Adrenal gland (hyper)

Question 1

What are the clinical features of Cushing’s disease?

Answer 1

1) Excess cortisol
2) Centripetal obesity
3) Moon face and buffalo hump
4) Proximal myopathy
5) Hypertension and hypokalaemia
6) Red striae, thin skin, and bruising
7) Osteoporosis and diabetes

Question 2

What are the main causes of Cushings?

Answer 2

• Overdose of oral corticosteroids
• Pituitary dependent Cushing’s disease
• Ectopic ACTH from lung cancer
• Adrenal adenoma secreting cortisol

Question 3

What are the investigations that are conducted to determine the cause of Cushing’s syndrome?

Answer 3

-24H urine collection for urinary free cortisol
-Late night cortisol (look for loss of diurnal variation)
-Low dose dexamethasone suppression test

Question 4

How is a deamethasone suppression test conducted?
What is a positive result for a low dose dexamethasone suppression test?

Answer 4

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

Question 5

What pharmacological interventions are implemented for patients with hypersecretion of cortisol from the adrenal cortex?
Whhat is the MoA?

Answer 5

Metryapone
Ketoconazole
((osilidrostat))
Inhibitors of steroid biosynthesis

Question 6

What is Conn’s syndrome?

Answer 6

Benign tumour of the zona glomerulosa, therefore leading to excess aldosterone

Question 7

Which enzyme is inhibited by metyrapone?

Answer 7

11B-hydroxylase

Question 8

What is the mechanism of action of metryapone?

Answer 8

Inhibition of 11B-Hydroxylase, this arrests steroid synthesis within the zona fasciculata at the 11-deoxycortisol stage

Question 9

Does 11-deoxycortisol exert negative feedback on the hypothalamus?

Answer 9

There is no negative feedback effect on the hypothalamus and pituitary gland.

Question 10

In what situations is metyrapone used?

Answer 10

Control of Cushing’s syndrome prior to surgery.
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)

Question 11

How should metyrapone dose be regulated in response to cortisol level?

Answer 11

Adjust oral dose according to cortisol level (aim for mean serum cortisol 150-300nmol/L).

Question 12

What are the unwanted actions of metryapone?

Answer 12

Hypertension on long-term administration (11-deoxycorstisone accumulation)
Hirsutism (increased adrenal androgen production in women)

Question 13

What toxic risk is associated with ketoconazole?

Answer 13

Hepatotoxicity
Therefore monitor liver function weekly, clinically and biochemically

Question 14

Which enzyme is inhibited by ketoconazole?

Answer 14

17-alpha hydroxylase

Question 15

In what situations is ketoconazole used?
What is its pharmacokinetics?

Answer 15

treatment and control of Cushing’s symptoms prior to surgery
orally active

Question 16

What is the 1st line of treatment for a patient with an ACTH-secreting pituitary adenoma?

Answer 16

Pituitary surgery (transsphenoidal hypophysectomy)

Question 17

What are the surgical interventions for the treatment of Cushing’s?

Answer 17

1) Transsphenoidal hypophysectomy
2) Bilateral adrenalectomy
3) Unilateral adrenalectomy for adrenal mass.

Question 18

What are the associated clinical features of Conn’s syndrome?

Answer 18

Hypertension
Hypokalaemia

Question 19

What type of hyperaldosteronism is Conn’s syndrome?

Answer 19

Primary hyperaldosteronism

Question 20

What impact does Conn’s syndrome have on the Renin-angiotensin system?

Answer 20

RAAS should be suppressed (exclude secondary hyperaldosteronism)

Question 21

What two main drugs are prescribed in patients with Conn’s syndrome?

Answer 21

Spironolactone
Epleronone

Mineralocorticoid receptor agonists

Question 22

What is the mechanism of action of spironolactone?

Answer 22

Converted to several active metabolites, including canrenone, a competitive antagonist of mineralocorticoid receptors (MR)

Blocks sodium reabsorption and potassium excretion in the kidney tubules (potassium sparing diuretic)

Question 23

Describe the pharmacokinetics of spironolactone?

Answer 23

Orally active
Highly protein bound and metabolised in the liver.

Question 24

What are the unwanted actions of spironolactone?

Answer 24

Menstrual irregularities (+progesterone receptor)

Gynaecomastia (inhibits androgen receptors)

Question 25

What type of antagonist is epleronone?

Answer 25

A mineralocorticoid receptor antagonist

Question 26

Which conn’s syndrome drug is better tolerated?

Answer 26

Epleronone

Question 27

Why is epleronone better tolerated than spironolactone?
Compare binding affinity of eplerenone to MR to that of spironolactone

Answer 27

Less binding to androgen and progesterone receptors compared to spironolactone
Similar affinity to the MR compared to spironolactone

Question 28

What is a phaechromocytoma?

Answer 28

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

Question 29

Clinical features of a phaeo

Answer 29

Hypertension in young people
Episodic severe hypertension (after abdominal palpation)
More common in certain inherited conditions

Question 30

What are the potential risks with a phaeochromocytoma?

Answer 30

Severe hypertension can cause myocardial infarction or stroke

High adrenaline can cause ventricular fibrillation + death

Thus this is a medical emergency

Question 31

What are the precautions required for patients with a phaeochromocytoma surgical excision?

Answer 31

Careful preparation as anaesthetic can precipitate a hypertensive crisis

Question 32

Management of a phaeo prior to surgery

Answer 32

Alpha blockade is first therapeutic step.
Patients may need intravenous fluid as alpha blockade commences
Beta blockade added to prevent tachycardia

Question 33

Phaeochromocytoma key facts

Answer 33

10 % extra-adrenal (sympathetic chain)
10 % malignant
10 % bilateral