Week 2: Cushing's Syndrome

Question 1

General tissue effects of glucocorticoid actions

Answer 1

1. connective tissue
   - decrease collagen formation
   - impair wound healing
2. CV
   - increase cardiac output
   - increase response to catecholamines
3. growth and dev.
   - inhibit skeletal growth
   - mature surfactant and liver
4. Calcium and bone
   - decrease serum Ca
   - decrease bone formation
5. Renal
   - increase renal blood flow
   - inhibit ADH
6. CNS
   - decrease libido
   - blunt TSH and LH/FSH

Question 2

Etiology of Cushing’s syndrome

Answer 2

ENDOGENOUS
1. ACTH dependent
-pituitary: pituitary adenoma *80%)
-ectopic: ACTH or CRH (1%)
2. ACTH-independent (20%)
-adenoma
-carcinoma
-nodular hyperplasia
EXOGENOUS
-iatrogenic/factitious

Question 3

Clinical features of Cushing’s disease

Answer 3

• women to men 4:1
• 24-45 yo
• symptoms usually present for 2-6 year, 5-10 years in mild cases
• ACTH is usually suppressible and stimulatable

Question 4

Symptoms and signs of Cushing’s Syndrome

Answer 4

SYMPTOMS
-weight gain !!!!
-weakness
-easy bruisability
-impotence
-acne, oily skin, hirsutism, polydipsia, polyuria
-headache, abdominal discomfort, back pain, loss of height, irregular menses
SIGNS
-proximal myopathy!!!
-centripedal obesity
-dorsal, supraclavicular fat, facial plethora, glucose intolerance, hirsutism, HTN, ecchymoses, oligo/amenorrhea, renal calculi

Question 5

Laboratory findings of Cushing’s syndrome

Answer 5

• hyperglycemia
• hypokalemia
• metabolic alkalosis
• decrase bone mineral density
• anemia, elevated WBCc, neutrophilia, lymphopenia

Question 6

Screening testing of Cushing’s syndrome

Answer 6

Screening tests

• 24 hr urinary free cortisol
• overnight dexamethasone suppression: 1mg dex po followed by AM cortisol. Normal fasting cortisol <2mcg/dl
• salivary cortisol (only detects severe)
• make sure to measure creatinine as well

Question 7

Pseudocushing’s syndrome

Answer 7

1. depression
2. obesity
3. illness
4. Alcohol: direct stimulator of adrenal axis
   RULE out these with dexamethasone suppression test. Will have normal suppression

Question 8

Tests of etiology and localization for Cushing’s Syndreom

Answer 8

1. tests of etiology
   - low dose DEX suppression
   - high dose DEX suppression: 2 day testing. pituitary is responsive, AM cortisol 50% of baseline. ACTH independent causes will have AM cortisol>50% of baseline
   - PM cortisol/ACTH
2. Tests of localization
   - MRI of sella truism
   - MRI of adrenal glands
   - inferior petrosal sinus sampling

Question 9

RX of Cushing’s syndrome

Answer 9

• pituitary: trenasphenoidal resection of micro adenoma. If failed, then can try reapportion or radiation, or medical therapy
• adrenal: adrenalectomy
• Ectopic ACTH: treat underlying disease for malignancy, surgical resection of carcinoid
• factitious: discontinue glucocorticoids and monitor for adrenal insufficiency

Question 10

Therapeutic agents for Cushings

Answer 10

1. mifepristone: GC receptor blocker. but has unopposed secretion of cortisol, increases risk of adrenal insufficiency and hypokalemia
2. Ketoconazole: antifungal
   - used in failed surgery. Lowers cortisol level, but has side effects and isn’t always effective
3. Pasireotide: inhibits ACTH release at level of pituitary adenoma. but may worsen hyperglycemia.