Hyperadrenal Disorders Flashcards
(35 cards)
Describe the effects of excess cortisol on protein and fat synthesis.
Decrease protein synthesis
Increase fat synthesis
Explain why people with Cushing’s disease get stretch marks.
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.
Describe the clinical features of Cushing’s syndrome.
Moon face Interscapular fat pad (buffalo hump) Proximal myopathy Easy bruising (lack proteins eg clotting proteins) Striae Thin skin Osteoporosis Diabetes Centripetal adiposity (lemon on sticks) Hypertension (Cortisol binds to MR receptors and acts as aldosterone) and hypokalaemia
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.
Pituitary adenoma
Ectopic ACTH
Oral glucocorticoid drugs
Adrenal adenoma
What are the three main tests used to diagnose Cushing’s syndrome?
- 24-hour urine free cortisol (collect urine throughout 24 hrs. Cortisol levels change throughout day and this should be the same in urine)
- Blood diurnal cortisol levels ie measure at different times of the day. Cortisol is highest in the morning 9am and lowest at night(midnight). Patients with Cushings will lose this rhythm and have high cortisol all the time. (same idea as urine)
- 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.
You would expect lower cortisol at night in a normal subject and high cortisol in the morning.
In someone with Cushing’s syndrome they would have high cortisol all the time.
NOTE: a problem with this test is that the cortisol levels are affected by stress and amount of sleep
Explain the scientific basis of the low dose dexamethasone suppression test.
Dexamethasone= very potent cortisol agonist. You give patient a low dose and see if their ACTH and cortisol is suppressed. If not, then its cushings because their production of cortisol is out of control
State some surgical treatments for Cushing’s syndrome.
Treatment is dependent on cause
Transsphenoidal Hypophysectomy (for Cushing’s disease)
Bilateral adrenalectomy
Unilateral adrenalectomy for adrenal mass
State two drugs that are used to treat Cushing’s syndrome before surgery.
Metyrapone
Ketoconazole
Draw the adrenal steroid synthesis pathway.
-
Which enzyme is inhibited by metyrapone?
11-Beta-hydroxylase
What effect does metyrapone have on the steroid synthesis pathway?
It prevents the conversion of 2 reactions in the steroid synthesis pathway
1. 11-deoxycorticosterone –> corticosterone
2. 11-deoxycortisol –> cortisol
This means that no corticosterone or cortisol is produced
State two uses of metyrapone.
- Preparation of a Cushing’s patient for surgery
(peri-operatively):
a. improves their healing abilities and makes them better surgical candidates as they lack protein synthesis and so normally bleed a lot and have weak skin
b. allows better post op recovery. High cortisol is immunosuppressive and may increase likelihood of post op infection
2.Treatment of Cushing’s syndrome symptoms following radiotherapy. Some patients get radiotherapy on their pituitary tumour (radiotherapy has a delayed effect)
State two negative aspects of metyrapone.
11b-hydroxylase blockage causes accumulation of 11-deoxycorticosterone (it doesn’t have any negative feedback effects on the ACTH axis)
This leads to 2 side effects:
1. 11-deoxycorticosterone has mineralocorticoid effects so causes SALT RETENTION and HYPERTENSION.
2.Metyrapone inhibits two limbs of the steroid synthesis pathway so it funnels the precursors towards the sex steroid synthesis pathway.
This leads to increased adrenal androgens, which has effects such as hirsuitism, acne.
State 2 unwanted effects of metyrapone.
Hypertension on long-term administration
Hirsutism
What is ketoconazole and why is it no longer used?
Ketoconazole is an anti-fungal, which had an effect on the steroidsynthesis pathway.
at higher concentrations, inhibits steroidogenesis – off-label use in Cushing’s syndrome
It is no longer used because of its hepatotoxicity.
What are the effects of ketoconazole on steroid production?
Ketoconazole inhibits cytochrome P450 short chain cleavage enzyme. (P450scc)
This enzyme converts cholesterol –> pregnenolone
This means that it inhibits the production of glucocorticoids, mineralocorticoids and sex steroids.
State some unwanted actions of ketoconazole.
MAIN concern: LIVER DAMAGE
monitor liver function weekly, clinically and biochemically
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. Another word for Conns syndrome
What can you test to exclude secondary hyperaldosteronism?
Check for suppression of the renin-angiotensin system
Measure aldosterone and if that’s high, measure the renin and that should be low because it would be suppressed by the high blood pressure.
What is the usual treatment plan for someone with Conn’s syndrome?
Medical management (spironolactone) Surgery to remove the tumour
