Cushing's syndrome

Question 1

Define Cushing’s syndrome

Answer 1

Syndrome associated w/ chronic inappropriate elevation of free circulating cortisol

Question 2

Aetiology of Cushing’s syndrome

2 + 2

Answer 2

ACTH dependent (80%)
Excess ACTH from pituitary adenoma (Cushing’s disease)
Ectopic ACTH (e.g. lung cancer, pulmonary carcinoid tumours)

ACTH independent (20%)
Benign adrenal adenoma
Adrenal carcinoma

Question 3

Epidemiology of Cushing’s syndrome

incidence, age

Answer 3

Incidence 2-/1,000,000 per year

Peak age 20-40 yrs

Question 4

Presenting symptoms of Cushing’s syndrome

13

Answer 4

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

Question 5

Signs of Cushing’s syndrome on physical examination

14

Answer 5

Moon face
Facial plethora
Interscapular fat pad
Proximal muscle weakness
Thin skin
Bruises
Central obesity
Pink/purple striae on abdomen/breast/thighs
Kyphosis (dut to vertebral fracture)
Poorly healing wounds
Hirsutism, acne, frontal balding
Hypertension
Ankle oedema 
Pigmentation in ACTH dependent causes

Question 6

Investigations for Cushing’s syndrome

general + 3 groups

Answer 6

(Must be performed on patients w/ a high pre-test probability)

Bloods
Initial high sensitivity tests
Tests to determine underlying cause

Question 7

Investigations for Cushing’s syndrome - bloods

2

Answer 7

U&Es - hypokalaemia due to mineralocorticoid effect

BM - high

Question 8

Investigations for Cushing’s syndrome - initial high sensitivity
(4)

Answer 8

Urinary free cortisol
Late night salivary cortisol
Overnight dexamethasone suppression test
Low dose dexamethasone suppression test (LDDST)
0.5mg dexamethasone orally every 6hrs for 48hrs
serum cortisol after 48hrs fails to suppress below 50nmol/l in cushing’s

Question 9

Investigations for Cushing’s syndrome - underlying cause

2,4,2

Answer 9

ACTH independent (adrenal adenoma/carcinoma)
Low plasma ACTH
CT/MRI of adrenals

ACTH dependent (pituitary adenoma)
High plasma ACTH
Pituitary MRI
High does dexamethasone suppression test
Inferior petrosal sinus sampling

ACTH dependent (ectopic)
If lung cancer suspected - CXR, sputum cytology, bronchoscopy, CT
Radiolabelled octreotide scans can detect carcinoid tumours because they express somatostatin receptors

Question 10

Management of Cushing’s syndrome

3 groups

Answer 10

Medical
Surgical
Radiotherapy

Question 11

Management of Cushing’s syndrome - medical

5

Answer 11

If iatrogenic discontinue steroid, use lower dose or steroid sparing agent
Medical treatment used pre operatively or if unfit for surgery
Inhibit cortisol synthesis w/ metyrapone or ketoconazole
Treat osteoporosis
Physio for muscle weakness

Question 12

Management of Cushing’s syndrome - surgical

4

Answer 12

Pituitary adenomas —> trans sphenoidal adenoma resection
Adrenal adenoma/carcinoma —> surgical removal of tumour
Ectopic ACTH —> treatment directed at tumour
Bilateral adrenalectomy in refractory disease

Question 13

Management of Cushing’s syndrome - radiotherapy

Answer 13

Performed in those not cured & have persistent high cortisol after trans sphenoidal resection of tumour

Question 14

Complications of Cushing’s syndrome

4

Answer 14

Diabetes
Osteoporosis
Hypertension
Pre dispostion to infections

Question 15

Complications of Cushing’s syndrome - surgery

5

Answer 15

CSF leakage
Meningitis
Sphenoid sinusitis
Hypopituitarism
Nelson’s syndrome

Question 16

Complications of Cushing’s syndrome - radiotherapy

3

Answer 16

Hypopituitarism
Radionecrosis
Increased risk of 2nd intracranial tumours & stroke

Question 17

Prognosis of Cushing’s syndrome

2

Answer 17

If untreated, 50% 5 yr survival

Depression persists for many years after treatment

Question 18

Define Nelson’s syndrome

Answer 18

Locally aggressive pituitary tumour causing skin pigmentation due to ACTH secretion
(complication of bilateral adrenalectomy)