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ENDOCRINOLOGY phase 1b > 1b Adrenal Disorders > Flashcards

1b Adrenal Disorders Flashcards

1
Q

What hormones are produced in the adrenal cortex?

A

Corticosteroids

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2
Q

What are the corticosteroids?

A

Mineralcorticosteroids
Glucocorticoids
Sex Steroids

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3
Q

What is the precursor for steroid hormones?

A

Cholesterol

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4
Q

What is the effect of angiotensin II on the adrenals?

A

Activation of the following enzymes
Side Chain Cleavage
3 Hydroxysteroid dehydrogenase
21 hydroxylase
11 hydroxylase
18 hydroxylase

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5
Q

What is the action of aldosterone?

A

Increases blood pressure, retains sodium and lowers potassium

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6
Q

What is the effect on ACTH on the adrenals:

A

Activation of the following enzymes
Side Chain Cleavage
3 Hydroxysteroid dehydrogenase
21 hydroxylase
11 hydroxylase
17 hydroxylase

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7
Q

Describe the rhythm of cortisol release?

A

Diurnal secretion

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8
Q

What is primary adrenal failure?

A

Autoimmune disease where the immune system destroys the adrenal cortex, therefore insufficient steroid hormone production

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9
Q

What are the symptoms of an adrenal crisis?

A

Fever
Syncope
Convulsions
Hypoglycaemia
Vomiting
Diarrhea

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10
Q

Why do patients with Addison’s have a good tan?

A

POMC is a large precursor
protein that is cleaved to form
a number of smaller peptides,
including ACTH, MSH and
endorphins
Thus people who have
pathologically high levels of
ACTH may become tanned

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11
Q

Describe the changes to the skin in patients with Addisons?

A

Autoimmune Vitiligo
Hyperpigmentation
Good Tan

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12
Q

What are the three causes of adrenocortical failure?

A

TB - tuberculous Addisons Disease
Autoimmune destruction - Autoimmune Addison’s disease
Born without the necessary enzymes - conhgenital adrenal hyperplasia

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13
Q

What is POMC?

A

Pro-opio melanocortin

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14
Q

Where is POMC made

A

Pituitary

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15
Q

What is POMC broken down into?

A

ACTH, MSH, Endorphins and enkephalins

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16
Q

What are the consequences of Adrenocortical Failure?

A

Fall in blood pressure (POSTURAL HYPOTENSION)
*Loss of salt in the urine (HYPONATRAEMIA)
*Increased plasma potassium (HYPERKALAEMIA)
*Fall in glucose due to glucocorticoid
deficiency
*High ACTH resulting in increased
pigmentation

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17
Q

Describe the visual symptoms of Addison’s?

A

Hyperpigmentation
Vitiligo
Mucous Membrane hyperpigmentation - therefore definately not sun tan as these areas are not accessible
Darkening of hair
Muscles weakness

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18
Q

What is the test for Addison’s?

A

SynACTHen test

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19
Q

How does the SynACTHen test work?

A

Measure cortisol at 9am
Administer injection of SynACTHen and remeasure cortisol levels

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20
Q

What test results of ACTH suggest Addisons?

A

Low Cortisol following synACTHen administration

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21
Q

Why can aldosterone not be given to patients with Addison’s?

A

Aldosterone has too short a half life, therefore would have to be given multiple times a day in order to be effective

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22
Q

What is give to patients with Addisons?

A

Fludrocortisone - does not exist in natural steroids, therefore presence slows metabolism. LONGER ACTING AND AGONIST FOR THE MINERALCORTICOID RECEPTOR

Prednisolone - longer half life and more potent than cortisol, rapidly absorbed with half life suitable for once daily administration

HYDROCORTISONE

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23
Q

What is the dose for prednisolone daily?

A

3 mg daily

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24
Q

What is the dosage of fludrocortisone?

A

50 to 100 mcg daily

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25
Q

What is the most common cause of congenital adrenal hyperplasia?

A

21-hydroxylase deficiency

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26
Q

Which hormones will be completely absent in complete 21-hydroxylase deficiency?

A

Aldosterone and Cortisol

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27
Q

How long can you survive without treatment with 21-hydroxylase deficiency?

A

less than 24 hours

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28
Q

Which hormones will be in excess in complete 21-hydroxylase deficiency?

A

Sex steroids like testosterone

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29
Q

What is the youngest age of presentation with Adrenal Disorders?

A

As a neonate with a salt losing Addisonian Crisis

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30
Q

How do female neonates with Addisonian Crises present?

A

may have ambigious genitalia - loo like they have a penis and scrotum, therefore immediately given saline to restore salt balance

31
Q

What happens to hormone levels in Partial 21 hydroxylase deficiency

A

a bit of aldosterone and cortisol to get by with

32
Q

Which hormones are deficient in partial 21 hydroxylase deficienfy?

A

Cortisol and Aldosterone

33
Q

Which hormones are in excess in partial 21 hydroxylase deficiency?

A

Sex steroids and testosterone

34
Q

What are the main problems in girls with partial 21 hydroxylase deficiency?

A

Hirsutism (hair growth) and virilisation (characteristics of male hormones)

35
Q

What are the main problems in boys with partial 21 hydroxylase deficiency?

A

Precocious puberty due to adrenal testosterone

36
Q

Deficiency of what hormone causes male escutcheon?

This is where the female pubic hair grows in a pattern similar to that of a male

A

Partial 21 hydroxylase defiency

37
Q

What builds up with a 11 hydroxylase deficiency?

A

11-deoxycortiocosterone

38
Q

what is important to note about 11-deoxycorticosterone?

A

Behaves like aldosterone, therefore excess can cause hypertension and hypokalaemia

39
Q

Which hormones are deficient in 11-hydroxylase deficiency

A

Cortisol and aldosterone

40
Q

Which hormones are in excess in 11-hydroxylase deficiency

A

Sex steroids, testosterone and 11-deoxycorticosterone

41
Q

What are the problems associated with 11-hydroxylase deficiency?

A

virilisation, hypertension and low potassium

42
Q

What hormones are deficient in 17-hydroxylase deficiency?

A

Cortisol and Sex Steroids

43
Q

What hormones are in excess in 17-hydroxylase deficiency?

A

11-deoxycorticosterone, aldosterone

44
Q

What are the problems associated with 17-hydroxylase deficiency?

A

Hypertension, Low K, Sex steroid deficiency and glucocorticoid deficiency

45
Q

What time in the day do cortisol levels peak?

A

8.32 am

46
Q

What are some of the signs seen in patients with cushings?

A

Red Striae
Buffalo Humps
Poor Wound Healing
Centripetal Obesity
Hyperplasia of the adrenal glands
Moon Face
Thin Skin
Proximal Myopathy
Diabetes

47
Q

List the four causes of Cushing’s syndrome?

A
  1. Taking too many steroids orally
  2. Pituitary dependant Cushing’s Disease 9\Pituitary adenoma)
  3. Ectopic ACTH from lung cancer
  4. Adrenal Adenoma secreting Cortisol
48
Q

What are the two ways to determine the cause of Cushing’s Syndrome?

A

24h urine collection for urinary free cortisol
Blood diurnal cortisol levels

49
Q

Describe how the cortisol levels of someone with Cushing’s syndrome differs from a normal person?

A

both have diurnal rhythm - but cushings patient will have a midnight sleeping cortisol which is not zero

50
Q

How does the low dose dexamethasone test work?

A

Dexamethasone is an artificial steroid which will suppress cortisol levels to zero in normal patients, but with Cushing’s patients, the levels will fail to fall to zero

51
Q

Which drugs are used to treat Cushings’?

A

Steroid biosynthesis inhibitors

52
Q

What are the two steroid biosynthesis inhibitors used to treat cushing’s?

A

Metyrapone and ketoconazole

53
Q

How does Metyrapone work?

A

Inhibits 11-hydroxylase, so cortisol levels drop as steroid synthesis in the zona fasciulata and zona reticularis are arrested at the 11- hydroxylase level

54
Q

How does the buildup of 11-deoxycortisol as a result on using metyrapone affect the axis?

A

No effect - does not exert a negative feedback effect

55
Q

What are the two main uses of Metyrapone?

A

Control of Cushing’s before surgery to improve patients post-op healing process (wound healing)

Control of Cushing’s after radiotherapy

56
Q

What are the side effects of metyrapone?

A

11-deoxycorticosterone accumulates in the zona glomerulosa and has aldosterone like effects, leading to salt retention and hypertension

57
Q

How does Metyrapone lead to Hirsutism?

A

Increased androgen production due to the lack of 11-hydroxylase leads to hirsutism in women as there is more testosterone produced

58
Q

Describe the mechanism of action for ketoconazole?

A

Mainly blocks 17 hydroxylase, which inhibits cortisol production

59
Q

What are the side effects of ketoconazole?

A

Liver damage - monitor liver function weekly

60
Q

Describe the mechanism of Osilidrostat?

A

Blocks 11 hydroxylase, therefore no cortisol produced

61
Q

What are the treatments for Cushing’s?

A

Pituitary surgery
Adrenalectomy

62
Q

What is Conn’s syndrome?

A

Where a benign adrenal cortical tumour causes an excess of aldosterone

63
Q

What are the effects of Conn’s syndrome?

A

Hypertension and hypokalaemia

64
Q

What is used to treat Conn’s syndrome?

A

Spironolactone

65
Q

How does Spironolactone work?

A

Converted into several active metabolites, including canrenone which is a competitive antagonist of the mineralcorticoid receptor which reverses the effects of aldosterone

Also blocks Na+ reabsorption and K+ excretion in the kidney tubules

66
Q

Where is Spironolactone metabolised?

A

it is highly protein bound and metabolised in the liver

67
Q

What are the side effects of spironolactone?

A

Menstrual irregularitie
Gynaecomastia

68
Q

What are the two drugs used to treat Conn’s syndrome?

A

Spironolactone
Epleronone

69
Q

Why is epleronone prefered over spironolactone?

A

Binds less to androgen and progesterone receptors, therefore less gynaecomastia

70
Q

What are phaeochromocytomas?

A

Tumours of the adrenal MEDULLA which secrete catecholamines liek Adrenaline and Nor Adrenalline

71
Q

What are the clinical features of a phaeochromocytoma?

A

Hypertension in young people
Episodic severe hypertension (after abdominal palpitation

72
Q

Why is a phaeochromocytoma considered a medical emergency?

A

High blood pressure can cause MI or stroke
High Adrenaline = cause ventricular fibrillation

73
Q

Why must you be careful when performing surgery for a phaeo?

A

Surgery - but have to be careful as anaesthetic can precipitate a hypertensive crisis

74
Q

How are Phaeo’s managed?

A

Alpha Blockade - give IV fluid while this
Beta Blockade - added to prevent tachy cardia

ENDOCRINOLOGY phase 1b (12 decks)

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