Cushing's syndrome

Question 1

Etiology - Cushing’s
ACTH producing adenoma

Answer 1

• Iatrogenic hypercortisolism is the most common cause of cushingoid features.
• other: Ectopic tumor ACTH production, cortisol producing adrenal adenomas, adrenal carcinoma, adrenal hyperplasia
• rare: ectopic tumor CRH production.

Question 2

ACTH producing tumors

Answer 2

small - microadenomas
account for 10-15% of all pituitary tumours
pituitary adenomas exhibit unrestrained ACTH secretion with resultant hypercortisolemia.

Question 3

features of cortisol excess

Answer 3

thin skin
central obesity
diastolic hypertension
plethoric moon facies
purple striae
easy bruisibility
glucose intolerance/DM
gonadal dysfunction
osteoporosis
proximal muscle weakness
signs of hyperandrogegism (acne, hirsutism)
Psychological disturbance (depression, mania, psychoses)

Question 4

haematopoetic features of hypercortisolism

Answer 4

leukocytosis, lymphopnemia, eosinopenia

Question 5

Immune suppression

Answer 5

Delayed hypersensitiivity, infection propensity

Question 6

Pituitary dependent ACTH secretion/Cushing’s syndrome

Answer 6

Hypertension
Hypokalemic alkalosis
glucose intolerance
edema
S K <3.3

Question 7

ACTH dependent cushing’s

Answer 7

Cushing’s disease - pituitary adenoma
ectopic ACTH syndrome due to ACTH secretion by bronchial/pancreatic carcinoid tumours, small cell lung ca, medullary thyroid ca, pheochromocytoma

Question 8

ACTH independent cushing’s

Answer 8

adrenocortical adenoma
adrenocortical carcnioma
rare - macronodular adrenal hyperplasia, primary pigmented nodular adrenal disease (micro/macro nodular) McCuneAlbright syndrome

Question 9

s/s of Cushing’s syndrome

Answer 9

• body fat - weight gain, central obesity, round face, fat pad on back of neck (buffalo hump)
• Skin - facial plethora, think and brittle skin, easy bruising, broad and purple stretch marks, acne, hirsutism
• Bone - Osteopenia, osteoporosis (vertebral fractures) decreased linear growth in children
• muscle - weakness, proximal myopathy (prominent atrophy of gluteal and upper leg muscles with difficulty climbing stairs or getting up from chair)
• cardiovascular system - HTN, hypokalaemia, oedema, atherosclerosis
• metabolism - glucose intolerance / diabetes, dyslipidemia
  Reproductive system - decreased libido, in F amenorrhoea (cortisol mediated inhibition of gnoadotrophin release)
• CNS - irritability, emotional liability, depression, sometimes cognitive deficits, in severe cases paranoid psychosis
• Blood & immune system - increased susceptibility to infections, increased WBC count, Eopsinopenia, hypercoagulation with increased DVT and PE

Question 10

Diagnosis

Answer 10

• 24 hour urine free cortisol excretion (inc above normal 3x)
• Dexamethasone overnight test (plasma cortisol >50 8-9am, after 1mg dex at 11pm)
  Midnight plasma cortisol >130nmol/L or midnight salivary cortisol >5nmol/L

Question 11

Differential diagnosis

Answer 11

ACTH dependent cushing’s - MRI pituitary, CRH test, high dose dex test
ACTH independent cushing’s - unenhanced CT adrenals

Question 12

treatment

Answer 12

ACTH independent - surgical removal of adrenal tumor
serve overt cushing’s - medical therapy
oral agents :
Metyrapone - inhibit cortisol synthesis at the level of 11beta hydroxylase
start 500mg TDS (max dose 6gm)
etokonazoe - antimicotic drug - inhibits early steps of steroidogenesis
200mg TDS