Cushing's disease and syndrome

Question 1

What is Cushing’s syndrome?

Answer 1

general term referring to chronic excessive and inappropriate elevated levels of circulating CORTISOL whatever the cause

Question 2

What is Cushing’s disease?

Answer 2

specifically refers to:

bilateral adrenal hyperplasia from ACTH-secreting pituitary adenoma

Question 3

Where is cortisol secreted.

Answer 3

zona fasciculata (middle) of adrenal cortex

Question 4

what are the functions of cortisol?

Answer 4

1. ↑ carb + protein catabolism (breakdown)
2. ↑ deposition of fat + glycogen
3. Na+ retention
4. ↑ renal K+ loss
5. Diminished host response to infection

Question 5

Explain the pattern in which cortisol is released?

Answer 5

Since CRH is released according to circadian rhythm and in response to stress:

• highest levels in morning
• lowest at midnight

Question 6

What type of hormone is cortisol

Answer 6

glucocorticoid

Question 7

What can the causes be divided into?

Answer 7

ACTH dependent

ACTH independent

Question 8

What are ACTH dependent causes

Answer 8

1. Cushings disease

2. Ectopic ACTH production - small cell lung cancer, carcinoid tumours

Question 9

What are ACTH independent causes?

Answer 9

1. Iatrogenic - administration of a glucocorticoid e.g. pred

2. Adrenal adenoma/carcinoma

Question 10

Explain pathophysiology behind ACTH dependent causing Cushings

Answer 10

XS ACTH stimulates XS cortisol release

Question 11

Explain pathophysiology behind ACTH independent causing Cushings

Answer 11

neoplasms in adrenals stimulate zona fasciscularis to release more cortisol
OR
ingesting XS glucocorticoid itself

Question 12

What are the sx?

Answer 12

Obese
Mood: depression, lethargy, irritability, psychosis
Proximal weakness - muscle atrophy
Gonadal dysfunction - irregular periods + ED
Acne
Recurrent Achilles tendon rupture

Question 13

What are the signs?

Answer 13

Central obesity
Plethoric 
Moon face
Buffalo hump - fat pad on back 
Skin + muscle atrophy 
Abdo striae 
Osteoporosis
HTN
Hyperglycaemia
Inf prone

Question 14

What causes muscle and skin atrophy?

Answer 14

protein catabolic effects of cortisol

Question 15

what investigations would u do to confirm Cushing’s syndrome?

Answer 15

1. Overnight dexamethasone suppression test - 1mg at 00:00, measure serum cortisol at 8am. Normal - suppression <50nmol/L, Cushing’s S - no suppression
2. 24hr urine free cortisol - normal <280nmol/24hr

Question 16

What tests would u do to localise the source of Cushings? How would u interpret the results?

Answer 16

Measure plasma ACTH
If ACTH is undetectable - adrenal tumour (ACTH independent cause)
If ACTH detectable - distinguish pituitary cause from ectopic ACTH + do high dose suppression test or CRH test

Question 17

How wold u interpret CRH stimulation test?

Answer 17

If there is a pituitary source - cortisol rises - Cushing’s disease
If ectopic/adrenal - no change

Question 18

What is the treatment of iatrogenic Cushings syndrome?

Answer 18

stop steroids!

Question 19

What is rx of Cushings w adrenal cause?

Answer 19

1. Adenoma - adrenalectomy

2. Carcinoma - radiotherapy + adrenolytic drug (mitotane)

Question 20

What is rx of Cushings due to ectopic ACTH

Answer 20

Surgery

Drugs inhibiting cortisone synthesis - metyrapone, ketoconazole, fluconazole

Question 21

What is the rx of Cushing’s disease?

Answer 21

selective removal of pituitary adenoma

if cant find pituitary source - bilateral adrenalectomy

Question 22

What is a complication of a bilateral adrenalectomy? How is it treated?

Answer 22

Nelsons syndrome:
Increase skin pigmentation due to significantly increased ACTH from an enlarging pituitary tumour as the adrenalectomy will remove the negative feedback
rx: radiotherapy to pituitary

Question 23

What is the major cause of mortality in pts w Cushing’s syndrome?

Answer 23

CVD

Question 24

What are complications?

Answer 24

CVD
HTN
DM
Osteoporosis

Question 25

Why does Cushings increase risk of osteoporosis?

Answer 25

Glucocorticoids cause decreased osteoblast activity and increased osteoclast activity - DO PERIODIC BONE ASSESSMENTS