Cushings syndrome Flashcards
What?
Clinical state of increased free circulating glucocorticoid
Excess cortisol
Hyperadrenalism
When does it occur?
Following therapeutic administration of synthetic steroids
Or excess endogenous secretion of ACTH
ACTH dependent causes?
Pituitary dependent (Cushing disease) Ectopic ACTH producing tumours
Non- ACTH dependent causes?
Adrenal adenomas
Adrenal carcinomas
Exogenous steroids
Effect of ACTH?
ACTH is produced by pituitary gland and controls production of another hormone (cortisol) which is produced by adrenal glands
Mechanism for excess cortisol?
Cortisol is a stress hormone -> tries to provide energy -> body thinks it is in acute stress
-> Protein loss
Mechanism of excess mineralocorticoid?
Cortisol binds to mineralocorticoid receptors cause fluid retention -> hypertension
What are mineralocorticoids?
Corticosteroids produced in adrenal cortex and influence salt and water balances
Primary mineralocorticoid?
Aldosterone
Three mechanisms?
Excess cortisol
Excess mineralocorticoid
Excess androgen
What does excess androgen lead to?
Virulism
Hirsutism
Acne
Oligo/ amenorrhoea
What does excess cortisol lead to?
Myopathy, wasting Osteoporosis + fractures Thin skin, striae - stretch marks Bruising Altered carbohydrate/ lipid metabolism, diabetes mellitus, obesity Altered psyche - psychosis, depression
Symptoms?
Change in appearance Weight gain (central) Hair growth + acne Thin skin/ easy bruising Mental changes (depression, psychosis, insomnia) Muscle weakness Back pain Amenorrhoea/ oligo Poor libido Growth arrest (children) Polyuria/ polydipsia
Signs?
Plethora (moon face) Hypertension Buffalo hump Central obesity Depression/ psychosis Glycosuria Oedema
Skin signs?
Thin skin Hirsutism Acne Bruising Poor wound healing Skin infections Striae (purple or red) Pigmentation
MSK signs?
Osteoporosis
Pathological fractures (vertebrae, ribs)
Kyphosis
Investigations?
Overnight 1mg dexamethasone suppression test Urine free cortisol Diurnal cortisol Low dose DST Check potassium and sodium
Overnight dexamethasone suppression test?
oral
Cortisol <50nmol/l next morning = normal
>130nmol/L = abnormal
Explain how the dexamethasone suppression test works?
Dexamethasone = man made steroid which binds to same receptor as cortisol
Dexamethasone reduces ACTH release in normal people -> therefore reducing cortisol levels
Won’t reduce in Cushings
Urine free cortisol?
24 hour urine collection
Total <250 is normal
Cortisol creasing
Diurnal cortisol variation?
Midnight - 8am
Normal is to have high cortisol at 8am and low levels at midnight
Loss of diurnal variation suspicious of Cushing’s
Low dose DST?
2 day 2mg/day Dexamethasone suppression test
Cortisol <50 nmol/l 6 hrs after last dose indicates that there is No Cushing’s
Cortisol >130 nmol/l – definitely Cushings]
Sodium and potassium?
Low potassium
High sodium
Management of pituitary causes?
Hypophysectomy (Trans sphenoidal route) and
External radiotherapy if recurs
Bilateral adrenalectomy – stops steroid production (last resort)
