Hyper adrenal disorders Flashcards
Cushing’s CF
caused by too much cortisol
centripetal obesity moon face buffalo hump - interscapular fat pad proximal myopathy striae, thin skin and easy bruising diabetes, osteoporosis hypertension and hypokalaemia
Causes of Cushing’s syndrome
Cushing’s disease - pituitary tumour
Oral steroids
Ectopic ACTH from lung cancer
Adrenal adenoma producing ACTH
Why do patients become become hypertensive and hypokalaemic
Cortisol binds to receptors in the kidneys that causes them to retain sodium and excrete potassium
Cortisol levels through the day
high in the morning
low when you sleep
Why are blood tests not used to measure cortisol levels
Pain/ stress causes increase in cortisol
Investigations to determine Cushing’s syndrome
1) 24 hour urine collection for free cortisol in the urine
2) Blood diurnal cortisol levels - should be low at midnight. If it is high, it’s suspicious
3) Low dose dexamethasone suppression test. Cushing’s will have high cortisol after test.
How does the low dose dexamethasone suppression test work
Normal person: The extra steroid is detected by the pituitary so ACTH is turned off and within hours will have 0 cortisol
Cushing’s disease: cortisol doesn’t decrease because tumour keeps releasing ACTH
Treatment of Cushing’s
Depends on cause:
- Pituitary surgery - transphenoidal hypophysectomy
- ## Unilateral / Bilateral adrenalectomy
Medical treatment of Cushing’s
Metyrapone
Ketoconazole
How Metyrapone works
Inhibits 11-beta-hydroxylase. Blocks cortisol synthesis
Negative aspects of metyrapone
11-beta-hydroxylase is involved in 2 parts of the pathway
It leads to an accumulation of 11-deoxycoticosterone and 11-deoxycortisol
11-deoxycoticosterone has mineralocorticoid properties – can cause hypertension and salt retention
blocking 2 limbs of pathway, all precursors funnel towards sex steroid synthesis –> hirsutism in women
Uses of metyrapone
control of cushing’s prior to surgery (decrease chance of infection, better wound healing)
Control of Cushing’s after radiotherapy (slow)
Uses of ketoconazole
Treatment of Cushings
- used to control Cushing’s before surgery
How ketoconazole works
Blocks cytochrome P450 SCC enzymes - blocking production of glucocorticoids, mineralocorticoids and sex steroids
Negative aspects of metyrapone
Nausea, vomiting, abdominal pain Alopecia Gynaecomastia, impotence, decreased libido LIVER DAMAGE (could be fatal)
Conn’s is
caused by
primary hyperaldosteronism
benign tumour in the adrenal cortex (zona glomerulosa makes aldosterone)
Clinical features of Conn’s
Hypertension and hypokalaemia
Diagnosis of Conn’s
Measure BP- high
Do blood test then if potassium high, suspect Conn’s
If aldosterone levels are high, RAAS suppressed - renin will be turned off
Measure the renin - should be low
High BP; low potassium; low renin
Treatment for Conn’s
Give a mineralocorticoid receptor antagonist -
Spironolactone –
Or Epleronone – similar affinity to MR as spironolactone but less binding to progesterone and androgen receptors so is better tolerated
then surgery to remove tumour
MOA of spironolactone
Spironolactone is converted into active metabolites e.g. canrenone - competitive antagonist for MR
blocks Na reabsorption and K excretion in kidney. Is a potassium sparing diuretic
Why do you need to first give someone medication (spironolactone before taking them in for surgery)
Want to reduce their BP because giving general anaesthetic to someone with high BP has added dangers
People with bilateral adrenal hyperplasia are given what treatment
LT spironolactone
Pharmacokinetics of sprionolactone
Oral
Highly protein bound and metabolised in liver
Daily dose / divided doses
Unwanted actions of spironolactone
very non-specific
progesterone receptor agonist–> menstrual irregularities
androgen receptor antagonist –> gynaecomastia in men
can cause GI irritation
Also renal/ hepatic disease
Patients needing a LT MR antagonist are more likely to be put on and why
Eplerenone due to its more specific binding to MR so has fewer side effects
Phaechromocytoma caused by
Tumours of the adrenal medulla
Secretion of catecholamines (NA and A)
Phaechromocytoma CF
Episodic severe HT in young people
stress/post abdominal palpation in big one/trauma –> increase in BP and release of lots of adrenaline
Severe HT can cause MI or stroke
Can cause ventricular fibrillation - sudden cardiac death
Management of phaeochromocytoma
Can’t directly give anaesthetic –> will cause adrenaline release
first give alpha blocker (IV fluid) –>blocks receptors to which adrenaline binds
Then beta blocker –> prevent tachycardia
then surgery to remove tumour
