Clinical Aspects of Adrenal Disorders Flashcards
What are the sex steroids?
Testosterone, progesterone, estrogen
(produced by the zona reticularis - the layer immediately next to the medulla)
What are the classes of adrenal disorders?
Functional - hyperfunction and hypofunction
Normal function - Mass effect symptoms of tumour
What is the most common cause of adrenal failure?
Autoimmune addison’s
What is the mechanism of action for autoimmune addison’s?
adrenal autoantibodies (to 21 - hydroxylase) in 70% cases
Lymphocytic infiltrate of adrenal cortex
What is another cause of primary adrenal insufficiency apart from addison’s?
Adrenal enzyme defects (congenital adrenal hyperplasia (most commonly 21-hydroxylase deficiency)
What are the other autoimmune diseases associated with addison’s?
Thyroid disease
Type 1 diabetes mellitus
Premature ovarian failure
What are the symptoms associated with primary adrenal failure?
Weakness, fatigue, anorexia, weight loss 100%
Skin pigmentation or vitiligo 92%
Hypotension 88%
Unexplained vomiting or diarrhoea 56%
Salt Craving 19 %
Postural symptoms 12%
How do we make the diagnosis of adrenal insufficiency?
Non-specific symptoms - so must think of the diagnosis in the first place
Routine bloods (U and E, glucose, FBC)
Random cortisol
Over 700 nmol/l (not addison’s)
Under 700 nmol/l (adrenal status is uncertain)
Syncathen test (and basal ACTH) If suspicion high & patient unwell, treat with steroids and do Synacthen test later
Syncathen test or ACTH stimulation test - A small amount of synthetic ACTH is injected, and the amount of cortisol (and sometimes aldosterone) that the adrenals produce in response is measured.
Look
What is involved in glucocorticoid replacement therapy?
Hydrocortisone
Prednisolone
Dexamethasone
Given in divided doses to mimic normal diurnal variation
What is involved in mineralcorticoid replacement?
Synthetic steroid - fludrocortisone
Dosing altered according to clinical status (postural blood pressure, oedema), U and E, plasma renin level
Who needs special care when on steroids?
Hypoadrenal patientes on replacement steroids
Patients on steroids with doses sufficient enough to suppress the pituitary adrenal axis (over 7.5mg prednisolone daily, or equivalent)
Patients who have received such treatment during the previous 18 months (the HPA axis may still be suppressed)
What should be done in short lived illness or stress for patients who need special care (they are on steroidal treatment)?
Double glucocorticoid dose
What should be done if there is major illness or operation for patients who are on steroids?
(especially if nil by mouth or GI upset)
100mg hydrocortisone iv stat
50-100mg HC iv 8-hourly
as stress abates, reduce HC by 50% per day until back on usual replacement dose
What are the three important self-care rules for patients on steroids?
Never miss steroids doses
Double the hydrocortisone in event of intercurrent illness (flu or UTI)
If severe vomiting or diarrhoea, call for help without delay (likely ot need IM hydrocortisone)
How does a dexomethosone test work?
Dexomethosone is given to the patient which mimics cortisol. The body normally responds by reducing cortisol production (negative feedback) however this is not the case for those with pathologies of cortisol production.
Negative feedback involves increase levels of cortisol followed by decreae levels of ACTH (anterior pituitary)
In the case of cushings syndrome (adrenal tumour) - cortisol production will not be influenced by ACTH as the tuomur is secreting too much cortisol. As a result when dexamethasone is introduced into the patient, there will be no change in cortisol production and ACTH will be very low or undetectable as a result of negative feedback.
In the case of cushing’s disease (tumour in the anterior pituitary) there is still some negative feedback function retained.
ACTH is normal / elevated and when low dose dexomethosone is introduced there is no suppression of cortisol production, but high doses of dex cause suppression of cortisol production
In the case of ectopic ACTH, there is massive elevation ACTH. Since the tumour is outwith the anterior pituitary there will be no negative feedback when dex levels rise so cortisol levels remain unchanged
How do you tell the difference between primary hyperaldosteronism and secondary hyperaldosteronism?
PA/PRA ratio is above 20 in primary
PA/PRA ratio is less than 20 in secondary although this is less reliable
(plasma aldosterone vs plasma renin activity)
Whatis the precursor for all the androgens?
DHEA
What is the direct effect of 21 hydroxylase deficiency?
Progesterone cannot be converted into deoxycorticosterone - this pathway would normaly produce aldosterone but it is now interrupted
Pathways producing DHEA are unaffected - may be why there are problems associated with sex hormones (genitalia / puberty / hirsuitism)?
