Endocrinology 6 - Hyperadrenal disorders Flashcards
List the symptoms of cushings disease
- Red cheeks
- Moon face
- Fat pads (buffalo hump)
- Thin skin
- High blood pressure
- Thin arms and legs - muscle weakness
- Red striae, thin skin and bruising
- Poor wound healing (breakdown of connective tissue and protein)
- Fat around the middle
- Pitting oedema
- Hirsutism (excess testosterone)
List the clinical features of cushings
- Too much cortisol
- Centripetal obesity
- Moon face and buffalo hump
- Proximal myopathy
- hypertension and hypokalaemia
- Oseoporosis and diabetes
List the causes of cushings
- Steroids (commonest in 2019)
- Pituitary dependent Cushings disease (disease = pituitary is involved)
- Ectopic ACTH (from lung cancer)
- Adrenal adenoma secreting cortisol
List the investigations to determine the cause of cushings syndrome
- 24 hour urine collection for urinary free cortisol
- Blood diurnal cortisol levels
- (Cortisol highest at 9am and lowest at midnight - blood sample taken while patient is asleep)
- Low dose dexamethasone suppression test (0.5mg 6 hourly for 48 hours, normal means cortisol reaches 0)
List the treatments of cushings disease
- Enzyme inhibitors
- Receptor blocking drugs
- Bilateral adrenalectomy (removing one adrenal is pointless)
Give examples of inhibitors of steroid biosynthesis and describe their use
- Metyrapone
- Ketoconazole
- Cushings syndrome (excess cortisol)
- CT/MRI for diagnosis
Give examples of MR antagonists and describe their use
- Spironolactone
- Epleronone
- Conn’s syndrome (aldosterone excess)
Describe the mechanism of action of metyrapone
- Inhibition of 11beta-hydroxylase (switches off corticosterone production and cortisol production) in zona fasciculata
- Blocks cortisol synthesis
- ACTH secretion increased
- Plasma deoxycortisol increased
List the uses of metyrapone
- Control of Cushings syndrome prior to surgery
- Adjust dose according to cortisol (150-300nmol/L)
- Improves patient symptoms and promotes better post op recovery
- Also used to control Cushings symptoms after radiotherapy (as radiotherapy is slow to take effect)
List the unwanted actions of metyrapone
- Hypertension on long-term administration (due to 11-dehydroxycortisterone having aldosterone-like activity)
- Hirsutism (increased adrenal sex steroids)
List the actions of ketoconazole
- Main use as an antifungal agent (withdrawn due to hepatotoxicity)
- Blocks 17alpha-hydroxylase
- At higher concentrations inhibits steroidogenesis
- Blocks production of glutocorticoids, mineralocorticoids and sex steroids
List the uses of ketoconazole
- Cushings syndrome (prior to surgery, orally active)
- Conns
- CYP450 inhibitor
List the unwanted actions of ketoconaxole
- Liver damage (possibly fatal)
- Liver function must be monitored weekly
List the possible treatments of cushings
- Depends on cause
- Pituitary surgery
- Bilareral adrenalectomy
- Unilateral adrenalectomy for adrenal mass
- Drugs
What is Conns syndrome?
- Benign adrenal corical tumour (zona glomerulosa)
- Aldosterone in excess
- Hypertension and hypohalaemia
Describe the diagnosis of conns syndrome
- Primary hyperaldosteronism
- Renin-angiotensin system should be suppressed (exclude secondary hyperaldosteronism)
List the uses and describe the mechanism of action of spironolactone
- Primary aldosteronism (Conns)
- Converted to several active metabolites including canrenone, a competitive antagonist of the mineralocorticoid receptor
- Blocks Na+ reabsorption and K+ exretion in the kidney tubules
List the unwanted actions of spironolactone
- Menstrual irregularites (stimulates progesterone receptor)
- Gynaecomastia (inhibits androgen receptor)
Describe the functions of epleronone
- A mineralocorticoid receptor antagonist
- Similar affinity to the MR compared to 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 (adrenaline/nor-adrenaline)
List the symptoms of phaeochromocytomas
- Headache
- Dizziness
- Sweating
- Vomiting
- Palpation
- Weakness
- Abdominal pain
- substernal pain
- Pallor
- Nervousness
List the clinical features of a phaeochromocytomas
- Hypertension in young people (can cause MI or stroke)
- Episodic severe hypertension
- More common in certain inherited conditions
List the result of high adrenaline
- Ventricular fibrillation and death
- Myocardial infarction or stroke due to severe hypertension
How are phaeochromocytomas managed?
- Eventually need surgery, but patient needs careful preparation (anaesthetic can cause hypertensive crisis)
- Alpha blockade is first step (may need IV to prevent high blood pressure, plus beta blockade to prevent tachycardia)
Where can paeochromocytomas be?
- 10% extra adrenal
- 10% malignant
- 10% bilateral
- The rest intraadrenal
How are phaeochromocytomas diagnosied?
- Metanephrines in the blood (adrenaline breakdown products)
- CT/MRI
Compare low and high dose dexamethasone suppression test
- Low dose used for cushings syndrome
- High dose for cushings disease
