Hyperadrenal disorders Flashcards
What are the clinical features of Cushing’s syndrome?
Too much cortisol- switches protein synthesis off and fat synthesis on. Centripetal obesity Moon face Interscapular fat pad Proximal myopathy Hypertension Hypokalaemia Red striae, thin skin and easy bruising Osteoporosis, diabetes
What are the causes of Cushing’s?
Taking too many steroids
Pituitary dependent (Cushing’s disease)
Ectopic ACTH from lung cancer
Adrenal adenoma secreting cortisol
What investigations may be carried out to determine the cause of Cushing’s syndrome?
24 hour urine collection for urinary free cortisol.
Blood diurnal cortisol levels- usually highest at 9am and lowest at midnight, if asleep- suspicious if high.
Low dose dexamethasone suppression test.
What is a low dose dexamethasone suppression test used for?
0.5mg 6-hourly for 48 hours.
Dexamethasone is an artificial steroid.
If normal, will suppress cortisol to zero.
Any cause of Cushing’s will fail to suppress.
How can steroids be pharmacologically manipulated?
Enzyme inhibitors- inhibit enzymes of steroid synthesis.
Receptor blocking drugs.
What is the treatment of Cushing’s syndrome?
Depends on cause.
Pituitary surgery (transsphenoidal hypophysectomy).
Bilateral adrenalectomy.
Unilateral adrenalectomy for adrenal mass.
What is Conn’s?
Too much aldosterone.
Where are catecholamines produced?
Adrenal medulla.
What is phaeochromocytoma?
Tumour of the adrenal medulla that leads to production of excess catecholamines.
How are the effects of excess catecholamines (e.g. in phaeochromocytoma) blocked?
Alpha blocker to reduce blood pressure caused by catecholamines binding to alpha receptors on vasculature and causing vasoconstriction.
Then beta blocker.
What are the actions of metyrapone?
Inhibition of 11 beta hydroxylase.
Steroid synthesis in the zona fasciculata (and reticularis) is arrested at the 11-deoxycortisol stage.
11-deoxycortisol has no negative feedback effect on the hypothalamus and pituitary gland so it accumulates. ACTH levels rise.
What is metyrapone used for?
Control of Cushing’s syndrome prior to surgery. Adjust oral dose according to cortisol (aim for mean serum cortisol 150-300nmol/L). Improves patient’s symptoms and promotes better postoperative recovery (better wound healing, less infection, etc.).
Control of Cushing’s symptoms after radiotherapy (usually slow to take effect).
What are the unwanted actions of metyrapone?
Hypertension on long-term administration.
Hirsutism.
What are the actions of ketoconazole?
Main use as an anti-fungal agent- withdrawn due to risk of hepatotoxicity.
At higher concentrations, inhibits steroidogenesis- off-label use in Cushing’s syndrome.
Blocks production of glucocorticoids, mineralocorticoids, and sex steroids.
What is ketoconazole used for?
Treatment and control of symptoms of Cushing’s syndrome prior to surgery- orally active.
What are the unwanted actions of ketoconazole?
Liver damage- possibly fatal. Monitor liver function weekly, clinically and biochemically.
What are two medical treatment options for Cushing’s syndrome?
Metyrapone
Ketoconazole
What are the clinical features of Conn’s syndrome?
Benign adrenocortical tumour (zona glomerulosa- makes aldosterone).
Aldosterone is in excess.
Retain sodium and lose potassium.
Hypertension and hypokalaemia.
How is primary hyperaldosteronism (Conn’s) diagnosed?
Hypertension and blood test showing low potassium.
How is secondary hyperaldosteronism excluded as a diagnosis?
Renin-angiotensin system should be suppressed. High aldosterone and low renin (suppressed by hypertension).
What is the treatment for Conn’s syndrome?
Aldosterone receptor antagonist: spironolactone.
Surgery: image and remove adenoma.
If bilateral adrenal hyperplasia, can stay on spironolactone.
What are the uses and mechanism of action of spironolactone?
Primary hyperaldosteronism (Conn's syndrome). Converted to several active metabolites, including canrenone, a competitive antagonist of the mineralocorticoid receptor (MR). Blocks sodium resorption and potassium excretion un the kidney tubules (potassium sparing diuretic).
Discuss the pharmacokinetics of spironolactone.
Orally active.
Highly protein bound and metabolised in the liver.
What are the unwanted actions of spironolactone?
Menstrual irregularities (agonist at progesterone receptor). Gynaecomastia (antagonist at androgen receptor).
What is epleronone’s significance?
It is a mineralocorticoid receptor antagonist with similar affinity to the MR compared to spironolactone, but with less binding to androgen and progesterone receptors- better tolerated.
What are the clinical features of phaeochromocytoma?
Hypertension in young people.
Episodic severe hypertension (after abdominal palpation).
More common in certain inherited conditions.
Severe hypertension can cause myocardial infarction or stroke.
High adrenaline can cause ventricular fibrillation and death- medical emergency.
How is phaeochromocytoma managed?
Eventually need surgery, but patient needs careful preparation as anaesthetic can precipitate hypertensive crisis.
Alpha blockade is first therapeutic step.
Beta blockade added to prevent tachycardia.
