Cushing's

Question 1

What is Cushing’s disease?

Answer 1

Pituitary adenoma which secretes ACTH resulting in hypercortisolism

Question 2

What is cortisol?

Answer 2

Glucocorticoid - zona fasciculata

Lipid soluble

Levels peak in the morning and drop at night

During times of stress cortisol promotes gluconeogenesis, proteolysis and lipolysis

Increases sensitivity of peripheral blood vessels to catecholamines

Dampens the inflammatory response

Question 3

What is the consequence of having too much cortisol?

Answer 3

• Muscle, skin and bone breakdown
• Hyperglycaemia
• High insulin levels which target a protein called lipoprotein lipase which facilitates the accumulation of fat cells
• Hypertension due to effects on blood vessels and because cortisol has some mineralocorticoid activity
• High cortisol levels inhibit GnRH and alters testicular and ovarian function
• Inflammatory and immune responses dampened so patients more prone to infections

Question 4

What is the difference in the zona fasciculata in Cushing’s syndrome and Cushing’s disease?

Answer 4

Cushing’s syndrome: mostly due to steroid use, zona fasciculata atrophies because the steroids negatively feedback on the pituitary which therefore stops releasing ACTH and the zona fasciculata is not stimulated

Cushing’s disease: zona fasciculata hypertrophies because the pituitary adenoma causes excess ACTH secretion

Question 5

Other than pituitary adenomas, what are the other sources of abberant ACTH?

Answer 5

Small cell lung cancer

Question 6

Clinical features of Cushing’s

Answer 6

Central weight gain - due to increased insulin release

Hair growth and acne

Thin skin and easy bruising

Depression

Psychosis

Insomnia

Muscular weakness - proteolysis

Back pain

Amenorrhoea

Growth arrest in children

Polyuria and polydipsia

Moon face

Buffalo hump

Glycosuria

Osteoporosis

Proximal muscle wasting

Question 7

Investigations to confirm presence of Cushing’s

Answer 7

• 24hr urinary free cortisol: Cushing’s confirmed if more than 2 samples has 3x the upper limit of normal
• Low dose dexamethasone suppression test: 1mg of dexamethasone given at 11pm and cortisol measured at 8am. Should cause a decrease in cortisol but won’t if Cushing’s is present

Question 8

Investigation to find the cause of Cushing’s

Answer 8

High dose dexamethasone test: 8mg dexamethasone is given, if the patient has Cushing’s disease (pituitary adenoma) this is usually enough to cause ACTH suppression and therefore reduced cortisol (low ACTH, low cortisol = Cushing’s disease)

If the cause of the high cortisol levels is an adenoma of the adrenal gland itself, a high dose of dexamethasone won’t affect cortisol levels (high cortisol, low ACTH = adrenal Cushing’s)

Exogenous cause of ectopic ACTH: adrenal gland is still stimulated as ectopic sources of ACTH don’t respond to dexamethasone so levels of cortisol and ACTH are high because the ACTH is coming from somewhere else

Question 9

Management of Cushing’s

Answer 9

Exogenous medication: withdraw

Pituitary adenoma: surgery

Metyrapone, ketoconazole, and mitotane can all be used to lower cortisol by directly inhibiting synthesis and secretion in the adrenal gland

Question 10

Prognosis of Cushing’s

Answer 10

Patients with uncontrolled Cushing’s have a poor prognosis but good prognosis if treated