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

Abstract 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.