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BRS Year 2 > Adrenal Disorders > Flashcards

Adrenal Disorders Flashcards

1
Q

What hormones does the adrenal cortex produce?

A

Corticosteroids:

  • Mineralocorticoids (Aldosterone)- zona glomerulosa
  • Glucocorticoids (Cortisol)- zona fasciculata
  • Sex steroids (Androgens, oestrogens)- zona reticularis
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2
Q

What is the effect of angiotensin II on the adrenals?

A 
Activation of the following enzymes:
3 Hydroxysteroid dehydrogenase
21 hydroxylase
11 hydroxylase
18 hydroxylase.

Plus stimulates aldosterone synthase to make aldosterone

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3
Q

What is the function of aldosterone?

A

Controls blood pressure- increases water reabsorption so increased BP
Stimulates sodium reabsorption
Stimulates potassium excretion

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4
Q

How is aldosterone produced?

A
  1. Cholesterol
  2. progesterone (21 hydroxylase)
  3. 11-deoxycorticosterone (11 hydroxylase)
  4. corticosterone (18 hydroxylase)
  5. aldosterone
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5
Q

How is cortisol formed?

A
  1. Cholesterol
  2. Progesterone (17 hydroxylase)
  3. 17-hydroxy progesterone (21 hydroxylase)
  4. 11- deoxycortisol (11 hydroxylase)
  5. cortisol
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6
Q

How are sex steroids and oestrogen produced?

A
  1. Cholesterol
  2. Progesterone (17 hydroxylase)
  3. 17-hydroxy progesterone
  4. Sex steroids
  5. Androgens
  6. Oestrogen
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7
Q

How do levels of cortisol change throughout the day?

A

Cortisol has a diurnal rhythm
It peaks at 8:30am
Rise in cortisol begins at 5am
Lowest at midnight

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8
Q

What is addison’s disease?

A

Primary adrenal failure
Autoimmune disease where the immune system decides to destroy the adrenal cortex (commonest in UK)
Tuberculosis of the adrenal glands (commonest cause worldwide)
Pituitary starts secreting lots of ACTH and hence MSH

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9
Q

What are symptoms of addison’s disease?

A 
Increased pigmentation
Hyperkalaemia
Autoimmune vitiligo may coexist
Weakness
Weight loss: anorexia, vomiting, diarrhoea
Low BP: No cortisol or aldosterone
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10
Q

Why do people with addison’s disease have a tan?

A

Pro-opio-melanocortin (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

What are causes of adrenocortical faliure?

A

Tuberculous Addison’s disease (commonest worldwide)

Autoimmune Addison’s disease (commonest in UK)

Congenital adrenal hyperplasia

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12
Q

What are consequences of adrenocortical failure?

A

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

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13
Q

What are tests used to diagnose addison’s disease?

A 
9am cortisol (should be high in a healthy patient)
ACTH level

Short synACTHen test - give 250 ug synacthen IM (synATCHENen mimics ACTH and stimulates cortisol release. In healthy patient cortisol should increase)

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14
Q

What diagnostic results would we expect in someone with addison’s disease?

A

9am cortisol = low

ACTH = high

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15
Q

What measurements of cortisol would we approx. see after administration of synACTHen in an addison’s disease patient

A

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

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16
Q

What synthetic drug is used for Addison’s disease that mimics aldosterone?

A

Fludrocortisone (50-100 mcg daily)
Used to control amount of sodium and fluids in body
Half life of aldosterone is too short for safe daily administration se we use Fludrocortisone.
It has a half life of 3.5h so slows metabolism. (effects seen for 18h)
It binds to both MR and GR

17
Q

Why can oral hydrocortisone not be administered for addison’s disease?

A

has a short half life: too short for once daily administration
Instead we use 1-2 dehydro-hydrocortisone or prednisolone. This has a longer half life and is more potent than cortisol (2.4x binding affinity than cortisol)

18
Q

What is the recommended dose for prednisolone?

A

Replacement dose 3-4mg ONCE daily

19
Q

What doses of prednisolone are available?

A

1mg, 2.5mg, 5mg
NOT enteric coated which
slows absorption
In some parts of the world they only give 5mg tablets which is too much so might need to break the pill

20
Q

What drugs should be given to a patient with addison’s disease?

A

Hydrocortisone three times daily (10 (morning) + 5 (lunch) + 2.5 (dinner)) OR
Prednisolone 3mg daily
AND
Fludrocortisone 50 to 100 mcg daily

21
Q

How does hydrocortisone compare to prednisolone?

A

2-4mg of prednisolone is equivalent to approx. 15-25mg hydrocortisone

22
Q

What causes congenital Adrenal Hyperplasia?

A

Commonest cause is by 21-hydroxylase deficiency (missing gene)
Can be complete (complete loss of gene) or partial (mutation)

23
Q

What hormones are affected in Congenital Adrenal Hyperplasia

A

Cortisol and aldosterone

24
Q

How long can you live with untreated Congenital Adrenal Hyperplasia?

A

Less than 24 hours

25
Q

At what age does complete Congenital Adrenal Hyperplasia cause symptoms?

A

At birth:
Before birth foetus gets steroid across placenta

After birth, baby has a salt losing addisonian crisis, BP falls and they become floppy and drowsy

To treta: saline given in hospital (replenish salts)

26
Q

What hormones are in excess in complete Congenital Adrenal Hyperplasia and what are symptoms of this?

A

Sex steroids and testosterone
In a female this can cause ambiguous genitalia- viralised (development of male physical characteristics) by adrenal testosterone

27
Q

What hormones are deficient in partial 21-hydroxylase deficiency?

A

Cortisol and aldosterone

28
Q

What hormones are in excess in partial 21-hydroxylase deficiency?

A

Sex steroids and testosterone

29
Q

At what age does partial 21-hydroxylase deficiency occur?

A

Any age as they survive birth

30
Q

What are symptoms of partial 21-hydroxylase deficiency?

A

Main problem in later life is hirsutism (heavy growth of bodily hair) and virilisation in girls and precocious (early) puberty in boys due to adrenal testosterone

31
Q

What happens if there is an 11- hydroxylase deficiency?

A

You get an excess buildup of 11-deoxycorticosterone which behaves like aldosterone
In excess it can cause hypertension and hypokalemia
You also get virilisation (due to excess testosterone)

32
Q

In 11- hydroxylase deficiency what hormones are in excess and which are deficient?

A

Deficient: Cortisol and aldosterone
Excess: Sex steroids and testosterone and 11-deoxycorticosterone

33
Q

In 17 hydroxylase deficient what hormones are deficient and which are in excess?

A

Deficient: cortisol and sex steroids
Excess: 11-deoxycorticosterone and aldosterone (mineralocorticoids)

34
Q

What are symptoms of 17 hydroxylase deficiency?

A

Hypertension, low K, sex steroid deficiency and glucocorticoid deficiency (low glucose).

BRS Year 2 (110 decks)

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