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

Causes of Hypocalcemia

Hypocalcemia results from two main pathophysiological categories: PTH-mediated disorders (primarily hypoparathyroidism) and non-PTH-mediated disorders (including vitamin D deficiency, chronic kidney disease, hypomagnesemia, and medication effects). 1, 2

PTH-Mediated Causes

Hypoparathyroidism

• Postsurgical hypoparathyroidism is the most frequent cause of hypocalcemia, typically occurring after thyroid or parathyroid surgery 3, 4
• Genetic disorders, particularly 22q11.2 deletion syndrome, carry an 80% lifetime prevalence of hypocalcemia due to underlying parathyroid dysfunction 5, 1
• Hypocalcemia in these patients can emerge at any age, with the majority experiencing recurrence after initial neonatal hypocalcemia 5

Pseudohypoparathyroidism

• This condition involves resistance to PTH action rather than PTH deficiency 6
• Patients exhibit elevated PTH levels despite low calcium 6

Non-PTH-Mediated Causes

Vitamin D Disorders

• Impaired production of 1,25-dihydroxyvitamin D reduces intestinal calcium absorption 1, 6
• Vitamin D deficiency decreases gut absorption of dietary calcium 2
• Vitamin D-dependent rickets type I represents a specific genetic defect in vitamin D metabolism 6

Chronic Kidney Disease

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

Hypomagnesemia

• Magnesium deficiency impairs PTH secretion and creates PTH resistance 1, 7
• Hypocalcemia will not resolve until magnesium levels are corrected 1, 7

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 5
• Citrate in blood transfusions can cause acute hypocalcemia during massive transfusion 1

Precipitating Factors and High-Risk Situations

Biological Stress

• Surgery, fractures, injuries, childbirth, and infection increase hypocalcemia risk 5, 1, 8
• Perioperative periods represent particularly vulnerable times for calcium decompensation 1
• Fever, ischemia, and hypoxia can trigger hypocalcemic episodes 5

Dietary and Lifestyle Factors

• Decreased oral calcium intake contributes to hypocalcemia 1
• Alcohol consumption worsens hypocalcemia 5, 1, 8
• Carbonated beverages, especially colas, may exacerbate hypocalcemia 5, 1, 8

Life Stages

• Puberty and pregnancy are high-risk periods for hypocalcemia manifestation 1
• Acute illness of any type increases vulnerability 1

Important Clinical Pitfalls

• Hypocalcemia can occur at any age in patients with underlying parathyroid dysfunction, even without prior history 5
• Symptoms may be subtle and confused with psychiatric conditions such as anxiety or depression 1
• Hyperprolinemia, seen in some genetic syndromes, can contribute to seizure risk independent of calcium levels 5
• Always measure pH-corrected ionized calcium (most accurate) rather than total calcium alone 1, 8
• Check magnesium levels in all hypocalcemic patients, as hypomagnesemia must be corrected first 1, 8