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Genetic Disorders of Adrenocortical Function

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Principles of Endocrinology and Hormone Action

Part of the book series: Endocrinology ((ENDOCR))

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Abstract

The first detailed description of the human adrenal glands was by Eustachius (1520–1574); their presence was confirmed by Piccolomini (1562–1605) and Casserius (1552–1616) (Vrezas et al. 2000). Their function, however, was largely unknown until the late nineteenth century. In the last 30 years, our growing understanding of adrenocortical development and function has led to the discovery of numerous genetic disorders that affect the adrenal glands. Developmental pathways have also been linked to the formation of adrenocortical tumors (ACTs), which represent a heterogeneous group of lesions of the adrenal cortex. ACTs have been found to be due to or associated with somatic or germline mutations in key molecular pathways, including the cyclic AMP (cAMP) and Wnt signaling pathways. In this chapter, we review the various genetic causes of adrenocortical disorders and focus on congenital causes of adrenal insufficiency associated with hypoplasia of the adrenal glands, genetic causes of autoimmunity that affect the adrenal glands, and genetic causes of benign and malignant adrenocortical tumors.

Conflict of Interest Statement

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

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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

BMAH:

Bilateral macronodular adrenal 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 nodular adrenocortical disease

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Acknowledgments

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

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  1. Section on Endocrinology & Genetics (SEGEN), 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 & Constantine A. Stratakis

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  1. Fady Hannah-Shmouni
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Correspondence to Constantine A. Stratakis .

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  1. Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy

    Antonino Belfiore

  2. Diabetes and Metabolism Clinical Researc, Clinical Research Institute at Rambam (C, Haifa, Israel

    Derek LeRoith

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All authors contributed equally to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work, drafting the work or revising it critically for important intellectual content, 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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Hannah-Shmouni, F., Stratakis, C.A. (2017). Genetic Disorders of Adrenocortical Function. In: Belfiore, A., LeRoith, D. (eds) Principles of Endocrinology and Hormone Action. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-27318-1_29-2

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    Genetic Disorders of Adrenocortical Function
    Published:
    21 March 2017

    DOI: https://doi.org/10.1007/978-3-319-27318-1_29-2

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    Genetic Disorders of Adrenocortical Function
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    16 January 2017

    DOI: https://doi.org/10.1007/978-3-319-27318-1_29-1

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