Hyperfunction of Parathyroid Glands

The parathyroid glands (PTs) chief cells are the most important calcium-sensing cells in the body, able to produce and store parathyroid hormone (PTH), which is modulated by the binding of Ca2+ to calcium-sensing receptors (CaSRs). Under physiological conditions, serum Ca2+ and PTH serum levels are inversely related, according to a negative feed-back mechanism, but in the presence of excessive secretion of PTH, there is a loss of the suppressive effect of circulating Ca2+ on PTs. The role of the PTs in human diseases is almost exclusively related to its hyperfunction, mainly mediated via primary HPT, which is a relatively common disease and is the main cause of hypercalcemia in outpatients. There are several imaging techniques for localizing enlarged PTs, including neck ultrasonography, CT scan, and MRI, but the most commonly used is double-phase or double-tracer parathyroid scintigraphy with 99mTc-sestamibi. It may reach up to 95% accuracy in combination with ultrasonography or using the SPECT/CT hybrid approach. Currently, 80-90% of patients with primary HPT are asymptomatic, as the disease is an incidental finding during routine hematologic screening or is discovered among postmenopausal women who undergo bone densitometry and bone mineral density (BMD) measurement. Tertiary HPT is a severe disease that can be observed as the end result of long-standing secondary HPT and chronic kidney disease but also in patients who have undergone kidney transplantation. Parathyroidectomy is indicated in all patients with primary HPT and overt clinical symptoms, although it should be more carefully considered in patients who are asymptomatic. Without surgery, the disease progresses in approximately 30% of patients, and BMD decreases in the majority of subjects. Non-surgical options to treat PTs hyperfunction is limited to cases of secondary HPT, which can be controlled by several drugs, including 1,25-Dixydroxyvitamin D3 analogues and calcimimetic agents (i.e., cinacalcet), alone or in combination. Some medical options have tentatively been suggested in selected patients with primary and tertiary HPT.