Cushing’s Syndrome

Question 1

What is the difference between Cushing’s syndrome and Cushing’s disease?

Answer 1

Syndrome= signs and symptoms which develop due to prolonged abnormal elevation of cortisol

Disease= pituitary adenoma secretes excess ACTH which leads to increased cortisol and causes Cushing’s syndrome

Question 2

How would someone with Cushing’s classically present? (I.e. classic physical features?

Answer 2

Round “moon” face 
Central obesity 
Abdominal striae 
Buffalo hump
Proximal limb muscle wastage 
Easy bruising and poor skin healing

Question 3

What signs might patient suffer from in Cushing’s syndrome which are due to high levels of stress hormone?

Answer 3

Hypertension 
Cardiac hypertrophy 
Hyperglycaemia 
Depression 
Insomnia
Problems with menstruation and libido

Question 4

What are the 4 main causes of Cushing’s syndrome?

Answer 4

Exogenous steroids= when people on long term high dose steroids (RA/Asthma)

Cushing’s disease= pituitary adenoma
-can present with mass-effects signs if macroadenoma
Eg visual changes/headaches/ compression of CN associated with cavernous sinus (III,IV,V1,V2,VI)

Adrenal adenoma

Paraneoplastic Cushings
-excess ACTH hormone from source outside pituitary eg Ectopic ACTH Small cell lung cancer

Question 5

What is the main method of investigation for Cushing’s syndrome?

Answer 5

Dexamethasone Suppression Test (DST)
Low dose test done first to determine if Cushing’s present
Abnormal result indicates the need for high dose test to distinguish cause

Process:

• dexamethasone given to patient at 10pm and then cortisol and ACTH measured in morning
• normal= dexamethasone causes negative feedback to hypothalamus and pituitary gland i.e. decreased morning cortisol spike
• abnormal= no suppression of cortisol so spike unaffected

Question 6

What is the process of high dose dexamethasone and what do the different results mean?

Answer 6

8mg dexamethasone used to distinguish between the different causes of Cushing’s syndrome

Pituitary adenoma/Cushing’s disease= suppressed Cortisol and ACTH (pituitary has some negative feedback to high enough levels of dexa)

Adrenal adenoma= Cortisol NOT suppressed (due to exogenous source) but ACTH suppressed

Ectopic ACTH= neither suppressed

Question 7

Apart from dexamethasone test what other investigations can be done for Cushing’s syndrome?

Answer 7

24h urinary free cortisol

U+E= may show hypokalaemia if aldosterone released by adrenal adenoma

MRI for adenoma

Petrosal blood sample near pituitary to see if it is the source of ACTH (when MRI negative)

CXR/Chest CT for small cell lung cancer

Abdominal CT for adrenal tumours

Question 8

What is the main form of treatment for Cushing’s disease?

Answer 8

Surgical removal of tumour causing the excess or ACTH or cortisol

Trans-sphenoidal removal of pituitary adenoma

Surgical removal of adrenal tumour = adrenalectomy

Radiotherapy of adrenal tumour

Surgical removal of ectopic ACTH producing tumour

Question 9

What is the normal function of cortisol?

Answer 9

Increased gluconeogenesis
Increased proteolysui
Increased lipolysis

Question 10

How can iatrogenic Cushing’s be managed? What is the possible complication of this?

Answer 10

Decreased/discontinue steroids or use alternate-day regimen to reduce exogenous cortisol

Can lead to adrenal sufficiency if medication stopped abruptly
-adrenals stop producing endogenous cortisol when there is exogenous source meaning there will be insufficient amount of cortisol present

Question 11

You do a dexamethosane and high dose dexamethasone test on 3 patients. Based on the results, which is the likely cause of their Cushing’s?
1= high ACTH + cortisol suppressed
2=high ACTH + cortisol not suppressed
3=low ACTH + cortisol not suppressed

Answer 11

1= pituitary problem (increased produced of ACTH + slight cortisol suppression due to tissue being responsive to high cortisol levels)

2= ectopic

3= adrenal (negative feedback for pituitary but excess cortisol production not regulated )