End-organ effects of primary hyperparathyroidism: A population-based study.

Background: Patients with primary hyperparathyroidism are at risk for skeletal and renal end-organ damage.

Methods: We studied patients with biochemically confirmed primary hyperparathyroidism from 1995-2014 and quantified the frequency of osteoporosis, nephrolithiasis, hypercalciuria, and decrease in renal function.

Results: The cohort comprised 9,485 patients. In total, 3,303 (35%) had preexisting end-organ effects (osteoporosis, 24%; nephrolithiasis, 10%; hypercalciuria, 5%). Of 6,182 remaining patients, 1,769 (29%) exhibited progression to 1 or more end-organ effects over a median 3.7 years. Among patients with classic primary hyperparathyroidism (calcium and parathyroid hormone increased), progression was unrelated to the degree of hypercalcemia (calcium >11.5 mg/dL, hazard ratio 1.03, 95% confidence interval 0.85-1.25; 11.1-11.5 mg/dL, HR 1.07, 95% confidence interval 0.93-1.23; 10.5-11.0 mg/dL = reference). Patients with nonclassic primary hyperparathyroidism (calcium increased, parathyroid hormone 40-65 pg/mL) had a lesser risk of progression (calcium >11.5 mg/dL, hazard ratio 0.68, 95% confidence interval 0.50-0.94; 11.1-11.5 mg/dL, hazard ratio 0.68, 95% confidence interval 0.56-0.82; 10.5-11.0 mg/dL, hazard ratio 0.66, 95% confidence interval 0.59-0.74). End-organ damage developed before or within 5 years of diagnosis for 62% of patients.

Conclusion: End-organ manifestations of primary hyperparathyroidism develop before biochemical diagnosis or within 5 years in most patients. End-organ damage occurred more frequently in patients with classic primary hyperparathyroidism versus nonclassic primary hyperparathyroidism, regardless of severity of hypercalcemia.