Cushing's disease/syndrome

Question 1

What is Cushing’s syndrome (an increase/decrease of)

Answer 1

Caused by prolonged glucocorticoid exposure - may be endogenous or exogenous.

Either ACTH dependant (this is elevated causing the high cortisol) or independent (ACTH is low but cortisol is high)

Question 2

A common cause of ectopic ACTH production?

Answer 2

small cell lung cancer

Question 3

Causes of cushings syndrome:

Answer 3

In order of how common they are

1) exogenous steroids
2) Cushing’s disease - pituitary adenoma (high ACTH)
3) ectopic ACTH secretion (SCLC, or any endocrine tumour
4i) ectopic cortisol secretion - unilateral adrenal adenoma
4ii) ectopic cortisol secretion - unilateral adrenal carcinoma

Question 4

Cortisol secretion mechanism - from hypothalamus

Answer 4

1) Hypothalamus: Corticotropin-releasing hormone (CRH)
2) Anterior pituitary gland - stimulated by CRH then releases ACTH (adrenocorticotropin hormone)
3) Adrenal cortex - ACTH causes it to release cortisol

High ACTH inhibits CRH secretion
high Cortisol inhibits ACTH and CRH secretion

Question 5

Clinical presentation of cushion’s syndrome

Answer 5

weight gain, moon face
proximal muscle wasting
skin: purple striae, hirsutism (male pattern thick hair growth), acne, pigmentation if ACTH^
depressed, emotionally labile
polydipsia (thirst), polyuria 
oedema

Question 6

bedside test results in cushion’s syndrome

Answer 6

high glucose
high blood pressure
WBC^
Hypokalaemia, metabolic acidosis

Question 7

diagnosis of cushings syndrome

Answer 7

24 hour urinary free cortisol (2/3 collections x3 normal limit)
dexamethasone suppression test - suppresses cortisol secretion normally
Should normally be ATCH diurnal variation (high in morning)
MRI pituitary gland (high ATCH)
CT adrenal glands (low ATCH)
?CT thorax (SCLC)

Question 8

management of cushings syndrome

Answer 8

1 - surgical resection of tumour (trans-sphenoidal microsurgery for pituitary)
-radiotherapy can be an adjunct

2 - medical
metyrapone/ketoconazole - rapid decrease in cortisol - but only short term - ACTH oversecretion
mitotane - slow onset but lasting effect of reduced cortisol

Question 9

cortisol ttm

Answer 9

lipid soluble, not water soluble - so most carried in blood by a protein - only 5% is free and biologically active
excess cortisol excreted in kidneys (urine)
- gluconeogenesis (proteolysis, lipolysis)
- makes blood vessels more sensitive to Ad/NAd (BP^)
-dampens immune responses

Question 10

excess cortisol effects - pathologically speaking

Answer 10

break down protein - damage to skin, bone and muscles
high glucose -> high insulin -> more fat cells -> central obesity
HTN - increase effect of NAd/Ad and cortisol similar to aldosterone so can active receptors
Inhibit gonadotrophin releasing hormone - sexual dysfunction
dampen immune response - more infections