Hypoadrenal disorders Flashcards
What is:
CRH, ACTH, POMC, MSH?
CRH - corticoptrophin releasing hormones
ACTH - adrenocorticotrophin hormone
POMC - proopiomelanocortin
MSH - melanocyte stimulating hormone
What are the three main steroid synthesis pathways?
cortisol, aldosterone and sex steroids
Describe the pathway converting progesterone to cortisol and enzymes
progesterone -> 17 OH progestrone -> 11 deoxycortisol -> cortisol
enzymes: 17, 21 and 11 hydroxylase
Describe the pathway converting progesterone to aldosterone including the enzymes
progestrone, 11 deoxycorticosterone, corticosterone, aldosterone
enzymes: 21, 11 and 18 hydroxylase
What are the causes of adrenal failure?
Adrenal glands destroyed:
- TB Addison’s disease (most common worldwide)
- Autoimmune Addison’s disease (most common in UK)
- Congenital adrenal hyperplasia (gland overgrows but does not function properly)
Enzymes in the steroid synthetic pathway not working
What are the signs and symptoms of adrenocortical failure?
- Hypotension
- Loss of salt in the urine
- Hyperkalaemia (caused by loss of aldosterone)
- Hypoglycaemia (due to glucocorticoid deficiency)
- High ACTH -> hyperpigmentation
- Eventual death due to severe hypotension
Why does high ACTH occur in Addison’s and how does this cause hyperpigmentation?
High ACTH due to loss of negative feedback by cortisol on the pituitary
POMC -> ACTH + MSH (leading to hyperpigmentation)
What would a blood test for Addison’s disease show?
9am Cortisol = 100 (normal range: 270-900)
ACTH = high
Which test can be used for Addison’s?
Short synacthen test
- Give 250 micrograms of synacthen (synthetic ACTH )– this is a large dose of ACTH and should induce a large response in a healthy individual
- Measure the cortisol response
- If the cortisol response barely changes (e.g. goes from 100 to 150) they have Addison’s
What is congenital adrenal hyperplasia?
CAH are inherited conditions that are congenital where the adrenal gland is hyperplastic. There is a missing enzyme that normally stimulates the adrenal glands to release the cortisol hormone
What are the four types of CAH?
Complete 21-hydroxylase deficiency
Partial 21-hydroxylase deficiency
11-hyroxylase deficiency
17-hydroxylase deficiency
What is the most common cause of CAH?
complete 21 hydroxylase deficiency
What happens in complete 21 hydroxylase deficiency?
Leads to noproduction of aldosterone or cortisol but excess of sex steroids
What is the presentation of individuals with complete 21 hydroxylase deficiency?
- This will usually be in the form of a salt losing Addisonian crisis
- In-utero the child will be fine as they receive steroids from the mother
- Girls present more obviously than boys due to ambiguous genitalia (virilisation) and may have clitoromegaly
What hormones are deficient in partial 21 hydroxylase deficiency?
Cortisol and aldosterone
What hormones are in excess in partial 21 hydroxylase deficiency?
Sex steroids: testosterone
What is the age of presentation for partial 21 hydroxylase deficiency?
Any age (as they survive)
The main problem is in later life with hirsutism and virilisation in girls and precocious puberty in boys
What are the signs and symptoms of partial 21 hydroxylase deficiency??
Acne, facial hirsutism, small breasts, clitoral enlargement, heavy arms/legs
What is the age of presentation for complete 21 hydroxylase deficiency?
Children with this will present at 1 week-old
What does 11- deoxycorticosterone behave like and what does this mean?
Behaves like aldosterone and so in excess (accumulation in zona glomerulosa) it can cause hypertension and hypokalaemia
What hormones are deficient in 11- hydroxylase deficiency?
Cortisol and aldosterone
What hormones are in excess in 11- hydroxylase deficiency?
Sex steroids and testosterone and 11-deoxycorticosterone
What are the signs and symptoms of 11 hydroxylase deficiency?
Virilisation, hypertension, hypokalaemia
What hormones are deficient in 17 hydroxylase deficiency?
Cortisol and sex steroids
