Abstract
Background: Multiple endocrine neoplasia type 1 (MEN1)-related primary hyperparathyroidism (MPHPT) belongs to genetic PHPT that accounts for 10% of all PHPT cases, being considered the most frequent hereditary PHPT (less than 5% of all PHPT). Objective: We aimed to provide an updated clinical perspective with a double purpose: to highlight the clinical features in MPHPT, particularly, the bone health assessment, as well as the parathyroidectomy (PTx) impact. Methods: A comprehensive review of the latest 5-year, English-published, PubMed-accessed original studies. Results: The sample-based analysis (n = 17 studies) enrolled 2426 subjects (1720 with MPHPT). The study design was retrospective, except for one prospective and one case-control study. The maximum number of patients per study was of 517. Female predominance (an overall female-to-male ratio of 1.139) was confirmed (except for three studies). Age at MPHPT diagnosis (mean/median per study): 28.7 to 43.1 years; age at PTx: 32 to 43.5 years. Asymptomatic PHPT was reported in 38.3% to 67% of MPHPT. Mean total calcium varied between 1.31 and 2.88 mmol/L and highest PTH was of 317.2 pg/mL. Two studies reported similar PTH and calcaemic levels in MPHPT vs. sporadic PHPT, while another found higher values in MPHPT. Symptomatic vs. asymptomatic patients with MPHPT had similar PTH and serum calcium levels (n = 1). Osteoporosis (n = 8, N = 723 with MPHPT) was reported in 10% to 55.5% of cases, osteopenia in 5.88% to 43.9% (per study); overall fracture rate was 10% (of note, one study showed 0%). Lower bone mineral density (BMD) at DXA (n = 4) in MPHPT vs. sporadic PHPT/controls was found by some studies (n = 3, and only a single study provided third distal radius DXA-BMD assessment), but not all (n = 1). Post-PTx DXA (n = 3, N = 190 with MPHPT) showed a BMD increase (e.g., +8.5% for lumbar spine, +2.1% for total hip, +4.3% for femoral neck BMD); however, post-operatory, BMD remains lower than controls. Trabecular bone score (TBS) analysis (n = 2, N = 142 with MPHPT vs. 397 with sporadic PHPT) showed a higher prevalence of reduced TBS (n = 1) or similar (n = 1). PTx analysis in MPHPT (n = 14): rate of subtotal PTx of 39% to 66.7% (per study) or less than subtotal PTx of 46.9% (n = 1). Post-PTx complications: persistent PHPT (5.6% to 25%), recurrent PHPT (16.87% to 30%, with the highest re-operation rate of 71% in one cohort); hypoparathyroidism (12.4% to 41.7%). Genetic analysis pointed out a higher risk of post-PTx recurrence in exon 10 MEN1 pathogenic variant. Post-PTx histological exam showed a multi-glandular disease in 40% to 52.1% of MPHPT, and a parathyroid carcinoma prevalence of 1%. Conclusions: MPHPT remains a challenging ailment amid a multi-layered genetic syndrome. Current data showed a lower age at MPHPT diagnosis and surgery than found in general population, and a rate of female predominance that is lower than seen in sporadic PHPT cases, but higher than known, for instance, in MEN2. The bone involvement showed heterogeneous results, more consistent for a lower BMD, but not necessarily for a lower TBS vs. controls. PTx involves a rather high rate of recurrence, persistence and redo surgery. About one out of ten patients with MPHPT might have a prevalent fracture and PTx improves the overall bone health, but seems not to restore it to the general population level, despite the young age of the subjects. This suggests that non-parathyroid components and potentially menin protein displays negative bone effects in MEN1.