(endo) hypoadrenalism Flashcards
give three causes of adrenocortical failure
1) tuberculous Addison’s disease
2) autoimmune Addison’s disease
3) congenital adrenal hyperplasia
what are the main consequences of adrenocortical failure?
mineralocorticoid deficiency
= 1) loss of sodium in the urine (hyponatraemia)
= 2) hyperkalaemia
= 3) hypotension
glucorticoid deficiency
= 1) hypoglycaemia
= 2) increased ACTH resulting in hyperpigmentation
= eventual death due to severe hypotension
explain the relationship between cortisol and insulin
cortisol has metabolic effects and so wants to reduce glucose storage and increase glucose bioavailability
= cortisol inhibits insulin
how does cortisol deficiency affect blood glucose compared to excess cortisol?
cortisol deficiency = hypoglycaemia
excess cortisol = impaired glucose tolerance/diabetes
what is POMC?
pro-opio melanocortin
where is POMC synthesised?
synthesised in the pituitary gland
what is POMC cleaved into and why is this significant?
cleaved into
- ACTH
- aMSH (hormone that stimulates skin pigmentation)
- endorphins
- enkephalins
which laboratory tests are carried out to test for Addison’s disease?
1) 9am cortisol
2) ACTH
3) short synACTHen test
for a patient with Addison’s disease, what are the expected 9am cortisol & ACTH results?
9am cortisol = low
ACTH = high
what is a short synACTHen test and how does it work?
synACTHen = synthetic ACTH
following low 9am cortisol and high ACTH, to confirm Addison’s disease, synACTHen is given
= should cause cortisol levels to increase in healthy patients BUT in those w Addison’s, cortisol remains low
for a patient with Addison’s disease, what are the expected short synACTHen test results?
following a low 9am cortisol & a high ACTH, if the short synACTHen test is also low
= confirms Addison’s disease
how is a short synACTHen test carried out?
measure 9am cortisol
give 250ug synACTHen IM
measure cortisol response
how is adrenal failure treated?
1) fludrocortisone (50-100mcg daily)
2) either hydrocortisone (x3 daily 10 - 5 - 2,5) OR prednisolone (3-4mg once daily)
what is fludrocortisone?
artificial analogue of aldosterone
= formed by adding fluorine atom to aldosterone
how does fludrocortisone compare to aldosterone?
fludorcortisone = longer half life for once daily administration + binds to both MR/GR
aldosterone = too short a half life for OD administration
why does fludrocortisone have a longer half life?
cannot be degraded due to fluoride atom
= longer half life
what does fludrocortisone replace as opposed to prednisolone/hydrocortisone?
fludrocortisone = replaces aldosterone (mineralocorticoid)
hydrocortisone/predinosolone = replaces cortisol (glucocorticoid)
why does oral hydrocortisone have to be taken thrice a day?
has too short a half life for once daily administration
why is prednisolone preferentially given over hydrocortisone to replace cortisol in adrenal failure?
prednisolone dose = 3-4mg
hydrocortisone dose total = 15mg
as the hydrocortisone dose is larger, increased risk of diabetes and hypertension = less safe
how does prednisolone compare to cortisol?
longer half life
more potent
x2.3 binding affinity
what is the function of an enteric coating on tablets?
1) speeds up intestinal absorption (i.e. keeps drug intact in the gastric environment)
2) reduces side effects
what is the most common cause of congenital adrenal hyperplasia?
21-hydroxylase deficiency
can be complete or partial
in complete 21-hydroxylase deficiency, which hormones are fully absent?
aldosterone and cortisol
in complete 21-hydroxylase deficiency, which hormones are present in excess and why?
sex steroids and testosterone
= lack of 21-hydroxylase results in a build-up of 17-OH progesterone leading to a build-up of sex steroids
