Hypoadrenal Disorders Flashcards
What two hormones are involved in the hypothalamo-pituitary-adrenal axis?
CRH - Corticotrophin releasing hormone
ACTH - AdrenoCorticoTrophic Hormone (corticotrophin)
Why are some of the ant. pituitary called “trophins”?
Cause growth of the gland
e.g. corticotrophin causes adrenal glands to grow and release cortisol
What is the precursor molecule of all steroids?
Cholesterol
What is the first molecule produced after enzyme action on cholesterol?
Pregnenolone
What steroid hormones do the zona glomerulosa, zona fasciculata, testes/ovaries make?
Zona glomerulosa - Aldosterone
Zona fasciculata - Cortisol
Testes/ovaries - sex steroids (testosterone, androgens, oestrogens)
What is the crucial enzyme type throughout steroid synthesis and why do they have different numbers?
Hydroxylases
- Numbered to reflect the carbon in the steroid they act on
Recreate, on paper, the pathway of steroid synthesis including aldosterone, cortisol and sex steroids. Include the number of the hydroxylase enzyme involved in each step. (Found in PPT)
Cholesterol to progesterone (general first step)
Progesterone –21–> 11 deoxycorticosterone –11–> corticosterone –18–> aldosterone
Progesterone –17–> 17 OH progesterone –21–> 11 deoxycortisol –11–> cortisol
Progesterone –17–> 17 OH progesterone –> sex steroids
What are the 3 causes of adrenocortical failure?
Addison’s disease is destruction of adrenal glands
- Tuberculous Addison’s disease
- Autoimmune Addison’s disease
- Congenital adrenal hyperplasia (hydroxylase enzymes missing so low cortisol, tons of ACTH make adrenal glands grow and grow so born with enormous adrenal glands that can’t make cortisol)
What are the consequences of adrenocortical failure?
- Fall in blood pressure
- Loss of salt in the urine
- Increased plasma potassium with low sodium
- Fall in glucose due to glucocorticoid deficiency
- High ACTH resulting in increased pigmentation
- Eventual death due to severe hypotension
Why does increased pigmentation occur in hypoadrenalism?
Pro-hormone for ACTH is POMC
- Pro-opio melanocortin
- Synthesised in pituitary and broken down into ACTH and MSH (melanocyte stimulating hormone) and a bunch of other stuff
- MSH is the key here
What other diseases can come with autoimmune Addison’s disease?
Autoimmune diseases go together
- e.g. autoimmune thyroid disease WITH autoimmune adrenal disease
- vitiligo (melanocyte destruction), loss of pigmentation in patches
What’s the first step in diagnosing Addison’s disease?
First step is to actually THINK of it
- listen to the patient and have it in the back of your mind
What are the tests for Addition’s disease?
9am cortisol = low (should be high)
ACTH = high (while cortisol is low)
Short synACTHen test
- given 250 micrograms synacthen intramuscularly
- measure cortisol response, should be high and rapid response, if not, Addison’s
What are the cortisol levels in a typical Addison’s patient at 9am and after IM synACTHen as well as normal parameters?
Cortisol at 9am = 100 (270-900)
Administer synACTHen intramuscularly
Cortisol at 9:30am = 150 (>600)
What is the commonest cause of congenital adrenal hyperplasia?
21-hydroxylase deficiency
What are the two types of congenital adrenal hyperplasia (CAH)?
Complete
Partial
In complete 21-hydroxylase deficiency, which hormones will be totally absent, how long can you survive, and which hormones will be in excess?
- Aldosterone and cortisol
- Less than 24 hours (out of womb)
- Sex steroids and testosterone
What is the age of presentation of complete 21 hydroxylase deficiency and what happens in girls who have this?
As a neonate with a salt-losing Addisonian crisis
- Before birth, (while in utero), foetus gets steroids across placenta normally, they’re born and lose that source of hormone and go straight into Addisonian crisis
Girls might have ambiguous genitalia (virilised by adrenal testosterone), very worrying as sign of complete 21 H deficiency, must be treated straight away before they go into Addisonian crisi
In partial 21-hydroxylase deficiency, which hormones are deficient, which hormones are in excess, and what age will they present?
- Cortisol and aldosterone
- Sex steroids and testosterone
- Any age as they will survive birth
Why does sex steroid and testosterone production get boosted in both complete and partial 21-hydroxylase deficiency?
Again, back to the diagram for steroid synthesis
- if 21-H is only partially working, cortisol levels will be low so more 17-OH prog is produced to try and make more cortisol, this boosts sex hormone/testosterone production above normal while getting cortisol levels to somewhere near normal
- if 21-H is not working at all, there is no cortisol so even more 17-OH prog is made with no cortisol production and huge sex steroid/testosterone production
What are the main problems with partial 21-hydroxylase deficiency in boys and girls and when do these problems present?
- Hirsutism (hairiness) and virilisation in girls
- Precocious puberty in boys
All due to adrenal testosterone
What changes take place in the adrenal glands of a partially 21-H deficient patient and why?
Hyperplasia (large growth) of adrenal glands
- never enough cortisol to suppress ACTH release via negative feedback thus constant stimulation of adrenal gland growth
In 11-hydroxylase deficiency, which steroid hormones are deficient and which hormones are in excess?
Consult the diagram (memorise it)
- Cortisol and aldosterone
- Sex steroids, testosterone and 11-deoxycorticosterone
Why are there aldosterone effects seen in 11-hydroxylase deficient children despite their inability to make aldosterone?
11-deoxycorticosterone is the steroid created after progesterone two steps before aldosterone production
- This steroid can bind to aldosterone receptors and so stimulates effects normally produced by aldosterone
