Hyperadrenal Disorders

Question 1

What disease is associated too much cortisol

Answer 1

Cushings

Question 2

What is Cushings cause by

Answer 2

Too much cortisol

Question 3

Clinical features of Cushings disease? (7)

Answer 3

• Too much cortisol
• Centripetal obesity
• Moon face/buffalo hump
• Proximal myopathy
• Hypertension and hypokalaemia
• Red striae, thin skin and bruising
• Osteoporosis, diabetes (DMII)

Question 4

Causes of Cushings? (3)

Answer 4

• Taking too many steroids
• Pituitary dependent Cushing’s disease
• Ectopic ACTH from lung cancer
• Adrenal adenoma secreting cortisol

Question 5

Tests for Cushings? (3)

Answer 5

• 24h urine collection for urinary free cortisol High level suggests Cushing’s syndrome
• Blood diurnal cortisol levels Should be lowest at midnight (high at 9am)
• Low dose dexamethasone suppression test Artificial analogue of cortisol Stops normal people making ACTH Normal people suppress their cortisol to zero, Cushings fails to do so

Question 6

When are Blood diurnal cortisol levels tested and why

Answer 6

Mignight, cortisol should be lowest here

Question 7

3 treatments for Cushings? (2 pharmacological methods)

Answer 7

1. Enzyme inhibitors
2. Receptor blocking drugs
   * Surgery is also an option

Question 8

2 Inhibitors of steroid synthesis?

Answer 8

• Metyrapone

- Ketoconazole

Question 9

• Metyrapone is an example of

Answer 9

Inhibitor of steroid synthesis

Question 10

• Ketoconazole is an example of

Answer 10

Inhibitor of steroid synthesis

Question 11

MoA of metyrapone?

Answer 11

• Inhibits 11beta-hyroxylase
• Steroid synthesis in the zona fasciculata (and reticularis) arrested at the 11-deoxycoritsol stage
• 11-deoxycortisol has no negative feedback effect on the hypothalamus or pituitary

Question 12

metyrapone inhibits what enzyme

Answer 12

11beta-hyroxylase

Question 13

Where in the adrenals is cortisol synthesised

Answer 13

zona fasciculata

Question 14

Uses of steroid synthesis inhibitors in Cushings? (3)

Answer 14

• Control of Cushing’s prior to surgery:
• Adjust dose (oral) according to cortisol (aim for mean serum cortisol 150-300 nmol/L)
• Improves patient symptoms and promotes best post-op recovery
• Control of Cushing’s symptoms while waiting for radiotherapy to work

Question 15

effects of 11-deoxycorticosterone when cortisol synthesis is halted at that stage?

Answer 15

: 11-deoxycorticosterone accumulates in the z. glomerulosa; it has aldosterone-like (mineralocorticoid) activity, leading to salt retention and hypertension

Question 16

What hormone effects does 11-deoxycorticosteron have similar effects to

Answer 16

Aldosterone

Question 17

What is ketoconazole used for

Answer 17

Cushings

Question 18

Side effects of ketoconazole?

Answer 18

• Liver damage Possibly fatal Monitor liver function weekly, clinically and biochemically

Question 19

What is the cause of Conns syndrome

Answer 19

Benign adrenal cortical tumour (Zona glomerulosa) Primary hyperaldosteronism

Question 20

Which zone of the adrenals produce aldosterone

Answer 20

Zona glomerulosa

Question 21

Zona glomerulosa produces…

Answer 21

Aldosterone

Question 22

Zona fasciculata produces….

Answer 22

Cortisol

Question 23

Symptoms of high aldosterone

Answer 23

• Hypertension and hypokalaemia

Question 24

How to diagnose primary vs secondary Hyperaldosteronism

Answer 24

• Renin-angiotensin system should be suppressed (this rules out secondary hyperaldosteronism) Zero/very low renin

Question 25

renin levels in primary Hyperaldosteronism?

Answer 25

Low

Question 26

renin levels in secondary Hyperaldosteronism?

Answer 26

high

Question 27

Treatment for primary Hyperaldosteronism?

Answer 27

Mineralocorticoid receptor antagonist] | - Surgery

Question 28

Mineralocorticoid receptor antagonist example?

Answer 28

SPIRONOLACTONE/EPLERONONE

Question 29

MoA of spironolactone?

Answer 29

- Converted to several active metabolites, including CANRENONE, a competitive antagonist of the MR - Blocks Na+ resportion and K+ excretion in the kidney tubules (potassium sparing diuretic)

Question 30

Effects of mineralocorticoid receptor antagonists?

Answer 30

- Blocks Na+ resportion and K+ excretion in the kidney tubules (potassium sparing diuretic)

Question 31

RoA of mineralocorticoid receptor antagonists

Answer 31

Oral

Question 32

Side effects of of mineralocorticoid receptor antagonists

Answer 32

- Menstrual irregularities (also an agonist of the progesterone receptor) - Gynaecomastia (antagonist of the androgen receptor) Painful

Question 33

Drug of choice for hyper-aldosteronism? why?

Answer 33

Epleronone ->- Less binding to androgen and progesterone receptors

Question 34

MoA of epleronone

Answer 34

- Converted to several active metabolites, including CANRENONE, a competitive antagonist of the MR - Blocks Na+ resportion and K+ excretion in the kidney tubules (potassium sparing diuretic)

Question 35

what is PHAEOCHROMOCYTOMAS:

Answer 35

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

Question 36

Risk of PHAEOCHROMOCYTOMAS

Answer 36

That the Tumour suddenly degranulates and produces loads of adrenaline which increases HR, anxiety and possible strokes/MRIs

Question 37

Clinical features of phaeochromocytomas (5)

Answer 37

- Hypertension in young people - Episodic severe hypertension (this can also be precipitated by abdominal palpation by the doctor) - More common in certain inherited conditions - Severe hypertension can cause MI or stroke - High adrenaline can cause ventricular fibrillation and death Medical emergency

Question 38

Management of phaeochromocytomas?

Answer 38

- Eventually need surgery, BUT patient needs preparation as anaesthetic can precipitate a hypertensive crisis - ALPHA BLOCKADE= first therapeutic step - Patients may need intravenous fluid as alpha blockade commences - Beta blockade added to prevent tachycardia

Question 39

First step in Management of phaeochromocytomas?

Answer 39

Alpha blockade

Question 40

What can happen if you give anaesthetic preop to a phaeocytochroma patient if they haven't been given alpha blockers

Answer 40

Release of adrenaline, boom, hypertensive crisis bitches