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# Cushing syndrome

Cushing syndrome is caused by too much cortisol over a long time, most often from steroid medicines; it causes weight gain, a round face and high blood sugar.

Updated 2026-10-29

## Structures involved

Tap one to see what it is and open it in 3D.

- [Right adrenal gland](https://durgical.com/en/anatomy/suprarenal-gland-abdomen/)
- [Left adrenal gland](https://durgical.com/en/anatomy/suprarenal-gland/)
- [Adrenal arteries](https://durgical.com/en/anatomy/middle-suprarenal-artery/)
- [Kidneys](https://durgical.com/en/anatomy/kidney/)
- [Inferior vena cava](https://durgical.com/en/anatomy/inferior-vena-cava/)

## In biochemistry

- [Phosphoenolpyruvate carboxykinase (PEPCK)](https://durgical.com/en/biochemistry/enzymes/phosphoenolpyruvate-carboxykinase/)
- [Steroid hormone synthesis (overview)](https://durgical.com/en/biochemistry/topics/steroid-hormone-synthesis/)
- [G protein-coupled receptors and cAMP](https://durgical.com/en/biochemistry/topics/g-protein-coupled-receptors-and-camp/)
- [Nuclear receptors](https://durgical.com/en/biochemistry/topics/nuclear-receptors/)
- [Hormone classes and mechanisms](https://durgical.com/en/biochemistry/topics/hormone-classes-and-mechanisms/)
- [Adrenal enzymes and congenital adrenal hyperplasia](https://durgical.com/en/biochemistry/topics/adrenal-enzymes-and-congenital-adrenal-hyperplasia/)
- [Protein kinase A (PKA)](https://durgical.com/en/biochemistry/enzymes/protein-kinase-a/)
- [11β-Hydroxylase (CYP11B1)](https://durgical.com/en/biochemistry/enzymes/11-hydroxylase/)
- [Cortisol](https://durgical.com/en/biochemistry/molecules/cortisol/)

## In histology

- [Adrenal cortex zones and medulla](https://durgical.com/en/histology/adrenal-cortex-zones-and-medulla/)

## In embryology

- [Adrenal gland: cortex from mesoderm, medulla from neural crest](https://durgical.com/en/embryology/adrenal-gland-cortex-from-mesoderm-medulla-from-neural-crest/)

## In the clinical exam

- [Diagnostic facies](https://durgical.com/en/clinical-exam/diagnostic-facies/)
- [Cushing syndrome and adrenal insufficiency: the signs](https://durgical.com/en/clinical-exam/cushing-syndrome-and-adrenal-insufficiency-the-signs/)

## In physiology

- [The HPA axis and its circadian rhythm](https://durgical.com/en/physiology/the-hpa-axis-and-its-circadian-rhythm/)
- [Actions of cortisol](https://durgical.com/en/physiology/actions-of-cortisol/)
- [Measuring hormones: stimulation and suppression tests](https://durgical.com/en/physiology/measuring-hormones-stimulation-and-suppression-tests/)
- [The adrenal cortex: zones, hormones and androgens](https://durgical.com/en/physiology/the-adrenal-cortex-zones-hormones-and-androgens/)
- [Bone remodeling](https://durgical.com/en/physiology/bone-remodeling/)
- [Metabolic alkalosis and its compensation](https://durgical.com/en/physiology/metabolic-alkalosis-and-its-compensation/)

## Why it happens

- [Hyperplasia: physiologic and pathologic](https://durgical.com/en/general-pathology/hyperplasia-physiologic-and-pathologic/)
- [Paraneoplastic syndromes: the table to know](https://durgical.com/en/general-pathology/paraneoplastic-syndromes-the-table-to-know/)

## What it is

Clinical syndrome caused by long-term exposure to excess glucocorticoid (cortisol), most often from steroid medication and otherwise from a pituitary, adrenal or ectopic source.

## Who gets it

Iatrogenic Cushing syndrome from prescribed or self-administered glucocorticoids is by far the most common form, and unprescribed steroid-containing products are a concern in the region. Endogenous disease is rare and more frequent in women; Cushing disease (pituitary) is its main cause.

## Causes

- Exogenous glucocorticoids (oral, inhaled, injected or topical): the most common cause
- Cushing disease: an ACTH-secreting pituitary adenoma (most endogenous cases)
- Ectopic ACTH secretion, e.g. small cell lung cancer or neuroendocrine (carcinoid) tumours
- Cortisol-secreting adrenal adenoma or carcinoma (ACTH-independent)
- Bilateral adrenal hyperplasia (rare)

## Risk factors

- Long-term or high-dose glucocorticoid treatment
- Use of unprescribed steroid-containing products
- Glucocorticoids combined with strong CYP3A4 inhibitors (e.g. some HIV protease inhibitors), which raise steroid levels
- Female sex (endogenous forms)
- Multiple endocrine neoplasia type 1 (pituitary tumours)

## Pathophysiology

Excess cortisol drives gluconeogenesis and insulin resistance, breaks down protein in muscle, [skin](https://durgical.com/en/anatomy/skin/) and bone, and moves fat to the trunk, face and back. It also suppresses immunity and raises blood pressure. In ACTH-dependent disease, ACTH stimulates both adrenals; with exogenous steroids or an adrenal tumour, ACTH is suppressed and the rest of the adrenal tissue atrophies.

## Classification

- ACTH-dependent: pituitary (Cushing disease) or ectopic ACTH
- ACTH-independent: exogenous glucocorticoids, adrenal adenoma, carcinoma or hyperplasia

## Symptoms and signs

- Central obesity with a rounded face (moon face) and a dorsocervical fat pad (buffalo hump)
- Wide purple striae on the [abdomen](https://durgical.com/en/anatomy/region/abdomen/), thighs and breasts
- Thin, fragile skin, easy bruising and poor wound healing
- Proximal muscle weakness
- Hypertension and diabetes or impaired glucose tolerance
- Osteoporosis and fractures
- Low mood, irritability and insomnia
- Menstrual changes, hirsutism and acne; in children, weight gain with slowed growth

## Red flags

- Rapid onset with marked hypokalaemia, hyperpigmentation or severe hypertension (ectopic ACTH or adrenal carcinoma)
- Virilisation in a woman (adrenal carcinoma)
- Headache or visual field loss (large pituitary tumour)
- Severe infection in a patient on long-term steroids
- Abrupt withdrawal of long-term steroids: risk of adrenal crisis

## Diagnosis

**Clinical**
Exogenous steroids are excluded first, including creams, inhalers, injections and unprescribed products. Testing is done when several features are present and progressive, especially the more specific ones: easy bruising, facial plethora, proximal myopathy and wide purple striae.

**Tests**
Screening with at least one of: overnight low-dose dexamethasone suppression test (morning cortisol fails to suppress), late-night salivary cortisol or 24-hour urinary free cortisol. After confirmation, plasma ACTH separates ACTH-dependent from independent causes; further dynamic tests and petrosal sinus sampling find the source.

**Imaging**
Only after biochemical confirmation: pituitary MRI for ACTH-dependent disease, adrenal CT for ACTH-independent disease, and [chest](https://durgical.com/en/anatomy/region/chest/) CT or functional imaging to find an ectopic source.

## Differential diagnosis

- Obesity with metabolic syndrome
- Pseudo-Cushing states: depression, alcohol use disorder, poorly controlled diabetes
- Polycystic [ovary](https://durgical.com/en/anatomy/ovary/) syndrome
- Pregnancy
- Adrenal incidentaloma without hormone excess

## Goal of treatment

Normalise cortisol exposure, remove the cause, treat the complications, and replace cortisol safely while the hypothalamic–pituitary–adrenal axis recovers.

## Treatment

**Medical**
Exogenous Cushing syndrome: supervised gradual tapering of glucocorticoids to the lowest effective dose or to withdrawal, to avoid adrenal insufficiency.

**Surgical**
Cushing disease: transsphenoidal resection of the pituitary adenoma.

**Surgical**
Adrenal adenoma or carcinoma: adrenalectomy (usually laparoscopic for adenomas); ectopic ACTH: resection of the tumour when possible.

**Medical**
Glucocorticoid replacement after surgery until the [axis](https://durgical.com/en/anatomy/axis/) recovers.

**Medical**
When surgery fails or is not possible: steroidogenesis inhibitors, pituitary-directed agents or glucocorticoid receptor antagonists; pituitary radiotherapy or bilateral adrenalectomy in selected cases.

**Medical**
Treatment of hypertension, diabetes and osteoporosis, and prevention of infection and venous thrombosis.

## Drugs for this condition

- [Dexamethasone](https://durgical.com/en/pharmacology/dexamethasone/)
- [Metyrapone](https://durgical.com/en/pharmacology/metyrapone/)

## Complications

- Hypertension, diabetes and cardiovascular disease
- Osteoporosis and vertebral fractures
- Infections
- Venous thromboembolism
- Depression and cognitive changes
- Adrenal crisis when steroids are stopped abruptly
- Nelson syndrome after bilateral adrenalectomy

## Prognosis

Untreated endogenous Cushing syndrome carries high cardiovascular and infection mortality. Successful surgery cures most patients, although some effects, such as bone loss and cardiovascular risk, may persist.

## Prevention

- Glucocorticoids at the lowest effective dose for the shortest time
- Avoiding abrupt withdrawal of long-term steroids
- Bone protection in long-term steroid users

## Test yourself

Think of the answer, then tap the question to see it.

## What is the most common cause of Cushing syndrome?

Exogenous glucocorticoids (iatrogenic Cushing syndrome).

## What is the most common cause of endogenous Cushing syndrome?

Cushing disease: an ACTH-secreting pituitary adenoma.

## Which screening tests are used for Cushing syndrome?

Overnight low-dose dexamethasone suppression test, late-night salivary cortisol and 24-hour urinary free cortisol.

## What does a suppressed plasma ACTH mean in confirmed Cushing syndrome?

An ACTH-independent cause: an adrenal tumour or exogenous steroids.

## Which features suggest ectopic ACTH rather than a pituitary cause?

Rapid onset, marked hypokalaemia, hyperpigmentation and very high ACTH, often with weight loss.

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## Related conditions

- [Adrenal insufficiency](https://durgical.com/en/conditions/adrenal-insufficiency/)
- [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/)
- [Arterial hypertension](https://durgical.com/en/conditions/arterial-hypertension/)
- [Osteoporosis](https://durgical.com/en/conditions/osteoporosis/)
- [Obesity](https://durgical.com/en/conditions/obesity/)
- [Metabolic syndrome](https://durgical.com/en/conditions/metabolic-syndrome/)
- [Polycystic ovary syndrome](https://durgical.com/en/conditions/polycystic-ovary-syndrome/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Hypercortisolism (Cushing Syndrome)](https://www.ncbi.nlm.nih.gov/books/NBK551526/) (StatPearls (NCBI Bookshelf), 2025).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/conditions/cushing-syndrome/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/cushing-syndrome/