The role of ARMC5 in human cell cultures from nodules of primary macronodular adrenocortical hyperplasia (PMAH)

Cavalcante, Isadora Pontes; Nishi, Mirian Yumie; Zerbini, Maria Cláudia Nogueira; Almeida, Madson Q.; Brondani, Vânia Balderrama; Botelho, Maria Luiza Anhaia de Arruda; Tanno, Fabio Y; Srougi, Victor; Chambô, José Luis; Mendonca, Berenice B.; Bertherat, Jérôme; Lotfi, Claudimara Ferini Pacicco; Fragoso, Maria Candida Barisson Villares

doi:10.1016/j.mce.2017.06.027

Cited by 43 publications

(30 citation statements)

References 34 publications

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“…On MR, relative to the liver, glands are usually hypointense on T1-weighted images and hyperintense on T2-weighted images (38). In limited studies using 2-(fluorine 18) fluoro-2dexoxy-D glucose positron emission tomography/CT (PET/CT) imaging, uptake in the macronodular adrenal glands of BMAH was higher than the liver, with maximum standardized uptake value (SUV max) >3.1 (3.3-8.9), thus reaching level usually seen in malignant tumors (37,39) although BMAH is well recognized as a benign disease. These findings need to be confirmed in larger series.…”

Section: Bilateral Macronodular Adrenal Hyperplasiamentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Differential diagnosis, investigation and therapy of bilateral adrenal incidentalomas

Bourdeau

Ghorayeb

Gagnon

et al. 2018

European Journal of Endocrinology

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The investigation and management of unilateral adrenal incidentalomas have been extensively considered in the last decades. While bilateral adrenal incidentalomas represent about 15% of adrenal incidentalomas (AIs), they have been less frequently discussed. The differential diagnosis of bilateral incidentalomas includes metastasis, primary bilateral macronodular adrenal hyperplasia and bilateral cortical adenomas. Less frequent etiologies are bilateral pheochromocytomas, congenital adrenal hyperplasia (CAH), Cushing's disease or ectopic ACTH secretion with secondary bilateral adrenal hyperplasia, primary malignancies, myelolipomas, infections or hemorrhage. The investigation of bilateral incidentalomas includes the same hormonal evaluation to exclude excess hormone secretion as recommended in unilateral AI, but diagnosis of CAH and adrenal insufficiency should also be excluded. This review is focused on the differential diagnosis, investigation and treatment of bilateral AIs.

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Section: Bilateral Macronodular Adrenal Hyperplasiamentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Differential diagnosis, investigation and therapy of bilateral adrenal incidentalomas

Bourdeau

Ghorayeb

Gagnon

et al. 2018

European Journal of Endocrinology

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“…The binding of these aberrant receptors to their ligands mimics the result of ACTH binding to MC2R, activating the PKA pathway and increasing cortisol production 101 . Additionally, the presence of ectopic POMC and ACTH in a subpopulation of cells within the hyperplastic nodules was described recently in several cases of PMAH in both tissue 102 and human cell cultures obtained from PMAH nodules 103 . The production of ectopic ACTH in the nodules is at least partially regulated by the PKA pathway and may act in autocrine and paracrine manners 103 , allowing a certain independence of cortisol synthesis in PMAH cells.…”

Section: Primary Macronodular Adrenal Hyperplasia (Pmah)mentioning

confidence: 67%

“…Although little is currently known about the function of ARMC5, its importance in regulating steroidogenesis, proliferation and apoptosis has been described in cell lines and in PMAH cell cultures 103 , 104 . Additionally, ARMC5 is important for the embryological development of mice, T cell differentiation, and immune response 109 , 110 .…”

Section: Primary Macronodular Adrenal Hyperplasia (Pmah)mentioning

confidence: 99%

The human adrenal cortex: growth control and disorders

Lotfi¹,

Kremer²,

Passaia³

et al. 2018

Clinics

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This review summarizes key knowledge regarding the development, growth, and growth disorders of the adrenal cortex from a molecular perspective. The adrenal gland consists of two distinct regions: the cortex and the medulla. During embryological development and transition to the adult adrenal gland, the adrenal cortex acquires three different structural and functional zones. Significant progress has been made in understanding the signaling and molecules involved during adrenal cortex zonation. Equally significant is the knowledge obtained regarding the action of peptide factors involved in the maintenance of zonation of the adrenal cortex, such as peptides derived from proopiomelanocortin processing, adrenocorticotropin and N-terminal proopiomelanocortin. Findings regarding the development, maintenance and growth of the adrenal cortex and the molecular factors involved has improved the scientific understanding of disorders that affect adrenal cortex growth. Hypoplasia, hyperplasia and adrenocortical tumors, including adult and pediatric adrenocortical adenomas and carcinomas, are described together with findings regarding molecular and pathway alterations. Comprehensive genomic analyses of adrenocortical tumors have shown gene expression profiles associated with malignancy as well as methylation alterations and the involvement of miRNAs. These findings provide a new perspective on the diagnosis, therapeutic possibilities and prognosis of adrenocortical disorders.

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“…Although ARMC5 function remains unclear, in vitro studies first suggest that ARMC5 controls adrenocortical steroidogenesis. Indeed, ARMC5 knockdown either in the human adrenocortical carcinoma cells line H295R or in cell culture from PBMAH wild-type for ARMC5 leads to a down-regulation of steroidogenic enzymes expression [57,71]. Consistently, mouse model heterozygote for Armc5 (Armc5 + /-), that are therefore, genetically close to PBMAH patients develop a decrease in glucocorticoids at 12 months supporting Armc5 role in steroidogenesis regulation [72].…”

Section: Armc5mentioning

confidence: 83%

Update of Genetic and Molecular Causes of Adrenocortical Hyperplasias Causing Cushing Syndrome

Berthon

Bertherat

2020

Horm Metab Res

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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.

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The role of ARMC5 in human cell cultures from nodules of primary macronodular adrenocortical hyperplasia (PMAH)

Cited by 43 publications

References 34 publications

MANAGEMENT OF ENDOCRINE DISEASE: Differential diagnosis, investigation and therapy of bilateral adrenal incidentalomas

MANAGEMENT OF ENDOCRINE DISEASE: Differential diagnosis, investigation and therapy of bilateral adrenal incidentalomas

The human adrenal cortex: growth control and disorders

Update of Genetic and Molecular Causes of Adrenocortical Hyperplasias Causing Cushing Syndrome

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