Hyperadrenal disorders Flashcards
(25 cards)
What are the clinical features of Cushing’s?
- centripetal obesity
- interscapular fat pads
- moon face
- striae
- thin skin, easy bruising
- proximal myopathy
- hypertension
- hypokalaemia
- oestoporosis
- diabetes
What are the causes of Cushing’s?
- steriods
- ectopic ACTH producing tumour in lung
- pituitary tumour
- adrenal adenoma
What investigations are conducted to determine Cushing’s - order?
1) Urinary free cortisol (24h)
2) Blood diurnal (varying levels depending upon time of day) cortisol analysis
Normal = cortisol high in morning and low at night.
Cushing’s = cortisol high all the time.
3) Low-dose dexamethasone suppression test.
0.5mg 6-hourly for 48 hours.
Normal = dexamethasone supresses cortisol to zero due to feedback inhibition.
Cushing’s = ANY cause will fail to suppress
How is Cushing’s treated?
Depends on the cause
- drugs (enzyme inhibitors, receptor blocking drugs)
- surgery (pituitary surgery, bilateral adrenalectomy, unilateral adrenaloectomy)
What are some examples of Cushing’s drugs?
metyrapone
ketoconazole
How does metyrapone work?
Inhibits 11-beta-hydroxylase.
- Blocks production of cortisol but raises ACTH secretion (feedback systems)
- Steroid synthesis in the zona fasciculata (and reticularis) is arrested at 11-deoxycortisol stage.
- 11-deoxycortisol has no feedback effect.
How is metyrapone used?
- Control of Cushing’s prior to surgery
- Dose adjusted to cortisol
- Improves patient’s symptoms and promotes post-op recovery
- Control of Cushing’s after radiotherapy
What are the unwanted effects of metyrapone?
- Hypertension on long-term administration – deoxycortisone accumulates in zona glomerulosa which has aldosterone - like activity leading to salt retention and hypertension.
- Hirsutism – increased androgen production
What do the different layers of the adrenal glands do?
Zona glomerulosa - mineralocorticoids, mainly aldosterone
Zona fasciculata - glucocorticoids, e.g. cortisol
Zona reticularis (innermost) - androgens, mainly DHEA
Medulla - catecholamines
How does ketoconazole work?
- Main use as an anti-fungal drug but not anymore.
- At high concentrations, inhibits steroidogenesis
- Blocks production of glucocorticoids, mineralocorticoids and sex steroids
When is ketaconazole used and its unwanted actions and how is it taken?
- Treatment and control of symptoms prior to surgery
- Orally active
- Liver damage
What is Conn’s syndrome?
- A benign adrenal cortical (zona glomerulosa) tumour
- Produces aldosterone in excess
What are the symptoms of Conn’s?
Hypertension and hypokalaemia due to water retention, aldosterone enhances sodium reabsorption and potassium excretion in the kidneys
How is Conn’s diagnosed?
- Primary hyperaldosteronism
- The renin-angiotensin system should be supressed to exclude secondary hyperaldosteronism
How is Conn’s treated?
Aldosterone receptor antagonists – Spironolactone, epleronone
Surgery
When is spironolactone used and what is the mechanism of action?
Mineralocorticoid Receptor Antagonists
- Treatment of primary hyperaldosteronism (Conn’s syndrome)
Mechanism of action:
Spironolactone is converted to several active metabolites including canrenone, a competitive antagonist of the MR
- Blocks Na+ reabsorption and K+ excretion – potassium sparing diuretic
Describe the pharmakokinetics of spironolactone?
- Orally active
- Highly protein bound and metabolised in the liver
What are the unwanted effects of spironolactone?
Menstrual irregularities – via progesterone receptor
Gynaecomastia – via androgen receptor
Epleronone - why is better than spironolactone
- Also a MR antagonist (similar affinity to MR as spironolactone)
- Less binding to androgen and progesterone receptors compared to spironolactone so better tolerated
What are phaeochromocytomas?
Tumours of the adrenal medulla which secrete catecholamines - can secrete adrenaline or noradrenaline.
What are the clinical features of a pheochromocytoma?
- Hypertension in young people
- Episodic severe hypertension (after abdominal palpation – squeezes more adrenaline out).
- Different to Conn’s hypertension as this is episodic in the older population.
- Can cause MI or stroke.
- Can cause VF and death if not treated.
- Hence classed as a medical emergency
How are pheochromocytomas treated?
Alpha-blockade is the first step. Patients may need IV fluids during alpha-blockade as BP will drop. Beta-blockade is added to prevent tachycardia.
Requires surgery but needs careful preparation as anaesthetic can precipitate a hypertensive crisis.
What are some facts about phaeochromocytomas?
- 10% are extra-adrenal (down the sympathetic chain).
- 10% are malignant.
- 10% are bilateral.
- very rare
What should be tested for after a patient has had adrenalectomy?
The short Synacthen test - assess adrenal function. The test is based on the measurement of serum cortisol before and after an injection of synthetic ACTH
