Cushing's Syndrome

Question 1

Define Cushing’s Syndrome

Answer 1

Hypercortisolism of any cause

Question 2

Aetiology of Cushing’s Syndrome

Answer 2

Exogenous (most common): excess steroid use

Endogenous: 
ACTH dependant (80%): Pituitary dependant Cushing's disease (80%) | Ectopic ACTH from lung cancer 
ACTH independent (20%): Adrenal adenoma/adrenal carcinoma secreting cortisol

Question 3

Symptoms of Cushing’s Syndrome

Answer 3

Thin skin
Easy bruising
Hypertension, hypokalaemia, hirsutism 
Moon face (facial plethora0< buffalo hump 
Proximal myopathy 
Irritability and mood swings, depression, anxiety, reduced libido 
Centripetal obesity, weight and fatigue 
Osteoporosis and diabetes
Menstrual irregularities/amenorrhoea
Acne

Question 4

Signs of Cushing’s Syndrome on examination

Answer 4

Thin skin and bruising 
Moon face
Centripetal obesity 
Striae
Proximal myopathy 
Hirsutism, acne, frontal balding 

ACTH-dependent: pigmentation

Question 5

Investigations for Cushing’s Syndrome

Answer 5

Urinary free cortisol: elevated
Overnight dexamethasone suppression test: cortisol elevated
Low-dose dexamethasone suppression test: cortisol elevated (failed suppression) to confirm Cushing’s syndrome
High-dose dexamethasone suppression test: Confirm Cushing’s Disease (Disease (pituitary) will show suppressed cortisol, ACTH-independent causes will not be suppressed)
Plasma ACTH: ACTH-dependent -> raised ACTH, ACTH-independent -> reduced ACTH

Urine pregnancy negative: exclude pregnancy
Salivary cortisol: elevated

FBC + serum glucose: mild hypokalaemia + elevated glucose

CT/MRI adrenals: may show adrenal adenoma/hyperplasia/tumour
MRI pituitary: may show pituitary adenoma
CXR/CT chest: localise ectopic tumour

Inferior petrosal sinus sampling: indicates Cushing’s disease

Question 6

Management for Cushing’s Syndrome

Answer 6

Exogenous exposure: discontinue admin or lower dose

Cushing’s disease:

1. Pre-operative therapy - mifepristone / metyrapone
2. Transsphenoidal pituitary adenomectomy
3. post-op hydrocortisone
4. Adjuncts: levothyroxine, testosterone/oestradiol, somatropin, desmopressin

Ectopic:

1. Pre-operative therapy - mifepristone / metyrapone
2. Surgical resectino or ablation of tumour + metastases
3. Adjunct - chemo or radio

Adrenal carcinoma/adenoma:

1. Pre-operative therapy - mifepristone / metyrapone
2. Unilateral/bilateral adrenalectomy or tumour resection

Question 7

Complications of Cushing’s syndrome

Answer 7

Diabetes Mellitus 
Osteoporosis
Adrenal insufficiency post treatment 
Cardiovascular disease
Hypertension
Nephrolithiasis 
Nelson's syndrome post bilat. adrenalectomy 
Pan-hypopituitarism
Hyponatraemia
Diabetes insipidus

Question 8

Prognosis for Cushing’s Syndrome

Answer 8

Survival rate 50% untreated at 5 years
Mortality rate similar to general population with treatment
Many features resolve with treatment