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

From the Guidelines

Hypocalcemia should be treated with an individualized approach, considering the severity, symptoms, and underlying cause, and patients with significant or symptomatic hypocalcemia could still benefit from correction to prevent adverse consequences. Treatment depends on the severity, symptoms, and underlying cause. For severe symptomatic hypocalcemia (with tetany, seizures, or QT prolongation), immediate intravenous calcium is necessary, usually as calcium gluconate 1-2 grams (10-20 mL of 10% solution) administered slowly over 10-20 minutes, followed by a continuous infusion of 0.5-1.5 mg/kg/hour until oral therapy can be established 1. For chronic or less severe hypocalcemia, oral calcium supplementation with calcium carbonate 1000-2000 mg elemental calcium daily in divided doses is recommended, along with vitamin D supplementation (typically calcitriol 0.25-1 mcg daily) to enhance intestinal calcium absorption 1. Underlying causes such as hypoparathyroidism, vitamin D deficiency, or kidney disease must be addressed simultaneously. Magnesium levels should be checked and corrected if low, as hypomagnesemia can cause refractory hypocalcemia by impairing parathyroid hormone secretion and action 1. Regular monitoring of serum calcium, phosphorus, magnesium, and kidney function is essential during treatment to prevent overcorrection, which can lead to hypercalcemia and kidney stones or calcification 1.

Some key points to consider in the treatment of hypocalcemia include:

• The use of calcium-based phosphate binders should be restricted in adult patients with CKD G3a to G5D receiving phosphate-lowering treatment 1.
• Decisions about phosphate-lowering treatment should be based on progressively or persistently elevated serum phosphate in patients with CKD G3a to G5D 1.
• The dialysate calcium concentration should be between 1.25 and 1.50 mmol/L (2.5 and 3.0 mEq/L) in patients with CKD G5D 1.
• Patients with 22q11.2 deletion syndrome are at increased risk of hypocalcemia and should receive daily calcium and vitamin D supplementation, as well as regular monitoring of calcium concentrations 1.

Overall, the treatment of hypocalcemia requires a comprehensive approach that takes into account the underlying cause, severity, and symptoms, as well as the potential risks and benefits of different treatment strategies.

From the FDA Drug Label

Maternal hypocalcemia can result in an increased rate of spontaneous abortion, premature and dysfunctional labor, and possibly preeclampsia Fetal/Neonatal adverse reactions Infants born to mothers with hypocalcemia can have associated fetal and neonatal hyperparathyroidism, which in turn can cause fetal and neonatal skeletal demineralization, subperiosteal bone resorption, osteitis fibrosa cystica and neonatal seizures Infants born to mothers with hypocalcemia should be carefully monitored for signs of hypocalcemia or hypercalcemia, including neuromuscular irritability, apnea, cyanosis and cardiac rhythm disorders

Hypocalcemia can result in serious complications for both the mother and the fetus, including:

• Increased risk of spontaneous abortion, premature and dysfunctional labor, and possibly preeclampsia
• Fetal and neonatal hyperparathyroidism, which can cause skeletal demineralization, subperiosteal bone resorption, osteitis fibrosa cystica, and neonatal seizures Infants born to mothers with hypocalcemia should be carefully monitored for signs of hypocalcemia or hypercalcemia 2 3.

From the Research

Definition and Causes of Hypocalcemia

• Hypocalcemia is a condition characterized by low serum calcium levels, which can be life-threatening if severe 4, 5.
• It can occur in conjunction with multiple disorders, including hypoparathyroidism, which is a classic cause of chronic hypocalcemia 4.
• Disorders that disrupt the metabolism of vitamin D can also lead to chronic hypocalcemia, as vitamin D is responsible for increasing the gut absorption of dietary calcium 4.

Symptoms and Diagnosis of Hypocalcemia

• Symptoms of acute hypocalcemia include neuromuscular irritability, tetany, and seizures, which are rapidly resolved with intravenous administration of calcium gluconate 4.
• Chronic hypocalcemia often has more subtle manifestations, and its diagnosis requires knowledge of the factors that influence the complex regulatory axes of calcium homeostasis in a given disorder 4.
• The diagnosis of hypocalcemia involves measuring serum calcium levels, and it can be divided into parathyroid hormone (PTH) and non-PTH mediated forms 5.

Treatment and Management of Hypocalcemia

• Treatment and management options for chronic hypocalcemia vary depending on the underlying disorder 4.
• Intravenous calcium infusion is essential to raise calcium levels and resolve or minimize symptoms in the setting of acute hypocalcemia 5.
• Oral calcium and/or vitamin D supplementation is the most frequently used treatment for chronic hypocalcemia 5.
• In hypoparathyroidism, providing the missing hormone with the use of the recombinant human (rh) PTH(1-84) has been recently approved and has the advantage of being effective for correcting serum calcium levels and significantly reducing the daily requirements of calcium and active vitamin D supplements 5, 6.

Complications and Long-term Management of Hypocalcemia

• Complications of current therapies for hypoparathyroidism include hypercalciuria, nephrocalcinosis, renal impairment, and soft tissue calcification 7.
• Long-term management of hypocalcemia requires careful monitoring of serum calcium levels and adjustment of treatment as needed to prevent complications 7.
• Hypocalcemia can lead to heart failure with reduced ejection fraction and dilated cardiomyopathy, and its treatment requires early recognition and aggressive correction 8.