Hypoadrenal Disorders Flashcards
what is the precursor to the steroids?
cholesterol
the 3 arms of steroid genesis?
aldosterone
cortisol
sex steroids
sources of sex hormones
main: gonads
secondary: adrenal cortex
enzymes involved in steroidogenesis?
deficiencies in
hydroxylases
17,21,11,18
methods that destroy the adrenal gland causing adrenal failure?
1) TB (developing world) - how Addison described it
2) autoimmune (developed world)- atrophy
3) congenital adrenal hyperplasia (overgrowth with dysfunction)–> crisis
manifestation of adrenocortical failure in terms of aldosterone problems
effects of low aldosterone:
- hypotension (postural as well)
- loss of salt
- hyperkalaemia
additional signs of Addisons
- hypoglycaemia (low glucocorticoid, cortisol mobilised glucose)
- hyper pigmentation
- vitiligo
- eventual death due to severe hypotension
why does hyperpigmentation occur in Addisons?
with the excess ACTH produced as a result of low cortisol (negative feedback)
a lot of MSH (melanocyte stimulating hormone) is produced
MSH is a product along with ACTH from the breakdown of precursor POMC, that causes pigmentation
what should cortisol levels be normally? How does this compare to an Addison’s patient?
in the morning it should be highest and at night it should be lowest.
morning 9am cortisol = 270-900
An Addison’s patient will have low cortisol throughout the day.
morning 9 am cortisol= 100
ACTH remains high
what does vitiligo determine for the patient?
the adrenal failure is of autoimmune cause. Also seen with Grave’s with thyroid destruction, here melanocytes are destroyed showing an autoimmune predisposition in the patient
what causes the loss of salt (in urine) and therefore the hyperkalaemia?
low aldosterone means that sodium in not reabsorbed as a result of RAS and therefore sodium is excreted while potassium remains unexchanged.
what test is used to identify Addison’s?
short synacthen
- 250 micrograms of synthetic ACTH administered i.m.
- this is a large dose to induce a large response
- cortisol response is measured: a poor response is indicative of Addisons (e.g. 100 to 150), Normally it should rise about 600
two types of Congenital Adrenal Hyperplasia (CAH)?
1) complete
2) partial
what are the four enzymatic deficiencies that caused CAH?
- complete 21- hydroxylase deficiency (most common)
- partial 21-hydroxylase deficiency
- 11-hydroxylase deficiency
- 17-hydroxylase deficiency
what is the most common cause of CAH?
complete 21-hydroxylase deficiency leading to no production of aldosterone or cortisol
how does hirsutism arise from complete 21-H deficiency?
overload of sex steroid production arm causing excess production as the other arms are useless
what is the presentation in children with 21-H deficiency?
- salt losing Addisonian crisis
- in utero the child receives steroids from the mother
- girls present more obvious effects that boys with ambiguous genitalia (virilisation) and may have clitormegaly.
- children survive for less than a few weeks
what happens in partial 21-H deficiency?
little amounts of aldosterone and cortisol are produced but not enough
sex steroids are still in excess
what is the presentation of partial deficiency of 21-H?
at any age, as they do survive
in later life hirsutism and virilisation for girls and precocious (early) puberty in boys
what are the symptoms of partial 21-H deficiency?
acne facial hirsutism small breasts clitoral enlargement heavy arms/legs
what occurs in the steroidogenesis pathway with 11-H deficiency
accumulation of the precursors of the products made by 11-H i.e. 11-deoxycorticosterone and 11- deoxycortisol, in the z.glomerulosa.
what are the consequences of 11-deoxycortisone accumulation due to 11-beta hydroxylase deficiency?
behaves like aldosterone so can cause hypertension (acts as weak mineralocorticoid)
and hypokalaemia (excess potassium excretion with aggravated RAS)
sex hormone shunting
what are the biochemical markers of 11-beta Hydroxylase deficiency?
- low cortisol and aldosterone
- excess sex steroids (sex steroid shunting)
and 11-deoxycorticosterone leads to virilisation, hypertension and hypokalaemia
what are the biochemical markers of 17-alpha Hydroxylase deficiency?
-low cortisol and SEX steroids
(17 OH progesterone precursor is not produced, 17 OH goes into sex steroids arm)
- high aldosterone: as progesterone remains only to make aldosterone in excess
what are the effects of 17-H deficiency?
- hypertension (excess aldosterone and 11-deoxycorticosterone)
- hypokalaemia
- sex steroid deficiency –> delayed puberty
- glucocorticoid deficiency (low cortisol) due to shunting into mineralocorticoids
what would a blood test for Addisons’ Disease show?
- low sodium (leads to hypotension)
- high potassium (due to low aldosterone–> low sodium retention, low potassium removal)
- ACTH and cortisol measurement
how can you diagnose Addisons with a short synacthen test?
if cortisol remains the same or barely changes
what leads to increased pigmentation?
POMC–> ACTH + MSH + endorphins and enkaphalins
continuous production of ACTH due to lack of negative feedback means MSH is made along side it continuously
MSH increase stimulation to melanocytes
what is the treatment for Addison’s?
- lifelong hydrocortisone
- steroid bracelet
- double dosage when ill
what is the treatment for Addisonian crisis?
- 0.9 saline (hyponatraemia)
- IV dextrose (hypoglycaemia–>cardiac arrest) and hydrocortisone
- IV insulin
what are the clinical features of Addisons?
low sodium
high potassium
low aldosterone
low cortisol
what are the effects of 21 hydroxylase deficiency?
- no aldosterone or cortisol
- sex steroid shunting (therefore ambiguous genitalia in neonates)
- Addisonian crisis (due to low aldosterone when suddenly stopping treatment, CAH or not doubling dose when ill)
what is looked at to detect 21 hydroxylase deficiency?
look for build up of 17 hydroxyprogesterone
what are the effects of partial 21 hydroxylase deficiency?
- there is some enzymatic activity
- therefore some aldosterone and some cortisol
- no Addisons crisis
- signs seen in early puberty
