Endo 6: Hyperadrenal Disorders Flashcards
List Clinical features of Cushing’s Disease
- excessive cortisol production
- centripetal obesity
- moon face
- buffalo hump
- proximal myopathy
- hypertension
- hypokalemia
- red stir, thin skin, bruising
- osteoporosis
- diabetes
What are some causes of Cushing’s?
- taking too much steroid
- pituitary dependent cushing’s
- ectopic ACTH (from lung cancer)
- adrenal adenoma (secretes cortisol)
What are 3 methods of investigation for cause of Cushing’s syndrome
- 24 hr urine collection for urinary free cortisol
(high = cushing’s syndrome) - blood diurnal cortisol levels
- low dose dexamethasone suppression test
What is the normal diurnal rhythm of cortisol?
highest level at 9am, lowest level at midnight
high all the time = cushing’s syndrome
Describe the low dose dexamethasone suppression test.
- dexamethasone = artificial steroid
0.5mg 6 hourly
for 48 hrs
if normal –> cortisol = suppressed to ZERO
ANY cause of cushing’s –> can’t suppress
What are the values for diagnosis Cushing’s?
Basal (9am) cortisol = 800 nM
End of LDDST = 680 nM
What are some methods of treating Cushing’s ?
- pituitary surgery
- bilateral adrenalectomy
- unilateral adrenalectomy for adrenal mass
- metyrapone
- ketoconazole
What is Conn’s syndrome?
- Benign adrenal cortical tumor (zona glomerulosa)
- aldosterone produced in excess
- results in hypertension + hypokalemia
How would you diagnose Conn’s Syndrome?
- primary hyperaldosteronism
- Renin-angiotensin system = suppressed
- -> measure aldosterone
- -> if high, measure renin (which would be suppressed by high BP)
+ low K+ = diagnosis
How would you treat Conn’s syndrome?
- remove tumor (surgery)
- to stop effect of excess aldosterone –> SPIRONOLACTONE (mineralocorticoid receptor antagonists)
note: if bilateral adrenal hyperplasia –> stay on spironolactone
What is a Phaeochromocytomas?
- tumour of the adrenal medulla
- which secretes catecholamines
(NA + A) - -> causes massive increase in BP (300/150)
- -> may cause sudden stoke / MI / ventricular fibrillation (due to high adrenaline)
What are symptoms of Phaeochromocytomas
- sudden onset of panic
- anxiousness
- tachycardia
- severe hypertension
note: episodic severe hypertension in young people –> could be Phaeochromocytomas
How would you manage phaeo?
- 1st therapeutic step = ALPHA blockade
- -> block receptor to which adrenaline binds
- (sudden drop in BP ) so give IV fluid
- then give BETA blockade
- -> to prevent tachycardia
- would eventually need surgery
note; but need to be careful –> anesthetic might precipitate hypertensive crisis
note:
- 10% extra-adrenal
- 90% inside the adrenal
- 10% are malignant
- 10% bilateral
- 90% are curable by operation
Phaeochromocytoma is EXTREMELY RARE
-
What drugs are used to treat Cushing’s syndrome?
give 2 examples
- inhibitors of steroid biosynthesis
e. g methyrapone, ketoconazole
What drugs are used to treat Conn’s syndrome?
- MR Antagonist
e. g Spironolactone, epleronone
Describe the mechanism of action of Metyrapone
Metyrapone:
- used as treatment for cushing’s
- it inhibits 11B-hydroxylase
- slows down cortisol synthesis pathway
- steroid synthesis in zona fasciculata = arrested at 11-deoxycortisol stage
- -> reduces cortisol + corticosterone
- as if you stop making cortisol, level of ACTH rises
- there is no -ve feedback exerted by 11-deoxycortisol
- so this accumulates
note: ACTH level also increases
Give 2 uses of Metyrapone
used to:
- control cushing’s syndrome prior to surgery
- -> improves symptoms + better post-op recovery
- -> excess cortisol –> increase susceptibility to infection as well - control cushing’s symptoms after radio therapy
What are some unwanted actions of metyrapone?
- nausea, vomiting
- hypertension on long term administration
- -> because it increases plasma deoxycortisol (which acts similarly to aldosterone)
- hirsutism
Describe the mechanism of action of Ketoconazole
Ketoconazole:
- main use = anti-fungal agent (but has risk of hepatotoxicity)
- at higher conc –> inhibits cortisol production
- ketoconazole inhibits cytochrome P450 SCC enzymes
- so you block production of gluco/mineralocorticoids + sex steroid
note:
SCC = side chain cleavage
What are uses of ketoconazole?
- uses = similar to metyrapone:
- treatment for cushing’s –> control of symptoms prior to surgery
What are some unwanted actions of ketoconazole?
- nausea, vomiting, abdominal pain
- alopecia
- liver damage
What is spironolactone used as a treatment for?
- Primary aldosteronism
aka Conn’s syndrome
Describe the mechanism of action of spironolactone
- spironolactone = converted to several active metabolites
e. g canrenone - -> a competitive antagonist of the mineralocorticoid receptor (MR) –> stops the effects of aldosterone
- SO it blocks Na+ resorption + K excretion in the Kidney tubules
- -> so basically you reverse hypertension.
