Hyperadrenal Disorders Flashcards
What disease is associated too much cortisol
Cushings
What is Cushings cause by
Too much cortisol
Clinical features of Cushings disease? (7)
- Too much cortisol
- Centripetal obesity
- Moon face/buffalo hump
- Proximal myopathy
- Hypertension and hypokalaemia
- Red striae, thin skin and bruising
- Osteoporosis, diabetes (DMII)
Causes of Cushings? (3)
- Taking too many steroids
- Pituitary dependent Cushing’s disease
- Ectopic ACTH from lung cancer
- Adrenal adenoma secreting cortisol
Tests for Cushings? (3)
- 24h urine collection for urinary free cortisol High level suggests Cushing’s syndrome
- Blood diurnal cortisol levels Should be lowest at midnight (high at 9am)
- Low dose dexamethasone suppression test Artificial analogue of cortisol Stops normal people making ACTH Normal people suppress their cortisol to zero, Cushings fails to do so
When are Blood diurnal cortisol levels tested and why
Mignight, cortisol should be lowest here
3 treatments for Cushings? (2 pharmacological methods)
- Enzyme inhibitors
- Receptor blocking drugs
* Surgery is also an option
2 Inhibitors of steroid synthesis?
- Metyrapone
- Ketoconazole
- Metyrapone is an example of
Inhibitor of steroid synthesis
- Ketoconazole is an example of
Inhibitor of steroid synthesis
MoA of metyrapone?
- Inhibits 11beta-hyroxylase
- Steroid synthesis in the zona fasciculata (and reticularis) arrested at the 11-deoxycoritsol stage
- 11-deoxycortisol has no negative feedback effect on the hypothalamus or pituitary
metyrapone inhibits what enzyme
11beta-hyroxylase
Where in the adrenals is cortisol synthesised
zona fasciculata
Uses of steroid synthesis inhibitors in Cushings? (3)
- Control of Cushing’s prior to surgery:
- Adjust dose (oral) according to cortisol (aim for mean serum cortisol 150-300 nmol/L)
- Improves patient symptoms and promotes best post-op recovery
- Control of Cushing’s symptoms while waiting for radiotherapy to work
effects of 11-deoxycorticosterone when cortisol synthesis is halted at that stage?
: 11-deoxycorticosterone accumulates in the z. glomerulosa; it has aldosterone-like (mineralocorticoid) activity, leading to salt retention and hypertension
What hormone effects does 11-deoxycorticosteron have similar effects to
Aldosterone
What is ketoconazole used for
Cushings
Side effects of ketoconazole?
- Liver damage Possibly fatal Monitor liver function weekly, clinically and biochemically
What is the cause of Conns syndrome
Benign adrenal cortical tumour (Zona glomerulosa) Primary hyperaldosteronism
Which zone of the adrenals produce aldosterone
Zona glomerulosa
Zona glomerulosa produces…
Aldosterone
Zona fasciculata produces….
Cortisol
Symptoms of high aldosterone
- Hypertension and hypokalaemia
How to diagnose primary vs secondary Hyperaldosteronism
- Renin-angiotensin system should be suppressed (this rules out secondary hyperaldosteronism) Zero/very low renin
renin levels in primary Hyperaldosteronism?
Low
renin levels in secondary Hyperaldosteronism?
high
Treatment for primary Hyperaldosteronism?
Mineralocorticoid receptor antagonist]
- Surgery
Mineralocorticoid receptor antagonist example?
SPIRONOLACTONE/EPLERONONE
MoA of spironolactone?
- Converted to several active metabolites, including CANRENONE, a competitive antagonist of the MR
- Blocks Na+ resportion and K+ excretion in the kidney tubules (potassium sparing diuretic)
Effects of mineralocorticoid receptor antagonists?
- Blocks Na+ resportion and K+ excretion in the kidney tubules (potassium sparing diuretic)
RoA of mineralocorticoid receptor antagonists
Oral
Side effects of of mineralocorticoid receptor antagonists
- Menstrual irregularities (also an agonist of the progesterone receptor)
- Gynaecomastia (antagonist of the androgen receptor) Painful
Drug of choice for hyper-aldosteronism? why?
Epleronone ->- Less binding to androgen and progesterone receptors
MoA of epleronone
- Converted to several active metabolites, including CANRENONE, a competitive antagonist of the MR
- Blocks Na+ resportion and K+ excretion in the kidney tubules (potassium sparing diuretic)
what is PHAEOCHROMOCYTOMAS:
Tumours of the adrenal MEDULLA which secrete catecholamines (make adrenaline and noradrenaline)
Risk of PHAEOCHROMOCYTOMAS
That the Tumour suddenly degranulates and produces loads of adrenaline which increases HR, anxiety and possible strokes/MRIs
Clinical features of phaeochromocytomas (5)
- Hypertension in young people
- Episodic severe hypertension (this can also be precipitated by abdominal palpation by the doctor)
- More common in certain inherited conditions
- Severe hypertension can cause MI or stroke
- High adrenaline can cause ventricular fibrillation and death Medical emergency
Management of phaeochromocytomas?
- Eventually need surgery, BUT patient needs preparation as anaesthetic can precipitate a hypertensive crisis
- ALPHA BLOCKADE= first therapeutic step
- Patients may need intravenous fluid as alpha blockade commences
- Beta blockade added to prevent tachycardia
First step in Management of phaeochromocytomas?
Alpha blockade
What can happen if you give anaesthetic preop to a phaeocytochroma patient if they haven’t been given alpha blockers
Release of adrenaline, boom, hypertensive crisis bitches
