What is the workup for hypocalcemia (low calcium levels)?

From the Guidelines

The workup for hypocalcemia should begin with confirming the low calcium level through repeat testing, including measurements of pH-corrected ionized calcium, magnesium, parathyroid hormone, and creatinine concentrations, as recommended in the management of adults with 22q11.2 deletion syndrome 1. The initial laboratory evaluation should include serum phosphorus, magnesium, albumin, creatinine, parathyroid hormone (PTH), and 25-hydroxyvitamin D levels to determine the underlying cause of hypocalcemia.

• If PTH is inappropriately low or normal in the setting of hypocalcemia, consider hypoparathyroidism or vitamin D deficiency, which are common in patients with 22q11.2 deletion syndrome 1.
• If PTH is elevated, this suggests secondary hyperparathyroidism due to calcium malabsorption, vitamin D deficiency, or renal disease. Additional tests may include urinary calcium excretion, alkaline phosphatase, and specific tests for suspected underlying conditions like celiac disease antibodies or genetic testing for familial hypocalcemia. Imaging studies such as renal ultrasound may be indicated if chronic kidney disease is suspected, or neck ultrasound if post-surgical hypoparathyroidism is a concern. Treatment depends on the severity and underlying cause but typically includes calcium supplementation and vitamin D supplementation, with daily calcium and vitamin D supplementation recommended for all adults with 22q11.2DS 1. Addressing the underlying cause is essential for long-term management, as is monitoring serum calcium, phosphorus, and urinary calcium to prevent complications from treatment, such as iatrogenic hypercalcemia, renal calculi, and renal failure 1.

From the FDA Drug Label

The usual adult dosage in hypocalcemic disorders ranges from 200 mg to 1 g (2 -10 mL) at intervals of 1 to 3 days depending on the response of the patient and/or results of serum ionized calcium determinations. Ionized calcium concentrations should be measured, to assist in dosage adjustment

The workup for hypocalcemia includes measuring serum ionized calcium levels to determine the severity of hypocalcemia and to guide treatment.

• Key steps in the workup include:
  • Measuring serum ionized calcium concentrations
  • Assessing the patient's symptoms and response to treatment
  • Adjusting the dosage of calcium replacement therapy based on the results of serum ionized calcium determinations 2

From the Research

Diagnosis of Hypocalcemia

The diagnosis of hypocalcemia involves measuring serum calcium levels, with levels below 2.15 mmol/L (<8.6 mg/dl) and ionized calcium below 1.15 mmol/L (4.6 mg/dl) considered hypocalcemic 3.

• Hypocalcemia can be divided into two categories: hypocalcemia with low serum phosphate level and hypocalcemia with normal to elevated serum phosphate level 4.
• The workup for hypocalcemia includes:
  • Measurement of serum calcium and phosphate levels
  • Measurement of parathyroid hormone (PTH) levels to differentiate between PTH-mediated and non-PTH mediated causes of hypocalcemia 5
  • Measurement of vitamin D levels to assess for disorders of vitamin D metabolism 6
  • Physical and laboratory findings, such as the time of onset of disease and accompanying illnesses, can provide clues to the underlying cause of hypocalcemia 4

Differential Diagnosis

The differential diagnosis of hypocalcemia includes:

• Hypoparathyroidism, characterized by impaired secretion of PTH 6, 4
• Disorders of vitamin D metabolism, such as vitamin D deficiency or resistance 6, 5
• Chronic renal failure, which can lead to hypocalcemia with high normal to high serum phosphate level 4
• Other causes, such as genetic abnormalities, parathyroid autoantibodies, and deposition of calcium in bone or soft tissues 4, 5

Treatment and Management

The treatment and management of hypocalcemia depend on the underlying cause and severity of the condition.

• Acute hypocalcemia is typically treated with intravenous calcium infusion to raise calcium levels and resolve symptoms 5, 7
• Chronic hypocalcemia is often treated with oral calcium and/or vitamin D supplementation 6, 5, 3
• In cases of hypoparathyroidism, recombinant human PTH(1-84) may be used to replace the missing hormone and correct serum calcium levels 5