Cushing's syndrome

Question 1

Etiology of cushing’s

Answer 1

• Either ACTH dependent or ACTH-independent
• ACTH dependent (70%): cushing’s disease (pituitary adenoma- most common cause), ectopic ACTH (enhanced expression of ACTH in non-pituitary tissues), ectopic CRH
• ACTH independent (30%): adrenal adenoma, 1o nodular hyperplasia, adrenal carcinoma, iatrogenic, factitious (self-induced)

Question 2

Signs and Sx of cushings

Answer 2

• Sx: weight gain (!), proximal muscle weakness (!) facial rounding and central adiposity, easy bruising, appearance of striae, hirsutism, irregular menses, thin extremities
• Signs: cervicodorsal and supraclavicular fat (!), thin extremities w/ muscle atrophy (!), HTN, striae, hyperpigmentation (ACTH-dependent)
• Required for Dx: weight gain and proximal muscle weakness
• Almost all will have diabetes, many will present w/ fractures due to decreased bone density

Question 3

Lab findings of cushings

Answer 3

• Hyperglycemia
• Hypokalemia
• Met alkalosis
• Decreased bone density (cortisol decreases osteoblast activity and accelerates osteoporosis)
• Elevated WBC: neutrophilia and lymphopenia

Question 4

Dx of cushings

Answer 4

• Pts are usually young (25-45) and often female (4:1)
• These pts lack normal rhythm of cortisol, thus an overnight dexamethasone suppression test will demonstrate an elevated AM cortisol (>5)
• 24 hr urinary free cortisol markedly elevated above normal

Question 5

Manifestations of cushings

Answer 5

• DM, osteoporosis/compression fractures
• Psychological or cognitive changes
• Oligo-amenorrhea
• Recurrent infections (esp fungal)
• Coagulopathy: increased clotting factors, fibrinogen, PAI, protein S

Question 6

Determining the etiology of cushings

Answer 6

• The pituitary remains responsive to exogenous GCCs, so if you give them the cortisol levels should go down
• High dose dexamethasone and measure AM cortisol: if its >50% of baseline its ACTH-independent cushings
• If AM cortisol is <50% baseline then its ACTH dependent cushings

Question 7

Localizing the lesion using high dose dexamethasone

Answer 7

• High dose dex leads to cortisol suppression (ACTH-dependent) or there is nl/elevated PM ACTH plus high PM cortisol means pituitary adenoma (cushing’s disease)
• No suppression w/ dex (ACTH-independent) or low PM ACTH plus high PM cortisol means primary adrenal disease (pituitary-adrenal relationship is appropriate so problem is in adrenals)
• No suppression w/ dex or markedly elevated PM ACTH plus high PM cortisol means ectopic ACTH production- image lungs and pancreas
• Ectopic ACTH is an ACTH-dependent disease but it will not respond to dex b/c dex only inhibits ACTH release from pituitary

Question 8

Rx of cushings

Answer 8

• Pituitary (cushings) disease: resection of micro adenoma
• Adrenal disease: adrenalectomy
• Ectopic ACTH: malignancy indicates Rx of underlying disease, but carcinoid indicates surgical resection
• Factitious: D/C GCCs and monitor for adrenal insufficiency
• Drug Rx: ketoconazole, mitotane, and metyrapone all inhibit cortisol release from adrenals

Question 9

Pseudocushing’s

Answer 9

• Associated w/ obesity, major depression d/o, etoh
• Due to cytokine (IL6)/etoh activation of ACTH/cortisol axis
• There is no ACTH/cortisol suppression to overnight dex, but there will be suppression to 3 days of dex
• Cortisol should fall bellow 50% of baseline after 3 days, and AM cortisol should be <5