Potential role of cinacalcet hydrochloride in sporadic primary hyperparathyroidism without surgery indication.

Abstract

Primary hyperparathyroidism (PHPT) is characterized by the chronic elevation of serum calcium (Ca) levels induced by a long-standing increase of PTH concentrations [1]. Surgical removal of the hyperfunctioning parathyroid tissue represents the only curative approach in this field [2, 3]. Besides symptomatic forms [4], parathyroidectomy (PTx) is indicated in asymptomatic PHPT subjects who have a more advanced disease status. According to the latest update [5], criteria for surgical intervention in asymptomatic PHPT are as follows: (a) serum Ca levels [ 1 mg/dl (0.25 mmol/l) above upper limits of normal; (b) a calculated creatinine clearance \ 60 ml/min; (c) a BMD T score of -2.5 or less at any site or previous fragility fracture (or both); or (d) age \ 50 years. Nevertheless, the management of those patients not having surgery indication is still a point of discussion. Indeed, the 15-year observational study by Rubin et al. [3] has found disease progression in 38 % of this subgroup. This suggests that current surgery criteria are effective in identifying a population with more advanced disease, but cannot effectively predict disease evolution. Cinacalcet hydrochloride is an allosteric modulator of the Ca-sensing receptor (CaSR), where it acts by mimicking an increase in levels of extracellular Ca [6]. In PHPT, this should result in the suppression of PTH secretion [7]. Cinacalcet has been approved in Europe and USA for the management of moderate-to-severe hypercalcemia in patients with PHPT who fulfill surgery indication but are unable to undergo parathyroidectomy [8]. Hence, careful monitoring represents the only indication in PHPT without surgery criteria. We here reported a retrospective, single-center analysis of sporadic PHPT patients who were subjected to treatment with cinacalcet, independently of the surgical indication. Our objective was to provide preliminary insights about the role of cinacalcet in PHPT patients without surgery indication by performing a comparative assessment with PHPTs fitting surgery criteria.