Endo - Adrenal Disorders 2

Question 1

Describe the rhythm of cortisol?

Answer 1

Diurnal rhythm

Question 2

What is a the concentration of cortisol at its peak

Answer 2

428nM

Question 3

What is the concentration of cortisol at its lowest

Answer 3

55nM

Question 4

When should we check if cortisol is too low

Answer 4

We should check it in the morning when it is meant to be highest ie 9am

Question 5

What may affect cortisol rhythm

Answer 5

Nightshift workers or people with altered body clock will have e different times as to when cortisol peaks

Question 6

What are the symptoms of Cushing’s?

Answer 6

Centripetal obesity
Moon face
Purple striae
Proximal myopathy 
Buffalo dumb between shoulders
Hypertension
Hypokalaemia 
Thin skin
Bruising 
Diabetes
Osteoporosis Pitting oedema

Question 7

What are the causes of Cushings

Answer 7

Steroid use
Pituitary dependent Cushing’s disease
Ectopic ACTH from lung cancer
Adrenal adenoma

Question 8

What are the steps to investigating Cushings

Answer 8

Establish a source for potential Cushings
24 hour urine collection for urinary free cortisol
Blood diurnal cortisol levels - measured at different times over the day/night

Question 9

Outline a LDDST

Answer 9

Low dose dexamethasone suppression test - this is a glucocorticoid with fluoride therefore we give 0.5mg every 6 hours for 48 hours to see if cortisol production is suppressed due to negative feedback (ACTH should go down) - If cortisol doesn’t go to 0 then there is Cushings

Question 10

What do we need to know before we start treating Cushings

Answer 10

We need to know where the source of Cushings is

Question 11

What must be done before an operation for Cushings

Answer 11

We must reduce cortisol via pharmacological manipulation of steroids

Question 12

What are examples of enzyme inhibitors?

Answer 12

Metyrapone

Ketoconcazole

Question 13

What are examples of receptor blockers

Answer 13

Spironolactone
Epleronone 
(Both block aldosterone receptors)

Question 14

How does metyrapone work?

Answer 14

Blocks 11-Beta-Hydroxylase therefore blocks the conversion of 11-deoxycortisol to cortisol. There is no negative feedback therefore this works well.

Question 15

How do we adjust dosage of metyrapone?

Answer 15

Aim for a serum cortisol of 150-300nmol/L

Question 16

When is metyrapone used?

Answer 16

Used after radiotherapy for Cushings

Question 17

What are the side effects of metyrapone?

Answer 17

We get increased adrenal androgen production therefore hirsutism in women.
We also get a build up of 11-dexoycorticosterone as it cannot be converted to aldosterone therefore we get hypertension (however, some 11-deoxycorticosterone is converted to aldosterone via aldosynthase)

Question 18

How does ketoconazole work?

Answer 18

Antifungal drug that blocks 17-alpha-hydroxyalse therefore inhibiting cortisol production

Question 19

What is a possible side effect of ketoconazole?

Answer 19

Risk of hepatotoxicity as it is an antifungal - at a higher concentration it inhibits steroidogenesis

Question 20

What surgery can be used for Cushings disease from the pituitary?

Answer 20

Transphenoidal hypophysectomy

Question 21

What Cushings surgery may we use if there is ectopic ACTH from lung cancer?

Answer 21

Bilateral adrenalectomy

Question 22

What surgery can be used for a one sided adrenal mass?

Answer 22

Unilateral adrenalectomy

Question 23

Is surgery preferred over drugs?

Answer 23

Yes

Question 24

What is Conn’s syndrome?

Answer 24

Benign tumour of the glomerulus therefore we get unregulated production of aldosterone

Question 25

What should we do if we ever find a high blood pressure?

Answer 25

Check if they have hypokalaemia - Conn's syndrome increases aldosterone which in turn increases blood pressure but excretes potassium

Question 26

Describe the RAAS in Conn's

Answer 26

Suppressed - aldosterone is high despite renin being low, this typically indicates Conn's

Question 27

How do we treat a Conn's adenoma?

Answer 27

Remove it

Question 28

What drugs should we use for Conn's before a surgery

Answer 28

use a drug that blocks aldosterone recpetors

Question 29

How does Spironolactone work?

Answer 29

Mineralocorticoid receptor antagonist, after being converted into canrenone to stop Na reabsorption or K excretion in the tubules. It is orally active and highly protein bound, and metabolised in the liver

Question 30

What are the side effects of spironolactone?

Answer 30

``` Menstrual irregularities (as it can stimulated the progesterone receptor) Gynaecomastia (as it blocks androgen receptor) ```

Question 31

How does epleronone work?

Answer 31

MR antagonist with a similar affinity to spironolactone

Question 32

Describe the side effects of epleronone

Answer 32

It binds less to other steroid receptors therefore has less side effects compared to spironolactone

Question 33

What is a phaeochromocytoma?

Answer 33

This is an adrenal medulla tumour therefore we get an increase in the production of catecholamines (noradrenaline and adrenalin)

Question 34

Why can phaeos cause a heart attack or stroke?

Answer 34

The tumour of the medulla acts as a neural syncytium therefore builds up adrenaline and doesn't release it until a certain moment and at this point, it releases a great quantity of adrenalin to cause this heart attack or stroke via random cell degranulation

Question 35

What are the clinical features of a phaeo?

Answer 35

Hypertension in young people Episodic severe hypetension (often triggered e.g. if you poke the abdomen) Cna cause sudden MI or CVA therefore death

Question 36

What are the 2 stages if phaeo management?

Answer 36

Stabilise patient | Surgery

Question 37

What drugs do we first give to a phaeo patient?

Answer 37

Alpha blockade to block alpha adrenoreceptors - this causes a fall in blood pressure

Question 38

Why may we get low blood pressure in a phaeo patient and how do we stop this?

Answer 38

Because patients are used to high adrenaline therefore a fall in adrenaline means their blood pressure drops too low, as they are resistant to lower levels of adrenaline. We. can treat this by giving IV fluids with blockade

Question 39

How do we prevent tachycardia in a phaeo patient?

Answer 39

Beta blockade (Beta blockers)

Question 40

What is the rule of 10 for phaeos?

Answer 40

10% are extra adrenal in the sympathetic chain 10% are malignant 10% are bilateral

Question 41

Can phaeos run in the family?

Answer 41

Yes - there are a few genes which put you at risk, and phaeos are more common in certain inherited conditions