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.