What are the possible causes of hypocalcemia?

From the Guidelines

Hypocalcemia can be caused by several conditions, including hypoparathyroidism, vitamin D deficiency, chronic kidney disease, magnesium deficiency, and certain medications, as well as critical illness and genetic disorders such as 22q11.2 deletion syndrome. The possible causes of hypocalcemia can be categorized into several groups, including:

• Hormonal imbalances, such as hypoparathyroidism, which can occur after thyroid or parathyroid surgery, or due to genetic disorders like 22q11.2 deletion syndrome 1
• Nutritional deficiencies, including vitamin D deficiency, which is essential for calcium absorption in the intestines, and magnesium deficiency, which impairs parathyroid hormone secretion and action
• Kidney disease, which can lead to hypocalcemia through reduced vitamin D activation and phosphate retention, as seen in chronic kidney disease 1
• Medications, such as bisphosphonates, denosumab, anticonvulsants, and some chemotherapy agents, which can induce hypocalcemia
• Critical illness, including sepsis, acute pancreatitis, and massive blood transfusions with citrated blood products, which can disrupt calcium regulation
• Genetic disorders, such as 22q11.2 deletion syndrome, which can cause hypocalcemia due to hypoparathyroidism, hypothyroidism, and hypomagnesemia 1 It is essential to recognize these causes to provide proper diagnosis and management of hypocalcemia, as untreated hypocalcemia can lead to fatigue, emotional irritability, abnormal involuntary movements, seizures, and cardiac arrhythmias. Regular investigations, including measurements of pH-corrected ionized calcium, magnesium, parathyroid hormone, and creatinine concentrations, are recommended, especially in individuals with a history of hypocalcemia or at risk of developing it 1.

From the FDA Drug Label

The kidneys of uremic patients cannot adequately synthesize calcitriol, the active hormone formed from precursor vitamin D. Resultant hypocalcemia and secondary hyperparathyroidism are a major cause of the metabolic bone disease of renal failure.

The possible cause of hypocalcemia is the inability of the kidneys to adequately synthesize calcitriol, leading to a deficiency in active vitamin D and subsequent disruption of calcium metabolism.

• Key factors that may contribute to hypocalcemia include:
  • Renal failure
  • Inadequate synthesis of calcitriol
  • Secondary hyperparathyroidism 2

From the Research

Possible Causes of Hypocalcemia

The possible causes of hypocalcemia can be categorized into several groups, including:

• Hypoparathyroidism, which can be caused by:
  • Iatrogenic factors, such as anterior neck surgery 3
  • Congenital or acquired disorders, including autoimmune diseases and genetic abnormalities 3
  • Destruction or infiltrative disorders of the parathyroids 3
• Vitamin D deficiency or altered vitamin D metabolism, which can contribute to hypocalcemia in patients with hypoparathyroidism 4
• Drug-induced hypocalcemia, which can be caused by:
  • Antiepileptics, such as phenytoin, particularly in patients with concomitant vitamin D deficiency 5, 6
  • Aminoglycosides and proton pump inhibitors 6
  • Bisphosphonates and cisplatin 6
• Other causes, including:
  • Kidney disease, which can lead to secondary hyperparathyroidism, but also primary hyperparathyroidism should be considered, especially if concomitant vitamin D deficiency is suspected 7
  • Hypomagnesemia or hypermagnesemia, which can impair secretion of parathyroid hormone (PTH) 3