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Year 2 - BRS > 3.11 - Adrenal disorders 2/2 > Flashcards

3.11 - Adrenal disorders 2/2 Flashcards

1
Q

What kind of rhythm does cortisol have?

A

Diurnal - increase starts from 5am, peaks around 8:30-9am, then decreases again (usually lowest around midnight if asleep)

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2
Q

What is the difference between Cushing’s syndrome and Cushing’s disease?

A
  • Cushing’s syndrome - excess cortisol in body
  • Cushing’s disease - type of Cushing’s syndrome where there is a pituitary corticotroph tumour causing excess cortisol
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3
Q

What are the clinical features of Cushing’s syndrome?

A
  • too much cortisol
  • centripetal obesity
  • moon face and buffalo hump
  • proximal myopathy
  • hypertension and hypokalaemia (11BHSD inhibited)
  • red striae, thin skin, bruising
  • osteoporosis, diabetes
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4
Q

How does 11-beta-hydroxysteroid dehydrogenase (11BHSD) protect the mineralocorticoid receptors from cortisol?

A
  • cortisol can bind to either its own receptor (glucocorticoid receptors - GR), or the aldosterone receptors (MR)
  • 11BHSD quickly deactivates cortisol into cortisone, protecting the MR and preventing cortisol from having mineralocorticoid effects
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5
Q

What happens to 11-beta-hydroxysteroid dehydrogenase in Cushing’s syndrome and how does this explain the hypertension/hypokalaemia observed?

A
  • excess cortisol means that 11BHSD is overwhelmed and not able to deactivate all the cortisol once secreted
  • cortisol has aldosterone-like effects in high concentrations
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6
Q

What are the causes of Cushing’s syndrome?

A
  • taking too many steroids (glucocorticoids)
  • pituitary dependent Cushing’s disease
  • ectopic ACTH from lung cancer
  • adrenal adenoma secreting cortisol
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7
Q

What investigations can be done to determine Cushing’s syndrome?

A
  • 24h urine collection for urinary free cortisol
  • blood diurnal cortisol levels (usually highest at 9am and lowest at 12am)
  • low dose dexamethasone suppression test
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8
Q

How does the low dose dexamethasone suppression test work?

A
  • dexamethasone = very potent artificial glucocorticoid (steroid)
  • give 0.5mg every 6h for 48h
  • healthy people will suppress cortisol to zero - pituitary will respond via -ve feedback thinking it is cortisol
  • any cause of Cushing’s will fail to suppress cortisol
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9
Q

What types of drugs can be used to deal with high cortisol?

A
  • enzyme inhibitors
  • receptor blocking drugs
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10
Q

What specific drugs are used to treat Cushing’s syndrome? (3)

A

Inhibitors of steroid (cortisol) biosynthesis:

  • metyrapone
  • ketoconazole
  • osilidrostat
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11
Q

What is the mechanism of action of metyrapone?

A
  • inhibition of 11B-hydroxylase
  • steroid synthesis in zona fasciculata (and reticularis) is arrested at 11-deoxycortisol stage
  • 11-deoxycortisol has no negative feedback on hypothalamus/pituitary
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12
Q

What are the uses of metyrapone?

A
  • control of Cushing’s prior to surgery and/or after radiotherapy (which is slow to take effect)
  • adjust oral dose according to cortisol (aim for mean serum cortisol 150-300 nmol/L)
  • improves patient’s symptoms and promotes better post-op recovery (better wound healing, less infection etc)
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13
Q

What are some unwanted actions of metyrapone?

A
  • inhibition of 11-hydroxylase causes accumulation of 11-deoxycorticosterone in zona glomerulosa –> aldosterone-like effects –> hypertension and salt retention on long-term administration
  • increased adrenal androgen production –> hirsutism (women)
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14
Q

What is the mechanism of action of ketoconazole?

A
  • main use as an antifungal agent - withdrawn in 2013 due to risk of hepatotoxicity
  • at higher concentrations, inhibits steroidogenesis = off-label use in Cushing’s syndrome
  • mainly blocks 17-alpha hydroxylase, inhibiting cortisol production
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15
Q

What is ketoconazole used for?

A
  • treatment and control of symptoms prior to surgery
  • orally active
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16
Q

What is an unwanted side effect of ketoconazole?

A

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

17
Q

What is the mechanism of action for osilidrostat?

A
  • similar to ketoconazole and blocks several enzymes in the steroid synthetic pathway
  • mainly blocks 11b and 17a hydroxylase, inhibiting cortisol production
  • newer agent - using in UK on named patient basis
18
Q

What are other treatments of Cushing’s syndrome (other than drugs suppressing cortisol synthesis)? (3)

A
  • pituitary surgery (trans-sphenoidal hypophysectomy)
  • bilateral adrenalectomy
  • unilateral adrenalectomy for adrenal mass
19
Q

What is Conn’s syndrome?

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

Might also see metabolic alkalosis due to excess H+ secretion

20
Q

What is a summary of the actions of aldosterone?

A
  • increases renal sodium reabsorption
  • increases renal potassium excretion
  • increases blood pressure (sodium and water retention)

Also increases H+ secretion (so excess –> metabolic alkalosis)

21
Q

How is Conn’s syndrome diagnosed?

A
  • primary hyperaldosteronism
  • renin-angiotensin system should be suppressed (exclude secondary hyperaldosteronism - normal physiological response)
22
Q

How do we treat Conn’s syndrome?

A

Mineralocorticoid antagonists - spironolactone, eplerenone

23
Q

What does spironolactone do?

A
  • competitive antagonist of the MR
  • blocks Na+ reabsorption and K+ excretion in the kidney tubules (potassium sparing diuretic)
24
Q

What is an unwanted side effect of spironolactone?

A

Gynaecomastia (blocks androgen receptor - anti-androgen drug means reduced testosterone)

25
Q

What does eplerenone do?

A
  • also a MR antagonist
  • similar affinity to the MR compared to spironolactone
  • less binding to androgen receptors compared to spironolactone, so better tolerated (less gynaecomastia)
26
Q

What are phaeochromocytomas?

A

Tumours of the adrenal medulla which secrete catecholamines (adrenaline and noradrenaline)

27
Q

What are the clinical features of a phaeochromocytoma?

A
  • hypertension in young people
  • episodic severe hypertension (after abdominal palpitation)
  • severe hypertension can cause MI/stroke
  • high adrenaline can cause ventricular fibrillation and death = medical emergency
  • more common in certain inherited conditions
28
Q

What is the management of a phaeochromocytoma?

A
  • eventually need surgery, but patient needs careful preparation as anaesthetic can precipitate a hypertensive crisis
  • alpha blockade is first therapeutic step to block adrenaline effects for surgery (alpha receptors on arteries cause vasoconstriction)
  • patients may need IV fluid as alpha blockade commences (blockage causes BP crash)
  • beta blockade added to prevent tachycardia
29
Q

Summary of three excess hormone pathologies.

A
  • excess cortisol = Cushing’s syndrome
  • excess aldosterone = Conn’s syndrome
  • excess adrenaline = phaeochromocytoma

Year 2 - BRS (84 decks)

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