Cushing's syndrome

Question 1

What is the definition of cushing’s syndrome?

Answer 1

Increased free circulating glucocorticoid

Question 2

How common is cushing’s syndrome?

Answer 2

Rare

Question 3

What is the pathology of cushing’s syndrome?

Answer 3

• Adrenal gland produces aldosterone, androgens, cortisol, adrenaline and noradrenaline (catecholamines)
• Glucocorticoid production is under the hypothalamic-pituitary control

Question 4

What are the risk factors/aetiology of cushing’s syndrome?

Answer 4

• Causes of Cushing’s syndrome subdivided into 2 groups: Primary (cortisol production) and secondary (pituitary)
• Cushing’s disease – pituitary dependent
• Steroids
• Adrenal adenoma/carcinoma
• Bilateral primary pigmented nodular hyperplasia (PPNH)
• Excess endogenous secretion of ACTH
• Alcohol induced pseudo-Cushing’s syndrome
• ACTH producing tumour (in pituitary or elsewhere)

Question 5

What are the signs/symptoms of cushing’s syndrome?

Answer 5

• Weight gain
• Growth arrest in children
• Hair growth
• Acne
• Moon face
• Plethora – red face
• Thin skin/easily bruising
• Depression/psychosis/insomnia
• Diabetes
• Hypertension
• Osteoporosis/fractures
• Kyphosis
• Proximal muscle weakness/wasting

Question 6

What investigations are carried out in suspected cushing’s syndrome?

Answer 6

• 48h low dose dexamthasome test: normally individuals supress their plasma level to <50nmol/L but in Cushing’s this compensation does not happen
• 24h urinary free cortisol measurement
• Circadian rhythm: after 48h in hospital cortisol samples are taken at 0900 and 2400. Normal individuals show a variation in levels but Cushing’s have a high 2400 reading
• Insulin stress test – if tests are normal but clinical suspicion is still there
• High dose dexamethasone suppression test
• Plasma ACTH levels
• Adrenal CT/MRI
• Pituitary MRI
• K+ levels – hypokalaemia is common with ectopic ACTH
• CRH test - ↑ ACTH and cortisol suggests pituitary dependent Cushing’s disease

Question 7

What are the surgical treatments for cushing’s syndrome?

Answer 7

• Trans-sphenoidal removal of the tumour
• Bilateral adrenalectomy
• Adrenal adenoma resectioning

Question 8

What are the pharmacological treatments for cushing’s syndrome?

Answer 8

• Metyrapone
• Ketoconazole
• External pituitary irradiation↑↑

Question 9

What are the non pharmacological treatments for cushing’s syndrome?

Answer 9

• None - TREAT AS LIFE THREATENING IF LEFT