Sporadic and MEN1-Related Primary Hyperparathyroidism: Differences in Clinical Expression and Severity

Abstract

Primary hyperparathyroidism (PHPT) is a common endocrine disease that is associated with multiple endocrine neoplasia type 1 (MEN1) in ;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 (21.33 ± 1.23 versus 20.74 ± 1.4, p = 0.008) and FN (21.13 ± 0.96 versus 20.6 ± 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.

Early-onset, progressive, frequent, extensive, and severe bone mineral and renal complications in multiple endocrine neoplasia type 1–associated primary hyperparathyroidism

“…In the latter patients, BMD values remained stable in all bone sites for the first 10 years of observation, followed by a progressive onset of bone loss in the 1/3DR until 15 years, but not in the LS or FN. (22)(23)(24) The current data also confirmed previous observations documenting frequent trabecular bone demineralization in MEN1, (14)(15)(16)20) in contrast to the findings reported in SPHPT. (17)(18)(19) Our BMD findings may be due to several factors.…”

“…(14)(15)(16)20) However, investigations of the outcome of bone mineral-and urolithiasis-related renal comorbidities in HPT/ MEN1 are lacking. In this study, our new BMD data indicate that bone demineralization in 36 MEN1-associated HPT patients was an early-onset, progressive, frequent, extensive, and severe event.…”

“…(1)(2)(3)(14)(15)(16) Thus relative protection of the trabecular bone has been documented in SPHPT, although up to 15% of these patients may present with vertebral osteopenia. (17)(18)(19) In contrast, high frequencies (>40%) and more severe degrees of lumbar spine (LS) demineralization have been reported in patients with HPT/MEN1.…”

“…(17)(18)(19) In contrast, high frequencies (>40%) and more severe degrees of lumbar spine (LS) demineralization have been reported in patients with HPT/MEN1. (14)(15)(16) Even though basal proximal onethird of the distal radius (1/3DR) bone mineral density (BMD) profiles are similar in both diseases, short-term bone recovery after PTX may differ. (1)(2)(3)15,17,20,21) In addition, the early and late natural history of the bone disease in SPHPT has been underscored in prospective studies of untreated patients with follow-ups of up to 15 years.…”

Application of an intracellular stability test of a novel missense menin mutant to the diagnosis of multiple endocrine neoplasia type 1

“…Although observed biochemical changes were subtle and imaging studies failed to detect any abnormalities in either individual, it is likely that they had already developed the disease. Indeed, in contrast to sporadic PHPT, a significant proportion of PHPT developed in MEN1 patients show marginal biochemical abnormalities [17]. Future surveillance for three sons was thus warranted.…”