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.
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 | Low | Bilateral atrophy | Steroid use |
| Pituitary corticotroph tumour (Cushing disease) | High-normal to high | Bilateral diffuse hyperplasia | Suppresses with high-dose dexamethasone |
| Ectopic ACTH | Very high | Bilateral marked hyperplasia | Lung tumour, hypokalaemia, no suppression |
| Adrenal adenoma | Low | Nodule with atrophy of the rest and of the other gland | Unilateral mass |
| Adrenal 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.
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.
Elsewhere in DurgiPedia
- The adrenal cortex: zones, hormones and androgens
- Cortisol
- Cushing syndrome and adrenal insufficiency: the signs
- Paraneoplastic syndromes: the table to know
- Atrophy
Connections
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) (StatPearls (NCBI Bookshelf), 2025).
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Representative model, for educational purposes only.