Addison's & Cushing's

Question 1

What is Cushing’s syndrome?

Answer 1

Set of symptoms caused by excessive cortisol.

Question 2

What is the most common cause of Cushing’s syndrome?

Answer 2

Cushing’s disease –> pituitary tumour secreting ACTH

Question 3

Give 2 ACTH dependent causes of Cushing’s syndrome

Answer 3

1) Cushing’s disease (80%)
2) ectopic ACTH production e.g. SCLC

Question 4

What is the most common cause of ectopic ACTH production?

Answer 4

Small cell lung cancer

Question 5

Clinical features of Cushing’s?

Answer 5

1) Central obesity & weight gain:
- moon facies
- buffalo hump
- abdominal striae

2) MSK:
- proximal myopathy
- osteopenia & osteoporosis
- avascular necrosis of femoral head

3) Derm:
- hirsutism
- acne & seborrheic dermatitis
- thn skin, easy bruising & poor wound healing

4) Endocrine:
- glucose interolance/T2DM
- menstrual irregularities
- ED

5) Neuropsychiatric:
- depression, anxiety, irritability, emotional lability
- insomnia or hypersomnia

6) CVS:
- HTN
- increased risk of VTE

7) Paediatric:
- growth retardation
- precocious puberty

Question 6

How can proximal myopathy present in Cushing’s?

Answer 6

Difficulty rising from seated position or climbing stairs

Question 7

Cause of growth retardation in Cushing’s in children?

Answer 7

Cortisol mediated suppression of GH

Question 8

Iatrogenic cause of Cushing’s?

Answer 8

Corticosteroid therapy

Question 9

What is an ACTH independent cause of Cushing’s?

Answer 9

Adrenal adenoma

Question 10

metabolic disturbance seen in Cushing’s?

Answer 10

Hypokalaemic metabolic alkalosis

Question 11

What are the 3 most commonly used tests to diagnose Cushing’s?

Answer 11

1) overnight (low-dose) dexamethasone suppression test –> 1st line

2) 24 hr urinary free cortisol

3) bedtime salivary cortisol

Question 12

result of overnight (low-dose) dexamethasone suppression test in Cushing’s?

Answer 12

patients with Cushing’s syndrome do not have their morning cortisol spike suppressed

Question 13

After the overnight (low-dose) dexamethasone suppression test has been used to detect Cushing’s syndrome, what test is used next to localise the pathology?

Answer 13

High dose dexamethasone suppression test

Question 14

Interpretation of results of high dose dex suppression test:

Cortisol not suppressed
ACTH suppressed

Answer 14

Cushing’s syndrome due to other causes (e.g. adrenal adenomas)

Question 15

Interpretation of results of high dose dex suppression test:

Cortisol suppressed
ACTH suppressed

Answer 15

Cushing’s disease (i.e. pituitary adenoma → ACTH secretion)

Note - high dose dex can suppress ACTH & cortisol in Cushing’s disease

Question 16

Interpretation of results of high dose dex suppression test:

Cortisol not suppressed
ACTH not suppressed

Answer 16

Ectopic ACTH syndrome

Question 17

1st line mx of Cushing’s disease?

Answer 17

Trans-sphenoidal removal of pituitary tumour (hypophysectomy)

Question 18

What is Addison’s disease also known as?

Answer 18

1ary adrenal insufficiency

Question 19

What is Addison’s disease?

Answer 19

Inadequate production of cortisol AND aldosterone by adrenal cortex.

Question 20

What is the most common cause of Addison’s?

Answer 20

Autoimmune destruction

Question 21

How can Addison’s disease cause hyperpigmentation of the skin?

Answer 21

Rise in ACTH (due to loss of adrenal cortex function) –> causes melanocyte-stimulating hormone (MSH) production –> hyperpigmentation.

Question 22

Clinical features of Addison’s?

Answer 22

• lethargy, weakness, anorexia, N&V, weight loss, ‘salt-craving’
• hyperpigmentation (especially palmar creases), vitiligo, loss of pubic hair in women, hypotension, hypoglycaemia
• hyponatraemia and hyperkalaemia may be seen
• crisis: collapse, shock, pyrexia

Question 23

Where is hyperpigmentation particularly seen in Addison’s?

Answer 23

Palmar creases

Question 24

What is the definitive investigation in Addison’s?

Answer 24

ACTH stimulation test (short Synacthen test)

Question 25

What occurs in the short Synacthen test?

Answer 25

Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM (this mimics ACTH).

Question 26

If an ACTH stimulation test is not readily available (e.g. in primary care), what investigation can be useful?

Answer 26

Sending a 9 am serum cortisol can be useful:

• > 500 nmol/l makes Addison’s very unlikely
• < 100 nmol/l is definitely abnormal
• 100-500 nmol/l should prompt a ACTH stimulation test to be performed

Question 27

What electrolyte abnormalities can be seen in Addison’s?

Answer 27

• hyperkalaemia
• hyponatraemia
• hypoglycaemia
• metabolic acidosis

Question 28

Mx of Addison’s?

Answer 28

Given glucocorticoid & mineralocorticoid replacement therapy:

• hydrocortisone
• fludrocortisone

Question 29

Mx of steroids in Addison’s during intercurrent illness?

Answer 29

The glucocorticoid dose should be doubled, with the fludrocortisone dose staying the same

Question 30

Give some complications of Addison’s

Answer 30

1) Adrenal crisis

2) Chronic complications e.g. fatigue weight loss, and electrolyte imbalances

3) Osteoporosis from long term steroid therapy

4) Increased susceptibility to infections

Question 31

What is an adrenal crisis?

Answer 31

An acute life-threatening condition characterised by severe hypotension, hypoglycemia, and altered mental status

Question 32

Mx of adrenal crisis?

Answer 32

IV hydrocortisone, fluids & electrolyte correction