Journal ArticleDOI
Update of Genetic and Molecular Causes of Adrenocortical Hyperplasias Causing Cushing Syndrome
Annabel Berthon,Jérôme Bertherat +1 more
TLDR
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, but more recently, the discovery of germline mutations in Armadillo repeat containing protein 5 (ARMC5) gene highlights its importance in the development ofPBMAH.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.read more
Citations
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Journal ArticleDOI
What Did We Learn from the Molecular Biology of Adrenal Cortical Neoplasia? From Histopathology to Translational Genomics
C. Christofer Juhlin,C. Christofer Juhlin,Jérôme Bertherat,Thomas J. Giordano,Gary D. Hammer,Hironobu Sasano,Ozgur Mete,Ozgur Mete,Ozgur Mete +8 more
TL;DR: A review of the histological, genetic, and epigenetic landscapes of benign and malignant adrenal cortical neoplasia from a modern surgical endocrine pathology perspective and highlight key mechanisms of value for diagnostic and prognostic purposes is provided in this paper.
Journal ArticleDOI
An Overview of the Heterogeneous Causes of Cushing Syndrome Resulting From Primary Macronodular Adrenal Hyperplasia (PMAH)
TL;DR: This review summarizes the most important aspects, including hormone secretion, clinical presentation, radiological imaging, and molecular mechanisms, involved in familial Cushing syndrome associated with PMAH.
Journal ArticleDOI
ARMC Subfamily: Structures, Functions, Evolutions, Interactions, and Diseases
Journal ArticleDOI
Cushing´s syndrome due to bilateral adrenal cortical disease: Bilateral macronodular adrenal cortical disease and bilateral micronodular adrenal cortical disease
TL;DR: The high-dose dexamethasone suppression test can be useful in identifying a paradoxical increase in 24h-urinary free cortisol, that is a quite specific in PPNAD.
Journal ArticleDOI
Cushing Syndrome in a Pediatric Patient With a KCNJ5 Variant and Successful Treatment With Low-dose Ketoconazole.
Christina Tatsi,Andrea Gutierrez Maria,Cole Malloy,Lin Lin,Edra London,Nick Settas,Chelsi Flippo,Meg Keil,Fady Hannah-Shmouni,Dax A. Hoffman,Constantine A. Stratakis +10 more
TL;DR: In this paper, a 10-year-old child with Cushing syndrome was placed on low-dose ketoconazole (KZL), which controlled hypercortisolemia and CS-related signs.
References
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Mutations of the gene encoding the protein kinase A type I-α regulatory subunit in patients with the Carney complex
Lawrence S. Kirschner,J A Carney,Svetlana Pack,Susan E. Taymans,Christoforos Giatzakis,Y S Cho,Yoon S. Cho-Chung,Constantine A. Stratakis +7 more
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Constantine A. Stratakis,J A Carney,J P Lin,D A Papanicolaou,M Karl,Daniel L. Kastner,E Pras,George P. Chrousos +7 more
TL;DR: The genetic defect responsible for Carney complex map(s) to the short arm of chromosome 2 (2p16) has exhibited cytogenetic aberrations in atrial myxomas associated with the complex, and has been characterized by microsatellite instability in human neoplasias.
Journal ArticleDOI
Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the Carney complex
Lawrence S. Kirschner,Fabiano Sandrini,Juahdi Monbo,Jing-Ping Lin,J. Aidan Carney,Constantine A. Stratakis +5 more
TL;DR: It is concluded that genetic heterogeneity exists in CNC; and all of the CNC alleles on 17q are functionally null mutations of PRKAR1A, the first human disease recognized to be caused by mutations of the PKA holoenzyme.
Journal ArticleDOI
Quantitative comparison of phosphodiesterase mRNA distribution in human brain and peripheral tissues.
TL;DR: Using quantitative real-time polymerase chain reaction and parallel analysis of a carefully selected group of reference genes, the relative expression of each PDE isoenzyme across the 24 selected tissues is determined, and the expression of selected PDEs to each other within a given tissue type is compared.