Hypoadrenal disorders Flashcards
Recall the 4 possible causes of primary adrenal insufficiency, in order of decreasing prevalence worldwide
- Addisons disease - TB
- Addisons disease - AI
- Congenital adrenal hyperplasia
- Acute adrenal insufficiency
Describe how an individual is tested for Addison’s disease
9am Cortisol level measured
If low: give synacthen intramuscularly
Re-measure cortisol, if below 600 is positive for Addison’s
Where is the dysfunction in secondary adrenal insufficiency?
Adenohypophysis
Recall the simplified synthesis of aldosterone from cholesterol, naming the enzyme in each step
Cholesterol (P450scc) Pregnenolone (3-beta-hydroxysteroiddehydrogenase) Progesterone (21-alpha-hydroxylase) 11-deoxycorticosterone (11-alpha hydroxylase) corticosterone (18-alpha-hydroxylase) Aldosterone
Recall the simplified synthesis of cortisol from cholesterol, naming the enzyme in each step
Cholesterol (P450scc) Pregnenolone (3-beta-hydroxysteroiddehydrogenase) Progesterone (17-beta-hydroxysteroiddehydrogenase) 17-hydroxy-progesterone (21-alpha-hydroxylase) 11-deoxycortisol (11-alpha hydroxylase) cortisol
Recall the simplified synthesis of androgens and oestrogens from cholesterol, naming the enzyme in each step
Cholesterol (P450scc) Pregnenolone (3-beta-hydroxysteroiddehydrogenase) Progesterone (17-beta-hydroxysteroiddehydrogenase) 17-hydroxy-progesterone --> sex steroids
Recall which zone of the adrenals produces each different steroid
Z. Glomerulosa - Aldosterone
Z. Fasciculata - Cortisol
Z. Reticularis - sex steroids
List and explain 5 clinical features of Addison’s disease
- High pigmentation due to excess POMC cleavage
- Hypotension due to lack of salt
- Low sodium with high potassium due to loss of Na+/K+ exchanger
- Fall in glucose due to GC and MC deficiency
- Vitiligo (In AI disease)
What is the main presenting feature of an Addisonian crisis?
Sudden severe hypotension
What is the most common cause of congenital adrenal hyperplasia?
21-hydroxylase deficienct
Recall the hereditary pattern of CAH
Always recessive
Recall the clinical features for neonates (M and F) of complete absence of 21-alpha-H
In baby girls: virilisation; clitoromegaly, labial fusion
Often missed in boys: return to A&E as “floppy baby”
What is “simple virilising congenital adrenal hyperplasia” and how does it present?
Partial loss of 21-alpha-H
Individuals survive, may present later with virilisation etc
How does treatment of 11-alpha-H deficiency and 21-alpha-H deficiency differ and why?
In 11-alpha-H deficiency, 11-deoxycorticosterone is still produced and can replace aldosterone, so only the cortisol (and not aldosterone) needs to be replaced
How and when do patients with an 11-alpha-hydroxylase deficiency usually present?
About 6 years old: virilisation and HYPERtension
What is unusual about the presentation of 11-alpha-H deficiency compared to other congenital adrenal hyperplasias?
Have hypertension (rather than hypotension) as there is excess 11-deoxycorticosterone acting in the place of aldosterone
What hormones will be deficient in 17-alpha-hydroxylase deficiency?
Cortisol, sex steroids
Recall 2 features of 17-alpha-hydroxylase deficiency
- No puberty
2. Low glucose due to GC deficiency
Recall 2 medical treatment options for replacement of cortisol
Dexamethosone (1/day)
Hydrocortisone (2=3/day)
Recall the 3 lines of treatment that are required in CAH
- Replace cortisol
- Replace aldosterone with salt-wasting analogue
- Suppress ACTH to prevent over-production of adrenal androgens
What drug is used to replace aldosterone in CAH?
Fludrocortisone
What would show the glucocorticoid dosage in CAH treatment to be too high/low?
Too high –> Cushingoid
Too low –> hirsuitism
What biochemical marker can be used to measure corticosterone replacement therapy?
17-hydroxy-progesterone
What is it also important to bear in mind when administering cortisol-replacement therapy?
Dosage must be increased when patient is particularly vulnerable to stress
How are patients managed pre-operatively if they have adrenal insufficiency?
o The anaesthetists need to give IV hydrocortisone before operation, and then at periods after their operation
