Issue 4: parathyroid surgery in familial HPT syndromes in the setting of underlying mutations in the calcium receptor (CASR) gene involves subtotal parathyroidectomy (no grade of recommendation).
We compared the expression of the calcium-sensing receptor (CaR) at the gene message and the protein level in parathyroid tissue obtained from patients with I degree non-uremic or II degree uremic hyperparathyroidism with that in normal parathyroid tissue, using in situ hybridization and immunohistochemistry techniques.
Here, we investigate a unique variant of familial hypercalcemia, unrelated to multiple endocrine neoplasia and hyperparathyroidism-jaw tumor syndromes, with hypercalcemia due to a point mutation in the intracellular part of the calcium receptor (CaR) gene.
In addition, it examines the use or potential use of CaSR agonists or antagonists (calcimimetics and calcilytics) and other drugs mediated through the CaSR, in the management of disorders as diverse as hyperparathyroidism, osteoporosis and gastrointestinal disease.
The CASR is a potential therapeutic target to treatment of diseases including hyperparathyroidism and osteoporosis, since its interaction with pharmacological compounds results in modulation of PTH secretion.
Cinacalcet therapy in an infant with an R185Qcalcium-sensing receptor mutation causing hyperparathyroidism: a case report and review of the literature.
A total of 21 patients were evaluated, seven of them with idiopathic hypoparathyroidism (suspected ADHH) and 14 with hyperparathyroidism (suspected FHH).
These include chromosomal deletions of the MEN1 locus on 11q in sporadic and MEN1 associated primary HPT, of RB1 on 13q in carcinomas, and of the FHH gene located on 3q in sporadic primary and secondary HPT.
The human calcium-sensing receptor (<i>CASR</i>) is the key controller of extracellular Ca<sub>o</sub><sup>2+</sup> homeostasis, and different mutations in the <i>CASR</i> gene have been linked to different calcium diseases, such as familial hypocalciuric hypercalcemia, severe hyperparathyroidism, autosomal-dominant hypocalcemia (ADH), and Bartter's syndrome type V. In this study, two generations of a family with biochemically and clinically confirmed ADH who suffered severe muscle pain, arthralgia, tetany, abdominal pain, and fatigue were evaluated for mutations in the <i>CASR</i> gene.
The calcium-sensing receptor (CaSR) plays an important role in sensing extracellular calcium ions and regulating parathyroid hormone secretion by parathyroid gland cells, and the receptor is a suitable target for the treatment of hyperparathyroidism.
Finally, we will comment on the development of drugs that modulate CaR function by either activating (calcimimetic drugs) or antagonizing it (calcilytic drugs), and on their potential therapeutic implications, such as medical control of specific cases of primary and uremic hyperparathyroidism with calcimimetic drugs and a potential treatment for osteoporosis with a calcilytic drug.
Parathyroid hormone gene regulatory region--cyclin D1 (PTH--cyclin D1) mice not only developed abnormal parathyroid cell proliferation, but also developed chronic biochemical hyperparathyroidism with characteristic abnormalities in bone and, notably, a shift in the relationship between serum calcium and PTH.
This genetic change is essentially limited to parathyroid adenomas (8%), although expression of CCND1 without translocation is common in uremic hyperparathyroidism.
We previously reported the suppressive effect of cinacalcet on PTH secretion in vivo in a PHPT model mouse, in which parathyroid-targeted overexpression of the cyclin D1 oncogene caused chronic biochemical hyperparathyroidism and parathyroid cell hyperplasia.