Hypoadrenal Disorders Flashcards
Number of carbons in cholesterol?
27
Pathway for aldosterone production from cholesterol?
Cholesterol -> 11deoxycorticosteron -> corticosterone -> aldosterone
Pathway for sex steroids production from cholesterol?
Progesterone -> 17hydroxyprogesterone -> sex steroids
Pathway for cortisol production from cholesterol?
Progesterone -> 17hydroxyprogesterone -> 11deoxycortisol -> cortisol
What molecule is produced from adding OH to C21, 11 and 18
aldosterone
What molecule is produced from adding OH to C17, 21 and 11
cortisol
which carbons are hydroxylated to produce aldosterone
C21, 11 and 18
which carbons are hydroxylated to produce cortisol
C17, 21 and 11
Non specific causes of ADRENOCORTICAL FAILURE? (2)
- Adrenal glands destroyed
2. Enzymes in the steroid synthetic pathway not working
CAUSES OF ADRENOCORTICAL FAILURE (SPECIFIC): (3)
- Tuberculosis Addison’s disease (COMMONEST WORLDWIDE)
- Autoimmune Addison’s disease (COMMONEST IN UK)
- Congenital adrenal hyperplasia
CONSEQUENCES OF ADRENOCORTICAL FAILURE:? (6)
- Fall in BP Loss of sodium (+water)
- Loss of salt in the urine
- Increased plasma potassium Loss of Na+/K+ exchanger
- Fall in glucose due to glucocorticoid deficiency
- High ACTH resulting in increased pigmentation ACTH co-secreted with MSH
- Eventual death due to hypotension
What is POMC
Synthesised in the pituitary and broken down into ACTH and MSH (and endorphins and enkephalins and other peptides)
Test for Addison? (3)
- 9am cortisol Low
- ACTH High Attempting to make adrenal glands release more cortisol
- Short synacthen test (synACTHen= synthetic ACTH) Give 250ug synacthen intramuscularly Measure cortisol response A normal person will release more cortisol, but someone with Addison’s won’t
What enzyme does the side chain cleavages in cholesterol product synthesis
P450 scc
CONGENITAL ADRENAL HYPERPLASIA:
Most commonly caused by ….
21-hydroxylase deficiency
COMPLETE 21-HYDROXYLASE DEFICIENCY results in …
No aldosterone or cortisol Can’t survive without these for more than 24hrs
Foetal survival with COMPLETE 21-HYDROXYLASE DEFICIENCY?
- Foetuses can survive in the placenta with maternal aldosterone and cortisol, but not after birth -> BP drops rapidly
Symptoms of COMPLETE 21-HYDROXYLASE DEFICIENCY in foetus? how to spot a foetus with it?
- Get excessive sex steroid synthesis Girls hard to identify sexuality- labial fusion and cliteromegaly (virilised) Sexual ambiguity is a key sign
Treatment for COMPLETE 21-HYDROXYLASE DEFICIENCY
Suppress ACTH, minimise excessive hormones, (surgically correct anatomical features Girls only), saline
How do neonates present with COMPLETE 21-HYDROXYLASE DEFICIENCY
As a neonate with a salt losing Addisonian crisis
What is Addisons disease
Adrenocortical failure to produce aldosterone and cortisol
Why does 11-HYDROXYLASE DEFICIENCY not result in hypotension?
No salt losing crisis (hypotension) because 11 deoxy corticosterone can act similarly to aldosterone
Symptoms of 11-HYDROXYLASE DEFICIENCY (5)
- High BP due to sodium retention
- Virilisation due to excess sex steroids
- Low potassium
- Excess sex steroids and testosterone and 11-deoxycorticosterone
- Deficient cortisol and aldosterone
17-HYDROXYLASE DEFICIENCY: results in (levels of XYZ hormones)?
- Cortisol and sex steroid deficiency
- Excess mineralocorticoids (11-deoxycorticosterone and aldosterone)
Problems with 17-hydroxylase deficiency?
hypertension, low K, sex steroid deficiency, glucocorticoid deficiency (low glucose)
