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endo > 1B adrenal disorders > Flashcards

1B adrenal disorders Flashcards

1
Q

What is Addison’s disease?

A
  • Primary adrenal failure- an autoimmune disease where the immune system decides to destroy the adrenal cortex
    (UK)
  • Autoimmune skin condition vitiligo may coexist
  • No cortisol or aldosterone so low bp
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2
Q

What does the pituitary do to deal with primary adrenal failure and what consequence therefore follows?

A

Starts secreting a lot more ACTH and hence MSH therefore causing increased pigmentation

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3
Q

What is the commonest cause of Addison’s worldwide?

A

Tuberculosis

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4
Q

What are the tests for Addison’s disease?

A
  • Morning 9am cortisol and ACTH. If cortisol is low and ACTH is high then we know its Addison’s
  • Short synACTHen test where you do cortisol blood test and then give 250μg synacthen IM and measure cortisol response- if little response then we know its Addison’s
  • Clinical suspicion: Hyponatraemia + hyperkalaemia and fatigue
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5
Q

Why do patients with Addison’s disease 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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6
Q

What are the consequences of adrenocortical failure?

A
  • Fall in bp (postural hypotension)
  • Loss of salt in urine (low sodium in plasma = hyponatraemia)
  • Increased plasma potassium (less potassium excreted in urine = hyperkalaemia)
  • Fall in glucose due to glucocorticoid deficiency
  • High ACTH resulting in increased pigmentation
  • Eventual death due to severe hypotension
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7
Q

What is the aldosterone treatment for Addison’s?

A

Aldosterone replacement

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8
Q

What is the issue with the standard treatment for Addison’s?

A

Half life of aldosterone is too short for safe once daily administration

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9
Q

How is the issue with Aldosterone’s half life fixed?

A
  • Solve this by sticking a fluorine on aldosterone to make fludrocortisone (F doesn’t exist in natural steroids so its presence slows down its metabolism a lot so it stays active for longer)
  • Fludrocortisone binds to both MR (mineralocorticoid) and GR (glucocorticoid) receptors
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10
Q

How much fludrocortisone is administered?

A

Usually give 50-100μg daily

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11
Q

What is the issue with hydrocortisone and how do we fix it?

A
  • Oral hydrocortisone has a short half life- too short for once daily administration
  • We give it 2 or 3 times daily because of this
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12
Q

What further problems of hydrocortisone are there?

A
  • Late peaks are harmful
  • We need a longer lasting version that we can take once and smoothly and slowly decreases across the day
  • If we add a double bond to hydrocortisol we get 1-2 dehydrohydrocortisone aka prednisolone
  • This has a longer half life and is more potent than cortisol with 2.3x the binding affinity of cortisol
  • Prednisolone is taken 2-4mg once daily (which is equivalent to 15-25mg of hydrocortisone per day)
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13
Q

What doses of prednisolone are available?

A
  • 1mg, 2.5mg, 5mg
  • Not enteric coated which slows absorption but avoids side effects

Treatment for Addison’s

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14
Q

What is the treatment of adrenal failure then altogether?

A
  • Fludrocortisone 50-100μg daily
  • Either hydrocortisone 3 times daily (10mg morning, 5mg afternoon, 2.5mg evening) or prednisolone 3mg daily
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15
Q

What is Congenital Adrenal Hyperplasia the third cause of and what are the other 2 causes?

A
  • 3rd cause of primary adrenal failure
  • Other 2 are TB Addison’s disease (commonest worldwide) and autoimmune Addison’s disease (commonest in UK)
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16
Q

What is the commonest cause of CAH?

A
  • 21-hydroxylase deficiency
  • Can be complete or partial deficiency
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17
Q

Which hormones will be totally absent in complete 21 hydroxylase deficiency/ classical CAH?

A

Aldosterone and cortisol

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18
Q

How long can a patient survive with classical CAH?

A

Less than 24 hours. Babies present within 1-3 weeks with a salt-losing crisis

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19
Q

Which hormones will be in excess in classical CAH?

A

Sex steroids and testosterone

Less of a problem if with male baby because there are lots of testosterone anyway.

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20
Q

What is the age of presentation for classical CAH?

A
  • As a neonate, with a salt losing Addisonian crisis
  • Before birth (in utero) the foetus gets steroids across the placenta
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21
Q

What is the difference between how girls and boys present in classical CAH?

A

Girls might have ambiguous genitalia (virilised by adrenal testosterone) but boys aren’t

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22
Q

What happens in partial 21 hydroxylase deficiency (aka non-classical CAH)?

A

There is still a bit of aldosterone and cortisol to get by with

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23
Q

Which hormones are deficient in partial 21 hydroxylase deficiency (aka non-classical CAH)?

A

Cortisol and aldosterone

24
Q

Which hormones are in excess in non-classical CAH?

A

Sex steroids and testosterone

25
Q

At what age will a patient present with non-classical CAH?

A

Any age as they survive

26
Q

What is the main problem for girls and boys in non-classical CAH?

A
  • Girls- hirsutism and virilisation
  • Boys- precocious puberty due to adrenal testosterone
27
Q

What happens if we have 11 hydroxylase deficiency?

A
  • There’s a build up of 11 deoxycorticosterone
  • This behaves like aldosterone and the excess of it means it can cause hypertension and hypokalaemia
28
Q

Which hormones are deficient in 11 hydroxylase deficiency?

A

Cortisol and aldosterone

29
Q

Which hormones are in excess in 11 hydroxylase deficiency?

A

Sex steroids, testosterone and 11-deoxycorticosterone

30
Q

What problems present with 11 hydroxylase deficiency?

A
  • Virilisation
  • Hypertension
  • Low K
31
Q

Which hormones are deficient in 17 hydroxylase deficiency?

A

Cortisol and sex steroids

32
Q

Which hormones are in excess in 17 hydroxylase deficiency?

A

11-deoxycorticosterone and aldosterone (mineralocorticoids)

33
Q

What problems does 17 hydroxylase deficiency cause?

A
  • Hypertension
  • Hypokalaemia
  • Sex steroid deficiency
  • Glucocorticoid deficiency (low glucose)
34
Q

What are the clinical features of Cushing’s syndrome?

A
  • Too much cortisol
  • Centripetal obesity (cortisol drives protein to be broken down and fat to be synthesised)
  • Moon face and buffalo hump
  • Proximal myopathy
  • Hypertension and hypokalaemia
  • Red striae, thin skin and bruising
  • Osteoporosis, diabetes
35
Q

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

A
  • Cushing’s syndrome is excess cortisol in body
  • Cushing’s disease is a type of Cushing’s syndrome where there’s a pituitary tumour causing excess cortisol
36
Q

How does the dexamethasone test work?

A
  • It’s a very potent artificial steroid
  • we give 0.5mg every 6 hours for 48 hours
  • Normal patients’ pituitary will respond via negative feedback (thinks its cortisol) and decrease cortisol production to 0
  • Any cause of Cushing’s will fail to suppress the cortisol production
37
Q

What is the diagnosis of Cushing’s?

A
  • Basal (9am) cortisol 800nM
  • End of LDDST: 680nM
38
Q

What is metyrapone and what action does it have?

A
  • Inhibition of 11beta-hydroxylase
  • Steroid synthesis in zona fasciculata (and reticularis) is therefore arrested at the 11-deoxycortisol stage
  • 11-deoxycortisol has no negative feedback effect on the hypothalamus and pituitary gland (pituitary keeps on making ACTH)
39
Q

How is metyrapone used and what for?

A
  • Adjust metyrapone 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)
  • Used to control Cushing’s symptoms prior to surgery and also after radiotherapy (which is usually slow to take effect)
40
Q

What does the accumulation of 11-deoxycorticosterone in the zona glomerulosa do?

A

Has aldosterone-like (mineralocorticoid) activity, leading to salt retention (hypokalaemia) and hypertension

41
Q

What does increased adrenal androgen production do?

A

Causes hirsutism in women

42
Q

What action does ketoconazole have?

A
  • Mainly blocks 17alpha hydroxylase, inhibiting cortisol production
  • Main use is as an antifungal agent- although withdrawn in 2013 due to risk of hepatotoxicity
  • At higher conc, inhibits steroidogenesis
43
Q

What is ketoconazole used for?

A
  • Treatment and control of symptoms prior to surgery
  • Orally active
44
Q

What is an unwanted side effect of ketoconazole?

A
  • Liver damage- possibly fatal
  • Monitor liver function weekly, clinically and biochemically
45
Q

What are the other treatments of Cushing’s

A

Depends on cause

  • Pituitary surgery (transsphenoidal hypophysectomy)
  • Bilateral adrenalectomy
  • Unilateral adrenalectomy for adrenal mass
46
Q

What is Conn’s syndrome?

A
  • Benign adrenal cortical tumour (zona glomerulosa)
  • Aldosterone in excess (aldosterone controls bp, Na and lowers K remember)
  • Hypertension and hypokalaemia
47
Q

How do we diagnose Conn’s syndrome?

A
  • It’s primary hyperaldosteronism
  • The renin-angiotensin system should be suppressed (exclude secondary hyperaldosteronism)
48
Q

What drugs are used to treat Conn’s syndrome?

A

Use an MR antagonist:

  • Spironolactone
  • Eplerenone
49
Q

What does spironolactone do?

A
  • Converted to several active metabolites in body, including canrenone, a competitive antagonist of the mineralocorticoid receptor (MR)
  • Blocks Na+ resorption and K+ excretion in the kidney tubules (potassium sparing diuretic)
50
Q

What are some unwanted side effects of spironolactone?

A
  • Menstrual irregularities (agonist for progesterone receptor)
  • Gynaecomastia (blocks androgen receptor)
51
Q

What does eplerenone do?

A
  • Also an MR antagonist
  • Similar affinity to the MR compared to spironolactone
  • Less binding to androgen and progesterone receptors compared to spironolactone, so better tolerated
52
Q

What is a phaeochromocytoma?

A

These are tumours of the adrenal medulla which secrete catecholamines (adrenaline and noradrenaline)

53
Q

What are clinical features of a phaeo?

A
  • Hypertension in young people- severe hypertension can cause myocardial infarction or stroke
  • Episodic severe hypertension (after abdominal palpitation)
  • High adrenaline can cause ventricular fibrillation & death- it’s a medical emergency
  • More common in certain inherited conditions
54
Q

What is the management of phaeo?

A
  • Eventually need surgery, but patient needs careful prep as anaesthetic can precipitate a hypertensive crisis
  • Alpha blockade is the first therapeutic step to block adrenaline effects for surgery
  • Patients may need intravenous fluid as alpha blockade commences (because blockade causes blood pressure crash so we need the fluid)
  • Beta blockade added to prevent tachycardia
55
Q

Key facts about phaeos

A
  • They’re extremely rare
  • 10% of them are extra-adrenal (sympathetic chain)
  • 10% are malignant
  • 10% are bilateral

endo (12 decks)

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