Hyperadrenal disorders Flashcards
List the clinical features of Cushing’s syndrome
- Too much cortisol
- Impaired glucose tolerance (due to chronic elevation of blood glucose)
- Centripetal obesity
- Moon face and buffalo hump
- Proximal myopathy
- Hypertension and hypokalaemia
- Red striae, thin skin and bruising
- Osteoporosis, diabetes
Describe the effects of excess cortisol on protein and fat synthesis
Decrease protein synthesis
Increase fat synthesis
Explain why people with Cushing’s get striae
They are putting on a lot of fat quickly, which stretches the skin.
Because protein synthesis is switched off, you can’t make the protein required for skin growth so the skin tears.
Why does Cushing’s syndrome cause hypertension and hypokalaemia?
At high concentrations, cortisol can have mineralocorticoid effects => increased sodium absorption and potassium excretion
State four causes of Cushing’s syndrome
- Too much oral glucocorticoid drugs
- Pituitary dependent Cushing’s disease (i.e. pituitary adenoma)
- Ectopic ACTH from lung cancer
- Adrenal adenoma secreting cortisol
What are the three main tests used to diagnose Cushing’s syndrome?
- 24-hour urine free cortisol levels
- Blood diurnal cortisol levels (or midnight serum cortisol)
- Low dose dexamethasone suppression test
Describe the results you’d expect from a normal subject and a patient with Cushing’s syndrome in the 24-hour urine free cortisol and blood diurnal cortisol tests.
NORMAL: lower cortisol at night and higher cortisol in the morning
Cushing’s syndrome: they would have high cortisol all the time
Explain the use of a low dose dexamethasone
Dosage = 0.5mg every 6 hrs for 48hrs
Dexamethasone is an artificial steroid so by giving this extra steroid, it should suppress ACTH and reduce cortisol production.
Normals will suppress cortisol to zero.
Any cause of Cushing’s will fail to suppress
State two drugs that are used to treat Cushing’s syndrome before surgery.
Metyrapone
Ketoconazole
Which enzyme is inhibited by metyrapone, and what effect does metyrapone have on the steroid synthesis pathway?
11-Beta-hydroxylase
It prevents the conversion of 11-deoxycorticosterone => corticosterone (in the z. glomerulosa)
and 11-deoxycortisol => cortisol (in the z. fasciculata)
What are the three biochemical effects of metyrapone?
- Cortisol synthesis blocked
- ACTH secretion increased
- Plasma deoxycortisol increased
When might metyrapone be used and why?
Control of Cushing’s syndrome prior to surgery:
- Adjust oral dose according to cortisol (aim for mean serum cortisol 150-300 nmol/L)
- Improves patient’s symptoms and promotes better post-op recovery
Control of Cushing’s symptoms after radiotherapy (which is usually slow to take effect)
What are the two unwanted effects of metyrapone and why do they occur?
- Hypertension on long-term administration:
- deoxycorticosterone accumulates in z. glomerulosa; its aldosterone-like activity leads to salt retention => hypertension. - Hirsutism:
- Increased adrenal androgen production in women (precursors are funnelled towards the sex steroid synthesis pathway)
What is the main use of ketoconazole and why is it no longer used for this purpose?
Antifungal agent
Withdrawn in 2013 due to risk of hepatotoxicity
What are the effects of ketoconazole on steroid production?
Ketoconazole inhibits cytochrome P450 short chain cleavage enzyme.
This enzyme converts cholesterol to pregnenolone
This means that it inhibits the production of glucocorticoids, mineralocorticoids and sex steroids.
When might ketoconazole be used and what is its unwanted effect?
Uses similar to metyrapone (orally active)
Unwanted effect = Liver damage (possibly fatal); monitor liver function weekly, clinically and biochemically
What are the surgical methods of treatment for Cushing’s?
Depending on the cause, you can have:
- Pituitary surgery (trans-sphenoidal hypophysectomy)
- Bilateral adrenalectomy
- Unilateral adrenalectomy for adrenal mass
What is Conn’s syndrome?
Aldosterone secreting adenoma of the adrenal gland (zona glomerulosa)
What are the two main features of Conn’s syndrome?
Hypertension
Hypokalaemia
What is primary hyperaldosteronism?
Hyperaldosteronism caused by an adrenal adenoma
What can you test to exclude secondary hyperaldosteronism?
Check for suppression of the renin-angiotensin system;
In primary hyperaldosteronism aldosterone is high but renin should be low (it would be suppressed by the high blood pressure)
What is the usual treatment plan for someone with Conn’s syndrome?
- Medical management using spironolactone
- Surgery to remove the tumour
How does spironolactone work?
- Converted to several active metabolites, including canrenone
- Canrenone is a competitive mineralocorticoid receptor antagonist
- Blocks Na+ resorption and K+ excretion in the kidney tubules (potassium-sparing diuretic effect)
What are the two unwanted effects of spironolactone?
- Menstrual irregularities (+progesterone receptor)
2. Gynaecomastia (-androgen receptor)
Name one other mineralocorticoid receptor (MR) antagonist? Why is it preferred?
Epleronone
Similar binding affinity to MRs but less so to androgen and progesterone receptors
What is a phaeochromocytoma?
A tumour of the adrenal MEDULLA which secrete catecholamines (adrenaline and noradrenaline)
What are the clinical features of phaeochromocytoma?
- Episodic severe hypertension (in the young)
- They will get sudden bursts of panic attacks, anxiety, palpitations and a rapid rise in blood pressure
State some fatal consequences of a phaeochromocytoma
- Severe hypertension can cause myocardial infarction or stroke
- High adrenaline can cause ventricular fibrillation + death
Describe the steps that must be taken when preparing a phaeochromocytoma patient for surgery
Anaesthetic could precipitate a hypertensive crisis;
- You give the patient an alpha-blocker to prevent the vasoconstriction caused by adrenaline binding to alpha-receptors.
- Alpha-blockers cause a drop in blood pressure so they are usually given with fluid.
- Then you give beta-blockers to prevent tachycardia.
Once all the receptors are blocked, it means that a massive release in adrenaline will not be able to have its effects.
State some key facts relating to phaeochromocytomas
- 10 % extra-adrenal (sympathetic chain)/90% intra-adrenal
- 10 % malignant
- 10 % bilateral
- Extremely rare
