6. Hyperadrenal disorders Flashcards
(35 cards)
What is the cause of Cushing’s disease?
- Pituitary tumour making ACTH
- ACTH makes adrenal gland grow
- Too much cortisol
What happens to protein and fat in Cushing’s syndrome?
- Cortisol switches protein synthesis off and fat synthesis on
- Lose protein and gain fat
What are the clinical features of Cushing’s syndrome?
- Too much cortisol
- Centripetal obesity
- Moon face
- Buffalo hump (interscapular fat pad)
- Proximal myopathy
- Hypertension and hypokalaemia
- Red striae, thin skin and easy bruising
- Osteoporosis, diabetes
Why is bruising common in Cushing’s syndrome?
- Normally, lots of protein in tissues under skin, used to heal
- Protein synthesis turned off - start to leak and get bruises
Why is hypertension and hypokalaemia common in Cushing’s?
- Cortisol starts to bind to receptors in the kidney
- Retention of sodium
- Excretion of potassium
What are the causes of Cushing’s syndrome?
- Taking too many steroids orally (first question to ask patient)
- Pituitary dependent Cushing’s disease
- Ectopic ACTH from lung cancer
- Adrenal adenoma making cortisol
How can you determine the cause of Cushing’s syndrome?
• CUSHINGS - LOW DOSE dexamethasone suppression test (gold standard)
- give patient extra steroid
- normally ACTH and cortisol should go to zero
• 24 hour urine collection for urinary free cortisol
- patients often forget to sample urine, not ideal
• Blood diurnal cortisol levels
- normally high in the morning and low when sleeping
- loss of rhythm, high levels at night - suspicious
How is the low dose dexamethasone suppression test carried out and how do people with Cushing’s react?
- Blood test before
- Give dexamethasone for 48 hours
- Cushing’s - keep making cortisol, no reaction to dexamethasone
- Does not tell you the cause
Why would people with Cushing’s die more quickly in the past?
- Infection
- Can’t synthesise proteins and heal
- Immunosuppressed
- Sepsis
How can Cushing’s be treated?
Inhibitors of steroid biosynthesis, e.g.
• metyrapone
• ketoconazole
What is Conn’s and how can it be treated?
• Too much aldosterone
• MR (mineralocorticoid receptor) antagonist
- spironolactone
- epleronone
What type of hormones are produced in the adrenal medulla?
Catecholamines
What is phaeochromocytoma?
- Tumour of adrenal medulla
* Excess catecholamines
How do you block the effects of excess catecholamines?
• First give alpha blocker
- urgent issue is really high BP caused by catecholamines binding to alpha receptors in vasculature => vasoconstriction
• When BP decreases, give beta blocker
- catecholamines stimulate beta receptors to cause vasodilation
- BB prevents too much vasodilation
- alpha blocker given first as you could have unopposed alpha mediated vasoconstriction causing a hypertensive crisis and possible stroke
Where is aldosterone, cortisol and 17b-oestradiol produced?
- Aldosterone - zona glomerulosa
- Cortisol - zona fasciculata
- 17b-oestradiol - zona reticularis
How does metyrapone work?
- Medication that inhibits 11b-hydroxylase
- Slows down cortisol synthesis pathway
- Reduces production of cortisol and corticosterone
- Treatment for Cushing’s
- ACTH levels rise because of this - no negative feedback from 11-deoxycorticosterone
When is metyrapone used?
• Control prior to surgery
- improves symptoms
- promotes better post-op recovery
- done as patients are predisposed to infection, very thin skin, weak blood vessels
• Control of Cushing’s symptoms after radiotherapy
- given for control until beneficial effects of radiotherapy come about
What is the normal dose of oral metyrapone the same as?
- Dose according to cortisol production
* Aim for mean serum cholesterol of 150-300 nmol/L
What are the negative (biochemical) aspects of metyrapone?
• Accumulation of 11-deoxycorticosterone and 11-deoxycortisol
• 11-deoxycorticosterone has mineralocorticoid properties (works like aldosterone)
- sodium retention
- potassium excretion
- hypertension
• When the drug blocks 2 limbs of the pathway, all the precursors funnel towards sex steroid synthesis
- increase in adrenal androgens
- hirsuitism and acne
What are the negative side effects of metyrapone?
- Nausea, vomiting, dizziness
- Sedation
- Hypoadrenalism - leads to impaired performance of skilled tasks
- Hypertension on long-term administration
- Hirsuitism
What is ketoconazole used for?
- Mainly used as anti-fungal agent - withdrawn due to hepatotoxicity
- Inhibits cortisol production at higher concentrations - unlicensed use for operation preparation
- Short-term use
How does ketoconazole work?
- Inhibits Cytochrome P450 SCC enzymes (cholesterol => pregnenolone)
- Blocked production of glucocorticoids, mineralocorticoids and sex steroids
What are the negative side effects of ketoconazole?
- Nausea, vomiting, abdominal pain
- Alopecia
- Gynaecomastia, oligospermia, impotence, decreased libido
- Ventricular tachycardias
- Liver damage - patients monitored ever week as it can be fatal
How can Cushing’s syndrome be treated (invasively)?
- Pituitary surgery (transsphenoidal hypophysectomy)
- Bilateral adrenalectomy - remove both adrenal glands, provide hormone replacement
- Unilateral adrenalectomy for adrenal mass
(round of medical treatment until patient is safe for one of the above operations, depending on cause)
