Bone and Mineral Metabolism Phenotypes in MEN1-Related and Sporadic Primary Hyperparathyroidism, before and after Parathyroidectomy

Francesca Marini,Francesca Giusti,Maria Luisa Brandi,Francesco Tonelli,Davide Maraghelli,Tiziana Cavalli,Federica Cioppi

doi:10.3390/cells10081895

Abstract

Primary hyperparathyroidism (PHPT) is the most common endocrinopathy in multiple endocrine neoplasia type 1 (MEN1). Persistent levels of increased parathyroid hormone (PTH) result in a higher incidence of osteopenia and osteoporosis compared to the general population. Surgical removal of hyper-functioning parathyroid tissue is the therapy of choice. This retrospective study evaluated the effect of parathyroidectomy (PTX) on bone metabolism and bone mass in two series of patients with MEN1 PHPT and sporadic PHPT (sPHPT) by comparing bone metabolism-related biochemical markers and bone mineral density (BMD) before and after surgery. Our data confirmed, in a higher number of cases than in previously published studies, the efficacy of PTX, not only to rapidly restore normal levels of PTH and calcium, but also to normalize biochemical parameters of bone resorption and bone formation, and to improve spine and femur bone mass, in both MEN1 PHPT and sPHPT. Evaluation of single-patient BMD changes after surgery indicates an individual variable bone mass improvement in a great majority of MEN1 PHPT patients. In MEN1 patients, PTX is strongly suggested in the presence of increased PTH and hypercalcemia to prevent/reduce the early-onset bone mass loss and grant, in young patients, the achievement of the bone mass peak; routine monitoring of bone metabolism and bone mass should start from adolescence. Therapy with anti-fracture drugs is indicated in MEN1 patients with BMD lower than the age-matched normal values.

Highlights

Primary hyperparathyroidism (PHPT) is a common endocrine disease characterized by persistent elevated levels of parathyroid hormone (PTH), leading to hypercalcemia
Twenty-eight multiple endocrine neoplasia type 1 (MEN1) PHPT patients (21.1%) did not undergo PTX at the time of their last follow-up at the Referral Center; all of them showed no instrumental evidence of PHPT at their last neck control
Many patients affected by PHPT, either in syndromic or sporadic forms, lack classical signs and symptoms traditionally associated with excessive PTH secretion and/or hypercalcemia

Summary

Introduction

Primary hyperparathyroidism (PHPT) is a common endocrine disease characterized by persistent elevated levels of parathyroid hormone (PTH), leading to hypercalcemia. In a majority of cases (90–95%), PHPT manifests as a sporadic form (sPHPT), but it can though rarely, be part of familial isolated or syndromic diseases (5–10%) [1]. PHPT with multiple hyperplasia and/or adenoma of the parathyroid glands is the most common endocrinopathy of multiple endocrine neoplasia type 1 (MEN1), a rare inherited multi-organ tumor syndrome affecting the parathyroids, the anterior pituitary gland, and the neuroendocrine cells of the gastro-entero-pancreatic tract [2]. MEN1 PHPT can remain asymptomatic for a long period, but mild-moderate hypercalcemia typically starts during adolescence [7], and almost all MEN1 patients are expected to have hypercalcemia by the age of 50 [6]

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