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# Cushing syndrome: causes and the adrenals

- Lesion

Cushing syndrome is too much cortisol. The cause is usually steroid medicines; otherwise a pituitary, lung or adrenal tumour.

Updated Nov 12, 2026

## Key points

- Exogenous steroids: bilateral cortical atrophy from ACTH suppression.
- Cushing disease (pituitary corticotroph microadenoma): commonest endogenous cause; bilateral diffuse hyperplasia; often women.
- Ectopic ACTH: small cell lung carcinoma, carcinoids, medullary thyroid carcinoma, pancreatic NETs; marked hyperplasia, hypokalaemia, hyperpigmentation.
- Adrenal adenoma or carcinoma: low ACTH, atrophy of the opposite cortex and of the adjacent cortex.
- Primary nodular hyperplasia: bilateral macronodular (PBMAH, ARMC5) or micronodular pigmented (PPNAD, PRKAR1A in Carney complex).
- Crooke hyaline change: glassy cytokeratin filaments in normal pituitary corticotrophs exposed to high cortisol.

## What it is

Hypercortisolism has exogenous and endogenous causes. Exogenous glucocorticoids are by far the commonest. Endogenous cases are ACTH-dependent (pituitary corticotroph tumour, called Cushing disease, or ectopic ACTH from a tumour such as small cell lung carcinoma) or ACTH-independent (adrenal adenoma, carcinoma or nodular hyperplasia). The adrenal glands tell which: atrophic, diffusely hyperplastic or nodular.

## Function

- Central obesity, moon face, buffalo hump, from fat redistribution.
- Proximal muscle weakness and wasting from protein catabolism.
- Thin skin, easy bruising and wide purple striae from collagen loss.
- Hyperglycaemia, hypertension, osteoporosis, poor wound healing, infections.
- Mood changes and psychosis; menstrual irregularity and hirsutism.

## Cause of Cushing syndrome and the adrenal picture

| Cause | ACTH | Adrenals | Clue |
| --- | --- | --- | --- |
| [Exogenous glucocorticoids](https://durgical.com/en/conditions/cushing-syndrome/) | Low | Bilateral atrophy | Steroid use |
| [Pituitary corticotroph tumour (Cushing disease)](https://durgical.com/en/conditions/pituitary-adenoma/) | High-normal to high | Bilateral diffuse hyperplasia | Suppresses with high-dose dexamethasone |
| [Ectopic ACTH](https://durgical.com/en/conditions/lung-cancer/) | Very high | Bilateral marked hyperplasia | Lung tumour, hypokalaemia, no suppression |
| [Adrenal adenoma](https://durgical.com/en/conditions/adrenal-incidentaloma/) | Low | Nodule with atrophy of the rest and of the other gland | Unilateral mass |
| [Adrenal carcinoma](https://durgical.com/en/conditions/adrenocortical-carcinoma/) | Low | Large invasive mass | Virilisation often added |
| Primary nodular hyperplasia | Low | Bilateral nodules (macro or pigmented micro) | Carney complex, ARMC5 |

## Clinical notes

- Screening uses late-night salivary cortisol, 24-hour urinary free cortisol, or the overnight dexamethasone test.
- Mild autonomous cortisol secretion is the commonest hormone finding in adrenal incidentalomas.

## Memory aid

Look at the adrenals to find the culprit: shrunken means pills, both swollen means ACTH, one lump with a shrunken partner means the adrenal did it.

## Test yourself

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

## Why are both adrenals atrophic in Cushing syndrome from steroid medication?

Exogenous glucocorticoid suppresses pituitary ACTH, so the cortex loses its trophic stimulus.

## What is Crooke hyaline change?

Accumulation of glassy intermediate keratin filaments in pituitary corticotrophs exposed to high cortisol.

## Which tumour is the classic source of ectopic ACTH?

Small cell carcinoma of the lung.

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## Elsewhere in DurgiPedia

- [The adrenal cortex: zones, hormones and androgens](https://durgical.com/en/physiology/the-adrenal-cortex-zones-hormones-and-androgens/)
- [Cortisol](https://durgical.com/en/biochemistry/molecules/cortisol/)
- [Cushing syndrome and adrenal insufficiency: the signs](https://durgical.com/en/clinical-exam/cushing-syndrome-and-adrenal-insufficiency-the-signs/)
- [Paraneoplastic syndromes: the table to know](https://durgical.com/en/general-pathology/paraneoplastic-syndromes-the-table-to-know/)
- [Atrophy](https://durgical.com/en/general-pathology/atrophy/)

## Connections

## Related 5

- [Pituitary neuroendocrine tumours (PitNETs): overview](https://durgical.com/en/general-pathology/pituitary-neuroendocrine-tumours-overview/)
- [Adrenocortical adenoma and carcinoma](https://durgical.com/en/general-pathology/adrenocortical-adenoma-and-carcinoma/)
- [Adrenocortical insufficiency](https://durgical.com/en/general-pathology/adrenocortical-insufficiency/)
- [Paraneoplastic syndromes: the table to know](https://durgical.com/en/general-pathology/paraneoplastic-syndromes-the-table-to-know/)
- [Pulmonary neuroendocrine tumours](https://durgical.com/en/general-pathology/pulmonary-neuroendocrine-tumours/)

## Related conditions 7

- [Cushing syndrome](https://durgical.com/en/conditions/cushing-syndrome/)
- [Adrenal incidentaloma](https://durgical.com/en/conditions/adrenal-incidentaloma/)
- [Lung cancer](https://durgical.com/en/conditions/lung-cancer/)
- [Pituitary adenoma](https://durgical.com/en/conditions/pituitary-adenoma/)
- [Osteoporosis](https://durgical.com/en/conditions/osteoporosis/)
- [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/)
- [Adrenocortical carcinoma](https://durgical.com/en/conditions/adrenocortical-carcinoma/)

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

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/general-pathology/cushing-syndrome-causes-and-the-adrenals/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/cushing-syndrome-causes-and-the-adrenals/