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Y2 LCRS 1 - Endocrinology > Therapeutic Use of Adrenal Steroids > Flashcards

Therapeutic Use of Adrenal Steroids Flashcards

1
Q

Name the three parts of the adrenal cortex and the steroids that each produces.

A

Zona Glomerulosa → aldosterone

Zona Fasciculata → cortisol

Zona Reticularis → sex steroids (androgens)

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2
Q

What stimulates the release of ACTH?

A

Factors stimulate CRH release from hypothalamus:

  • Circadian stimuli (with light levels being the main stimulus)
  • Stress

CRH release → ACTH release from anterior pituitary

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3
Q

Decribe the negative feedback effect of cortisol.

A

Negative feedback on anterior pituitary → reduced ACTH

Negative feedback on hypothalamus → reduced CRH → reduced ACTH

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4
Q

Which adrenal cortical hormones do ACTH stimulate the release of?

A

Cortisol - main

Adrenal sex steroids (androgens)

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5
Q

What controls the production of aldosterone?

A

Angiotensin II

  • Aldosterone release occurs via the renin-angiotensin-aldosterone system (RAAS)
    • Angiotensinogen (liver) → angiotensin I by renin (kidneys)
    • Angiotensin I → angiotensin II by ACE (lungs)
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6
Q

State four triggers of aldosterone release

A
  • Hyperkalaemia
  • Hyponatraemia (leads to decreased BP)
  • Drop in renal blood flow (i.e. decreased renal perfusion pressure = BP in afferent arteriole)
  • β1-adrenoceptor stimulation (i.e. sympathetic stimulation)

These factors trigger renin secretion and hence stimulate aldosterone secretion via the RAAS

The point of aldosterone is to maintain BP

NOTE: Generally hyperkalaemia and hyponatraemia go hand in hand due to action of the Na+/K+ pump (ions travel in opposite directions)

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7
Q

What is the principal physiological action of aldosterone?

A

Increases Na+ reabsorption

  • in order to promote water reabsorption
  • therefore maintain BP

Increases K+ excretion

  • as a by-process
  • due to action of the Na+/K+ pump)
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8
Q

State the differences between glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs).

A
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9
Q

Describe how MRs are protected from cortisol stimulation.

A

Enzyme: 11β-hydroxysteroid dehydrogenase 2

  • Converts cortisol (active) to the cortisone (inactive)
  • Present in tissues which have MRs (i.e. want to respond to aldosterone - like the kidneys)
  • Therefore, it protects these tissues/MRs from the effects of cortisol
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10
Q

State 4 drugs and their receptor selectivity.

A

Hydrocortisone (synthetic cortisol)

  • Glucocorticoid - so can stimulate GR
  • Has mineralocorticoid activity at high doses - so can stimulate MR but only has an effect at high doses when the enzyme is saturated and therefore cannot inactivate cortisol

Prednisolone

  • Glucocorticoid - so can stimulate GR
  • Weak mineralocorticoid activity - i.e. you need more of the drug to stimulate MRs (compared to hydrocortisone)

Dexamethasone

  • Glucocorticoid - so can stimulate GR
  • No mineralocorticoid activity - cannot stimulate MR

Fludrocortisone

  • Aldosterone analogue - used as an aldosterone substitute
  • Can stimulate MR
  • Cannot stimulate GR
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11
Q

What does prednisolone tend to be used for?

A

Immunosuppression

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12
Q

What does dexamethasone tend to be used for?

A

Acute anti-oedema E.g. used clinically for things like brain metastases where there is a lot of oedema

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13
Q

Name an aldosterone analogue.

A

Fludrocortisone

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14
Q

How are these drugs (synthetic corticosteroids) administered?

A

Orally

NOTE: Hydrocortisone and dexamethasone can also be delivered via the parenteral route (IV or IM)

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15
Q

Describe the distribution of the glucocorticoid drugs in the systemic circulation.

A

The bind to plasma proteins - the same as circulating cortisol

  • Cortisol Binding Globulin (CBG
  • Albumin
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16
Q

What is the duration of action (half-life) of the glucocorticoid drugs?

A
  • Hydrocortisone – 8 hours
  • Prednisolone – 12 hours
  • Dexamethasone – 40 hours
17
Q

Where are the corticosteroid drugs metabolised and how are they excreted?

A

Hepatic metabolism Excreted in the bile and urine

18
Q

State 4 reasons for giving corticosteroid replacement therapy

A
  • Primary adrenocortical failure
  • Secondary adrenocortical failure
  • Acute adrenocortical failure
  • Congenital adrenal hyperplasia
19
Q

State two causes of primary adrenocortical failure.

A

Addison’s disease Chronic adrenal insufficiency

20
Q

What is the usual treatment for primary adrenocortical failure (Addison’s disease)?

A

Patients lack cortisol and aldosterone

  • Treat with hydrocortisone (synthetic cortisol) and fludrocortisone (synthetic aldosterone) by mouth
21
Q

What is the treatment for secondary adrenocortical failure?

A

The adrenal gland itself is fine but there is a problem with the pituitary gland → ACTH deficiency → patients lack cortisol

Therefore, there is normal aldosterone production (because aldosterone isn’t dependent on ACTH)

  • Treat with hydrocortisone (synthetic cortisol)
22
Q

What is the treatment for acute adrenocortical failure (Addisonian Crisis)?

A
  • IV 0.9% sodium chloride solution to rehydrate patient (
    • The patient would be hyponatraemic - excessive renal sodium excretion
    • Leads to increased water loss in the urine → dehydration
  • High dose hydrocortisone
    • IV infusion or IM every 6h
    • This has a mineralocorticoid effect at high dose (11βHSD overwhelmed/saturated)
  • 5% dextrose if hypoglycaemic
    • But the hyrdocortisone should increase bloo glucose concentration anyway

NOTE:

  • Acute adrenal crisis = life-threatening state caused by insufficient levels of cortisol
  • In Addison’s disease cortisol is low anyway, but you get a crisis when it is very below what it needs to be
23
Q

What is congenital adrenal hyperplasia (CAH)?

A

Congenital lack of enzymes needed for adrenal steroid synthesis

24
Q

What is the most common cause of congenital adrenal hyperplasia?

A

21-hydroxylase deficiency (approx. 95% of cases)

25
Q

What are the consequences of 21-hydroxylase deficiency?

A

17α-hydroxyprogesterone accumulates, as this is immediately before the enzyme ‘block’

  • This leads to an excess of adrenal sex steroid production
26
Q

Describe the ACTH levels in 21-hydroxylase deficiency and explain its consequences.

A

High ACTH

  • This is because no cortisol is being produced
  • So, there is no negative feedback on the hypothalamo-pituitary axis

Consequences

  • ACTH stimulates both cortisol sex steroid synthesis pathway
  • Because the cortisol synthesis pathway is blocked, the sex steroid synthesis pathway is stimulated in excess by high levels of ACTH
  • This leads to increase in adrenal sex steroid (androgen) production → hirsutism, virilisation
27
Q

How do you treat CAH?

A
  • Replace cortisol
    • Hydrocortisone (2-3/day) - high dose in the pm
    • OR dexamethasone (1/day) - pm
    • Cortisol replacement will suppress the ACTH axis to reduce adrenal sex steroid production
      • NOTE: Not highest dose in morning like normal cortisol release - probably to do with trying to suppress adrenal sex steroid production
  • Replace aldosterone with fludrocortisone
28
Q

How do you monitor 21 hydroxylase deficiency?

A

Measure 17α-hydroxyprogesterone

  • Should be lower with treatment as there is ACTH is being supressed
  • Therefore, adrenal sex steroid production should decrease
  • So levels of the precursor of the androgens (17α-hydroxyprogesterone) should decrease

Clinical assessment:

  • Cushingoid (i.e. symptoms of excess cortisol) – mean glucocorticoid dose too high
  • Hirsutism – means glucocorticoid dose too low (and hence ACTH has risen)
29
Q

When would you change the dose of glucocorticoid?

A

If they are under any particular stress such as illness

30
Q

What is iatrogenic adrenocortical failure?

A

Long-term, high dose glucocorticoid therapy can suppress the HPA axis and hence suppress adrenal function so that they no longer produce cortisol by themselves They need to keep a steroid dependence bracelet

Y2 LCRS 1 - Endocrinology (20 decks)

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