Cushing's syndrome is caused by chronic excess cortisol — most commonly from long-term steroid medications, or from a pituitary or adrenal tumor. Symptoms include central obesity, purple stretch marks, easy bruising, muscle weakness, high blood pressure, and diabetes. Diagnosis requires specialized cortisol testing; treatment is usually surgical.
Cushing's syndrome results from prolonged exposure to high cortisol levels — either from external sources (steroid medications) or from the body overproducing cortisol. It affects virtually every organ system and, if untreated, carries significant cardiovascular, metabolic, and psychological consequences. Early diagnosis and treatment dramatically improve outcomes.
Causes
- Exogenous (most common): Long-term use of corticosteroids (prednisone, dexamethasone, methylprednisolone) for any condition — this is iatrogenic Cushing's syndrome
- Cushing's disease (pituitary, ~70% of endogenous): A benign pituitary adenoma secretes excess ACTH, which drives both adrenal glands to overproduce cortisol
- Adrenal adenoma (~15%): A benign tumor in one adrenal gland produces cortisol autonomously, suppressing ACTH
- Ectopic ACTH (~15%): A non-pituitary tumor (lung carcinoid, small cell lung cancer, thymic tumor) secretes ACTH — often presents with more severe hypercortisolism
💊 Most Common Cause: The most common cause of Cushing's syndrome worldwide is steroid medication prescribed for other conditions. Always inform your endocrinologist of all steroid use (including inhalers, skin creams, and joint injections in high doses) as these can cause or contribute to Cushing's syndrome.
Signs & Symptoms
- Central obesity — fat accumulates in the abdomen, face, and upper back
- Moon face — rounded, full face
- Buffalo hump — fat pad at the back of the neck/upper back
- Wide purple striae — stretch marks >1cm wide, purplish-red, typically on abdomen, breasts, thighs
- Easy bruising and thin fragile skin
- Proximal muscle weakness — difficulty rising from a chair, climbing stairs
- High blood pressure and high blood sugar (often new diabetes)
- Osteoporosis and frequent fractures
- Irregular periods or loss of periods in women
- Depression, anxiety, cognitive difficulties, insomnia
- Recurrent infections (immune suppression)
Diagnosis
Diagnosis requires demonstrating sustained cortisol excess. Two abnormal results from the following tests are needed:
- 24-hour urine free cortisol (UFC): Collects all cortisol excreted over 24 hours; elevated in Cushing's
- Late-night salivary cortisol (×2): Cortisol normally falls to its lowest at 11pm–midnight; in Cushing's it remains elevated
- Overnight 1mg dexamethasone suppression test (DST): Take 1mg dexamethasone at 11pm; normal result is cortisol below 1.8 mcg/dL next morning; Cushing's = failure to suppress
After biochemical confirmation, an ACTH level distinguishes ACTH-dependent (pituitary or ectopic) from ACTH-independent (adrenal) causes. Then imaging (MRI pituitary with gadolinium, CT adrenals) localizes the source.
Treatment
| Cause | Primary Treatment | Cure Rate |
|---|---|---|
| Cushing's disease (pituitary) | Transsphenoidal pituitary surgery | 65–90% |
| Adrenal adenoma | Laparoscopic adrenalectomy | >95% |
| Ectopic ACTH | Resection of primary tumor if possible | Variable |
| Failed surgery / not surgical candidate | Medications: Isturisa, Korlym, Recorlev; radiation | Remission with medications |
After successful surgery, the remaining adrenal function may be suppressed for months to years — patients require cortisol replacement and careful monitoring during this recovery period.
Key Takeaways
- Cushing's syndrome = chronic cortisol excess — most commonly from steroid medications, then pituitary or adrenal tumors
- Classic signs: central obesity, moon face, purple stretch marks, easy bruising, proximal muscle weakness
- Diagnosis requires 2 abnormal tests from: 24hr UFC, late-night salivary cortisol, or overnight DST
- ACTH level distinguishes pituitary/ectopic (ACTH-dependent) from adrenal (ACTH-independent) causes
- Surgery is the primary treatment — pituitary surgery cures 65–90% of Cushing's disease
- After cure, adrenal function may be suppressed for months — cortisol replacement is required during recovery
- Medical therapies (Isturisa, Korlym, Recorlev) are available when surgery fails or is not possible
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