Calcium-Creatinine Clearance Ratio is not Helpful in Differentiating Primary Hyperparathyroidism from Familial Hypercalcemic Hypocalciuria: A Study of 1,000 Patients

Objective: With increasing recognition of more subtle presentations of primary hyperparathyroidism (pHPT), laboratory values are frequently seen in a range that would be expected for patients who have familial hypercalcemic hypocalciuria (FHH). Calcium-creatinine clearance ratio (CCCR) has been advocated as a diagnostic tool to differentiate between these two disorders. However, it is limited by an indeterminate range (0.01 to 0.02). The aim of this study was to assess the relevance of CCCR in a modern series of patients with surgically managed pHPT.Methods: We performed a retrospective cohort study of 1,000 patients who underwent parathyroid surgery for pHPT over 11 years. CCCR was evaluated by degree of biochemical derangement, single versus multiple gland disease, and interfering medications.Results: Patient demographics and resected histopathology were typical for a current series of patients with pHPT. In retrospect, none of the patients were suspected to have FHH postoperatively. CCCR was <0.01 for 19.0%, between 0.01 and 0.02 for 43.7%, and >0.02 in 37.3%. Distribution of CCCR for patients free from interfering medications and different histologic subtypes were the same. One-third of the cohort had mild calcium elevations, more typical for FHH. Of these, almost two-thirds had a CCCR in a range suspect for FHH (<0.02).Conclusion: To our knowledge, this is the largest series to evaluate the validity of CCCR for patients with surgically confirmed pHPT. The utility of CCCR in screening for FHH is limited, as 63% of modern patients with confirmed pHPT have low values.Abbreviations: CaSR = calcium sensing receptor; CCCR = calcium-creatinine clearance ratio; CeE = calcium excretion; FHH = familial hypercalcemic hypocalciuria; pHPT = primary hyperparathyroidism; PTH = parathyroid hormone