Adrenal disorders 2

Question 1

Why may someones cortisol be high at midnight and not have hypoadrenalism?

Answer 1

Sleep schedule e.g. night shifts or time zones

Question 2

What are the clinical features of cushings’?

Answer 2

Overactive adrenal gland due to increased ACTH :

• Too much cortisol
• Centripetal Obesity
• Moon face and buffalo hump
• Proximal myopathy
• Hypertension and hypokalaemia
• Red Striae, thin skin bruising
• Osteoporosis

Question 3

What are the common causes of Cushings’?

Answer 3

–> Taking too many steroids!

• Pituitary dependent Cushings’ disease
• Ectopic ACTH from lung cancer
• Adrenal adenoma secreting cortisol

CUSHINGS IS SECONDARY HYPERCORTISOLISM

Question 4

How to investigate the cause of Cushing’s syndrome?

Answer 4

• 24h urine collection ( for urinary free cortisol ) *total cortisol not affected by time
• Blood diurnal cortisol levels *dependent on time of day so highest at 9am

Question 5

What is the low dose dexamethasone suppression test? ( a steroid )

Answer 5

Also a test of cushings’ syndrome cause

potent
pituitary sees it and reacts to it as if it is cortisol so will make no ATCH. Cortisol should be 0 however Cushings will still remain high

Question 6

How much dexamethasone is given for the test?

Answer 6

0.5mg 6 hourly for 48 hours

Question 7

How do we know to diagnose Cushings?

Answer 7

If 9am cortisol is 800nM and suppression test is given and it only drops to 680nM (due to diurnal) then this is Cushings’

Is anyone else it should drop to 0

Question 8

What is pitting eodema?

Answer 8

If high aldoesterol or cortisol : have it

Question 9

What are the pharmacological treatments?

Answer 9

• Enzyme inhibitors
• Receptor blocking drugs

to control excess cortisol

Question 10

What drug is used to inhibit tsteroid biosynthesis?

Answer 10

Metryapone + ketoconazole

Question 11

What is Conn’s syndrome?

Answer 11

Benign adrenal cortical tumour - zona glomerulosa

Excess aldoesterone

Question 12

What medication is given for Conn’s?

Answer 12

MR antgonist:

spironolactone, epleronone

Question 13

How does Metryapone work?

Answer 13

Inhibition of 11beta-hydroxlase in zona fasciuclata which drops level of cortisol

So reaction ends at 11-deoxycortisol

Question 14

How do we control Cushing’s syndromes before surgery?

Answer 14

• 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)
• can give metyrapone whilst waiting for for radiotherapy to work

Question 15

What are the side effects of metyrapone?

Answer 15

Hypertension on long term administration

Hirsutism

Question 16

How does Ketoconazole work?

Answer 16

main use as an antifungal agent – although withdrawn in 2013 due to risk of hepatotoxicity

at higher concentrations, inhibits steroidogenesis – off-label use in Cushing’s syndrome

Blocks 17alpha hyrdroxylase

Question 17

What are the side effects of ketoconazole?

Answer 17

Liver damage - possibly fatal - monitor liver function weekly, clinically and biochemically

Question 18

What surgeries are available for Cushing’s?

Answer 18

( Depends on cause )

• Pituitary surgery - transsphenoidal hypophysectomy
• Bilateral adrenalectomy
• Unilateral adrenalectomy for adrenal mass

Question 19

What are the symptoms of Conn’s syndrome?

Answer 19

Hypertension + hypokalaemia

Question 20

How to diagnose Conn’s syndrome?

Answer 20

Primary hyperalodosteronism

Renin : angiotensin system should be suppressed if this is the case to exclude secondary hyperalodosteronism

Question 21

How does Spironlactone work?

Answer 21

For Conns

Converted to sevreal metbabolites includng canrenone acting as a copetitive antagonist of the mineralcorticoid receptor

Blocks Na+ resorption and K+ excretion

• it is orally taken and is very protein bound

Question 22

What side effects does spironolactone cause?

Answer 22

Menstrual irregularities (+ progesterone receptor)
Gynaecomastia (- androgen receptor)

Question 23

How does Epleronone does?

Answer 23

Mineralcorticoid receptor antagonist

Similar affinity for MR compared to spionolactone

Less binding to androgen and progesterone receptors compared to spironolactone, so better tolerated

Question 24

What are phaemochyromocytomas?

Answer 24

These are tumours of the adrenal MEDULLA which secrete catecholamines

ADRENALINE and noadrenaline made

Question 25

What are the clinical features of phaeochromocytoma?

Answer 25

• Hypertension in young people
• Episodic severe hypertension when adrenaline builds and is released ( due to neural cell type effect ) after abdominal palpation

More common in certain inherited condition

Question 26

What can the severe hypertension in Phaeo cause?

Answer 26

Can cause myocardial infarction strokes

High adrenaline can cause ventricular fibrillation + death

MEDICAL EMERGENCY

Question 27

How to manage Phaeo?

Answer 27

Eventually need surgery, but patient needs careful preparation as anaesthetic can precipitate a hypertensive crisis

Question 28

What are the therapuetic management plans for Phaeo?

Answer 28

• alpha blockade is first therapuetic step
• May need IVF fluid as alpha blockade causes blood pressure crash
• Beta blockade added to prevent tachycardia