What are the causes of hypocalcemia (low calcium levels) in a hospitalized patient?

Causes of Hypocalcemia in Hospitalized Patients

Hypocalcemia in hospitalized patients results from multiple mechanisms including hypoparathyroidism (most commonly post-surgical), vitamin D deficiency, acute kidney injury, critical illness with hypomagnesemia, drug-induced causes, and gastrointestinal losses from diarrhea.

Primary Endocrine and Metabolic Causes

Hypoparathyroidism

• Post-surgical hypoparathyroidism accounts for 75% of all hypoparathyroidism cases, typically following thyroid or parathyroid surgery, resulting in impaired PTH secretion and inability to maintain calcium homeostasis 1, 2.
• Primary hypoparathyroidism represents the remaining 25% of cases and leads to chronic hypocalcemia requiring careful management 1.
• PTH deficiency or resistance disrupts the body's ability to mobilize calcium from bone and enhance renal calcium reabsorption 2.

Vitamin D Disorders

• Vitamin D deficiency is a major cause of hypocalcemia as it impairs intestinal absorption of dietary calcium 2, 3.
• Disorders disrupting vitamin D metabolism prevent adequate gut calcium absorption, leading to progressive hypocalcemia 2.

Renal Causes

Acute Kidney Injury and Chronic Kidney Disease

• Kidney failure is characterized by multiple electrolyte abnormalities including hypocalcemia, along with hypokalemia, hypomagnesemia, and hypophosphatemia 4.
• Renal insufficiency impairs vitamin D activation (1,25-dihydroxyvitamin D production), reducing calcium absorption 5.
• Moderate to severe renal failure directly contributes to hypocalcemia through disrupted calcium-phosphate homeostasis 5.

Drug-Induced Hypocalcemia

Common Medications

• Bisphosphonates and cisplatin are well-recognized causes of drug-induced hypocalcemia 6.
• Loop diuretics promote calciuresis (urinary calcium loss), particularly problematic in elderly patients with baseline renal impairment 5.
• Glucocorticoid therapy causes sodium retention and calciuresis, worsening hypocalcemia 5.
• Antiepileptics, aminoglycosides, and proton pump inhibitors can induce hypocalcemia during routine clinical use 6.
• Drug-related hypocalcemia is frequently missed due to multiple coexisting factors contributing to low calcium levels 6.

Critical Illness and Electrolyte Disturbances

Hypomagnesemia

• Hypomagnesemia (serum magnesium <0.70 mmol/L) is present in up to 60-65% of critically ill patients and frequently accompanies hypocalcemia 4.
• Magnesium deficiency impairs PTH secretion and creates PTH resistance, making hypocalcemia refractory to treatment until magnesium is corrected 4.

Metabolic Alkalosis

• Metabolic alkalosis increases protein binding of calcium, reducing ionized calcium levels even when total calcium appears adequate 7.
• This mechanism is particularly relevant in patients with vomiting or receiving diuretics 7.

Gastrointestinal Losses

Diarrhea and Malabsorption

• Acute diarrhea causes hypocalcemia through direct intestinal losses and is recognized by multiple professional societies as a significant cause 7.
• Diarrheal states commonly cause hypomagnesemia (60-65% incidence in critically ill patients) and hypokalemia (12-25% prevalence), which compound hypocalcemia 7.
• Intestinal losses of phosphate through diarrhea can contribute to broader electrolyte disturbances 8.

Hospital-Specific Risk Factors

Kidney Replacement Therapy

• Kidney replacement therapy is a significant risk factor, with hypophosphatemia prevalence rising to 80% during prolonged KRT modalities, often accompanied by hypocalcemia 8.
• Dialysis solutions should contain potassium, phosphate, and magnesium to prevent electrolyte disorders during therapy 4.

Refeeding Syndrome

• Refeeding syndrome triggers significant hypophosphatemia and can precipitate hypocalcemia in malnourished hospitalized patients 8.

Clinical Severity and Presentation

Acute vs. Chronic Hypocalcemia

• Severe acute hypocalcemia (<2.0 mmol/L) manifests as hypocalcemic tetany with neuromuscular irritability, tetany, and seizures requiring immediate IV calcium replacement 1, 2.
• Chronic hypocalcemia presents with more subtle manifestations and requires identification of the underlying disorder for appropriate management 2.
• Ionized calcium <1.1 mmol/L or symptomatic hypocalcemia warrants calcium replacement, with calcium chloride preferred over calcium gluconate for acute correction 7.

Important Clinical Pitfalls

Cardiac Manifestations

• Hypocalcemia can cause heart failure in elderly patients, particularly when combined with renal failure, vitamin D deficiency, and diuretic use 5.
• Prolonged QT interval on ECG indicates clinically significant hypocalcemia and increases arrhythmia risk 7.
• Combined electrolyte deficiencies (calcium, magnesium, potassium) significantly increase cardiac risk 4.

Diagnostic Considerations

• Drug-induced hypocalcemia is usually mild and asymptomatic but can be severe, requiring awareness of pharmaceutical compounds affecting calcium levels 6.
• Multiple coexisting factors in hospitalized patients make identifying the primary cause challenging 6, 5.
• Serum calcium, phosphorus, intact PTH, electrophoresis, and renal function parameters guide further diagnostic workup to identify the underlying cause 1.