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Year 2 - LCRS - Endocrinology > Hyperadrenal disorders > Flashcards

Hyperadrenal disorders Flashcards

10.10.2019

1
Q

What are the clinical feature of Cushing’s?

A
  • Too much cortisol
  • Centripetal obesity
  • Moon face
  • buffalo hump
  • Proximal myopathy
  • Hypertension and hypokalaemia
  • Red striae
  • thin skin
  • bruising
  • osteoporosis
  • diabetes
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2
Q

What are the causes of Cushing’s?

A
  • Taking too many steroids
  • Pituitary dependent Cushing’s disease
  • Ectopic ACTH from lung cancer
  • adrenal adenoma secreting cortisol
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3
Q

Investigations to determine the cause of Cushing’s Syndiome

A
  • 24 h urine collection for urinary free cortisol
  • Blood diurnal cortisol levels
  • (cortisols usually highest at 9am and lowest at midnight, if asleep)
  • low dose dexamethasone suppression test
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4
Q

How does the low dose dexamethasone suppression test work?

A
  • 0.5 mg 6 hourly for 48 hrs
  • Dexamethasone = artificial steroid
  • Normals will suppress cortisol to zero
  • Any cause of Cushing’s will fail to suppress
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5
Q

What are pharmacological manipulations of steroids?

A
  • Enzyme inhibitors

- Receptor blocking drugs

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6
Q

What is the diurnal rhythm of cortisol in Cushing’s syndrome like?

A
  • constantly high

(usually it is highest in the morning, drops throughout the day and ‘‘recharges’’ at night.

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7
Q

Name 2 inhibitors of steroid synthesis

A
  • Metyrapone

- Ketonazole

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8
Q

What drugs can you treat Cushing’s with?

A

Inhibitors of steroid biosynthesis

  • metyrapone
  • ketonazole
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9
Q

What drugs can you treat Conn’s syndrome with?

A

MR antagonists

  • spironolactone
  • epleronone
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10
Q

Name 2 MR antagonists

A
  • spironolactone

- epleronone

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11
Q

Metyrapone - mechanism of action and effects

A
  • inhibits 11-beta-hydroxylase
  • cortisol synthesis blocked
  • ACTH secretion increased
  • plasma deoxycortisol increased
  • steroid synthesis in the zona fasciculata [and reticularis] is arrested at the 11-deoxycortisol stage
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12
Q

What are the zones if the adrenal gland and what is produced where?

A

Medulla - catecholamines (A, NA)
Zona reticularis - sex steroids
Zona fasciculata - glucocorticoids (cortisol)
Zona glomerulosa - mineralcorticoids (aldosterone)

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13
Q

Uses of metyrapone

A
  • Control of Cushing’s syndrome prior to surgery.
    • adjust dose (oral) 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)
  • Control of Cushing’s symptoms after radiotherapy (which is usually slow to take effect)
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14
Q

What are some side effects/unwanted actions of metyrapone?

A
  • Increased adrenal androgen production HIRSUTISM
    in women
  • Hypertension on long term admin. Deoxycorticosterone accumulates in z. glomerulosa; it has aldosterone-like (mineralocorticoid) activity, leading to salt retention and hypertension.
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15
Q

What is the mechanism of action of ketoconazole?

A
  • main use as an antifungal agent – although withdrawn in 2013 due to risk of hepatotoxicity
  • Blocks production of glucocorticoids, mineralocorticoids& sex steroids
  • at higher concentrations, inhibits steroidogenesis – off-label use in Cushing’s syndrome
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16
Q

When is ketoconazole used?

A

Cushing’s syndrome
- treatment and control of symptoms prior to surgery

  • orally active
17
Q

What are unwanted actions of ketoconazole?

A
  • Liver damage
    • possibly fatal
    • monitor liver function weekly, clinically and
      biochemically
18
Q

How do you treat Cushing’s?

A
  • Depends on cause
  • Pituitary surgery (transsphenoidal hypophysectomy)
  • Bilateral adrenalectomy
  • Unilateral adrenalectomy for adrenal mass
19
Q

Drugs for medical treatment of Cushing’s

A
  • Metyrapone

- Ketoconazole

20
Q

What are the features of Conn’s syndrome?

A
  • Benign adrenal cortical tumour (zona glomerulosa)
  • Aldosterone in excess
  • Hypertension and hypokalaemia
21
Q

Drugs for medical treatment of Conn’s Syndrome

A
  • spironolactone
  • epleronone

OR surgery

22
Q

Uses of spironolactone

A
  • primary hyperaldosteronism (Conn’s syndrome)
23
Q

Spironolactone: Mechanism of action

A
  • Converted to several active metabolites, including canrenone, a competitive antagonist of the mineralocorticoid receptor (MR).
  • Blocks Na+ resorption and K+ excretion in the kidney tubules (potassium sparing diuretic).
24
Q

Diagnosis of Conn’s syndrome

A

Measure in Blood:

  • if aldoserone is high and
  • RAS is suppressed (exclude secondary hyperaldosteronism)

=> the person has Conn’s syndrome

25
Q

What are some unwanted actions of spironolactone?

A
  • Menstrual irregularities (+ progesterone receptor)

- Gynaecomastia (- androgen receptor)

26
Q

Properties of epleronone

A
  • mineralocorticoid receptor (MR) antagonist
  • Similar affinity to the MR compared to spironolactone
  • Less binding to androgen and progesterone receptors compared to spironolactone, so better tolerated
27
Q

What are phaeochromocytomas?

A
  • tumors of the adrenal medulla

- secrete catecholamines (A and NA)

28
Q

What are features of phaeochromocytoma?

A
  • Hypertension in young people
  • Episodic severe hypertension (after abdominal palpation)
  • More common in certain inherited conditions
  • Severe hypertension can cause MI or stroke
  • High adrenaline can cause ventricular fibrillation + death

= medical emergency

29
Q

What are some dangerous things that can happen in pheochromocytoma?

A
  • Severe hypertension: can cause MI or stroke
  • High adrenaline: can cause V-fib + death

=> medical emergency

30
Q

Management of Phaeochromocytoma

A
  • first therapeutic step: alpha blockade
  • patients may need i.v. fluid as alpha blockade commences
  • beta-blockade added to prevent tachycardia

=> then they will need surgery

31
Q

Key facts about phaeochromocytoma

A
  • 10 % extra-adrenal (sympathetic chain)
  • 10 % malignant
  • 10 % bilateral
  • more than 10% is genetic
  • Phaeo’s are extremely rare
    (House loves rare…)
32
Q

Why do you block alpha receptors first in phaeochromocytoma?

A
  • BP goes down

this is why you should also give i.v. fluid before

33
Q

What is known to be the 10% tumor disease?

A
  • Phaeochromocytoma

10% malignant, 10% extra-aderenal, 10% bilateral

Year 2 - LCRS - Endocrinology (18 decks)

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