Isolated glucocorticoid deficiency: Genetic causes and animal models

The Journal of Steroid Biochemistry and Molecular Biology
Avinaash MaharajLeonardo Guasti

Abstract

Hereditary adrenocorticotropin (ACTH) resistance syndromes encompass the genetically heterogeneous isolated or Familial Glucocorticoid Deficiency (FGD) and the distinct clinical entity known as Triple A syndrome. The molecular basis of adrenal resistance to ACTH includes defects in ligand binding, MC2R/MRAP receptor trafficking, cellular redox balance, cholesterol synthesis and sphingolipid metabolism. Biochemically, this manifests as ACTH excess in the setting of hypocortisolaemia. Triple A syndrome is an inherited condition involving a tetrad of adrenal insufficiency, achalasia, alacrima and neuropathy. FGD is an autosomal recessive condition characterized by the presence of isolated glucocorticoid deficiency, classically in the setting of preserved mineralocorticoid secretion. Primarily there are three established subtypes of the disease: FGD 1, FGD2 and FGD3 corresponding to mutations in the Melanocortin 2 receptor MC2R (25%), Melanocortin 2 receptor accessory protein MRAP (20%), and Steroidogenic acute regulatory protein STAR (5-10%) respectively. Together, mutations in these 3 genes account for approximately half of cases. Whole exome sequencing in patients negative for MC2R, MRAP and STAR mutations, identified mutations ...Continue Reading

Citations

Nov 29, 2020·The Journal of Clinical Endocrinology and Metabolism·Donatella CapalboMariacarolina Salerno
Jan 17, 2021·Molecular and Cellular Endocrinology·Katia Mariniello, Leonardo Guasti
Jan 1, 2021·Frontiers in Pediatrics·Federica BuonocoreJohn C Achermann
Sep 24, 2020·Bone Reports·Tsuyoshi SatoDai Chida
Feb 20, 2021·Molecular and Cellular Endocrinology·Emanuele Pignatti, Christa E Flück
Jul 15, 2021·Journal of the Endocrine Society·Federica BuonocoreJohn C Achermann
Jul 17, 2021·Journal of Pediatric Endocrinology & Metabolism : JPEM·Mehmet Nuri ÖzbekHuseyin Demirbilek
Jan 13, 2022·Problemy e̊ndokrinologii·O V GlazovaP Y Volchkov

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