Recent data suggest an increase in the overall incidence of
parathyroid disorders, with
primary hyperparathyroidism (PHPT) being the most prevalent
parathyroid disorder. PHPT is associated with morbidities (fractures,
kidney stones,
chronic kidney disease) and increased risk of death. The symptoms of PHPT can be nonspecific, potentially delaying the diagnosis. Approximately 15% of patients with PHPT have an underlying heritable form of PHPT that may be associated with extraparathyroidal manifestations, requiring active surveillance for these manifestations as seen in
multiple endocrine neoplasia type 1 and 2A. Genetic testing for heritable forms should be offered to patients with multiglandular disease, recurrent PHPT, young onset PHPT (age ≤40 years), and those with a family history of parathyroid
tumors. However, the underlying genetic cause for the majority of patients with heritable forms of PHPT remains unknown. Distinction between sporadic and heritable forms of PHPT is useful in surgical planning for
parathyroidectomy and has implications for the family. The genes currently known to be associated with heritable forms of PHPT account for approximately half of sporadic parathyroid
tumors. But the genetic cause in approximately half of the sporadic parathyroid
tumors remains unknown. Furthermore, there is no systemic
therapy for
parathyroid carcinoma, a rare but potentially fatal cause of PHPT. Improved understanding of the molecular characteristics of parathyroid
tumors will allow us to identify
biomarkers for diagnosis and novel targets for
therapy.