Cushings syndrome

Question 1

What?

Answer 1

Clinical state of increased free circulating glucocorticoid
Excess cortisol
Hyperadrenalism

Question 2

When does it occur?

Answer 2

Following therapeutic administration of synthetic steroids

Or excess endogenous secretion of ACTH

Question 3

ACTH dependent causes?

Answer 3

Pituitary dependent (Cushing disease)
Ectopic ACTH producing tumours

Question 4

Non- ACTH dependent causes?

Answer 4

Adrenal adenomas
Adrenal carcinomas
Exogenous steroids

Question 5

Effect of ACTH?

Answer 5

ACTH is produced by pituitary gland and controls production of another hormone (cortisol) which is produced by adrenal glands

Question 6

Mechanism for excess cortisol?

Answer 6

Cortisol is a stress hormone -> tries to provide energy -> body thinks it is in acute stress
-> Protein loss

Question 7

Mechanism of excess mineralocorticoid?

Answer 7

Cortisol binds to mineralocorticoid receptors cause fluid retention -> hypertension

Question 8

What are mineralocorticoids?

Answer 8

Corticosteroids produced in adrenal cortex and influence salt and water balances

Question 9

Primary mineralocorticoid?

Answer 9

Aldosterone

Question 10

Three mechanisms?

Answer 10

Excess cortisol
Excess mineralocorticoid
Excess androgen

Question 11

What does excess androgen lead to?

Answer 11

Virulism
Hirsutism
Acne
Oligo/ amenorrhoea

Question 12

What does excess cortisol lead to?

Answer 12

Myopathy, wasting
Osteoporosis + fractures
Thin skin, striae - stretch marks
Bruising
Altered carbohydrate/ lipid metabolism, diabetes mellitus, obesity
Altered psyche - psychosis, depression

Question 13

Symptoms?

Answer 13

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

Question 14

Signs?

Answer 14

Plethora (moon face)
Hypertension
Buffalo hump
Central obesity
Depression/ psychosis
Glycosuria
Oedema

Question 15

Skin signs?

Answer 15

Thin skin
Hirsutism
Acne
Bruising
Poor wound healing
Skin infections
Striae (purple or red)
Pigmentation

Question 16

MSK signs?

Answer 16

Osteoporosis
Pathological fractures (vertebrae, ribs)
Kyphosis

Question 17

Investigations?

Answer 17

Overnight 1mg dexamethasone suppression test
Urine free cortisol
Diurnal cortisol
Low dose DST
Check potassium and sodium

Question 18

Overnight dexamethasone suppression test?

Answer 18

oral
Cortisol <50nmol/l next morning = normal
>130nmol/L = abnormal

Question 19

Explain how the dexamethasone suppression test works?

Answer 19

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

Question 20

Urine free cortisol?

Answer 20

24 hour urine collection
Total <250 is normal
Cortisol creasing

Question 21

Diurnal cortisol variation?

Answer 21

Midnight - 8am
Normal is to have high cortisol at 8am and low levels at midnight
Loss of diurnal variation suspicious of Cushing’s

Question 22

Low dose DST?

Answer 22

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]

Question 23

Sodium and potassium?

Answer 23

Low potassium

High sodium

Question 24

Management of pituitary causes?

Answer 24

Hypophysectomy (Trans sphenoidal route) and
External radiotherapy if recurs
Bilateral adrenalectomy – stops steroid production (last resort)

Question 25

Management of adrenal causes?

Answer 25

Adrenalectomy

Question 26

Management of ectopic causes?

Answer 26

Remove source
OR bilateral adrenalectomy
Treat ectopic syndrome

Question 27

Drug treatment?

Answer 27

Metyrapone (if other treatments fail)
Ketoconazole
Pasireotide

Question 28

SE of metyrapone?

Answer 28

Nausea and vomiting