Generalized glucocorticoid resistance syndrome

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ORPHA:786OMIM:615962E25.8
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Overview

Generalized glucocorticoid resistance syndrome (also called Chrousos syndrome or primary cortisol resistance) is a rare inherited condition where the body's cells do not respond properly to cortisol, the main stress hormone made by the adrenal glands. Cortisol plays a vital role in managing stress, blood sugar, inflammation, and many other body functions. In this condition, a genetic change in the glucocorticoid receptor — the 'docking station' that cortisol attaches to — means the hormone cannot do its job properly. Because the body senses that cortisol is not working well enough, it tries to compensate by producing much more of it. This leads to very high levels of cortisol and related hormones in the blood. The extra hormones spill over and activate other hormone pathways, particularly those involving androgens (male-type hormones) and mineralocorticoids (hormones that control salt and blood pressure). This causes a wide range of symptoms depending on age and sex. Symptoms can include high blood pressure, low potassium levels, fatigue, and signs of excess male hormones such as acne, irregular periods in women, or early puberty in children. Importantly, despite very high cortisol levels, people with this condition do NOT develop the typical features of Cushing's syndrome (like weight gain and stretch marks), because the cortisol is not working effectively at the cellular level. Treatment focuses on giving high doses of a synthetic steroid (like dexamethasone) to suppress the overproduction of these hormones and relieve symptoms.

Key symptoms:

High blood pressure (hypertension)Low potassium levels in the bloodExtreme tiredness and fatigueAcne or oily skinIrregular or absent menstrual periods in womenExcess body or facial hair in women (hirsutism)Enlarged clitoris in females (clitoromegaly)Early puberty in children (precocious puberty)Infertility in both men and womenHeadachesMuscle weaknessAnxiety or mood changesSwelling due to fluid retention

Clinical phenotype terms (21)— hover any for plain English
Increased circulating ACTH levelHP:0003154Decreased circulating aldosterone concentrationHP:0004319Increased urinary cortisol levelHP:0012030Adrenal hyperplasiaHP:0008221Abnormal circulating testosterone concentrationHP:0030087Metabolic alkalosisHP:0200114OligozoospermiaHP:0000798Frontal baldingHP:0002292Increased circulating cortisol levelHP:0003118Female pseudohermaphroditismHP:0010458
Inheritance

Variable

Can be inherited in different ways depending on the underlying gene

Age of Onset

Variable

Can begin at different ages, from infancy through adulthood

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Generalized glucocorticoid resistance syndrome.

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No actively recruiting trials found for Generalized glucocorticoid resistance syndrome at this time.

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No specialists are currently listed for Generalized glucocorticoid resistance syndrome.

View NORD Rare Disease Centers ↗Undiagnosed Disease Network ↗

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to Generalized glucocorticoid resistance syndrome.

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Community

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Caregiver Resources

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Questions for your doctor

Bring these to your next appointment

  • Q1.What dose of dexamethasone do I need, and how will we know if it is working?,How often should I have blood tests to check my hormone and potassium levels?,What should I do if I become seriously ill or need surgery — do I need extra steroid doses?,Should other family members be tested for this condition?,Will this condition affect my ability to have children, and are there treatments that can help?,Are there any long-term risks to my heart or kidneys, and how can I reduce them?,Should I wear a medical alert bracelet, and what information should it include?

Common questions about Generalized glucocorticoid resistance syndrome

What is Generalized glucocorticoid resistance syndrome?

Generalized glucocorticoid resistance syndrome (also called Chrousos syndrome or primary cortisol resistance) is a rare inherited condition where the body's cells do not respond properly to cortisol, the main stress hormone made by the adrenal glands. Cortisol plays a vital role in managing stress, blood sugar, inflammation, and many other body functions. In this condition, a genetic change in the glucocorticoid receptor — the 'docking station' that cortisol attaches to — means the hormone cannot do its job properly. Because the body senses that cortisol is not working well enough, it tries t