Cushing’s syndrome

Definition:

Cushing’s syndrome can defined as signs and symptoms caused by excessive activation of glucocorticoid receptors and is characterized by truncal obesity, glucosuria, fatigability and weakness, hypertension, amenorrhea, hirsutism, edema, purplish abdominal striae, osteoporosis etc.

Classification of cushing’s syndrome (Along with causes):

1. ACTH-dependent:

a) Pituitary adenoma secreting ACTH- causing bilateral adrenal hyperplasia (i.e. Cushing’s disease)
b) Ectopic ACTH syndrome (e.g. bronchial carcinoid, small-cell carcinoma of the lung)
c) Iatrogenic (ACTH therapy)

2. ACTH-independent:

a) Iatrogenic (chronic glucocorticoid therapy)
b) Adrenal adenoma or carcinoma

3. Pseudo-Cushing’s syndrome:

Here there is increased cortisol level due to other illness like-

i) Excess intake of alcohol
ii) Obesity
iii) Major depressive illness.

Clinical manifestations Cushing’s Syndrome:

• Moon face
• Buffalo hump
• Truncal obesity
• Muscle weakness
• Proximal myopathy
• Fatigability
• Hypertension
• Hyperglycemia
• Peptic ulcer
• In women-acne, hirsutism, hair thinning, oligomenorrhea or amenorrhea
• Broad cutaneous striae
• Decreased skin thikness
• Easy bruisability
• Osteoporosis that may cause collapse of vertebral bodies and pathologic fractures of other bones
• Tendency to infection
• Poor wound healing
• Emotional changes like-irritability, emotional lability, severe depression, confusion, or psychosis.

Investigations:

1. 24-hour urinary free cortisol- more than140 nmol/d (50 gm/d) is suggestive of Cushing’s syndrome
2. Overnight dexamethasone suppression test- failure of suppression indicates Cushing’s syndrome
3. Standard low-dose dexamethasone suppression test -failure of plasma cortisol to fall to less than 140 nmol/L (5 gm/dL) or of urinary cortisol to fall to less than 25 nmol/d (10 gm/d)- definitive diagnosis of Cushing’s syndrome is then established
4. Diurnal rhythm of plasma cortisol: Serum cortisol level at 8 am and 12 midnight shows loss of circadian rhythm,evening level is more than 75% of morning level in Cushing’s syndrome.
5. Plasma ACTH level-useful in distinguishing ACTH-dependent from ACTH-independent Cushing syndrome
6. CXR- to exclude bronchial carcinoid
7. CT and MRI scan of the abdomen- for localizing adrenal tumors and for diagnosing bilateral adrenal hyperplasia
8. CT and MRI scan of the skull- to exclude Cushing’s disease
9. Other useful tests-

• Plasma electrolytes
• Plasma glucose
• Glycosylated haemoglobin
• Bone mineral density measurement.

Treatment of cushing’s syndrome:

Treatment of Cushing’s syndrome is as below-

Most of the cases are treated surgically with giving medical therapy for a few weeks before operation, the drugs are- metyrapone, aminoglutethimide and ketoconazole.

Treatment for Cushing’s disease-

Trans-sphenoidal surgery and selective removal of the adenoma.

Treatment for Adrenal tumors-

Surgical removal of the tumors.

Treatment for Ectopic ACTH syndrome-

Treatment of the cause, e.g. -treatment for bronchial carcinoid.