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eLCRS - 엔도 > Endo 6: Hyperadrenal Disorders > Flashcards

Endo 6: Hyperadrenal Disorders Flashcards

1
Q

List Clinical features of Cushing’s Disease

A
  • excessive cortisol production
  • centripetal obesity
  • moon face
  • buffalo hump
  • proximal myopathy
  • hypertension
  • hypokalemia
  • red stir, thin skin, bruising
  • osteoporosis
  • diabetes
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2
Q

What are some causes of Cushing’s?

A
  • taking too much steroid
  • pituitary dependent cushing’s
  • ectopic ACTH (from lung cancer)
  • adrenal adenoma (secretes cortisol)
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3
Q

What are 3 methods of investigation for cause of Cushing’s syndrome

A
  • 24 hr urine collection for urinary free cortisol
    (high = cushing’s syndrome)
  • blood diurnal cortisol levels
  • low dose dexamethasone suppression test
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4
Q

What is the normal diurnal rhythm of cortisol?

A

highest level at 9am, lowest level at midnight

high all the time = cushing’s syndrome

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5
Q

Describe the low dose dexamethasone suppression test.

A
  • dexamethasone = artificial steroid

0.5mg 6 hourly
for 48 hrs

if normal –> cortisol = suppressed to ZERO

ANY cause of cushing’s –> can’t suppress

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6
Q

What are the values for diagnosis Cushing’s?

A

Basal (9am) cortisol = 800 nM

End of LDDST = 680 nM

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7
Q

What are some methods of treating Cushing’s ?

A
  • pituitary surgery
  • bilateral adrenalectomy
  • unilateral adrenalectomy for adrenal mass
  • metyrapone
  • ketoconazole
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8
Q

What is Conn’s syndrome?

A
  • Benign adrenal cortical tumor (zona glomerulosa)
  • aldosterone produced in excess
  • results in hypertension + hypokalemia
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9
Q

How would you diagnose Conn’s Syndrome?

A
  • primary hyperaldosteronism
  • Renin-angiotensin system = suppressed
  • -> measure aldosterone
  • -> if high, measure renin (which would be suppressed by high BP)

+ low K+ = diagnosis

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10
Q

How would you treat Conn’s syndrome?

A
  • remove tumor (surgery)
  • to stop effect of excess aldosterone –> SPIRONOLACTONE (mineralocorticoid receptor antagonists)
    note: if bilateral adrenal hyperplasia –> stay on spironolactone
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11
Q

What is a Phaeochromocytomas?

A
  • tumour of the adrenal medulla
  • which secretes catecholamines
    (NA + A)
  • -> causes massive increase in BP (300/150)
  • -> may cause sudden stoke / MI / ventricular fibrillation (due to high adrenaline)
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12
Q

What are symptoms of Phaeochromocytomas

A
  • sudden onset of panic
  • anxiousness
  • tachycardia
  • severe hypertension

note: episodic severe hypertension in young people –> could be Phaeochromocytomas

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13
Q

How would you manage phaeo?

A
  • 1st therapeutic step = ALPHA blockade
  • -> block receptor to which adrenaline binds
  • (sudden drop in BP ) so give IV fluid
  • then give BETA blockade
  • -> to prevent tachycardia
  • would eventually need surgery

note; but need to be careful –> anesthetic might precipitate hypertensive crisis

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14
Q

note:

  • 10% extra-adrenal
  • 90% inside the adrenal
  • 10% are malignant
  • 10% bilateral
  • 90% are curable by operation

Phaeochromocytoma is EXTREMELY RARE

A

-

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15
Q

What drugs are used to treat Cushing’s syndrome?

give 2 examples

A
  • inhibitors of steroid biosynthesis

e. g methyrapone, ketoconazole

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16
Q

What drugs are used to treat Conn’s syndrome?

A
  • MR Antagonist

e. g Spironolactone, epleronone

17
Q

Describe the mechanism of action of Metyrapone

A

Metyrapone:
- used as treatment for cushing’s

  • it inhibits 11B-hydroxylase
  • slows down cortisol synthesis pathway
  • steroid synthesis in zona fasciculata = arrested at 11-deoxycortisol stage
  • -> reduces cortisol + corticosterone
  • as if you stop making cortisol, level of ACTH rises
  • there is no -ve feedback exerted by 11-deoxycortisol
  • so this accumulates

note: ACTH level also increases

18
Q

Give 2 uses of Metyrapone

A

used to:

  1. control cushing’s syndrome prior to surgery
    - -> improves symptoms + better post-op recovery
    - -> excess cortisol –> increase susceptibility to infection as well
  2. control cushing’s symptoms after radio therapy
19
Q

What are some unwanted actions of metyrapone?

A
  • nausea, vomiting
  • hypertension on long term administration
  • -> because it increases plasma deoxycortisol (which acts similarly to aldosterone)
  • hirsutism
20
Q

Describe the mechanism of action of Ketoconazole

A

Ketoconazole:

  • main use = anti-fungal agent (but has risk of hepatotoxicity)
  • at higher conc –> inhibits cortisol production
  • ketoconazole inhibits cytochrome P450 SCC enzymes
  • so you block production of gluco/mineralocorticoids + sex steroid

note:
SCC = side chain cleavage

21
Q

What are uses of ketoconazole?

A
  • uses = similar to metyrapone:

- treatment for cushing’s –> control of symptoms prior to surgery

22
Q

What are some unwanted actions of ketoconazole?

A
  • nausea, vomiting, abdominal pain
  • alopecia
  • liver damage
23
Q

What is spironolactone used as a treatment for?

A
  • Primary aldosteronism

aka Conn’s syndrome

24
Q

Describe the mechanism of action of spironolactone

A
  • spironolactone = converted to several active metabolites
    e. g canrenone
  • -> a competitive antagonist of the mineralocorticoid receptor (MR) –> stops the effects of aldosterone
  • SO it blocks Na+ resorption + K excretion in the Kidney tubules
  • -> so basically you reverse hypertension.
25
Q

other than as a treatment for conn’s syndrome, what other uses does spironolactone have ?

A
  • potassium sparing diuretic

- -> blocks Na+ reabsorption + K+ excretion in kidney tubules

26
Q

Why are people with bilateral adrenal hyperplasia placed on long term spironolactone?

A
  • because you don’t want to take out both adrenal

- or else you don’t have production of cortisol or aldosterone

27
Q

Describe the pharmacokinetics of spironolactone

A
  • orally active
  • highly protein bound
  • metabolized in liver
28
Q

What are some unwanted actions of Spironolactone?

A
  • progesterone receptor agonist –> so menstrual irregularities
  • androgen receptor antagonist –> so gynecomastia
  • GI tract irritation
29
Q

What is eplerenone and its effect?

A

Eplerenone

  • also MR antagonist
  • fewer side effect than spironolactone
  • -> less binding to androgen + progesterone receptors compared to spironolactone
30
Q

note: cortisol turns off protein synthesis .

A
  • enzyme inhibitors

- receptor blocking drugs

eLCRS - 엔도 (20 decks)

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