Adrenal gland (hyper) Flashcards
What are the clinical features of Cushing’s disease?
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
What are the main causes of Cushings?
- Overdose of oral corticosteroids
- Pituitary dependent Cushing’s disease
- Ectopic ACTH from lung cancer
- Adrenal adenoma secreting cortisol
What are the investigations that are conducted to determine the cause of Cushing’s syndrome?
-24H urine collection for urinary free cortisol
-Late night cortisol (look for loss of diurnal variation)
-Low dose dexamethasone suppression test
How is a deamethasone suppression test conducted?
What is a positive result for a low dose dexamethasone suppression test?
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
What pharmacological interventions are implemented for patients with hypersecretion of cortisol from the adrenal cortex?
Whhat is the MoA?
Metryapone
Ketoconazole
((osilidrostat))
Inhibitors of steroid biosynthesis
What is Conn’s syndrome?
Benign tumour of the zona glomerulosa, therefore leading to excess aldosterone
Which enzyme is inhibited by metyrapone?
11B-hydroxylase
What is the mechanism of action of metryapone?
Inhibition of 11B-Hydroxylase, this arrests steroid synthesis within the zona fasciculata at the 11-deoxycortisol stage
Does 11-deoxycortisol exert negative feedback on the hypothalamus?
There is no negative feedback effect on the hypothalamus and pituitary gland.
In what situations is metyrapone used?
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)
How should metyrapone dose be regulated in response to cortisol level?
Adjust oral dose according to cortisol level (aim for mean serum cortisol 150-300nmol/L).
What are the unwanted actions of metryapone?
Hypertension on long-term administration (11-deoxycorstisone accumulation)
Hirsutism (increased adrenal androgen production in women)
What toxic risk is associated with ketoconazole?
Hepatotoxicity
Therefore monitor liver function weekly, clinically and biochemically
Which enzyme is inhibited by ketoconazole?
17-alpha hydroxylase
In what situations is ketoconazole used?
What is its pharmacokinetics?
treatment and control of Cushing’s symptoms prior to surgery
orally active
What is the 1st line of treatment for a patient with an ACTH-secreting pituitary adenoma?
Pituitary surgery (transsphenoidal hypophysectomy)
What are the surgical interventions for the treatment of Cushing’s?
1) Transsphenoidal hypophysectomy
2) Bilateral adrenalectomy
3) Unilateral adrenalectomy for adrenal mass.
What are the associated clinical features of Conn’s syndrome?
Hypertension
Hypokalaemia
What type of hyperaldosteronism is Conn’s syndrome?
Primary hyperaldosteronism
What impact does Conn’s syndrome have on the Renin-angiotensin system?
RAAS should be suppressed (exclude secondary hyperaldosteronism)
What two main drugs are prescribed in patients with Conn’s syndrome?
Spironolactone
Epleronone
Mineralocorticoid receptor agonists
What is the mechanism of action of spironolactone?
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)
Describe the pharmacokinetics of spironolactone?
Orally active
Highly protein bound and metabolised in the liver.
What are the unwanted actions of spironolactone?
Menstrual irregularities (+progesterone receptor)
Gynaecomastia (inhibits androgen receptors)
What type of antagonist is epleronone?
A mineralocorticoid receptor antagonist
Which conn’s syndrome drug is better tolerated?
Epleronone
Why is epleronone better tolerated than spironolactone?
Compare binding affinity of eplerenone to MR to that of spironolactone
Less binding to androgen and progesterone receptors compared to spironolactone
Similar affinity to the MR compared to spironolactone
What is a phaechromocytoma?
Tumours of the adrenal medulla which secrete catecholamines (adrenaline and noradrenaline)
Clinical features of a phaeo
Hypertension in young people
Episodic severe hypertension (after abdominal palpation)
More common in certain inherited conditions
What are the potential risks with a phaeochromocytoma?
Severe hypertension can cause myocardial infarction or stroke
High adrenaline can cause ventricular fibrillation + death
Thus this is a medical emergency
What are the precautions required for patients with a phaeochromocytoma surgical excision?
Careful preparation as anaesthetic can precipitate a hypertensive crisis
Management of a phaeo prior to surgery
Alpha blockade is first therapeutic step.
Patients may need intravenous fluid as alpha blockade commences
Beta blockade added to prevent tachycardia
Phaeochromocytoma key facts
10 % extra-adrenal (sympathetic chain)
10 % malignant
10 % bilateral
