Endo 6 - Hyperadrenal disorders Flashcards
Cushings syndrome is caused by too much?
Cortisol
What are 6 clinical features of Cushings?
- Centripetal obesity
- Moon face and buffalo hump
- Proximal myopathy
- Hypertension and hypokalaemia
- Red striae/thin skin / bruising
- Osteoporosis / diabetes
What are 4 causes of Cushings?
- Taking too many steroids (exogenous)
- Pituitary dependent Cushings
- Ectopic ACTH from lung cancer
- Adrenal adenoma secreting cortisol
Name 3 investigations to determine the cause of Cushings syndrome
- 24h urine collection measuring urinary free cortisol
- Blood diurnal cortisol levels
- Low dose dexamethasone suppression test
In someone with Cushings, what is the diurnal cortisol rhythm like?
It is high all the time
What are the results of giving low dose dexamethasone ?
If normal = cortisol suppressed to 0
Any cause of Cushings = failure to suppress cortisol to 0
What is Conns syndrome?
Excess aldosterone
What medication is given to treat patients with Cushings syndrome?
Steroid biosynthesis inhibitors -
Ketoconazole, metyrapone
Where in the adrenal cortex are aldosterone, cortisol and oestradiol produced?
Aldosterone - zona glomerulosa
Cortisol - zona fasciculata
Oestradiol - zona reticularis
How does metyrapone work?
It inhibits 11-B-hydroxylase
Which causes an accumulation of 11-deoxycortisol
Also causes increased ACTH secretion
What are the uses of metyrapone?
- Control Cushings syndrome before surgery
2. Control Cushings syndrome after radiotherapy
What are 2 side effects of metyrapone?
- Increased salt retention and hypertension due to 11-deoxycortisone (Arrested) accumulating in z.glomerulosa
- Increased adrenal androgen production - hirsutism in women
What is the mechanism of action of ketoconazole
Ketoconazole = anti fungal
Blocks production of glucocorticoids, mineralocorticoids and sex steroids
What are the uses of ketoconazole
Treatment and management of Cushings Syndrome prior to surgery
It is a tablet
What is the unwanted action of ketoconazole
Liver damage - could be fatal.
MUST CHECK LIVER FUNCTION REGULARLY
What surgical treatments are there for Cushings?
- Pituitary surgery
- Bilateral adrenalectomy
- Unilateral adrenalectomy
Conns syndrome is due to XS aldosterone. What does this cause
- Hypertension and hypokalaemia
If primary hyperaldosteronism (Conns), how is it diagnosed?
High aldosterone, low renin = Conns
RAS system suppression = exclude secondary hyperaldosteronism
How is Conns syndrome treated?
Block Mineralocorticoid (MR) receptor - MR antagonist
e.g. Spironolactone, epleronone
Spironolactone - mechanism of action
Converted into canrenone = competitive MR antagonist
Blocks Na resorption and K excretion in kidney tubules (K sparing diuretic) - combats effects of increased aldosterone
What are the unwanted action of spironolactone?
- Menstrual irregularities (progesterone agonist)
2. Gynaecomastia (androgen receptor antagonist)
Epleronone - mechanism of action
- MR antagonist
2. Less binding to progesterone/androgen receptors = less side effects and better tolerated
What are phaeochromocytomas?
Adrenal medulla tumours - which secrete catecholamines
What are the clinical features of a phaeo?
- Hypertension in young people
- Episodic severe hypertension attacks
- More common in certain inherited conditions
What are the problems with phaeo?
- Severe hypertension - can cause MI or stroke
2. High Adrenaline - can cause VF / death
How are phaeos managed?
- Alpha blockade
- Give IV as alpha blockade commences
- Beta-blocker to prevent tachycardia
- Surgery
What is the 10% rule of phaeochromocytomas?
- 10% extra-adrenal
- 10% malignant
- 10% bilateral
Phaeos = very very rare
