Management of adrenal failure Flashcards
What are the clinical features of cortisol?
Too much cortisol (always high) Centripetal obesity Moon face and buffalo hump Proximal myopathy Hypertension and hypokalaemia Red striae, thin skin and 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
How is Cushing’s diagnosed?
24 h urine collection for urinary free cortisol
Blood diurnal cortisol levels
(cortisol’s usually highest at 9am and lowest at midnight, if asleep)
Low dose dexamethasone suppression test
How does the Low dose dexamethasone suppression test work?
Potent glucocorticoid should suppress cortisol
Give 1/2 mg 6 hourly for 48 hours
Cortisol would be zero the next day if normal
Does not tell you what type of Cushing’s they have
What drugs can be given to treat Cushing’s?
Enzyme inhibitors
Receptor blocking drugs
Which drugs inhibit steroid biosynthesis?
Metyrapone
Ketoconazole
What is the action of Metyrapone?
Inhibition of 11b-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.
How do we control cortisol prior to surgery?
adjust dose (oral) according to cortisol (aim for mean serum cortisol 150-300 nmol/L)
improves patient’s symptoms and promotes better post-op recovery (better wound healing, less infection etc)
What are the side effects of metyrapone?
high blood pressure
high testosterone
What was the main use of Ketoconazole?
main use as an antifungal agent – although withdrawn in 2013 due to risk of hepatotoxicity
at higher concentrations, inhibits steroidogenesis – off-label use in Cushing’s syndrome
What is the mechanism of action for Ketoconazole?
Inhibition of 17-hydroxylase
Summarise the invasive treatments for Cushing’s?
Depends on cause
Pituitary surgery (transsphenoidal hypophysectomy)
Bilateral adrenalectomy
Unilateral adrenalectomy for adrenal mass
Summarise the medical treatments for Cushing’s?
Metyrapone
Ketoconazole
What are the side effects of Ketoconazole?
Liver damage - possibly fatal - monitor liver function weekly, clinically and biochemically
What causes Conn’s syndrome?
Benign adrenal cortical tumour (zona glomerulosa)
Aldosterone in excess
Hypertension and hypokalaemia
How do you diagnose Conn’s syndrome?
Primary hyperaldosteronism
Renin - angiotensin system should be suppressed (exclude secondary hyperaldosteronism)
What are the treatment’s for Conn’s syndrome?
spironolactone, epleronone
What is the mechanism of action for spironolactone?
Converted to several active metabolites, including canrenone, a competitive antagonist of the mineralocorticoid receptor (MR).
Blocks Na+ resorption and K+ excretion in the kidney tubules (potassium sparing diuretic).
Therefore also used by cardiologists as a hypertensive
What are the side effects of spironolactone?
Menstrual irregularities (+ progesterone receptor) Gynaecomastia (- androgen receptor)
What are the main features of epleronone?
Also a mineralocorticoid receptor (MR) antagonist
Similar affinity to the MR compared to spironolactone
Less binding to androgen and progesterone receptors compared to spironolactone, so better tolerated
What are phaeochromaocytomas?
These are tumours of the adrenal MEDULLA which secrete catecholamines
(adrenaline and nor-adrenaline)
What are the effects of phaeochromaocytomas?
Blood pressure elevation Increased cardiac output BMR elevation Bronchodilation Glycogenolysis Hyperglycaemia CNS excitability
What are the clinical features of phaeochromaocytomas?
Intermittent episodes of high BP (after abdominal palpitation)
As the tutor gets bigger they will have more attacks
Hypertension in young people
More common in certain inherited conditions
When do patients with phaeochromaocytomas present?
They just think they are having unexplained panic attacks
It is only when they collapse that the tumour is discovered
What can phaeo’s cause?
Hypertension in young people
Episodic severe hypertension (after abdominal palpation)
More common in certain inherited conditions
How do you manage a phaeo?
Eventually need surgery, but patient needs careful preparation as anaesthetic can precipitate a hypertensive crisis
Needs to prepped for surgery
How to prep a patient for a phaeo surgery?
Alpha blockade is first therapeutic step
Patients may need intravenous fluid (to maintain BP) as alpha blockade commences
Beta blockade added to prevent tachycardia
What happens the weekend before a surgery for phaeo?
High does alpha blockade in hospital
By the surgery they have absolutely no adrenal function
What are some key facts about phaeochromocytoma’s?
10 % extra-adrenal (sympathetic chain)
10 % malignant
10 % bilateral
Phaeo’s are extremely rare
