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Update of Genetic and Molecular Causes of Adrenocortical Hyperplasias Causing Cushing Syndrome.
- Source :
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Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme [Horm Metab Res] 2020 Aug; Vol. 52 (8), pp. 598-606. Date of Electronic Publication: 2020 Feb 25. - Publication Year :
- 2020
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Abstract
- Bilateral hyperplasias of the adrenal cortex are rare causes of chronic endogenous hypercortisolemia also called Cushing syndrome. These hyperplasias have been classified in two categories based on the adrenal nodule size: the micronodular types include Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and isolated Micronodular Adrenal Disease (iMAD) and the macronodular also named Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH). This review discusses the genetic and molecular causes of these different forms of hyperplasia that involve mutations and dysregulation of various regulators of the cAMP/protein kinase A (PKA) pathway. PKA signaling is the main pathway controlling cortisol secretion in adrenocortical cells under ACTH stimulation. Although mutations of the regulatory subunit R1α of PKA (PRKAR1A) is the main cause of familial and sporadic PPNAD, inactivation of two cAMP-binding phosphodiesterases (PDE11A and PDE8B) are associated with iMAD even if they are also found in PPNAD and PBMAH cases. Interestingly, PBMAH that is observed in multiple familial syndrome such as APC, menin, fumarate hydratase genes, has initially been associated with the aberrant expression of G-protein coupled receptors (GPCR) leading to an activation of cAMP/PKA pathway. However, more recently, the discovery of germline mutations in Armadillo repeat containing protein 5 (ARMC5) gene in 25-50% of PBMAH patients highlights its importance in the development of PBMAH. The potential relationship between ARMC5 mutations and aberrant GPCR expression is discussed as well as the potential other causes of PBMAH.<br />Competing Interests: The authors declare that they have no conflict of interest.<br /> (© Georg Thieme Verlag KG Stuttgart · New York.)
- Subjects :
- Adrenal Cortex Diseases complications
Adrenal Cortex Diseases genetics
Cushing Syndrome etiology
Cushing Syndrome genetics
Humans
Hyperplasia complications
Hyperplasia genetics
Prognosis
Adrenal Cortex Diseases pathology
Biomarkers, Tumor genetics
Cushing Syndrome pathology
Genetic Predisposition to Disease
Hyperplasia pathology
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1439-4286
- Volume :
- 52
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
- Publication Type :
- Academic Journal
- Accession number :
- 32097969
- Full Text :
- https://doi.org/10.1055/a-1061-7349