Cushing's Syndrome

Question 1

Define Cushing’s syndrome

Answer 1

Chronic elevation of free circulating cortisol

Question 2

What are the causes/risk factors of Cushing’s syndrome?

Answer 2

• Exogenous steroid use

ACTH dependent
• Cushing’s disease – excess

ACTH from pituitary adenoma
• Ectopic ACTH e.g. small cell lung carcinoma, pulmonary carcinoid tumours

ACTH independent
• Adrenal hyperplasia/adenoma/carcinoma – excess cortisol

Question 3

What are the symptoms of Cushing’s syndrome?

Answer 3

• Increasing weight
• Fatigue
• Muscle weakness
• Myalgia
• Thin skin
• Easy bruising
• Poor wound healing
• Fractures
• Hirsutism
• Acne
• Frontal balding
• Oligo-/amenorrhoea
• Decreased libido
• Depression/psychosis

Question 4

What are the signs of Cushing’s syndrome?

Answer 4

• Facial plethora
• Facial fullness/rounding
• Interscapular fat pad
• Proximal myopathy
• Thin skin
• Bruises
• Central obesity
• Purple striae
• Kyphosis – premature osteoporosis and fractures

Mineralocorticoid effect
• Hypertension
• Ankle oedema

Glucose intolerance/diabetes

Question 5

What investigations are carried out for Cushing’s syndrome?

Answer 5

• Urinary free cortisol – elevated
• Late night salivary cortisol –elevated
• Dexamethasone suppression test
- LDDST – 0.5mg every 6h for 48h, >50nmol/L (failure of suppression)
- HDDST – 2mg every 6h for 48h, suppression <50% suggests pituitary origin,
no suppression suggests other causes of Cushing’s syndrome
• Inferior petrosal sinus sampling – elevated central:peripheral ACTH ratio suggests
pituitary origin
• Plasma ACTH
- >4pmol/L = pituitary/ectopic
- <1pmol/L = adrenal
• Adrenal CT/MRI
• MRI brain
• CXR/bronchoscopy/CT

Question 6

What is the management for Cushing’s syndrome?

Answer 6

Iatrogenic
• Discontinue steroids
• Lower steroid dose
• Use steroid sparing agents

Medical
• Metyrapone
• Ketoconazole

Surgical
• Transsphenoidal resection
• Adrenal tumour
resection/unilateral adrenalectomy
• Ectopic tumour resection or
therapy or bilateral adrenalectomy

Question 7

What are the complications of Cushing’s syndrome?

Answer 7

• Diabetes
• Osteoporosis
• Hypertension
• ↑ susceptibility to infection