Definition:
Cushing’s syndrome refers to a constellation of clinical manifestations resulting from chronic exposure to elevated levels of glucocorticoids, regardless of the source. Cushing’s disease is a specific form of Cushing’s syndrome caused by excess ACTH secretion from a pituitary adenoma, leading to adrenal hyperplasia and hypercortisolism.
Classification / Etiology:
Cushing’s syndrome can be classified based on whether cortisol excess is ACTH-dependent or ACTH-independent:
A. Exogenous (Iatrogenic) Cushing’s Syndrome (Most Common)
- Cause: Prolonged administration of corticosteroid medications (e.g., prednisone).
- ACTH levels are low due to negative feedback.
- Adrenal glands show atrophy.
B. Endogenous Cushing’s Syndrome (Rare):
1. ACTH-dependent:
- Cushing’s Disease (Pituitary-dependent):
- Pituitary adenoma secreting excessive ACTH.
- Most common cause of endogenous Cushing’s.
- Affects mainly women (20–40 years).
- Ectopic ACTH syndrome:
- ACTH secretion by non-pituitary tumors, commonly:
- Small cell carcinoma of the lung
- Bronchial carcinoid
- Rapid onset, very high ACTH.
2. ACTH-independent:
- Adrenal causes:
- Adrenal adenoma or carcinoma secreting cortisol.
- ACTH suppressed due to feedback inhibition.
- May occur in McCune-Albright syndrome or primary pigmented nodular adrenocortical disease.
3. Others:
- Alcohol-induced pseudo-Cushing's syndrome (reversible).
- Depression, obesity, poorly controlled diabetes may show Cushingoid features (pseudo-Cushing’s).