7. Hypoadrenal disorders

Question 1

What 3 main hormones are involved in the hypothalamo-pituitary-adrenal axis?

Answer 1

• CRH - Corticotrophin Releasing hormone
• ACTH - Adrenocorticotrophic hormone/corticotrophin
• Cortisol

Question 2

What do -trophic hormones do?

Answer 2

Cause target to grow

Question 3

How many carbon atoms does cholesterol have?

Answer 3

27

Question 4

What 2 main changes can be made to cholesterol to make different steroids?

Answer 4

Enzymes can hydroxylate or oxidise it at different positions

Question 5

How is cortisol and aldosterone formed in the adrenal gland?

Answer 5

• 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

Question 6

What steroid synthesis pathways are present in the ovaries and testes?

Answer 6

• Sex steroid pathways/enzymes

* None of the mineralocorticoid and glucocorticoid pathways/enzymes

Question 7

What turns glucocorticoid and sex steroid synthesis enzymes on?

Answer 7

• Stress detected by pituitary

* ACTH produced - turns on these enzymes

Question 8

What turns on the enzymes in mineralocorticoid pathway to produce aldosterone?

Answer 8

Renin and angiotensin II

Question 9

What is the most common cause of adrenocortical failure worldwide?

Answer 9

Tuberculous Addison’s Disease (particularly when stopping TB treatment early)

Question 10

What is the most common cause of adrenocortical failure in the UK?

Answer 10

• Autoimmune Addison’s disease

* Immune system destroys adrenal gland

Question 11

What is Congenital Adrenal Hyperplasia?

Answer 11

• Enzyme deficiency - hormones not made properly
• Stimulated by ACTH
• Adrenal gland become enlarged
• Born with big adrenals

Question 12

What are the features of Addison’s disease?

Answer 12

• Pigmentation in mouth
• Darker hair, more pigmented skin, patches of vitiligo (antibodies against melanin)
• Tiredness
• Very low BP just before death

Question 13

What are the consequences of adrenal failure in the body?

Answer 13

• 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

Question 14

What is the link between adrenal failure and increased pigmentation?

Answer 14

• 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

Question 15

How do you test for Addison’s and what values should a normal person have?

Answer 15

• 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

Question 16

What values would a typical Addison’s patient show after testing?

Answer 16

• Low 9am cortisol - 100 (normal is 270-900)
• Very high ACTH
• Cortisol of 150, half an hour after IM synacthen (normal is >600)

Question 17

What is the most common cause of Congenital Adrenal Hyperplasia?

Answer 17

• 21-hydroxylase deficiency

* Recessive

Question 18

Describe the development and presentation of complete 21-hydroxylase deficiency in a baby

Answer 18

• 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

Question 19

Describe the presentation and treatment of partial 21-hydroxylase deficiency

Answer 19

• 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

Question 20

Describe the presentation and treatment of 17-hydroxylase deficiency

Answer 20

• 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)