Hyperadrenal disorders Flashcards
what are the clinical features of Cushing’s Syndrome?
- hypernatraemia
- hypokalaemia
- high cortisol
fat:
- centripetal obesity
- moon face
- buffalo hump
- proximal myopathy
skin:
- red striae
- thin skin and bruising
metabolic:
- osteoporosis
- diabetes
- hypertension
what are the causes of Cushing’s Syndrome?
ACTH dependent:
- pituitary dependent Cushing’s Disease
- ectopic ACTH (lung cancer) secretion
ACTH independent:
- too many steroids (exogenous)
- adrenal adenoma producing cortisol
what are the investigations to determine the cause of Cushing’s?
1) urinary free cortisol (24 hr)
2) blood diurnal (depending on time of day) cortisol analysis
3) low-dose dexamethasone suppression test
what results can you get in the blood diurnal cortisol test?
normal= cortisol is high in the morning and low in the night
Cushings= cortisol remains high all the time
what is the dosage given for the dexamethasone suppression test?
0.5 mg in 6 hours periods over 48 hours
what results can you getting the dexamethasone supression test?
normal= dexamethasone suppresses cortisol and it falls to 0 due to feedback inhibition
Cushings= any cause of Cushing’s will fail to suppress the cortisol
what drugs can be given to treat Cushing’s?
enzyme inhibitors
receptor blocking drugs
e.g metyrapone, ketoconazole
what type of surgery can be done to treat Cushing’s
pit. surgery
bilateral adrenalectomy
unilateral adrenalectomy
what is the mechanism of action of metyrapone
reduces cortisol production: inhibits 11 alpha hydroxylase
prevents the production of corticosterone from deoxycorticosterone and therefore cortisol
raises ACTH secretion due to feedback
process has been arrested at 11-deoxycortisol (precursor to cortisol) which has no feedback effect
what are the uses of metyrapone?
- prior to surgery
- dose is adjusted to cortisol
- improve patients symptoms
- promotes post-op recovery
- used to control Cushing’s after radiotherapy
what are the two unwanted actions of metyrapone
1) hypertension on long term administration
2) hirsutism with androgen production
why does metyrapone cause hypertension
deoxycortisol accumulates in the zona glomerulosa
it has aldosterone-like activity
leads to salt retention and hypertension
how is ketoconazole used to treat Cushing’s
in high concentrations it inhibits steroidogenesis
controls symptoms prior to surgery and is orally active
what is the unwanted effect of ketoconazole?
liver damage
SEP too significant to be used anymore
what is Conn’s Syndrome?
benign adrenal (Z.glomerulosa) tumour
producing excess aldosterone
what are the consequences of Conn’s?
hypertension
hypernatraemia and hypokalaemia
what causes hypertension and therefore hypernatraemia and hypokalaemia in Conn’s?
due to water retention caused by aldosterone
enhancing sodium reabsorption (in exchange for potassium which is then excreted)
what are the diagnoses of Conns?
- young person with hypertension
- primary hyperaldosteronism (high steroids)
- RAS should be suppressed to exclude secondary hyperaldosteronism
- high sodium
- low potassium
what is the treatment of Conn’s?
- aldosterone receptor antagonists e.g. spironolactone
- surgical resection
what is the mechanism of action of spironolactone?
converted to several metabolites e.g. canrenone
becomes a competitive inhibitor of MR
blocks Na reabsorption and K excretion (potassium sparing diuretic)
describe the pharmacokinetics of spironolactone
aldosterone receptor antagonist
orally active
highly protein bound
metabolised in the liver
what are the unwanted actions of spironolactone?
menstrual irregularities (progesterone receptor)
gynaecomastia (androgen receptor)
why is eplerone a better alternative to spironolactone?
MR antagonists
similar affinity to MR as spironolactone
less binding to androgen and progesterone receptors therefore better tolerated than spironolactone
what is a phaeochromocytoma?
tumour of the adrenal medulla
secretion of catecholamines (adrenaline and noradrenaline)
medical emergency
more common in certain inherited conditions
what are the clinical features of phaeochromocytoma?
- hypertension in young people
- episodic severe hypertension in older people (after abdominal palpitation to squeeze out more adrenaline)
- double vision
- chest pain, palpitations
- sweating
how is Conn’s hypertension different to that in phaechromocytoma
Conn’s hypertension is not episodic
what are the consequences of severe hypertension in phaec
MI
stroke
ventricular fibrillation
death if not treated
precautions when treating phaec
the patient requires surgery but needs careful prep as anaesthesia can precipitate a hypertensive crisis
what is the first step treatment of phaechromocytoma?
1) alpha blockade (alpha receptors) –> prevent reflex tachycardia
IV fluids needed for the associated BP drop
beta blockade to prevent tachycardia
what are the 4 different origins of phaechromocytoma?
10% extra-adrenal (in sympathetic chain)
10% malignant
10% bilateral
10% familial
but very rare
Most common variety of congenital adrenal hyperplasia
21 hydroxylase deficiency
Congenital adrenal hyperplasia is generally caused by a deficiency in adrenal enzymes
when is surgery for phaecochromocytoma done?
Surgery is only done after the alpha and beta blockers are in full effect
alpha blocker for reflexive tachycardia
First therapeutic step in phaeochromocytoma
Administration of alpha blockade
Aldosterone receptor antagonists and agonist examples
Antagonist- spironolactone
Agonist- fludrocortisone
what are the main symptoms of Cushing’s?
proximal obesity hirsutism early menopause hyperglycaemia hypertensive.
what tests would confirm a diagnosis of Cushing’s syndrome?
1) Urinary free cortisol
– over 24 hours and carried out twice.
2) Synthetic steroid administration (dexamethasone) – administered at night and then in the morning, cortisol levels measured
– cortisol should be LOW as you’ve administered a large dose of ACTH analogue (should negatively influence cortisol production
what will a young person with multi drug resistant hypertension most likely be presenting with?
Conn’s
what are there symptoms of phaechromocytoma?
- sudden episodic headaches
- double vision
- malignant hypertension
- chest pain
- palpitations
- sweating
what are the investigations for phaec?
- urinary catecholamines
- CT for adrenal tumour
