Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BRS Flashcards (Y2) > Adrenal Disorders > Flashcards

Adrenal Disorders Flashcards

1
Q

What is a steroid?

A

A hormone derived from cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What three types of steroids are made in the adrenal cortex?

A

Mineralcorticoids (aldosterone)
Glucocorticoids (cortisol)
Sex steroids (androgens, oestrogens)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the effect of angiotensin II on the adrenals?

A

Production of aldosterone from cholesterol:
Side chain cleavage -> pregnenolone
3 hydroxysteroid dehydrogenase -> progesterone
21 hydroxylase -> 11-deoxycorticosterone
11 hydroxylase -> corticosterone
18 hydroxylase -> aldosterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the role of aldosterone?

A

Controls blood pressure
Sodium retention
Lowers potassium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Where is aldosterone made?

A

Zona glomerulosa of adrenal cortex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the effect of ACTH on the adrenals?

A

Cortisol production from cholesterol:
Side chain cleavage -> pregnenolone
3 hydroxysteroid dehydrogenase -> progesterone
17 hydroxylase -> 17-alpha-hydroxyprogesterone
21 hydroxylase -> 11-deoxycortisol
11 hydroxylase -> cortisol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Where is cortisol produced?

A

Zona fasciculata of adrenal cortex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is Addison’s disease?

A

Primary adrenal failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What causes Addison’s Disease?

A

Autoimmune - immune system decides to destroy adrenal cortex
Tuberculosis of the adrenal glands (commonest worldwide cause)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Why do people with Addison’s Disease tan?

A

Pituitary starts secreting lots of ACTH and therefore MSH (melanocyte-stimulating hormone) - same precursor pro-opiomelanocortin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are some features of Addison’s Disease?

A

Increased pigmentation
Low BP - no cortisol or aldosterone
Autoimmune vitiligo may coexist
Weight loss

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the features of adrenal crisis?

A

Fever
Syncope (low BP)
Convulsions
Hypoglycaemia
Hyponatraemia
Severe vomiting and diarrhoea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the causes of adrenocortical failure?

A

Tuberculous Addison’s Disease
Autoimmune Addison’s Disease
Congenital adrenal hyperplasia (enzyme deficiency)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the consequences of adrenocortical failure?

A

Fall in BP
Loss of salt in urine
Increased plasma potassium
Fall in glucose due to glucocorticoid deficiency
High ACTH resulting in increased pigmentation
Eventual death due to severe hypotension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the tests for Addison’s?

A

9 am cortisol (low in Addison’s)
ACTH (high in Addison’s)
Short synACTHen test

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What happens in the short synACTHen test?

A

Give 250 micrograms synachten IM
Measure cortisol response - do blood test before and after injection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the response of a typical Addison’s patient to the short synACTHen test?

A

Cortisol at 9am = 100 (270-900)
Administer injection of synacthen
Cortisol at 9.30 = 150 (>600)nM

*Typical values for no Addison’s in brackets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Why isn’t aldosterone given as a steroid replacement?

A

Half life is too short for once daily administration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What medication is given to replace aldosterone and what makes it suitable?

A

Fludrocortisone (50-100mcg daily)
Has an added fluorine - fluorine doesn’t exist in natural steroids - this slows metabolism giving it a longer half life - effects seen for 18 hrs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What happens when you give a high dose of hydrocortisone?

A

It acts on both aldosterone and cortisol receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Why isn’t hydrocortisone the most ideal steroid replacement treatment?

A

Short half-life - too short for once daily administration
Given three times daily - doesn’t mimic diurnal rhythm very well
Late cortisol peaks may be harmful

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the benefits of taking prednisolone over hydrocortisone?

A

Contains an extra double bond - longer half life
More potent than cortisol - 2.3x binding affinity
3-4mg ONCE daily

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the minimum dose of prednisolone in many developing countries and what may this cause?

A

5mg - too high?
Increased mortality due to excess steroid exposure
Prednisolone typically given in high doses for autoimmune conditions (e.g. asthma) but not adrenal failure so researchers still trying to pinpoint appropriate dosage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the commonest cause of congenital adrenal hyperplasia?

A

21-hydroxylase deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What hormones are deficient in congenital adrenal hyperplasia?

A

Cortisol and aldosterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What hormone do you have in excess in congenital adrenal hyperplasia and what does this cause?

A

Precursor in excess - 17-OH progesterone
Used to make testosterone - excess testosterone

27
Q

How long can you survive with 21-hydroxylase deficiency?

A

Up to 24 hours after birth

28
Q

What is the age of presentation with complete 21 hydoxylase deficiency?

A

Neonate with salt losing Addisonian crisis
In utero foetus gets steroids across placenta
Girls may have ambiguous genitalia due to excess testosterone (given saline)
Boys more likely to have crisis as they look normal

29
Q

What happens in partial 21 hydroxylase deficiency?

A

Cortisol and aldosterone are deficient but enough for functioning
Excess testosterone

30
Q

What signs of partial 21 hydroxylase deficiency arise later in life?

A

Hirsutism and virilsation in girls
Precocious puberty in boys - grow really quickly then stop prematurely
Male escutcheon - male appearance in someone who’s female

31
Q

Where is 21 hydroxylase deficiency more common?

A

More common in populations with consanguineous marriages
Autosomal recessive condition

32
Q

What happens when people are born with 11 hydroxylase deficiency?

A

No cortisol and aldosterone
Excess testosterone
However, excess pre-cursor 11 deoxycorticosterone behaves like aldosterone so causes hypertension and hypokalaemia

33
Q

What are the problems caused by 11 hydroxylase deficiency?

A

Virilisation
Hypertension
Low potassium

34
Q

How does 17 hydroxylase deficiency present?

A

Sex steroid deficiency - No testosterone
Don’t go through puberty - appearance of a child in adulthood
Slightly hypoglycaemic - glucocorticoid deficiency
Excess aldosterone - hypertension and hypokalaemia

35
Q

How does excess cortisol affect protein synthesis?

A

Turns off protein synthesis
Increases fat storing and decreases protein synthesis

36
Q

Is a low or high cortisol needed for wound healing?

A

Low cortisol

37
Q

What effect does excess cortisol have on the immune system?

A

Dampens the immune system making people more susceptible to infection

38
Q

What are the clinical features of Cushing’s Syndrome?

A

Excess cortisol:
Centripetal obesity
Moon face and buffalo hump
Proximal myopathy
Hypertension and hypokalaemia
Red striae, thin skin and bruising
Osteoporosis, diabetes

39
Q

What are the causes of Cushing’s Syndrome?

A

Taking too many steroids
Pituitary dependent Cushing’s Disease
Ectopic ACTH from lung cancer
Adrenal adenoma secreting cortisol

40
Q

What investigations are used to diagnose Cushing’s Syndrome?

A

24h urine collection for urinary free cortisol
Blood diurnal cortisol levels - midnight cortisol (high in Cushing’s)
Low dose dexamethasone suppression test

41
Q

How does a low dose dexamethasone suppression test work?

A

Dexamethasone = artificial steroid
0.5mg every 6 hours for 48 hours
No Cushing’s - cortisol level would be suppressed to zero
Any cause of Cushing’s will fail to suppress

42
Q

Aside for surgery, what other treatment options are there for Cushing’s?

A

Enzyme inhibitors
Receptor blocking drugs

43
Q

What is the action of Metyrapone?

A

Inhibits steroid synthesis through inhibition of 11-beta-hydroxylase
Steroid synthesis arrested at 11-deoxycortisol stage
11-deoxycortisol has no negative feedback effect on hypothalamus and pituitary
Rapidly puts Cushing’s in remission

44
Q

When is Metyrapone used?

A

Control of Cushing’s prior to surgery:
- adjust oral dose according to cortisol level (aim for 150-300 nmol/L mean serum cortisol)
- improves patient’s symptoms and promotes better post-op recovery
Control of Cushing’s symptoms after radiotherapy (slow to take effect)

45
Q

What are the side effects of Metyrapone?

A

Hypertension due to accumulation of 11-deoxycorticosterone (aldosterone-like mineralcorticoid activity)
Hirsutism due to increased adrenal androgen production

46
Q

What was the main use of Ketoconazole in the past?

A

Antifungal agent - withdrawn in 2013 due to hepatotoxcity risk
Inhibits steroidogenesis at higher concentrations (off-label use)

47
Q

What is the mechanism of action of Ketoconazole?

A

Inhibits 17-alpha-hydroxylase

48
Q

What is the benefit of using Ketoconazole over Metyrapone?

A

Ketoconazole actually reduces testosterone - doesn’t cause hirsutism

49
Q

What is an unwanted action of Ketoconazole?

A

Can cause liver damage that is possibly fatal
Have to monitor liver function weekly - clinically and biochemically

50
Q

What is the mechanism of action of Osilidrostat?

A

Mainly blocks 11-beta-hydroxylase and 17-alpha-hydroxylase

51
Q

Was it the benefit of Osilidrostat over Metyrapone and Ketoconazole?

A

Less of nausea and vomiting side effects

52
Q

What surgeries can be used for treatment of Cushing’s?

A

Depends on cause
Pituitary surgery - transsphenoidal hypophysectomy
Bilateral adrenalectomy
Unilateral adrenalectomy for adrenal mass

53
Q

What are the features of Conn’s Syndrome?

A

Benign adrenal cortical tumour (Zona glomerulosa)
Excess aldosterone
Hypertension and hypokalaemia

54
Q

How is Conn’s Syndrome diagnosed?

A

Primary hyperaldosteronism
Renin-angiotensin system should be suppressed

55
Q

What is the mechanism of action of Spironolactone?

A

Converted to several active metabolites including canrenone - a competitive antagonist of the mineralcorticoid receptor
Blocks Na+ resorption and K+ excretion in kidney tubules

56
Q

Describe the pharmacokinetics of Spironolactone?

A

Orally active
Highly protein bound, metabolised in liver

57
Q

What are the unwanted side effects of spironolactone?

A

Menstrual irregularities
Gynaecomastia

58
Q

What is epleronone and how do its effects compare to spironolactone?

A

Also a mineralcorticoid receptor (MR) antagonist
Similar affinity as spironolactone to MR
Better tolerated as less binding to androgen and progesterone receptors

59
Q

What are phaeochromocytomas?

A

Tumours of the adrenal medulla that secrete catecholamines

60
Q

What are the clinical features of a phaeochromocytoma?

A

Hypertension in young people
Episodic severe hypertension (e.g. after abdominal palpation)
More common in certain inherited conditions
Severe hypertension-> MI or stroke
High adrenaline -> ventricular fibrillation and death

61
Q

How are pheos managed prior to surgery?

A

First therapeutic step is alpha blockade
IV fluid may be given with alpha blockers (drop in BP)
Beta blockers then given to prevent tachycardia

62
Q

Why do patient with phaeochromocytomas require careful preparation prior to surgery?

A

Anaesthetic may precipitate a hypertensive crisis

63
Q

List some extra facts about phaeochromocytomas

A

10% extra-adrenal (sympathetic chain)
10% malignant
10% bilateral
Extremely rare

BRS Flashcards (Y2) (79 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions