Surgical approach in hereditary hyperparathyroidism.

Primary hyPerParathyroidism is determined by a solitary benign adenoma in nearly 80% of cases. The other 20% of PhPT is due to a parathyroid multiglandular involvement, with carcinoma of the parathyroid glands representing no more than 0.5% of the cases. Generally, PhPT occurs after the sixth decade of life, being a rare entity in children and young adults. When PhPT has an early onset, it usually happens in the context of a genetic syndrome. These forms of PhPT are often associated to parathyroid multiglandular tumors. in the last decades, mutations in specific genes have been identified as responsible of various hereditary types of PhPT and new insights on parathyroid tumorigenesis have been consequently acquired. These hereditary syndromes, transmissed by an autosomal dominant pattern, include: multiple endocrine neoplasia types 1 (men1), 2a (men2a) and 4 (men4), hereditary hyperparathyroidism-jaw tumours (hPT-JT), familial isolated hyperparathyroidism (fihP), familial hypocalciuric hypercalcemia (fhh) severe neonatal hyperparathyroidism (nshPT) and autosomal dominant moderate hyperparathyroidism (admh) [1] (Table 1). an excessive and unregulated secretion of parathormone represents the pathogenetic basis in these hereditary forms of PhPT with: either 1) the inactivation of tumour suppressor genes (in men1, men4, fiPh, and hPT-JT); or 2) the activation of oncogenes with an increase of cellular proliferation (in men2a); or 3) the disregulation of the calcium set point with loss of the normal feedback control on PTh secretion (in fhh, admh and nshPT) (Tables 2 and 3). Genetic diagnosis of these forms is the gold standard for the correct diagnosis, the surveillance of the proband and his/her relatives, the appropriate choice of treatment and the timing and type of surgery.