Cushing syndrome

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 20 Aug 2025

Last updated: 10 Jun 2025

Cushing syndrome is the clinical manifestation of pathologic hypercortisolism from any cause.

Exogenous corticosteroid exposure is the most common cause of Cushing syndrome.

Cushing disease, which is hypercortisolism caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma, is the most common cause of endogenous Cushing syndrome, and is responsible for 70% to 80% of cases.

It may be difficult to distinguish patients with mild Cushing syndrome from those with the metabolic syndrome (central obesity with insulin resistance, and hypertension). Features more specific to Cushing syndrome include proximal muscle weakness, supraclavicular fat pads, facial plethora, violaceous striae, easy bruising, premature osteoporosis, and hypokalemia.

After excluding exogenous corticosteroid use, patients with suspected Cushing syndrome should be tested for hypercortisolism with one of three high-sensitivity tests (late-night salivary cortisol, 1 mg overnight low-dose dexamethasone suppression testing, or 24-hour urinary free cortisol).

At least one additional test should be performed to confirm hypercortisolism in patients with a positive initial screening test.

Once endogenous hypercortisolism is confirmed, plasma ACTH should be measured. If ACTH is suppressed, diagnostic testing should focus on the adrenal glands. If ACTH is not suppressed, pituitary or ectopic disease should be sought.

Surgical resection of the pituitary, adrenal, or neuroendocrine tumor that is causing hypercortisolism is the primary treatment of choice in the vast majority of patients with endogenous Cushing syndrome.

Definition

Cushing syndrome is the clinical manifestation of pathologic hypercortisolism from any cause. Patients often display weight gain with central obesity, facial rounding and plethora, proximal muscle weakness, and thinning of the skin. They also develop metabolic complications including diabetes mellitus, dyslipidemia, metabolic bone disease, and hypertension. The most common cause of Cushing syndrome is exogenous corticosteroid exposure. Endogenous causes are ACTH-secreting pituitary tumors (termed Cushing disease), ectopic ACTH-secreting tumors, and autonomous adrenal cortisol overproduction (ACTH-independent Cushing syndrome).[1][2]

History and exam

Key diagnostic factors

facial plethora
supraclavicular fullness
violaceous striae
absence of pregnancy
menstrual irregularities
absence of malnutrition
absence of alcoholism
absence of physiologic stress
linear growth deceleration in children

Full details

Other diagnostic factors

female sex
hypertension
glucose intolerance or diabetes mellitus
premature osteoporosis or unexplained fractures
weight gain and central obesity
acne
psychiatric symptoms
decreased libido
easy bruisability
weakness
facial rounding
dorsocervical fat pads
unexplained nephrolithiasis
venothrombolic event
hirsutism

Full details

Risk factors

exogenous corticosteroid use
pituitary adenoma
adrenal adenoma
adrenal carcinoma
neuroendocrine tumors
thoracic or bronchogenic carcinoma

Full details

Diagnostic investigations

1st investigations to order

urine pregnancy test
serum glucose
late-night salivary cortisol
1 mg overnight dexamethasone suppression test
24-hour urinary free cortisol
48-hour 2 mg (low-dose) dexamethasone suppression test

Full details

Tests to avoid

serum cortisol

Full details

Investigations to consider

morning plasma adrenocorticotropic hormone (ACTH)
plasma dehydroepiandrosterone sulfate (DHEAS) level
pituitary MRI
adrenal imaging
high-dose dexamethasone suppression test
inferior petrosal sinus sampling (IPSS)
CT of chest, abdomen, and pelvis
MRI chest
octreotide scanning
gallium-68 dotatate PET/CT

Full details

Treatment algorithm

ONGOING

Cushing disease (adrenocorticotropic hormone [ACTH]-secreting pituitary tumor)

ectopic ACTH or corticotropin-releasing hormone (CRH) syndrome

ACTH-independent due to unilateral adrenal carcinoma or adenoma

ACTH-independent due to bilateral adrenal disease (hyperplasia or adenoma)

mild autonomous cortisol secretion (previously known as subclinical Cushing syndrome)

Contributors

Authors

Maria Fleseriu, MD, FACE

Professor of Medicine (Endocrinology) and Neurological Surgery

Director

Pituitary Center

Oregon Health & Science University

Portland

Disclosures

MF is on the Endocrine Society's Board of Directors. She holds a research grant to the university for clinical studies as principal investigator for Crinetics and Sparrow Pharmaceuticals, and is an occasional scientific consultant for Crinetics, Recordati, Sparrow Pharmaceuticals, and Xeris Pharmaceuticals. MF is an author of several references cited in this topic.

Acknowledgements

Dr Maria Fleseriu would like to gratefully acknowledge Dr Ty Carroll and Dr James Findling, contributors to a previous version of this topic.

Disclosures

TC is an author of a number of references cited in this topic. He is an investigator in clinical trials sponsored by Corcept. JF is an author of a number of references cited in this topic. He is a consultant for, and investigator in, clinical trials sponsored by Corcept and Novartis.

Peer reviewers

Paul M. Stewart, FRCP FMedSci

Professor of Medicine

Director of Research

College of Medical and Dental Sciences

University of Birmingham

Honorary Consultant Physician

Queen Elizabeth Hospital

Birmingham

Disclosures

PMS declares that he has no competing interests.

Antoine Tabarin, MD

Head

Department of Endocrinology

University Hospital of Bordeaux

Pessac

France

Disclosures

AT declares that he has no competing interests.

Liliana Contrersas, MD

Chief

Endocrine Research Department

Instituto de Investigaciones Médicas A. Lanari

University of Buenos Aires and IDIM-CONICET

Buenos Aires

Argentina

Disclosures

LC declares that she has no competing interests.

Philip R. Orlander, MD

Professor of Medicine

Director

Division of Endocrinology, Diabetes & Metabolism

University of Texas Medical School

Houston

Disclosures

PRO declares that he has no competing interests.

Mouhammed Amir Habra, MD, FACP, FACE

Assistant Professor

Department of Endocrine Neoplasia and Hormonal Disorders

Division of Internal Medicine

University of Texas MD Anderson Cancer Center

Houston

Disclosures

MAH declares that he has no competing interests.

Peer reviewer acknowledgements

BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.

Disclosures

Peer reviewer affiliations and disclosures pertain to the time of the review.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Fleseriu M, Auchus R, Bancos I, et al. Consensus on diagnosis and management of Cushing's disease: a guideline update. Lancet Diabetes Endocrinol. 2021 Dec;9(12):847-75.Full text Abstract

Nieman LK, Biller BM, Findling JW, et al. Treatment of Cushing’s syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015 Aug;100(8):2807-31.Full text Abstract

Feelders RA, Newell-Price J, Pivonello R, et al. Advances in the medical treatment of Cushing's syndrome. Lancet Diabetes Endocrinol. 2019 Apr;7(4):300-12. Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Obesity
- Metabolic syndrome
- Primary aldosteronism
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Guidelines
- NCCN clinical practice guidelines in oncology: neuroendocrine and adrenal tumors
- Clinical practice guideline on the management of adrenal incidentalomas
More Guidelines
Patient information
Cushing syndrome caused by an internal problem
Cushing syndrome caused by medication
More Patient information
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Cushing syndrome

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Tests to avoid

Investigations to consider

Treatment algorithm

Cushing disease (adrenocorticotropic hormone [ACTH]-secreting pituitary tumor)

ectopic ACTH or corticotropin-releasing hormone (CRH) syndrome

ACTH-independent due to unilateral adrenal carcinoma or adenoma

ACTH-independent due to bilateral adrenal disease (hyperplasia or adenoma)

mild autonomous cortisol secretion (previously known as subclinical Cushing syndrome)

Contributors

Authors

Maria Fleseriu, MD, FACE

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Paul M. Stewart, FRCP FMedSci

Disclosures

Antoine Tabarin, MD

Disclosures

Liliana Contrersas, MD

Disclosures

Philip R. Orlander, MD

Disclosures

Mouhammed Amir Habra, MD, FACP, FACE

Disclosures

Peer reviewer acknowledgements

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Patient information

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