ADRENAL FAILURE Flashcards
Detail where all the adrenal hormones are made
Mineralocorticoids (aldosterone) - glomerulosa
Glucocorticoids (cortisol) - fasciculata
Sex steroids (androgens/oestrogens) - fasciculata/reticularis
Catecholamines - medulla
Which enzymes does angiotensin II activate?
Side chain cleavage 3 hydroxysteroid dehydrogenase 21 hydroxylase 11 hydroxylase 18 hydroxylase
Which enzymes foes ACTH activate?
Side chain cleavage 3 hydroxysteroid dehydrogenase 21 hydroxylase 11 hydroxylase 17 hydroxylase
What is Addison’s disease?
Primary adrenal failure destroying adrenal cortex.
Lack of aldosterone and cortisol
What are the causes of Addison’s?
Autoimmune (most common in UK)
Tuberculosis infection (most common worldwide)
Congenital adrenal hyperplasia
What are some symptoms (including clinical) of Addison’s?
Increased pigmentation (high MSC) Autoimmune vitligo Low blood pressure Salt in urine Increased plasma potassium Fall in blood glucose (glucocorticoid def) High ACTH
Eventual death due to severe hypotension
What are some tests for Addison’s?
9 am cortisol
blood ACTH test
Short synacthen test
What is the short synacthen test?
Measure cortisol at 9:00am
Give injection of synacthen (synthetic ACTH)
Measure cortisol at 9:30am
If Addison’s, patient won’t respond and serum cortisol will remain similar
What are the treatments for adrenal failure?
Fludrocortisone 50-100 mcg daily
Prednisolone 2-4mg once daily
What is fludrocortisone and why do we use it?
Same as aldosterone but has a F instead of H on one of the carbons. This slows its metabolism and thus has a longer half-life (3.5hrs) and longer lasting effects (18hrs)
What is prednisolone and why do we use it?
Same as cortisol but has C double bond. This means it has a longer half life and is more potent than cortisol (2.3x binding affinity)
Cannot give oral hydrocortisone (medical cortisol) because its half life too short so have to administer 3 times daily. This causes 3 peaks throughout the day which are harmful
Prednisolone mimics the diurnal/circadian rhythm
What is congenital adrenal hyperplasia’s commonest cause?
21-hydroxylase deficiency
Explain what complete and partial congenital adrenal hyperplasia is
Complete - missing gene for 21-hydroxylase
Partial - mutated gene for 21-hydroxylase
Which hormones will be fully absent in complete congenital adrenal hyperplasia?
aldosterone
cortisol
How long can a baby survive once born with complete congenital adrenal hyperplasia without treatment?
< 24 hrs because salt-losing addisonian crisis
Which hormones will be in excess in congenital adrenal hyperplasia?
sex steroids e.g. testosterone which in girls will cause ambiguous genitalia
Why won’t a foetus with congenital adrenal hyperplasia die before it is born?
It is supplied with steroids/lacking hormones via placenta from mother
What are the main problems with partial congenital adrenal hyperplasia?
Hirsutism and virilisation in girls later in life
Precocious puberty in boys due to excess testosterone
What does 11-hydroxlase deficiency cause?
No cortisol or aldosterone
Excess sex steroids and 11-deoxycorticosterone
11-deoxycorticosterone acts similar to aldosterone so excess causes hypertension and hypokalaemia
What does 17-hydroxlase deficiency cause?
No cortisol or sex steroids
Excess 11-deoxycorticosterone and aldosterone
Hypertension, hypokalaemia, sex steroid deficiency, glucocorticoid deficiency (low glucose)
