Causes of Hypocalcemia
Hypocalcemia is commonly caused by hypoparathyroidism, vitamin D deficiency, magnesium deficiency, chronic kidney disease, and certain medications, with symptoms ranging from mild neuromuscular irritability to life-threatening seizures and cardiac arrhythmias. 1
Primary Causes
Parathyroid Hormone (PTH) Related Causes
- Hypoparathyroidism
Vitamin D Related Causes
- Vitamin D deficiency
- Disorders of vitamin D metabolism
- Vitamin D resistance 1
Mineral Imbalances
- Hypomagnesemia - critical as magnesium deficiency impairs parathyroid hormone release and action 4
- Hyperphosphatemia - especially in chronic kidney disease 3
Medication-Induced Hypocalcemia
- Bisphosphonates
- Cisplatin
- Antiepileptics
- Aminoglycosides
- Proton pump inhibitors 5
- Calcium channel blockers 6
Other Causes
- Acute pancreatitis
- Tumor lysis syndrome
- Hungry bone syndrome (post-parathyroidectomy)
- Critical illness
- Massive blood transfusions (citrate binding)
Special Populations and Considerations
22q11.2 Deletion Syndrome
- 80% of patients have lifetime history of hypocalcemia 3
- Typically due to hypoparathyroidism as part of the syndrome
- Hypocalcemia can recur during periods of biological stress:
- Surgery
- Childbirth
- Infection
- Puberty 3
- Can be worsened by alcohol or carbonated beverages 3
Chronic Kidney Disease
- Phosphate retention leads to hypocalcemia
- Decreased production of 1,25-dihydroxycholecalciferol
- Skeletal resistance to PTH 3
Clinical Manifestations
Neuromuscular
- Tetany
- Paresthesias
- Muscle cramps
- Tremors
- Rigidity 3
Neurological
- Seizures (may be first sign of hypocalcemia in 22q11.2DS) 3
- Confusion
- Behavioral changes
Cardiovascular
- Prolonged QT interval
- Cardiac arrhythmias
- Hypotension
- Bradycardia 6
Diagnostic Approach
Laboratory Evaluation
- Serum calcium (total and ionized)
- Parathyroid hormone (PTH)
- Vitamin D levels (25-OH and 1,25-OH)
- Magnesium
- Phosphate
- Creatinine/kidney function 3, 7
Key Diagnostic Patterns
- Low calcium + low/inappropriately normal PTH = hypoparathyroidism
- Low calcium + high PTH = secondary hyperparathyroidism (vitamin D deficiency, CKD)
- Low calcium + low magnesium = consider magnesium deficiency first 4
Management Considerations
Acute Symptomatic Hypocalcemia
- Intravenous calcium gluconate for rapid correction 6, 7
- Monitor ECG during administration, especially with concurrent cardiac glycosides 6
Chronic Hypocalcemia
- Oral calcium and vitamin D supplementation
- Magnesium replacement if deficient 4
- For hypoparathyroidism: recombinant human PTH may be considered 7
Important Clinical Pearls
- Hypocalcemia in the setting of normal PTH should prompt evaluation for magnesium deficiency 4
- Refractory hypocalcemia often indicates underlying magnesium deficiency 4
- Patients with 22q11.2 deletion syndrome require vigilant monitoring, especially during periods of stress 3
- Medication review is essential in any patient presenting with hypocalcemia 5
- Treatment of hypocalcemia in CKD patients should follow specific guidelines based on their stage of kidney disease 3
By understanding these various causes and their mechanisms, clinicians can better diagnose and manage hypocalcemia, potentially preventing serious complications such as seizures, cardiac arrhythmias, and decreased quality of life.