Hypoparathyroidism

Hypoparathyroidism is characterized by hypocalcemia and hyperphosphatemia due to a lack of parathyroid hormone (PTH) secretion or action. Hypoparathyroidism may occur as part of a pluriglandular autoimmune disorder or as a complex congenital defect, as for example, in the autosomal dominant DiGeorge or hypoparathyroidism-deafness-renal dysplasia syndromes. In addition, hypoparathyroidism may occur as a solitary endocrinopathy, and this has been called isolated or idiopathic hypoparathyroidism. Familial occurrences of isolated hypoparathyroidism with autosomal dominant, autosomal recessive, and X-linked inheritance have been established. Studies of patients with these forms of hypoparathyroidism and mouse models with parathyroid defects have elucidated important roles for transcription factors (e.g., TBX1, GATA3, GCMB, AIRE, and SOX3), the tubulin-specific chaperone (TBCE), and the mitochondrial genome in determining parathyroid development; the calcium-sensing receptor (CaSR) and G-protein subunit α11 in regulating extracellular calcium and PTH secretion; and PTH gene expression for synthesis and secretion of PTH. Moreover, recombinant PTH and a synthetic PTH receptor agonist, as well as drugs targeting the CaSR, have been shown to be of benefit for the management of hypoparathyroidism.