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Genetics of Benign Adrenocortical Tumors

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Management of Adrenal Masses in Children and Adults

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Abstract

Benign adrenocortical tumors (ACT) represent a heterogeneous group of lesions. Cortisol-producing lesions are due mostly to defects of the cyclic AMP (cAMP) signaling pathway, whereas the majority of aldosterone-producing lesions are the result of mutations in KCNJ5. Bilateral adrenal hyperplasias were recently linked to ARMC5 defects; the ARMC5 protein has an unknown function. Finally, benign ACTs are found in the context of a number of other conditions from multiple endocrine neoplasia type 1 (MEN-1) to Carney triad and others. In this chapter, we review all newly identified genetic associations and diseases associated with ACTs.

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Abbreviations

AC:

Adenyl cyclase

ACTH:

Adrenocorticotropic hormone

AIMAH:

ACTH-independent macronodular adrenal hyperplasia

Alleles:

Alternative forms of a gene

AMP/ATP:

Adenosine monophosphate/adenosine triphosphate

BAH:

Bilateral adrenocortical hyperplasia

cAMP:

Cyclic adenosine monophosphate

CNC:

Carney complex

CS:

Cushing syndrome

Genes:

Units of inheritance at specific locations (loci) on a chromosome

GMP/GDP/GTP:

Guanosine monophosphate/guanosine diphosphate/guanosine triphosphate

GPCRs:

G protein-coupled receptors

Heterozygous:

A genotype with two different alleles of a gene for a particular trait

Homozygous:

A genotype with the same allele of a gene for a particular trait

MMAD:

Massive macronodular adrenocortical disease

Mutations:

Alteration of genetic material producing a new variation

PBAD:

Primary bimorphic adrenocortical disease

PBMAH:

Primary bilateral macronodular adrenocortical hyperplasia

PDEs:

Phosphodiesterases

Phenotype:

Detectable expression of a genotype

PKA:

Protein kinase A

PPNAD:

Primary pigmented micronodular adrenocortical disease

PRKAR1A:

Protein kinase A regulatory subunit type 1

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Acknowledgments

This work was supported by the intramural program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (NIH), protocol HD008920.

Author and Contributors

All authors contributed equally to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND drafting the work or revising it critically for important intellectual content; AND final approval of the version to be published; AND agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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The authors declare that the research was conducted in absence of any potential conflict of interest.

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  1. Section on Endocrinology and Genetics (SEGEN), Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, Room 1-3330, 10 Center Dr., MSC1103, Bethesda, MD, 20892, USA

    Fady Hannah-Shmouni M.D. & Constantine A. Stratakis M.D., D(Med)Sc.

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  1. Fady Hannah-Shmouni M.D.
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  2. Constantine A. Stratakis M.D., D(Med)Sc.
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Correspondence to Constantine A. Stratakis M.D., D(Med)Sc. .

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  1. Endocrine Oncology Branch, National Institutes of Health National Cancer Institute, Bethesda, Maryland, USA

    Electron Kebebew

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Hannah-Shmouni, F., Stratakis, C.A. (2017). Genetics of Benign Adrenocortical Tumors. In: Kebebew, E. (eds) Management of Adrenal Masses in Children and Adults. Springer, Cham. https://doi.org/10.1007/978-3-319-44136-8_3

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  • DOI: https://doi.org/10.1007/978-3-319-44136-8_3

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