Endo - Adrenal Disorder (overactive) Flashcards
What are the clinical features of Cushing’s Disease?
→ too much cortisol → centripetal obesity → moon face + buffalo hump → proximal myopathy → hypertension + hypokalaemia → red striae, thin skin, bruising → osteoporosis + diabetes
What are the causes of Cushing’s Disease?
→ too many steroids
→ pituitary dependent Cushing’s disease
→ ectopic ACTH from lung cancer
→ adrenal adenoma secreting cortisol
What investigations determine the cause of Cushing’s Syndrome?
→ 24 hour urine collection for urinary free cortisol
→ blood diurnal cortisol levels
→ low dose dexamethasone
What is a low dose dexamethasone suppression test?
→ dexamethasone = artificial cortisol that has fluorine and can last ages
→ should suppress ACTH and cortisol in normal people
→ however, in Cushing’s, cortisol will still be produced
What’s the difference between Cushing’s Syndrome and Cushing’s Disease?
cushing’s syndrome is having excess cortisol
cushing’s disease is having adrenal tumour
When is cortisol the lowest according to the diurnal rhythm?
midnight
Why does ectopic ACTH from lung cancer cause Cushing’s disease?
if lung cancer expresses protein that produces ACTH, it can stimulate adrenal glands to produce cortisol
What is Cushing’s disease/syndrome?
too much cortisol
What are the two ways in which steroids can be pharmacologically manipulated?
→ enzyme inhibitors
→ receptor blocking drugs
What drugs inhibit cortisol biosynthesis?
→ metyrapone
→ ketoconazole
What drugs inhibit aldosterone biosynthesis?
→ spironolactone
→ epleronone
What is metyrapone’s mechanism of action?
→ inhibition of 11-beta-hydroxylase
→ steroid synthesis in the zona fasciculata is stopped at the 11-deoxycortisol stage
→ 11-deoxycortisol has no negative feedback effect in hypothalamus + pituitary gland
What are the specific clinical uses of metyrapone?
→ control of Cushing’s syndrome prior to surgery
→ control of Cushing’s symptoms after radiotherapy (as it has very slow effects)
What are the unwanted consequences of metyrapone?
→ hypertension on long-term administration
→ hirsutism
What are the main uses of ketoconazole?
→ main use = anti-fungal agent
→ higher concentrations inhibits steroidogenesis
What is the mechanism of action of ketoconazole?
blocks 17-alpha-hydroxylase, preventing production of cortisol
What are the unwanted consequences of ketoconazole?
possibly fatal liver damage
How do you treat Cushing’s Disease?
→ pituitary surgery
→ bilateral adrenalectomy
→ unilateral adrenalectomy for adrenal mass
What is Conn’s disease?
too much aldosterone
What can cause Conn’s disease?
benign adrenal cortisol tumour
What are the clinical features of Conn’s syndrome?
→ hypokalaemia (low potassium)
→ hypertension
How do you distinguish between primary and secondary hyperaldosteronism?
renin-angiotensin system should be suppressed for primary hyperaldosteronism?
What are the main uses of spironolactone?
treats primary hyperaldosteronism before surgery
What is the mechanism of spironolactone?
→ converted to several active metabolites, including canrenone (competitive antagonist of mineralocorticoid receptor)
→ blocks Na+ absorption and K+ excretion in kidney tubules
What are the unwanted consequences of spironolactone?
→ menstrual irregularities
→ gynaecomastia (man boobs)
What are the pharmacokinetics of spironolatone?
→ orally active
→ highly protein bound + metabolised in liver
Why is a higher dose of epleronone given in comparison to spironolactone?
→ less binding to androgen and progesterone receptors compared to spironolactone
→ more highly tolerated
What are spironolactone and epleronone examples of?
MR antagonists
mineralocorticoid antagonists
What are tumours of the adrenal medulla called?
phaeochromocytomas
What do phaeochromocytomas do?
secretes catecholamines (adrenaline + nor-adrenaline)
What are the clinical features of a phaeo?
→ hypertension in young people
→ episodic severe hypertension (abdominal palpation)
→ more common in certain inherited conditions
What are the consequences of some of the clinical features in a phaeo?
→ severe hypertension = myocardial infarction or stroke
→ high adrenaline = ventricular fibrillation + death
How is phaeo managed?
→ eventually needs surgery
→ needs careful prep as anaesthetic can precipitate a hypertensive crisis
How can phaeo be managed pharmacologically?
→ alpha blockade
→ beta blockade to prevent tachycardia
How can phaeo be managed pharmacologically before surgery?
→ alpha blockade (patient may need IV fluids alongisde)
→ beta blockade to prevent tachycardia
Why are IV fluids given when alpha blockades are given?
huge drop in blood pressure may be too much for body
