Incidence and Clinical Spectrum of Thiazide-associated Hypercalcemia

Purpose: The study determines the incidence of thiazide-associated hypercalcemia and clarifies its clinical features and natural history. Methods: In a population-based descriptive study, Olmsted County, Minn, residents with thiazide-associated hypercalcemia were identified through the Rochester Epidemiology Project and the Mayo Clinic Laboratory Information System. Changes in incidence rates were evaluated by Poisson regression. Results: Seventy-two Olmsted County residents (68 women and 4 men; mean age, 64 years) with thiazide-associated hypercalcemia first recognized in 1992 to 2001 were identified. The overall annual age- and sex-adjusted (to 2000 US whites) incidence was 7.7 (95% confidence interval [CI], 5.9-9.5) per 100,000. There was an increase in incidence after 1996, peaking at 16.3 (95% CI, 8.3-24.3) per 100,000 in 1998. The highest rate was 55.3 per 100,000 in 70- to 79-year-old women. Hypercalcemia was identified a mean of 6 ± 7 years after thiazide initiation, and the average highest serum calcium was 10.7 ± 0.3 mg/dL with serum parathyroid hormone (obtained in 53 patients) of 4.8 ± 2.7 pmol/L. Of 33 patients who discontinued the thiazide, 21 (64%) had persistent hypercalcemia. Patients subsequently diagnosed with primary hyperparathyroidism had the highest average serum calcium and parathyroid hormone levels of 11.0 ± 0.3 mg/dL and 6.3 ± 2.4 pmol/L, respectively. Conclusion: The persistence of hypercalcemia in patients discontinuing thiazides, and similarities in the clinical spectrum, suggest that underlying primary hyperparathyroidism is common in patients who develop hypercalcemia while taking thiazide diuretics.