Pseudohypoparathyroidism-Literature Update 2018
Annals of Endocrinology and Metabolism
Pseudohypoparathyroidism (PHP) is a rare heterogenous group of disorders characterized by end-organ resistance to PTH, specifically at the proximal renal tubule. The term PHP encompasses PHP 1A, PHP 1B, PHP 1C, PHP 2 and pseudopseudohypoparathyroidism (PPHP). The two most common subtypes are PHP 1A and PHP 1B, PHP 1A, PHP 1C and PPHP have the Albrights hereditary osteodystrophy (AHO) phenotype, in addition to end-organ resistance to PTH in the two former subtypes. Recently, the European
... he European Pseudohypoparathyroidism (EuroPHP) network have proposed a novel classification of PHP which encompasses all disorders of the PTH receptor and its signaling pathway, known as inactivating PTH/PTH-related protein signaling disorders (iPPSD) [1-6]. PHP is caused by molecular alterations within the GNAS locus. The GNAS gene encodes an alpha subunit of the stimulatory G protein (Gsα) that mediates the actions of PTH and other hormones including TSH and gonadotropins. It is a defect in these stimulatory G-protein coupled receptors, that results in end-organ resistance to parathyroid hormone and select other hormones. Mutations of the GNAS gene are associated with iPPSD2 (PHP 1A, PHP 1C, PPHP, progressive osseous heteroplasia (POH)) whereas methylation defects are identified at the GNAS locus and associated with iPPSD3 (PHP 1B, including autosomal dominant-PHP 1B and sporadic-PHP 1B). This year, the first international consensus statement on the diagnosis and management of pseudohypoparathyroidism was published and is informative to physicians with limited experience treating these rare disorders. It is important to establish a diagnosis to enable appropriate medical treatment of the endocrine complications and provide accurate genetic and prenatal counselling of individuals and their first-degree relatives.