GIE disorders

What is cushing’s sundrome?

Too much cortisol - hypercorticolism

What causes cushings syndrome?

Latrogenic effects

• Steroid medications

Pituitary adenoma

• Secretes excess ACTH

• Benign (mainly), women 5:1 men

Ectopic ACTH tumour

• Malignant or benign, men 3:1 women

Adrenal tumours

• Secrete excess cortisol & other adrenal hormones

• Non-malignant adenomas, onset >40 years, uncommon, rapid onset of symptoms: women > men

What is ACTH?

Adrenocorticotropic hormone released by pituitary to stimulate adrenal gland to release cortisol

What are the clinical features of cushings syndrome?

• Weight gain

  • Increase in body fat

  • Rounded face, flushed, prominent cheeks

• Easily bruised skin

• Violaceous striae

• Hypertension

• Glucose intolerance

• Depression or psychosis

• Osteoporosis

What drug has the same side effects as cushings syndrome presentation?

Corticosteroids

• Mimicks steroids

How is cushings diagnosed?

• Patient history, physical examination, biochemical tests, scan for tumours

• Saliva cortisol test

• 24 hour free cortisol in the urine - Level >50-100mcg/day ⇒ Cushing’s?

• Dexamethasone suppression test (DST) corticosteroid – blood

  • Low dose – presence of Cushing’s

  • High dose - distinguishes between pituitary and ectopic (lungs) ACTH-secreting tumours

  • Only pituitary ACTH suppressed by dexamethasone

Why is the saliva cortisol test for Cushings done at night (bed time)?

Levels should be lower

What happens to ACTH and cortisol levels if the pituitary and cortisol number is normal?

Pituitary suppressed → ACTH decreased → cortisol decreased

What happens to ACTH and cortisol levels if there’s pituitary adenoma (cushings) and cortisol number is high?

Less suppression → ACTH decreased a little → cortisol decreased a little

• Tumour retains some negative feedback sensitivity

What happens to ACTH and cortisol levels if there’s ectopic adenoma and cortisol number is high?

Dex has no effect

• Ectopic tumours do not have glucocorticoid receptors, so they ignore negative feedback.

• ACTH high → cortisol high

What drugs are used to manage Cushings?

Ketoconzaole

• Licensed for endogenous cushings

• Targets multiple CYP enzymes in steroid biosynthesis pathway including II-beta-hydroxylase

Metyrapone

• Inhibits 11β-hydroxylation in the adrenal cortex

• Inhibition of cortisol production

Osilodrostat

• Licensed for endogenous Cushing’s syndrome

• Steroidogenesis inhibitor that inhibits 11-beta-hydroxylase

• Not routinely commissioned by NHS England

When is surgery necessary for Cushings?

If it’s endogenous (tumour)

• If removed what might happen to patients endogenous steroid levels after surgery

• HPA axis would take a while to get back to normal

• Risk of precipitating hypocorticolism

• Steroids might need to be given while resetting HPA axis

What is Addison’s disease?

Too little cortisol - hypocorticolism

What are the causes of primary Addison’s?

Destruction of the adrenal cortex

• Cortisol AND aldosterone levels⇓⇓⇓

• Immune mediated, strong link with TB

• Adrenal insufficiency when 90%+ cortex destroyed

• Also associated with fungal infections, metastasis, amyloid and surgical removal of adrenals

What are the causes of secondary Addison’s?

Lack of ACTH

• Cortisol decreases

• Can be temporary - Due to sudden stoppage of chronic exogenous glucocorticoid therapy

  • HPA takes a long time to reset after prolonged suppression with steroids

  • Body no longer has enough endogenous cortisol secretion to respond to stress

• Can be permanent

  • Surgical removal of ACTH-secreting tumours of pituitary (causing Cushing’s)

  • Piuitary atrophy, or lack of ACTH production (tumours, infections, radiation, other damage)

What are the clinical features of Addisons?

• Anorexia

• Weight loss

• Weakness and fatigue

• GI disturbances

• Hypotension

• Salt cravings

• Increased thirst

• Postural dizziness

• Muscle or joint pain

• Skin hyperpigmentation

What happens to the body during an Addison’s crisis?

Acute response to stress in a compromised patient

• Sudden penetrating pain in lower back, abdomen or legs

• Severe vomiting, diarrhoea, dehydration

• Blood pressure decreases, loss of consciousness

• FATAL if untreated

Caused by body’s inability to respond to stress because of adrenal insufficiency

How is Addison’s diagnosed?

Morning serum cortisol taken (exclusion test)

• <150 nmol/L - may have adrenal insufficiency

• 150nmol/L – 300nmol/L – probability is uncertain

• >300 nmol/L – adrenal insufficiency is very unlikely

Synacthen test (ACTH stimulation test)

• Serum cortisol levels checked before and 30 mins after giving synthetic analogue of ACTH (tetracosactide)

Test urea - would be low

Test K+ - would be high

Does the adrenal gland respond to ACTH?

• If the answer is NO: primary insufficiency most likely

How is Addison’s treated?

• Replacement of glucocorticoid and mineralocorticoid (sometimes androgen)

• Glucocorticoid - usually hydrocortisone

• Mineralocorticoid - fludrocortisone

• Sick day rules

• Emergency treatment pack

  • IM hydrocortisone for self-administration - changes to IV at hospital

Biggest dose in morning, smaller dose at lunch, smallest dose at night but before 6pm