Cushing’s Syndrome

1. What is Cushing’s syndrome?

Cushing’s syndrome is an endocrine disorder that occurs when the body produces too much of the hormone cortisol, a hormone produced by the adrenal glands. This condition causes a variety of symptoms due to the chronic, uncontrolled increase of glucocorticoid hormones.

2. Causes of Cushing’s syndrome

• Most common cause:

• Cushing’s syndrome caused by medication: Long-term use of corticosteroid medications.

• Other causes:

• Pituitary dysfunction:

• Pituitary adenoma: This is the most common cause of Cushing’s syndrome, caused by the pituitary gland secreting too much ACTH, which stimulates the adrenal glands to produce cortisol.

• Hypothalamic dysfunction: The hypothalamus controls the pituitary gland, and when the hypothalamus malfunctions, it can cause increased ACTH secretion.

• Adrenal gland disease:

• Adrenal tumor: This includes adenoma (benign tumor) or carcinoma (malignant tumor) that secrete excess cortisol.

• Ectopic ACTH secretion:

• Small cell lung cancer: Some types of this cancer can secrete ACTH or CRH, leading to Cushing’s syndrome accompanied by hypokalemia and skin pigmentation.

3. Characteristics of people with Cushing’s syndrome

• Body shape:

• Round, red face, moon face: Due to fat accumulation in the face.

• Obesity in the face, neck, chest, and abdomen: Fat accumulation in the upper body.

• Thin arms and legs: Due to muscle wasting.

• Skin:

• Red and thin skin: Due to atrophy of the epidermis and subcutaneous tissue.

• Stretch marks: Due to loss of connective tissue, elastin, and collagen in the subcutaneous tissue.

• Susceptibility to fungal infections: Due to immunosuppression from high cortisol blood levels.

• Hirsutism and acne: Due to increased androgen secretion, mainly occurring in women.

• Hypertension: Both systolic and diastolic, increasing the risk of cardiovascular, kidney, and eye complications.

• Reproductive disorders:

• Women: Hirsutism, acne, amenorrhea.

• Men: Decreased testosterone secretion due to cortisol inhibiting LH.

• Mental disorders: Proportional to the level of cortisol in the blood.

• Muscle weakness: Weakness in the proximal extremities, while the distal extremities remain strong.

• Osteoporosis: Can occur in young people.

• Kidney stones: Due to increased calcium excretion.

• Diabetes.

4. Pathophysiology of Cushing’s syndrome

• Pituitary adenoma: Tumors smaller than 1 cm in the sella turcica cause random increased ACTH secretion, leading to an increased cortisol level that is not regulated by the day-night rhythm.

• Increased ACTH secretion that is not negatively feedbacked by glucocorticoids: This leads to chronic increased glucocorticoid secretion, with high ACTH levels throughout the day and night.

• During stress: High cortisol levels inhibit the hypothalamus, decreasing CRH secretion, leading to the hypothalamus losing control over the pituitary gland.

5. What does Cushing’s syndrome cause due to increased androgen secretion?

• Women: Hirsutism, acne, amenorrhea.

• Men: Decreased testosterone secretion, although the adrenal glands increase androgen secretion, it is not enough to compensate.

6. Ectopic ACTH secretion Cushing’s syndrome (Paraneoplastic Cushing’s):

• ACTH secretion with or without biological activity: Due to small cell tumors in the lungs, thymus, intestines, pancreas, or ovaries.

• Higher ACTH and cortisol levels: However, typical signs of Cushing’s syndrome are less common.

7. Classification of Cushing’s syndrome

• Cushing’s syndrome due to medication

• ACTH-dependent Cushing’s syndrome:

• Pituitary Cushing’s syndrome: Increased ACTH secretion, more common in women.

• Non-pituitary tumors: More common in men.

• ACTH-independent Cushing’s syndrome:

• Due to the adrenal gland: Spontaneous increase in glucocorticoid secretion, suppressing ACTH.

• More common in women.

• Adenoma is more common than carcinoma.

8. Clinical presentation of Cushing’s syndrome

• Body shape and obesity:

• Fat accumulation: Abdomen, mediastinum, under the skin of the face, and neck are the earliest manifestations.

• No weight gain, but the face remains round and fat deposits remain in the body: In adrenal cancer or paraneoplastic Cushing’s syndrome.

• Skin: Red, thin skin, stretch marks, susceptibility to fungal infections.

• Hirsutism and acne: Due to increased androgen secretion, mainly in women.

• Hypertension: Increased risk of cardiovascular, kidney, and eye complications.

• Reproductive disorders:

• Women: Hirsutism, acne, amenorrhea.

• Men: Decreased testosterone secretion.

• Mental disorders.

• Muscle weakness: Weakness in the proximal extremities.

• Osteoporosis.

• Kidney stones.

• Diabetes.

9. Changes in cortisol blood levels throughout the day:

• Highest at 8 am.

• Lowest at 8 pm.

10. Specific tests:

• Cortisol blood level: Increased, loss of day-night rhythm.

• Free cortisol level in urine: Increased.

• 17 OHCS in urine: Increased.

• Low-dose dexamethasone suppression test: Not suppressed.

• X-ray of the sella turcica: Widened sella turcica and pituitary stalk atrophy.

11. High-dose dexamethasone suppression test:

• Cushing’s syndrome: Suppressed.

• Adenoma, adrenal cancer: Not suppressed.

• Ectopic ACTH Cushing’s syndrome: Poor response.

12. Alcohol use:

• Increased cortisol blood levels and clinical presentation similar to Cushing’s syndrome: But free cortisol levels in urine are normal.

Note: This is only general information about Cushing’s syndrome and does not replace the advice of a doctor. If you suspect you have Cushing’s syndrome, consult a doctor for timely diagnosis and treatment.