Beyond Bone: Infectious Diseases and Immunity in Parathyroid Disorders

High lymphocyte signature genes expression in parathyroid endocrine cells and its downregulation linked to tumorigenesis

“…In our study, another unusual observation associated with the high expression levels of CD4 and CD226 in parathyroid endocrine cells is the almost absence of CD4 T helper cells in the normal parathyroid glands. Lymphocytes have been documented to express the type 1 PTH receptor (PTH1R) and patients suffering from primary or secondary hyperparathyroidism have elevated levels of PTH and immune alterations, 25 suggesting physiological levels of PTH may be necessary for a proper immune response. In vitro studies with high concentrations of PTH have shown a dose-dependent decreases in helper/suppressor ratio.…”

“…In vitro studies with high concentrations of PTH have shown a dose-dependent decreases in helper/suppressor ratio. 25 Within the parathyroid glands, the presence of locally extremely high concentration of PTH may strongly affect immune cell functions. Whether the presence of CD4 and CD226 in the can prevent the infiltration of CD4 positive T cells in parathyroid glands, or the parathyroid environment favour the maturation of double negative T cells, needs further investigation.…”

Safety and Efficacy of PTH 1-34 and 1-84 Therapy in Chronic Hypoparathyroidism: A Meta-Analysis of Prospective Trials

“…(64) Future studies should ideally address specific aspects, such as more standardized analyses of the effects of PTH replacement therapy on QoL and the risk of bone adverse events in hypoparathyroidism. There is also a need to evaluate its effects on other possible complications of hypoparathyroidism, such as basal ganglia calcifications, (65) alterations in immune profile, (2,3) nephrocalcinosis and kidney stone formation, (66) and cardiovascular complications. (67,68) Future trials should include patients who do not achieve adequate control with conventional therapies, because most subjects included in this meta-analysis were at target for serum calcium on enrollment in their respective studies.…”

“…( 1 ) Conventional therapy is based on supplementation with oral calcium salts and active vitamin D, but this often fails to normalize biochemical parameters other than serum calcium. Although the latter can be maintained at target levels in most patients, the failure to control serum phosphate levels, calcium phosphate product, and calcium and phosphate excretion increases the risk of peripheral calcifications, kidney stone formation, kidney infections, ( 2,3 ) and, ultimately, impaired kidney function. ( 4 )…”

“…(1) Conventional therapy is based on supplementation with oral calcium salts and active vitamin D, but this often fails to normalize biochemical parameters other than serum calcium. Although the latter can be maintained at target levels in most patients, the failure to control serum phosphate levels, calcium phosphate product, and calcium and phosphate excretion increases the risk of peripheral calcifications, kidney stone formation, kidney infections, (2,3) and, ultimately, impaired kidney function. (4) Over the last two decades, several attempts have been made to develop a physiological replacement therapy for hypoparathyroidism, the only endocrine deficiency for which replacement with the missing hormone is not currently the standard of care.…”