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Primary Generalized Glucocorticoid Resistance or Chrousos Syndrome: Allostasis Through a Mutated Glucocorticoid Receptor

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The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease

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Abstract

Primary generalized glucocorticoid resistance or Chrousos syndrome is a rare familial or sporadic condition, which affects almost all organs and is characterized by partial target tissue insensitivity to glucocorticoids. Patients with this condition may be asymptomatic or may present with clinical manifestations of mineralocorticoid and/or androgen excess. The molecular basis of Chrousos syndrome has been associated with point mutations, insertions or deletions in the NR3C1 gene that expresses the human glucocorticoid receptor, a member of the steroid receptor family of the nuclear receptor superfamily of transcription factors. We and others have systematically investigated the molecular mechanisms of action of the mutant glucocorticoid receptors causing Chrousos syndrome by applying standard methods of molecular and structural biology. In this chapter, we discuss the clinical manifestations, pathophysiology, molecular pathogenesis, diagnostic approach, and therapeutic management of Chrousos syndrome.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

AP-1:

Activator protein 1

AVP:

Arginine vasopressin

CRH:

corticotropin-releasing hormone

DBD:

DNA-binding domain

DHEA:

Dehydroepiandrosterone

DHEAS:

DHEA-sulfate

GFP:

Green fluorescent protein

GR:

Glucocorticoid receptor

GREs:

Glucocorticoid response elements

GRIP1:

Glucocorticoid receptor-interacting protein 1

GST:

Glutathione-S-transferase

HDL:

High density lipoprotein

HPA axis:

Hypothalamic–pituitary–adrenal axis

HSPs:

Heat shock proteins

LBD:

Ligand-binding domain

LDL:

Low density lipoprotein

NF-kB:

Nuclear factor kB

NTD:

N-terminal domain

STAT:

Signal transducer and activator of transcription

UFC:

Urinary free cortisol

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Author information

Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 4 Soranou tou Efessiou Street, Athens, 11527, Greece

    Nicolas C. Nicolaides M.D., Ph.D., Agaristi Lamprokostopoulou M.Sc., Ph.D., George P. Chrousos MD, MACP, MACE, FRCP (London) & Evangelia Charmandari MD, MSc, PhD, MRCP(UK), CCST(UK)

  2. Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, University of Athens Medical School, “Aghia Sophia” Children’s Hospital, Thivon and Papadiamantopoulou Street, Athens, 11527, Greece

    Amalia Sertedaki B.Sc., Ph.D., George P. Chrousos MD, MACP, MACE, FRCP (London) & Evangelia Charmandari MD, MSc, PhD, MRCP(UK), CCST(UK)

  3. UNESCO Chair on Adolescent Health Care, University of Athens Medical School, “Aghia Sophia” Children’s Hospital, Thivon and Papadiamantopoulou Street, Athens, 11527, Greece

    George P. Chrousos MD, MACP, MACE, FRCP (London)

  4. National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA

    George P. Chrousos MD, MACP, MACE, FRCP (London)

  5. King Abdulaziz University, Jeddah, Saudi Arabia

    George P. Chrousos MD, MACP, MACE, FRCP (London)

Authors
  1. Nicolas C. Nicolaides M.D., Ph.D.
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  2. Agaristi Lamprokostopoulou M.Sc., Ph.D.
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  3. Amalia Sertedaki B.Sc., Ph.D.
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  4. George P. Chrousos MD, MACP, MACE, FRCP (London)
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  5. Evangelia Charmandari MD, MSc, PhD, MRCP(UK), CCST(UK)
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Corresponding author

Correspondence to Nicolas C. Nicolaides M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Division of Endocrinology, Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Eliza B. Geer

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Nicolaides, N.C., Lamprokostopoulou, A., Sertedaki, A., Chrousos, G.P., Charmandari, E. (2017). Primary Generalized Glucocorticoid Resistance or Chrousos Syndrome: Allostasis Through a Mutated Glucocorticoid Receptor. In: Geer, E. (eds) The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-45950-9_13

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  • DOI: https://doi.org/10.1007/978-3-319-45950-9_13

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  • Online ISBN: 978-3-319-45950-9

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