Summary
Definition
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
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
Risk factors
- exogenous corticosteroid use
- pituitary adenoma
- adrenal adenoma
- adrenal carcinoma
- neuroendocrine tumors
- thoracic or bronchogenic carcinoma
Diagnostic tests
1st tests 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
Tests to avoid
- serum cortisol
Tests 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
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
Professor of Medicine (Endocrinology) and Neurological Surgery
Director
Pituitary Center
Oregon Health & Science University
Portland
OR
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
UK
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
TX
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
TX
Disclosures
MAH declares that he has no competing interests.
References
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
More DifferentialsGuidelines
- NCCN clinical practice guidelines in oncology: neuroendocrine and adrenal tumors
- Clinical practice guideline on the management of adrenal incidentalomas
More GuidelinesPatient information
Cushing syndrome caused by an internal problem
Cushing syndrome caused by medication
More Patient informationLog in or subscribe to access all of BMJ Best Practice
Use of this content is subject to our disclaimer