How is the urinary calcium to serum calcium ratio calculated for suspected Familial Hypocalciuric Hypercalcemia (FHH)?

From the Research

The urinary calcium to serum calcium ratio for suspected Familial Hypocalciuric Hypercalcemia (FHH) is calculated by dividing the 24-hour urinary calcium excretion (in mg) by the serum calcium level (in mg/dL), yielding the calcium to creatinine clearance ratio (CCCR), with a value less than 0.01 strongly suggesting FHH. To perform this test, collect a complete 24-hour urine sample while simultaneously measuring serum calcium and creatinine levels. The formula is: CCCR = (24-hour urine calcium × serum creatinine) ÷ (serum calcium × 24-hour urine creatinine) × 100. This ratio is particularly useful because FHH patients have a genetic defect in the calcium-sensing receptor that causes increased renal calcium reabsorption, resulting in inappropriately low urinary calcium excretion despite elevated serum calcium levels, as noted in studies such as 1. Accurate collection of the 24-hour urine sample is essential for reliable results, and patients should maintain their normal diet and fluid intake during collection. A CCCR value less than 0.01 (or 1%) strongly suggests FHH, while values above 0.02 (or 2%) typically indicate other causes of hypercalcemia such as primary hyperparathyroidism, as supported by the most recent and highest quality study 1. Key points to consider in the calculation and interpretation of the urinary calcium to serum calcium ratio include:

• The importance of accurate 24-hour urine collection for reliable results
• The use of the CCCR formula to calculate the ratio
• The interpretation of CCCR values, with less than 0.01 suggesting FHH and values above 0.02 suggesting other causes of hypercalcemia
• The consideration of genetic testing for confirmation of FHH, as discussed in studies such as 2. Overall, the calculation and interpretation of the urinary calcium to serum calcium ratio are critical in differentiating FHH from other causes of hypercalcemia, and should be performed with attention to detail and consideration of the most recent and highest quality evidence, such as that provided by 1.