Cushing’s syndrome describes the signs and symptoms associated with prolonged exposure to inappropriately high levels of the hormone cortisol. The most common cause of this is by taking glucocorticoid drugs, or diseases that result in excess cortisol, adrenocorticotropic hormone (ACTH), or CRH levels.
Cushing’s disease refers to a pituitary-dependent cause of Cushing’s syndrome: a tumor (adenoma) in the pituitary gland produces large amounts of ACTH, causing the adrenal glands to produce elevated levels of cortisol. It is the most common non-iatrogenic cause of Cushing’s syndrome, responsible for 70% of cases excluding glucocorticoid related cases.
This lecture on Cushing’s syndrome has been provided by: Medical Institution
Cushing’s syndrome is defined as the signs and symptoms associated with long term exposure to inappropriately high levels of Cortisol. The most common causes of Cushing’s syndrome are:
1) Exogenous causes of Cushing’s syndrome:
- Exogenous (iatrogenic) steroids, such as glucocorticoid drugs are the number one cause of Cushing’s syndrome. Steroid are which leads to decrease levels of Corticotropin-releasing hormone (CRH) and Adrenocorticotropic hormone (ACTH) due to negative feedback of cortisol (steroids).
2) Endogenous causes of Cushing’s syndrome:
- Cushing’s disease (70%)—due to ACTH secretion from pituitary adenoma; “Increase ACTH“
- Ectopic ACTH “paraneolplastic tumor” (15%)—from non-pituitary tissue making ACTH (e.g., small cell lung cancer, bronchial carcinoids); “Increase ACTH“
- Adrenal adenoma (15%), carcinoma, nodular adrenal hyperplasia; “Decrease ACTH” due to negative feedback
- Weight gain,
- Moon facies,
- Truncal obesity,
- Buffalo hump,
- Hyperglycemia (insulin resistance),
- Skin changes (thinning, striae),
- Immune suppression
- Cushing’s syndrome is also a common cause of anovulation.
Dexamethasone suppression test, is a test that is done to differentiate between different causes of Cushing’s syndrome.
- Healthy: Decrease cortisol after low dose.
- ACTH-producing pituitary tumor: Increase cortisol after low dose; Decrease cortisol after high dose.
- Ectopic ACTH-producing tumor (e.g., small cell carcinoma): Increase cortisol after low and high dose.
- Cortisol-producing tumor: Increase cortisol after low and high dose.
- Adrenal zona fasciculata.
- Maintains Blood pressure (permissive effect with epinephrine—upregulates alpha1 receptors on arterioles)
- Decrease Bone formation
- Decrease Immune function
- Increase Gluconeogenesis, lipolysis, proteolysis
- CRH (hypothalamus) stimulates ACTH release from the pituitary gland, causing cortisol production in adrenal zona fasciculata.
- Excess cortisol –> Decreases CRH, ACTH, and cortisol secretion.