Cushing's Syndrome - MADE SIMPLE

Cushing syndrome is defined as: Increase cortisol due to a variety of causes.

• Exogenous (iatrogenic) steroids—#1 cause leading to “Decrease CRH & ACTH” due to negative feedback of cortisol (steroids)
• Endogenous

Endogenous causes:

• 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.

Findings:

• Hypertension,
• Weight gain,
• Moon facies,
• Truncal obesity,
• Buffalo hump,
• Hyperglycemia (insulin resistance),
• Skin changes (thinning, striae),
• Osteoporosis,
• Amenorrhea,
• Immune suppression
• Cushing syndrome is also a common cause of anovulation.

Dexamethasone (synthetic glucocorticoid) suppression test:

• 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.

Causes and Differentiation:

Mnemonic: 

Click on the image to enlarge.

_______________________________________________________________________________________

CORTISOL:

Source:

• Adrenal zona fasciculata.

Function:

1. Maintains Blood pressure (permissive effect with epinephrine—upregulates alpha1 receptors on arterioles)
2. Decrease Bone formation
3. Anti-Inflammatory
4. Decrease Immune function
5. Increase Gluconeogenesis, lipolysis, proteolysis

Regulation:

• CRH (hypothalamus) stimulates ACTH release from the pituitary gland, causing cortisol production in adrenal zona fasciculata.

• Excess cortisol –> Decreases CRH, ACTH, and cortisol secretion.

Read More