Hyperadrenal Disorders Flashcards Preview

Y2 LCRS 1 - Endocrinology - Laz COPY > Hyperadrenal Disorders > Flashcards

Flashcards in Hyperadrenal Disorders Deck (35)
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1
Q

Describe the effects of excess cortisol on protein and fat synthesis.

A

Decrease protein synthesis

Increase fat synthesis

2
Q

Explain why people with Cushing’s disease get stretch marks.

A

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.

3
Q

Describe the clinical features of Cushing’s syndrome.

A
Moon face 
Interscapular fat pad (buffalo hump) 
Proximal myopathy 
Easy bruising  
Striae 
Thin skin 
Osteoporosis 
Diabetes  
Centripetal adiposity (lemon on sticks) 
Hypertension and hypokalaemia
4
Q

Why does Cushing’s syndrome cause hypertension and hypokalaemia?

A

At high concentrations, cortisol can have mineralocorticoid effects –> increased sodium absorption and potassium excretion

5
Q

State four causes of Cushing’s syndrome.

A

Pituitary adenoma
Ectopic ACTH
Oral glucocorticoid drugs
Adrenal adenoma

6
Q

What are the three main tests used to diagnose Cushing’s syndrome?

A

24-hour urine free cortisol
Blood diurnal cortisol levels (or midnight serum cortisol)
Low dose dexamethasone suppression test

7
Q

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.

A

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.

8
Q

Explain the scientific basis of the low dose dexamethasone suppression test.

A

Dexamethasone is a glucocorticoid so by giving this extra glucocorticoid, it should suppress ACTH and reduce cortisol production.
So in a normal subject undertaking the dexamethasone suppression test, you would expect zero cortisol.
In a Cushing’s patient, cortisol will remain high despite the presence of dexamethasone.

9
Q

State some surgical treatments for Cushing’s syndrome.

A

Treatment is dependent on cause
Transsphenoidal Hypophysectomy (for Cushing’s disease)
Bilateral adrenalectomy
Unilateral adrenalectomy for adrenal mass

10
Q

State two drugs that are used to treat Cushing’s syndrome before surgery.

A

Metyrapone

Ketoconazole

11
Q

Draw the adrenal steroid synthesis pathway.

A

-

12
Q

Which enzyme is inhibited by metyrapone?

A

11-Beta-hydroxylase

13
Q

What effect does metyrapone have on the steroid synthesis pathway?

A

It prevents the conversion of: 11-deoxycorticosterone –> corticosterone
11-deoxycortisol –> cortisol
This means that no corticosterone or cortisol is produced

14
Q

State two uses of metyrapone.

A

Preparation of a Cushing’s patient for surgery (improves their healing abilities and makes them better surgical candidates)
Treatment of Cushing’s syndrome symptoms following radiotherapy (radiotherapy has a delayed effect)

15
Q

State two negative aspects of metyrapone.

A

Metyrapone causes the accumulation of 11-deoxycorticosterone (because it doesn’t have any negative feedback effects on the ACTH axis)
11-deoxycorticosterone has mineralocorticoid effects so causes SALT RETENTION and HYPERTENSION.
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.

16
Q

State some unwanted effects of metyrapone.

A

Nausea, vomiting, dizziness
Hypertension
Hirsuitism
Sedation, hypoadrenalism

17
Q

What is ketoconazole and why is it no longer used?

A

Ketoconazole is an anti-fungal, which had an effect on the steroidsynthesis pathway.
It is no longer used because of its hepatotoxicity.

18
Q

What are the effects of ketoconazole on steroid production?

A

Ketoconazole inhibits cytochrome P450 short chain cleavage enzyme.
This enzyme converts cholesterol –> pregnenolone
This means that it inhibits the production of glucocorticoids, mineralocorticoids and sex steroids.

19
Q

State some unwanted actions of ketoconazole.

A

Nausea, vomiting, abdominal pain
Alopecia
Gynaecomasia, oligospermia, impotence, decreased libido Ventricular tachycardias
LIVER DAMAGE (could be fatal)
These unwanted effects are due to loss of sex steroids, glucocorticoids and mineralocorticoids

20
Q

What is Conn’s syndrome?

A

Aldosterone secreting adenoma of the adrenal gland (zona glomerulosa)

21
Q

What are the two main features of Conn’s syndrome?

A

Hypertension

Hypokalaemia

22
Q

What is primary hyperaldosteronism?

A

Hyperaldosteronism caused by an adrenal adenoma.

23
Q

What can you test to exclude secondary hyperaldosteronism?

A

Check for suppression of the renin-angiotensin system
Measure aldosterone and if that’s high, measure the renin and that should be low because if would be suppressed by the high blood pressure.

24
Q

What is the usual treatment plan for someone with Conn’s syndrome?

A
Medical management (spironolactone) 
Surgery to remove the tumour
25
Q

What is spironolactone and how does it work?

A

Spironolactone is an aldosterone receptor antagonist

It reduces the effects of aldosterone so it decreases sodium reabsorption and decreases potassium excretion.

26
Q

What is the active metabolite of spironolactone that acts as a mineralocorticoid receptor antagonist?

A

Canrenone

27
Q

What treatment would you give for someone with bilateral adrenal hyperplasia?

A

Long-term spironolactone
You don’t want to remove both adrenals because then they wouldn’t produce any cortisol or aldosterone so you give them long-term spironolactone to reduce the effects of excess aldosterone.

28
Q

Describe the pharmacokinetics of spironolactone.

A

Orally active
Given daily in single or divided doses
Highly protein-bound and metabolised in the liver

29
Q

State some unwanted effects of spironolactone.

A

Spironolactone is very non-specific so it has several side effects
Progesterone receptor agonist –> menstrual irregularities
Androgen receptor antagonist –> gynaecomastia
GI tract irritation
Contra-indications:
 Renal and hepatic disease

30
Q

Name another mineralocorticoid receptor antagonist that has fewer side effects than spironolactone.

A

Eplerenone

31
Q

What is phaeochromocytoma?

A

Tumour of the adrenal medulla that is producing excessive amounts of catecholamines

32
Q

What are the features of phaeochromocytoma?

A

Episodic severe hypertension (in the young)

They will get sudden bursts of panic attacks, anxiety, palpitations and a rapid rise in blood pressure.

33
Q

State some fatal consequences of phaeochromocytoma.

A

Myocardial infarction and stroke
It can also cause sudden cardiac death through ventricular fibrillation
It is a MEDICAL EMERGENCY

34
Q

Describe the steps that must be taken when preparing a phaeochromocytoma patient for surgery.

A

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 a bit of 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.

35
Q

What percentage of phaeochromocytoma is intra-adrenal?

A

90%

It is a very rare condition.