Cushing's disease/ syndrome

Question 1

What is Cushing’s syndrome?

Answer 1

Any condition that causes adrenal glands to produce xs cortisol

Question 2

What is Cushing’s disease?

Answer 2

When a pituitary adenoma secretes xs ACTH

Question 3

Describe the HPA axis

Answer 3

Hypothalamus
           v
        CRH
           v
  Ant. pituitary 
           v
        ACTH
           v
 Adrenal glands
           v
      Cortisol
           v 
Metabolic effects

Cortisol has negative feedback on the ant. pituitary and hypothalamus

Question 4

Where is cortisol produced in the adrenal glands?

Answer 4

Zona fasciculata

**Mnemonic - the deeper the sweeter
GFR - salt, sugar, sex

Question 5

What are the functions of cortisol?

Answer 5

• Carb and protein breakdown
• Increases K renal excretion
• Causes Na retention
• Increases fat + glycogen deposition
• In short bursts = boost immune system
• Chronic high levels = hinders immune system

Question 6

What are the causes?

What is the most common cause?

Answer 6

Exogenous > endogenous

ACTH dependent:

• pituitary adenoma
• ectopic ACTH e.g. SCLC

ACTH independent:

• iatrogenic - steroids (MOST COMMON)
• adrenal tumour

Pseudocushing’s

Question 7

What is pseudocushing’s?

How do you differentiate between cushing’s and pseudocushing’s?

Answer 7

Mimics Cushing’s and is usually due to alcohol xs or severe depression

Causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
**Insulin stress test may be used to differentiate

Question 8

Other than stress, what can normal cortisol secretion be determined by?

And when will it be highest?

Answer 8

Circidian rhythm

Highest at 7/9am

Question 9

What is the anatomy of the adrenal cortex?

What does the adrenal medulla secrete?

Answer 9

Zona glomerulosa - aldosterone
Zona fasciculata - glucocorticoid (cortisol)
Zona reticularis - sex hormones

Adrenal medulla - catecholamines (Ad, NAd)

Question 10

What are the sx?

Answer 10

Wt gain
Mood changes - lethargy, depression, irritability
Weakness
Gonadal dysfunction

Question 11

What are the signs?

Answer 11

Moonface 
Central obesity 
Buffalo hump
Easy bruising
Muscle atrophy
Purple abdo. striae
Thin limbs
Acne + hirsutism

Hypokalaemic metabolic alkalosis

Question 12

What are the 2 glucocorticoid effects of xs cortisol?

Answer 12

Obesity

DM

Question 13

What are the 2 mineralocorticoid effects of xs cortisol?

Answer 13

HTN

Hypokalaemia

Question 14

What are the 2 Ix that can be used to confirm cushing’s?

Answer 14

24h urinary free cortisol

Overnight dex suppression test

Question 15

What is the first line localisation test?

How are the results interpreted?

What Ix would you do if ACTH independent?

Answer 15

9am and midnight plasma ACTH + cortisol levels

If ACTH is suppressed = ACTH independent cause e.g. adrenal tumour

CT adrenal

Question 16

Name another localisation test

Answer 16

High dose overnight dex suppression test

Question 17

Explain how low-dose and high-dose overnight dex suppression test works

Answer 17

Give dex at 10pm and measure ACTH + cortisol at 9am next morning

Low-dose (1mg): Confirms Cushing’s

• Low cortisol = normal
• High/normal cortisol = Cushing’s

High-dose (8mg): localises Cushing’s

• Low cortisol = cushing’s disease
• high/ normal cortisol + low ACTH = adrenal cushing’s
• high/normal cortisol + high ACTH = SCLC ectopic ACTH secretion

Question 18

What is the mx?

Answer 18

Rx cause:

• Pituitary adenoma: trans-sphenoidal excision
• Adrenal adenoma: adrenelectomy
• Ectopic ACTH: tumour excision

Question 19

What is Nelson’s syndrome?

What sx?

Answer 19

Rapid enlargement of pituitary adenoma following bilateral adrenelectomy for cushing’s

SX:

• Bitemporal hemianopia
• Hyperpigmentation