7. Hypoadrenal disorders Flashcards
What 3 main hormones are involved in the hypothalamo-pituitary-adrenal axis?
- CRH - Corticotrophin Releasing hormone
- ACTH - Adrenocorticotrophic hormone/corticotrophin
- Cortisol
What do -trophic hormones do?
Cause target to grow
How many carbon atoms does cholesterol have?
27
What 2 main changes can be made to cholesterol to make different steroids?
Enzymes can hydroxylate or oxidise it at different positions
How is cortisol and aldosterone formed in the adrenal gland?
• Start with cholesterol • Pregnenolone formed in cortex • OH group put on: - 17, 21 and 11 => Cortisol - 21, 11 and 18 => Aldosterone • Enzymes are: number of OH position + hydroxylase e.g. 17-hydroxylase
What steroid synthesis pathways are present in the ovaries and testes?
- Sex steroid pathways/enzymes
* None of the mineralocorticoid and glucocorticoid pathways/enzymes
What turns glucocorticoid and sex steroid synthesis enzymes on?
- Stress detected by pituitary
* ACTH produced - turns on these enzymes
What turns on the enzymes in mineralocorticoid pathway to produce aldosterone?
Renin and angiotensin II
What is the most common cause of adrenocortical failure worldwide?
Tuberculous Addison’s Disease (particularly when stopping TB treatment early)
What is the most common cause of adrenocortical failure in the UK?
- Autoimmune Addison’s disease
* Immune system destroys adrenal gland
What is Congenital Adrenal Hyperplasia?
- Enzyme deficiency - hormones not made properly
- Stimulated by ACTH
- Adrenal gland become enlarged
- Born with big adrenals
What are the features of Addison’s disease?
- Pigmentation in mouth
- Darker hair, more pigmented skin, patches of vitiligo (antibodies against melanin)
- Tiredness
- Very low BP just before death
What are the consequences of adrenal failure in the body?
- Fall in BP - lack of aldosterone
- Loss of salt and rise in potassium - lack of aldosterone
- Fall in glucose - glucocorticoid deficiency (not too much due to insulin decrease)
- High ACTH - pigmentation
- Death due to severe hypotension
- Addisonian Crisis = happens suddenly
What is the link between adrenal failure and increased pigmentation?
- POMC from pituitary makes ACTH and MSH (melanocyte stimulating hormone)
- No adrenal gland - no cortisol - no negative feedback
- More ACTH produced - more MSH produced too
- Increased pigmentation
How do you test for Addison’s and what values should a normal person have?
• Measure hormones at 9am - normally high cortisol in morning • Measure diurnally - also low cortisol at night • Measure ACTH - normal levels • Short synACTHen test - injection of synthetic ACTH - 250mg of synacthen IM - sample cortisol before and after - normally lots of cortisol produced after
What values would a typical Addison’s patient show after testing?
- Low 9am cortisol - 100 (normal is 270-900)
- Very high ACTH
- Cortisol of 150, half an hour after IM synacthen (normal is >600)
What is the most common cause of Congenital Adrenal Hyperplasia?
- 21-hydroxylase deficiency
* Recessive
Describe the development and presentation of complete 21-hydroxylase deficiency in a baby
- Deficiency of aldosterone and cortisol
- Receive hormones from mother in utero, but not after birth
- Neonatal pituitary will make lots of ACTH
- After 9 months, huge but useless adrenal glands
- Adrenals can still make sex steroids - overflow of 17-hydroxyprogesterone
- Can’t survive a day without cortisol and aldosterone, but newborn has cortisol from mother for one day
- Loss of consciousness as they have a ‘salt losing Addisonian crisis’ after one day
- Doctors firstly give saline
- Sex steroids in excess - Testosterone causes clinical problems
- Virilisation - development of male physical characteristics in females
- Ambiguous genitalia
Describe the presentation and treatment of partial 21-hydroxylase deficiency
- Some enzymes work - low aldosterone and cortisol
- High ACTH
- A bit hypotensive but won’t die
- Long period of slightly raised testosterone
- May present at any age as they survive and don’t have an Addisonian crisis - present whenever they are unhappy with effects e.g. hirsuitism
- Treated with cortisol => reduces ACTH so less testosterone produced
Describe the presentation and treatment of 17-hydroxylase deficiency
• High levels of aldosterone - hypertensive and hypokalaemic
- No Addisonian crisis, despite missing cortisol
- Never go through puberty - no sex steroids
• Present around pubertal age
• Borderline hypoglycaemia
• Lot of infections - cortisol needed to cope with stress of infection
• Treated with missing hormones
- cortisol
- testosterone (boys) or oestrogen (girls)
