Cushing's syndrome

Question 1

summarise a typical presentation of a patient with cushing’s syndrome?

Answer 1

• Increasing weight
• fatigue
• easy bruising
• thin skin
• poor wound healing
• moon face
• facial plethora
• interscapular fat pads
• proximal muscle weakness
• central obesity and pink/purple striae

Question 2

define cushing’s syndrome?

Answer 2

syndrome associated with innapropriate elevation of free circulating cortisol

Question 3

what are the risk factors for cushings?

Answer 3

exogenous corticosteroid use

pituitary adenoma

adrenal adenoma

adrenal carcinoma

Question 4

explain the aetiology/ risk factors for cushing’s syndrome?

Answer 4

• It can be divided into ACTH Dependent (80%) and ACTH Independent (20%)
• ACTH Dependent
• Excess ACTH from a pituitary adenoma (Cushing’s disease)
• Ectopic ACTH (e.g. lung cancer, pulmonary carcinoid tumours)

• ACTH Independent

• Benign adrenal adenoma
• Adrenal carcinoma

• TAKING STEROIDS - would cause bilateral adrenal atrophy

Question 5

summarise the epidemiology of cushing’s syndrome?

Answer 5

• Incidence: 2-4/1,000,000 per year

Peak incidence 20-40 yrs

Question 6

what are the presenting symptoms of cushing’s

Answer 6

• Increasing weight 
• Fatigue 
• Muscle weakness 
• Myalgia 
• Thin skin 
• Easy bruising 
• Poor wound healing 
• Fractures 
• Hirsuitism 
• Acne 
• Frontal balding 
• Oligomenorrhoea/amenorrhoea 
Depression or psychosis

Question 7

what are the signs of of cushing’s on physical examination?

Answer 7

• Moon face 
• Facial plethora 
• Interscapular fat pad 
• Proximal muscle weakness 
• Thin skin 
• Bruises 
• Central obesity 
• Pink/purple striae on abdomen/breast/thighs 
• Kyphosis (due to vertebral fracture) 
• Poorly healing wounds 
• Hirsuitism, acne, frontal balding 
• Hypertension
• Ankle oedema (due to salt and water retention from the mineralocorticoid effect of excess cortisol) 
Pigmentation in ACTH dependent cases

Question 8

outline the prognosis for cushing’s syndrome?

Answer 8

• Untreated - 5 yr survival = 50%

Depression persists for many years following treatment

Question 9

what are the investigations for cushing’s syndrome?

Answer 9

urine pregnancy test
bloods
initial high sensitivity tests
tests to determine underlying cause ( measure plasma ACTH levels)

Question 10

describe bloods in cushing’s syndrome?

Answer 10

U&Es - hypokalaemia due to mineralocorticoid effect

BM - high glucose

Question 11

outline the initial high sensitvity tests for cushing’s syndrome?

Answer 11

24 hr Urinary free cortisol

9am cortisol

Late-night salivary cortisol

Overnight low-dose dexamethasone suppression test
▪ THIS IS USUALLY DONE
▪ 2mg dexamethanasone 11pm midnight
▪ Morning have blood test and failure to suppress cortisol

Low dose dexamethasone suppression test (LDDST)
▪ Give 0.5 mg dexamethasone orally ever 6 hrs for 48 hrs
In Cushing’s syndrome, serum cortisol measured 48 hrs after the first dose of dexamethasone fails to suppress below 50 nmol/L

Question 12

what are the tests to investigate the underlying cause of cushing’s syndrome?

Answer 12

○ ACTH-dependent (pituitary adenoma)
▪ High plasma ACTH
▪ Pituitary MRI
▪ High-dose dexamethasone suppression test - uses 2mg which is capable of producing partial/complete suppression of cortisol if the problem is a pituitary tumour (since the pituitary retains some feedback control)
▪ Inferior petrosal sinus sampling (SUPERIOR to high-dose dexamethasone suppression test)
• Central: peripheral ratio of venous ACTH > 2:1 (or > 3:1 after CRH administration) in Cushing’s disease

○ ACTH-dependent (ectopic)
▪ an ectopic source of ACTH would not be responsive to exogenous feedback and so it’s not suppressed by the High-dose Dexamethasone suppression test
▪ If lung cancer suspected: CXR, sputum cytology, bronchoscopy, CT san
▪ Radiolabelled octreotide scans can detect carcinoid tumours because they express somatostatin receptors

○ ACTH-independent (adrenal adenoma/carcinoma)
▪ Low plasma ACTH
CT or MRI of adrenals

Question 13

if the cause of cushion’s is iatrogenic- what should you do?

Answer 13

discontinue steroids, use lower dose or use a steroid-sparing agent

Question 14

what are the 2 drugs used in the medical treatment of cushion’s syndrome?

Answer 14

metyrapone or ketoconazole

Question 15

outline the medical management of cushing’s syndrome?

Answer 15

Used pre-operatively or if unfit for surgery

Inhibit cortisol synthesis with metyrapone or ketoconazole

Treat osteoporosis

Physiotherapy for muscle weakness

Question 16

outline the surgical management of cushing’s syndrome

Answer 16

○ Pituitary Adenomas - trans-sphenoidal adenoma resection

○ Adrenal adenoma/carcinoma - surgical removal of tumour

○ Ectopic ACTH - treatment directed at the tumour

Bilateral adrenalectomy may be performed in refractory Cushing’s disease

Question 17

when is radiotherapy performed in cushion’s syndrome?

Answer 17

Performed in those who are not cured and have persistent high cortisol after trans-sphenoidal resection of the tumour

Question 18

what are the possible complications of cushing’s syndrome?

Answer 18

• Diabetes
• Osteoporosis
• Hypertension
• Pre-disposition to infections

• Complications of surgery: 
○ CSF leakage 
○ Meningitis 
○ Sphenoid sinusitis
○ Hypopituitarism 

• Complications of radiotherapy:
○ Hypopituitarism
○ Radionecrosis
○ Increased risk of second intracranial tumours and stroke

Bilateral adrenalectomy may be complicated by the development of Nelson’s syndrome (locally aggressive pituitary tumour causing skin pigmentation due to ACTH secretion)