Sporadic and MEN1-related primary hyperparathyroidism: differences in clinical expression and severity

Primary hyperparathyroidism (PHPT) is a common endocrine disease that is associated with multiple endocrine neoplasia type 1 (MEN1) in approximately 2% of PHPT cases. Lack of a family history and other specific expressions may lead to underestimated MEN1 prevalence in PHPT. The aim of this study was to identify clinical or biochemical features predictive of MEN1 and to compare the severity of the disease in MEN1-related versus sporadic PHPT (sPHPT). We performed a 36-mo cross-sectional observational study in three tertiary referral centers on an outpatient basis on 469 consecutive patients with sporadic PHPT and 64 with MEN1-related PHPT. Serum calcium, phosphate, PTH, 25(OH)D(3), and creatinine clearance were measured, and ultrasound examination of the urinary tract/urography was performed in all patients. In 432 patients, BMD was measured at the lumbar spine (LS) and femoral neck (FN). MEN1 patients showed lower BMD Z-scores at the LS (-1.33 +/- 1.23 versus -0.74 +/- 1.4, p = 0.008) and FN (-1.13 +/- 0.96 versus -0.6 +/- 1.07, p = 0.002) and lower phosphate (2.38 +/- 0.52 versus 2.56 +/- 0.45 mg/dl, p = 0.003) and PTH (113.8 +/- 69.5 versus 173.7 +/- 135 pg/ml, p = 0.001) levels than sPHPT patients. Considering probands only, the presence of MEN1 was more frequently associated with PTH values in the normal range (OR, 3.01; 95% CI, 1.07-8.50; p = 0.037) and younger age (OR, 1.61; 95% CI, 1.28-2.02; p = 0.0001). A combination of PTH values in the normal range plus age <50 yr was strongly associated with MEN1 presence (OR, 13.51; 95% CI, 3.62-50.00; p = 0.0001). In conclusion, MEN1-related PHPT patients show more severe bone but similar kidney involvement despite a milder biochemical presentation compared with their sPHPT counterparts. Normal PTH levels and young age are associated with MEN1 presence.