Endo 7: Hypoadrenal disorders

Question 1

Why is it called ACTH?

Answer 1

Trophic means growth! So it makes the adrenal gland hypertrophy as well as release cortisol

Question 2

What does ACTH do

Answer 2

Switches on enzymes in the zona fasciculata which allow cortisol production (17 alpha hydroxylase, 3b-HSD, 21 hydroxylase and 11beta hydroxylase). For aldosterone, RAAS activates these enzymes

Question 3

Pathway of aldosterone from progesterone

Answer 3

progesterone –>(by 21 hydr.) 11 deoxycorticosterone –> (by 11 hydroxy) corticosterone –> (by 18 hydrox.0 aldosterone

Question 4

Pathway of progesterone to cortisol

Answer 4

progesterone –>(by 17 hydrox.) 17OH progesterone –> (by 21) 11 deoxycortisol –> (by 11) cortisol

Question 5

Causes of adrenocortical failure

Answer 5

2 forms o

1. adrenal glands being destroyed
2. steroid synhesis enzyme deficiency

Question 6

Most common cause of adrenocortical failure (in world)

Answer 6

Tuberculous Addison’s disease

Question 7

Other form of adrenal gland destruction

Answer 7

Autoimmune Addison’s disease (commonest in UK)

Question 8

What disease results from steroid synthesis enzyme deficiency

Answer 8

Congenital adrenal hyperplasia (born with huge glands as they are stimulated by ACTH but have an enzyme deficiency so cannot produce it!)

Question 9

Consequences of adrenocortical failure

Answer 9

Hypotension (not enough aldosterone)
Loss of salt to the urine
Increase plasma K+
Fall in glucose due to glucocorticoid deficiency
High ACTH resulting in increased pigmentation
Vitiligo (another autoimmune disease)–> really stark in addisons because antibodies wipe out melanocytes (giving pale area) and really dark area because of the stimulate melanocytes)

Question 10

Why are addisons patients tanned

Answer 10

POMC –> MSH and ACTH and endorphins and enkephalins and other peptides

So because all the ACTH is being made as there’s no negative feedback due to lack of cortisol, lots of MSH is being released and this is stimulating melanocytes and leading to tanning.

Question 11

Why is addisons dangerous

Answer 11

Blood pressure keeps falling because you’re losing loads of salt (due to lack of aldosterone) so you die

Question 12

How do you test for addisons

Answer 12

1. You test ACTH in the morning.
   At 9am, cortisol is normally to be high, so ACTH should be low. If the cortisol is low and ACTH high at 9am, then you need to investigate further. Normal cortisol at 9am (270-900nm), so addisons might be 100nm.
2. SynACTHen test
   Give them 250ug im synACTHen. The cortisol should increase to over 600nm. If it increased from 100nm –> 150nm, it would be a fail and then they have addisons

Question 13

Commonest cause congenital adrenal hyperplasia

Answer 13

21 hydroxylase deficiency (recessive condition) –> complete and partial

Question 14

Differentiate effect of complete and partial hyperplasia

Answer 14

if complete- only 24 hours to live because you have no aldosterone and no cortisol

If partial

Question 15

Which steroids will there be an abundance of in complete 21 hydroxylase deficiency, and what will there be a lack of

Answer 15

excess sex steroids especially testosterone (so very virilised- and you get floppy baby)

lack of cortisol and aldosterone

So they cannot retain any salt or make any sugars

Question 16

Why do neonates not die in utero if they have 21 hydroxylase deficiency

Answer 16

Because they get the hormones from their mum- but once born if they have complete deficiency they’ll have an addisonian crisis- or a ‘salt losing’ crisis because they lose all their salt and become very hypotensive and die of shock

Question 17

What is the age of presentation and symptom of complete 21 hydroxylase deficiency

Answer 17

As neonate with salt losing addisonian crisis and girls may have ambiguous genitalia (due to excess testosterone- they have a fused labia like a scrotum)- this could really indicate that they’re about to die of a salt losing crisis.

Present in 24 hrs.

So girls are VIRILISED by adrenal testosterone

Question 18

Which steroids will there be an abundance of in partial 21 hydroxylase deficiency, and what will there be a lack of . Symptoms

Answer 18

Cortisol and aldosterone are deficient but not absent. Sex steroids and testerone in excess.

They can present at any age, as they survive at birth.

Question 19

Problems with partial 21 hydroxylase deficiency

Answer 19

Main problem in later life is hirsutism and virilisation in girls and precocious puberty in boys due to adrenal testosterone

Question 20

Appearance of partial 21 hydroxylase decifiency in female

Answer 20

Facial hair, small breasts, ACTH high, cortisol low, testosterone causes baldness and acne and clitoris enlargement and large adrenal glands, variable pigmentation, heavy muscular arms and legs

Question 21

What are consequences of 11 hydroxylase deficiency

Answer 21

11 deoxycorticosterone (usually only in the adrenal cortex as a precursor to aldosterone) builds up, enters circulation and acts like aldosterone so binds to MR so you have hypertension and hypokalaemia, which is the opposite of what you’d expect with aldosterone deficiency!

So the kids are born with no salt losing crisis.

Their problem is with virilisation.

So virilisation, HTN and low K+

Question 22

Which hormones are deficient in 11 hydroxylase deficiency and whcih in excess

Answer 22

cortisol and aldosterone deficient

excess is 11 deoxycorticosterone and sex steroids and testosterone.

Question 23

Which hormones are deficient in 17 hydroxylase deficiency and whcih in excess

Answer 23

Cortisol and sex steroid deficiency

Lots of aldosterone and 11 deoxycorticosterone

Question 24

Problems with 17 hydroxylase

Answer 24

Hypertension, low K, sex steroids deficiency, and glucocorticoid deficiency (low glucose) because enzyme is deficient in testes and ovaries too. Never go through puberty!