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BRS YR2 > Adrenal Disorders > Flashcards

Adrenal Disorders Flashcards

1
Q

What does the adrenal cortex produce?

A

Corticosteroids

  • mineralcorticosteroids (aldosterone)
  • glucocorticoids (cortisol)
  • sex steroids (androgens and oestrogens)
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2
Q

What is the precursor for corticosteroids?

A

Cholesterol

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3
Q

What is the effects of angiotensin II on the adrenal glands?

A

Activation of:

  • 3 hydroxysteroid dehydrgenase
  • 21 hydroxylase
  • 11 hydroxylase
  • 18 hydroxylase
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4
Q

How does angiotensin II activate enzymes?

A

By side chain cleavage

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5
Q

What is the action of aldosterone?

A

Controls blood pressure, sodium and lowers potassium

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6
Q

What is the effect of ACTH on the adrenal glands?

A

Activates:

  • 3 hydroxysteroid dehydrogenase
  • 21 hydroxylase
  • 11 hydroxylase
  • 17 hydroxylase
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7
Q

What does 17 hydroxylase catalyse?

A

the conversion of progesterone to 17-OH progesterone

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8
Q

What does 21 hydroxylase catalyse?

A
  • the conversion of progesterone to 11-deoxycorticosterone
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9
Q

What does 11 hydroxylase catalyse?

A
  • 11-deoxycorticosterone to corticosterone or cortisol
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10
Q

What does 18 hydroxylase catalyse?

A

the conversion of corticosterone to aldosterone

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11
Q

What rhythm does cortisol have?

A

Diurnal (peaks at 8:30)

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12
Q

What is Addison’s disease?

A

Primary adrenal failure
Autoimmune disease where the immune system decides to destroy the adrenal cortex
(most commonly: tuberculosis of the adrenal glands)

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13
Q

What is the result of Addison’s disease

A

The pituitary gland secretes a lot of ACTH and therefore MSH

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14
Q

What are the symptoms of Addison’s Disease?

A
  • Increased pigmentation
  • Autoimmune vitiligo
  • low blood pressure (no cortisol or aldosterone)
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15
Q

What are the general causes of adrenocortical failure?

A
  • enzymes in the steroid synthetic pathway not working

- adrenal glands are destroyed

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16
Q

What are the causes of adrenocortical failure?

A
  • Tuberculosis Addison’s disease (common worldwide)
  • Autoimmune Addison’s disease (common UK)
  • Congenital adrenal hyperplasia
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17
Q

What are the consequences of adrenocortical failure?

A 
Increase:
- ACTH
- pigmentation
- plasma K+
Decrease:
- blood pressure (can cause death)
- salt in urine
- glucose (due to glucocorticoid deficiency)
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18
Q

Why does high ACTH levels cause increased pigmentation?

A

POMC (pro-propio-melanocortin) is a large precursor protein which is cleaved to form ACTH, MSH and endorphins

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19
Q

Where is Pro-propio melanocortin synthesised?

A

In the pituitary

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20
Q

How do you test for Addison’s disease?

A
  • 9 am cortisol (low)
  • ACTH (high)
  • short synACTH test
  • give 250ug synACTHen (IM)
  • measure cortisol response
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21
Q

What results would you expect when doing a short synACTH test in someone with Addison’s disease?

A
  • 9am cortisol, 100nM (270-900)
  • administer IM injection of synACTHen
  • 9:30am cortisol, 150nM (>600)
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22
Q

Why isn’t aldosterone administered in HRT during adrenal failure?

A

The half-life of aldosterone is too short for safe 1 x daily administration

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23
Q

What is used to replace Aldosterone in HRT and why?

A

Fludrocortisone (50-100mcg daily)

Doesn’t exist in natural steroids and therefore the presence slows metabolism significantly.

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24
Q

What is the mechanism of Fludrocortisone?

A
  • binds to both MR and GR
  • half life: 3.5 hours
  • effects seen for 18 hours
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25
Q

Why isn’t cortisol (hydrocortisone) used in HRT during adrenal failure?

A

Half-life is too short for 1x daily administration

Causes multiple/late peaks in cortisol which is harmful

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26
Q

What is used instead of cortisol and why?

A

Prednisolone (1-2 dehydro-hydrocortisone)

  • longer half life
  • more potent
  • 2.3 x binding affinity than cortisol
  • replacement dose is 3-4mg 1x daily
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27
Q

What doses of prednisolone are available?

A
  • 1mg, 2.5mg, 5mg

- not enteric coated (slows absorption)

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28
Q

What dosage of prednisolone should be given to a patient?

A
  • depends on the patient (more research required)
  • generally: 3.75mg (2-4mg)
  • starting is 4mg, aim is to be between 15-25mcg/l at 8 hours
  • equivalent to 15-25mg of hydrocortisone daily
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29
Q

What is the risk of replacement prednisolone?

A
  • excess steroid exposure

- sub-clinical Cushing’s disease

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30
Q

What is the general treatment given for adrenal failure?

A
  • Hydrocortisonm 3 x daily (10+5+2.5)
    OR
  • Prednisolone 3mg 1 x daily
  • Fludrocortisone 50-100mcg 1 x daily
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31
Q

What is the most common cause of congenital adrenal hyperplasia?

A

21-hydroxylase deficiency

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32
Q

What hormones will be absent in COMPLETE 21-hydroxylase deficiency?

A
  • aldosterone

- cortisol

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33
Q

How long can you survive with COMPLETE 21-hydroxylase deficiency?

A

<24 hours

34
Q

What hormones will be in excess with COMPLETE 21-hydroxylase deficiency?

A
  • Sex steroids

- Testosterone

35
Q

At what age does COMPLETE 21-hydroxylase deficiency present?

A
  • neonate in a salt losing Addisonian crisis
  • Pre-birth (in utero), foetus gets steroids from across the plasma
  • Girls may have ambiguous genitalia (due to adrenal testosterone).
36
Q

What hormones are deficient in PARTIAL 21-hydroxylase deficiency?

A
  • cortisol

- aldosterone

37
Q

Which hormones are in excess in PARTIAL 21-hydroxylase deficiency?

A
  • sex steroids

- testosterone

38
Q

At what age does PARTIAL 21-hydroxylase deficiency?

A
  • any age as survival is likely
39
Q

What is the main problem associated with PARTIAL 21-hydroxylase deficiency?

A 
In later life:
- hirsutism in girls
- virilisation in girls
- precocious puberty in boys 
due to the adrenal testosterone
40
Q

What does 11-deoxycorticosterone behave like?

A

Aldosterone

41
Q

What can excess 11-deoxycorticosterone cause?

A
  • hypertension

- hypokalaemia

42
Q

What hormones are deficient in 11-hydroxylase deficiency?

A
  • cortisol

- aldosterone

43
Q

Which hormones are in excess in 11-hydroxylase deficiency?

A
  • sex steroids
  • testosterone
  • 11-deoxycorticosterone
44
Q

What problems are associated with 11-hydroxylase deficiency?

A
  • virilisation
  • hypertension
  • low potassium
45
Q

What hormones are deficient in 17-hydroxylase deficiency?

A
  • cortisol

- sex steroids

46
Q

What hormones are in excess in 17-hydroxylase deficiency?

A
  • 11-deoxycorticosterone
  • aldosterone
    (mineralcorticoids)
47
Q

What problems are associated with 17-hydroxylase deficiency?

A
  • hypertension
  • low potassium
  • sex steroid deficiency
  • glucocorticoid deficiency (low glucose)
48
Q

What are the clinical features of Cushing’s disease?

A
  • excess cortisol
  • centripetal obesity
  • moon face
  • buffalo hump
  • proximal myopathy
  • hypertension
  • hypokalaemia
  • red striae, thin skin and bruising
  • osteoporosis
  • diabetes
49
Q

What are the causes of Cushing’s disease?

A
  • excess steroid exposure
  • pituitary dependent Cushing’s disease
  • Ectopic ACTH (from lung cancer)
  • Adrenal adenoma secreting cortisol
50
Q

What are the investigations used to confirm Cushing’s disease?

A
  • 24hour urine collection (for urinary free cortisol)
  • blood diurnal cortisol levels
    (cortisol highest at 9am, lowest at midnight)
  • low dose dexamethasone suppression test
51
Q

What is involved in a low dose dexamethasone suppression test?

A
  • 0.5mg every 6 hours for 48 hours
    (dexamethasone=artificial steroid)
  • normal will suppress cortisol to 0
  • ANY cause of Cushing’s will fail to suppress
52
Q

What values would confirm a diagnosis of Cushing’s disease?

A
  • basal (9am) cortisol, 800nM

- end of low dose dexamethasone test, 680nM

53
Q

What drugs are involved in the manipulation of steroids?

A
  • Enzyme inhibitors

- Receptor blocking drugs

54
Q

What is Conn’s syndrome?

A

Excess aldosterone

55
Q

Which drugs are inhibitors of steroid biosynthesis?

A
  • metyrapone

- ketoconazole

56
Q

What is the action of metyrapone?

A
  • The inhibition of 11beta-hydroxylase
  • steroid synthesis (in zona fasiculata) is arrested at the 11-deoxycortisol stage
  • 11-deoxycortisol has NO negative feedback effects on the hypothalamus and the pituitary gland
57
Q

What are the main 2 uses of Metyrapone?

A
  • control of Cushing’s syndrome prior to surger

- Control of Cushing’s symptoms after radiotherapy (slow to take effect)

58
Q

How can metyrapone be used to control Cushing’s syndrome prior to surgery?

A
  • adjust oral dose according to cortisol, aim: serum cortisol = 150-300nmol/l
  • improves patients symptoms and promotes better post-op recovery
59
Q

What are the unwanted side effects of metyrapone?

A
  • hypertension with long term use

- hirsutism

60
Q

How does metyrapone cause hypertension in the long term?

A

the excess 11-deoxycorticosterone accumulates in the zona glomerulosa, has aldosterone-like activity causing salt retention and therefore, hypertension.

61
Q

How does metyrapone cause hirsutism in women?

A

Increased adrenal androgen production

62
Q

What is the actions of ketoconazole?

A
  • main use: antifungal (withdrawn due to hepatotoxicity risk)
  • at higher concentrations, inhibits steroidogenesis (use in Cushing’s is off label)
63
Q

What is the mechanism of action of ketoconazole?

A

Blocks 17alpha-hydroxylase, inhibiting cortisol production

64
Q

What is ketoconazole used for?

A

treatment and control of symptoms prior to surgery

orally active

65
Q

What is the unwanted actions of ketaconazole?

A 
Liver damage (possibly fatal)
- monitor liver function weekly (clinically and biochemically)
66
Q

What are possible treatments of Cushing’s disease?

A 
Depends on the cause
Surgical:
- pituitary surgery (transsphenoidal hypophysectomy)
- bilateral adrenalectomy 
- unilateral adrenalectomy (for adrenal mass)
Medication:
- metyrapone
- ketoconazole
67
Q

What are the characteristics of Conn’s disease?

A
  • benign adrenal cortical tumour (zona glomerulosa)
  • aldosterone in excess
  • hypertension
  • hypokalaemia
68
Q

What are the key aspects of Conn’s syndrome required for diagnosis?

A
  • primary hyperaldosteronism

- renin-angiotensin system is suppressed (to excluse secondary hyperaldosteronism)

69
Q

What type of drugs are involved in treating Conn’s disease?

A

Mineralcorticoid Receptor antagonists:

  • spironolactone
  • elperonone
70
Q

What is the mechanism of action of spironolactone?

A
  • Converted into several active metabolites, including canrenone - competitive antagonist of the mineralcorticoid receptor
  • Blocks sodium resorption and potassium excretion in the kidney tubules
    (potassium sparing diuretic)
71
Q

Describe the pharmacokinetics of spironolactone?

A
  • orally active

- highly protein bound and metabolised in the liver

72
Q

What are the unwanted actions of spironolactone?

A
  • menstrual irregularities (+progesterone receptor)

- gynaecomastia (-androgen receptor)

73
Q

What is the difference between spironolactone and epleronone?

A

Epleronone binds less to andorgen and progesterone receptors, adn therefore is better tolerated.

74
Q

What are Phaeochromocytomas?

A

tumours of the adrenal medulla which secretes catecholamines
(adrenaline or nor-adrenaline)

75
Q

What are the clinical features of a Phaeochromocytoma?

A
  • hypertension (young people)
  • episodic severe hypertension post abdominal palpation
  • more common nin certain inherited conditions.
  • severe hypertension > myocardial infarction or stroke
  • high adrenaline > ventricular fib. and death (medical emergency)
76
Q

What is the management of a Phaeochromocytoma?

A
  • First step: alpha blockade
  • may need to be accompanied by IV fluids
  • addition of beta blockade to prevent tachycardia
  • Need surgery eventually BUT careful prep as anaesthetic can cause a hypertensive crisis
77
Q

10% of Phaeochromocytomas are …

A
  • extra-adrenal (sympathetic chain)
  • malignant
  • bilateral
78
Q

How is Conn’s definitively diagnosed?

A

The presence of excess aldosterone with suppressed renin

79
Q

What hormones do you need to double when ill or septic?

A
  • double their prednisolone
    IF INCREDIBLY ILL
  • IV hydrocortisone
80
Q

Why do you not use fludrocortisone in emergency situations?

A

Long-acting, therefore takes time to come into action

81
Q

What do you use instead of fludrocortisone in emergency situations?

A
  • cortisol

- prednisolone

82
Q

What to test for when TSH is normal, with high blood pressure, and high pulse?

A
  • ADRENALINE

- test for urine catecholamines

BRS YR2 (70 decks)

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