalcemia will not resolve until magnesium levels are corrected 2
• Always check magnesium levels in all hypocalcemic patients 2

Medication-Induced Causes

Several medications can precipitate hypocalcemia and should be reviewed in any hypocalcemic patient. 2

• Loop diuretics induce hypocalcemia through increased urinary calcium excretion 2
• Calcium channel blockers may reduce calcium levels by affecting calcium homeostasis 2
• Antipsychotic medications can precipitate hypocalcemia, particularly in vulnerable patients 2
• Bisphosphonates (such as alendronate) can contribute to hypocalcemia, especially in patients with underlying parathyroid dysfunction 5
• Citrate in blood transfusions causes acute hypocalcemia during massive transfusion by chelating calcium 1, 2

Precipitating Factors and High-Risk Situations

Even patients with stable calcium levels can decompensate during periods of biological stress. 1, 2

• Surgery, fractures, injuries, childbirth, and infection increase hypocalcemia risk 2
• Perioperative periods represent particularly vulnerable times for calcium decompensation 2
• Fever, ischemia, and hypoxia can trigger hypocalcemic episodes 2
• Puberty and pregnancy are high-risk periods for hypocalcemia manifestation 2
• Acute illness of any type increases vulnerability 2

Dietary and Lifestyle Factors

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

Critical Diagnostic Pitfalls to Avoid

• 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, as hypomagnesemia must be corrected first or hypocalcemia will persist 2
• Symptoms may be subtle and confused with psychiatric conditions such as anxiety or depression 2
• Hypocalcemia can occur at any age in patients with underlying parathyroid dysfunction, even without prior history 2
• In pregnant women, hypocalcemia can result in increased spontaneous abortion, premature and dysfunctional labor, and possibly preeclampsia 6
• Infants born to mothers with hypocalcemia can have associated fetal and neonatal hyperparathyroidism, skeletal demineralization, and neonatal seizures 6