Hyperadrenal disorders

Question 1

What are the clinical features of Cushing’s?

Answer 1

• centripetal obesity
• interscapular fat pads
• moon face
• striae
• thin skin, easy bruising
• proximal myopathy
• hypertension
• hypokalaemia
• oestoporosis
• diabetes

Question 2

What are the causes of Cushing’s?

Answer 2

• steriods
• ectopic ACTH producing tumour in lung
• pituitary tumour
• adrenal adenoma

Question 3

What investigations are conducted to determine Cushing’s - order?

Answer 3

1) Urinary free cortisol (24h)

2) Blood diurnal (varying levels depending upon time of day) cortisol analysis
Normal = cortisol high in morning and low at night.
Cushing’s = cortisol high all the time.

3) Low-dose dexamethasone suppression test.
0.5mg 6-hourly for 48 hours.
Normal = dexamethasone supresses cortisol to zero due to feedback inhibition.
Cushing’s = ANY cause will fail to suppress

Question 4

How is Cushing’s treated?

Answer 4

Depends on the cause

• drugs (enzyme inhibitors, receptor blocking drugs)
• surgery (pituitary surgery, bilateral adrenalectomy, unilateral adrenaloectomy)

Question 5

What are some examples of Cushing’s drugs?

Answer 5

metyrapone

ketoconazole

Question 6

How does metyrapone work?

Answer 6

Inhibits 11-beta-hydroxylase.

• Blocks production of cortisol but raises ACTH secretion (feedback systems)
• Steroid synthesis in the zona fasciculata (and reticularis) is arrested at 11-deoxycortisol stage.
• 11-deoxycortisol has no feedback effect.

Question 7

How is metyrapone used?

Answer 7

• Control of Cushing’s prior to surgery
• Dose adjusted to cortisol
• Improves patient’s symptoms and promotes post-op recovery
• Control of Cushing’s after radiotherapy

Question 8

What are the unwanted effects of metyrapone?

Answer 8

• Hypertension on long-term administration – deoxycortisone accumulates in zona glomerulosa which has aldosterone - like activity leading to salt retention and hypertension.
• Hirsutism – increased androgen production

Question 9

What do the different layers of the adrenal glands do?

Answer 9

Zona glomerulosa - mineralocorticoids, mainly aldosterone

Zona fasciculata - glucocorticoids, e.g. cortisol

Zona reticularis (innermost) - androgens, mainly DHEA

Medulla - catecholamines

Question 10

How does ketoconazole work?

Answer 10

• Main use as an anti-fungal drug but not anymore.
• At high concentrations, inhibits steroidogenesis
• Blocks production of glucocorticoids, mineralocorticoids and sex steroids

Question 11

When is ketaconazole used and its unwanted actions and how is it taken?

Answer 11

• Treatment and control of symptoms prior to surgery
• Orally active
• Liver damage

Question 12

What is Conn’s syndrome?

Answer 12

• A benign adrenal cortical (zona glomerulosa) tumour

- Produces aldosterone in excess

Question 13

What are the symptoms of Conn’s?

Answer 13

Hypertension and hypokalaemia due to water retention, aldosterone enhances sodium reabsorption and potassium excretion in the kidneys

Question 14

How is Conn’s diagnosed?

Answer 14

• Primary hyperaldosteronism

- The renin-angiotensin system should be supressed to exclude secondary hyperaldosteronism

Question 15

How is Conn’s treated?

Answer 15

Aldosterone receptor antagonists – Spironolactone, epleronone

Surgery

Question 16

When is spironolactone used and what is the mechanism of action?

Answer 16

Mineralocorticoid Receptor Antagonists

• Treatment of primary hyperaldosteronism (Conn’s syndrome)
  Mechanism of action:

Spironolactone is converted to several active metabolites including canrenone, a competitive antagonist of the MR
- Blocks Na+ reabsorption and K+ excretion – potassium sparing diuretic

Question 17

Describe the pharmakokinetics of spironolactone?

Answer 17

• Orally active

- Highly protein bound and metabolised in the liver

Question 18

What are the unwanted effects of spironolactone?

Answer 18

Menstrual irregularities – via progesterone receptor

Gynaecomastia – via androgen receptor

Question 19

Epleronone - why is better than spironolactone

Answer 19

• Also a MR antagonist (similar affinity to MR as spironolactone)
• Less binding to androgen and progesterone receptors compared to spironolactone so better tolerated

Question 20

What are phaeochromocytomas?

Answer 20

Tumours of the adrenal medulla which secrete catecholamines - can secrete adrenaline or noradrenaline.

Question 21

What are the clinical features of a pheochromocytoma?

Answer 21

• Hypertension in young people
• Episodic severe hypertension (after abdominal palpation – squeezes more adrenaline out).
• Different to Conn’s hypertension as this is episodic in the older population.
• Can cause MI or stroke.
• Can cause VF and death if not treated.
• Hence classed as a medical emergency

Question 22

How are pheochromocytomas treated?

Answer 22

Alpha-blockade is the first step. Patients may need IV fluids during alpha-blockade as BP will drop. Beta-blockade is added to prevent tachycardia.

Requires surgery but needs careful preparation as anaesthetic can precipitate a hypertensive crisis.

Question 23

What are some facts about phaeochromocytomas?

Answer 23

• 10% are extra-adrenal (down the sympathetic chain).
• 10% are malignant.
• 10% are bilateral.
• very rare

Question 24

What should be tested for after a patient has had adrenalectomy?

Answer 24

The short Synacthen test - assess adrenal function. The test is based on the measurement of serum cortisol before and after an injection of synthetic ACTH

Question 25

What investigation could be done once a patient’s results show they have Cushing’s syndrome not disease?

Answer 25

CT of adrenals