7. Hypoadrenal disorders

Question 1

where are corticotrophin releasing hormone and adrenocorticotrophin hormone (corticotrophin) produced?

Answer 1

corticotrophin releasing hormone (CRH) - hypothalamus

adrenocorticotrophin hormone (corticotrophin) - pituitary

Question 2

what is cholesterol converted to and where?

Answer 2

pregnenolone

converted by enzymes in the zona glomerulosa

Question 3

how is cholesterol converted to aldosterone?

Answer 3

in the cortex by adding OH groups in various positions

Question 4

why is the glucocorticoid route different to the mineralocorticoid route?

Answer 4

the glucocorticoid route is different because the zona fasciculata has slightly different enzymes

Question 5

outline the conversion of cholesterol to aldosterone

Answer 5

cholesterol -> pregnenolone -> progesterone -> 11-deoxycorticosterone -> corticosterone -> aldosterone

Question 6

outline the conversion of cholesterol to cortisol

Answer 6

cholesterol -> pregnenolone -> progesterone -> 17𝛼-hydroxyprogesterone -> 11-deoxycortisol -> cortisol

Question 7

outline the conversion of cholesterol to 17𝛽-oestradiol

Answer 7

cholesterol -> pregnenolone -> 17𝛼-hydroxypregnenolone -> 17𝛼-hydroxyprogesterone -> androstenedione -> testosterone ->1 7𝛽-oestradiol (⇄ oestrone)

Question 8

what does P450scc do?

Answer 8

it is the enzyme involved in side chain cleavage

Question 9

what are glucocorticoid synthesis enzymes and sex steroid synthesis enzymes turned on by?

Answer 9

ACTH (pituitary detects stress and produces ACTH to make more cortisol)

Question 10

what are the causes of adrenocortical failure?

Answer 10

tuberculosis addison’s disease - occurs when you stop a course of treatment early (MOST COMMON IN WORLD)

autoimmune addison’s disease - occurs when the immune system makes a mistake and wipes out the adrenal gland (MOST COMMON IN UK)

congenital adrenal hyperplasia - autosomal recessive disorder which means you’re born with bigger adrenal glands that have an enzyme deficiency so you can’t make hormones properly

Question 11

what are the signs and symptoms of addison’s disease?

Answer 11

• fall in BP (no aldosterone) -> eventual death due to severe hypotension
• loss of salt in urine (less Na retention)
• increased plasma potassium (less K excretion)
• fall in glucose (glucocorticoid deficiency)
• increased pigmentation in mouth, hair and skin (due to high MSH)
• patches of vitiligo

Question 12

what is the link between adrenal failure and increased pigmentation?

Answer 12

ACTH is made from POMC (pro-opio melanocortin) which has 2 compartments: ACTH and MSH (melanocyte stimulating hormone)

because there is no adrenal gland there is no cortisol, so there is no -ve feedback and lots of ACTH is released

high ACTH = high MSH = increased pigmentation

Question 13

what is the test for addison’s?

Answer 13

measure the hormones at 9am (cortisol should be high)

if cortisol is low this may be addison’s

ACTH should therefore be really high

give injection of synthetic ACTH (250mg synacthen) - if adrenals are functioning they should produce cortisol

Question 14

what signs do a typical addison’s patient show after testing for addison’s?

Answer 14

low 9am cortisol (normal is 270-900)

cortisol of 100 1/2 hour after administering synacthen (should be >600 in normal)

Question 15

what is congenital adrenal hyperplasia caused by and what does it present with?

Answer 15

commonly caused by 21-hydroxylase deficiency (complete or partial)

presents with hypotension and virilisation (development of male physical characteristics in females)

Question 16

what is complete 21-hydroxylase deficiency?

Answer 16

aldosterone and cortisol are completely absent

Question 17

how does complete 21-hydroxylase deficiency present?

Answer 17

people present with congenital adrenal hyperplasia (CAH) by 1 week old

• sex steroids and testosterone will be in XS (due to XS 17-hydroxyprogesterone)
• girls may have ambiguous genitalia
• if there is ambiguity there is a risk of death because this is a sign of CAH
• in boy’s the genitalia is normal so CAH may be missed

Question 18

what is the treatment of complete 21-hydroxylase deficiency?

Answer 18

the baby can survive for a day because of the mother’s cortisol and aldosterone

• after a day the baby loses consciousness and has salt-losing addisonian crisis -> give SALINE
• the baby is given hydrocortisone and fludrocortisone to replace aldosterone

Question 19

what is partial 21-hydroxylase deficiency?

Answer 19

aldosterone and cortisol are still absent but patient is born with just enough aldosterone and cortisol

Question 20

how does partial 21-hydroxylase deficiency present?

Answer 20

people present with CAH at any age as they don’t have addisonian crisis

• sex steroids and testosterone in XS
• hirsutism (hair growth) and virilisation (male physique) in girls in later life
• early puberty in boys due to adrenal testosterone

Question 21

what are the signs of partial 21-hydroxylase in females?

Answer 21

• receding hair line/baldness
• acne
• facial hair
• variable pigmentation
• small breasts
• clitoral enlargement
• muscular arms and legs
• facial flush

Question 22

what is 11-𝛽 hydroxylase deficiency?

Answer 22

RECESSIVE

• results in a build up of 11-deoxycorticosterone (active aldosterone receptor agonist)
• patients are technically deficient in both aldosterone and cortisol but behave like they have XS aldosterone

Question 23

what do patients with 11-𝛽 hydroxylase deficiency present with?

Answer 23

• hypertensive in childhood
• hypokalaemic
• virilisitation

Question 24

what is 17 hydroxylase deficiency?

Answer 24

RECESSIVE

• high levels of aldosterone but are missing cortisol and sex steroids
• aldosterone and 11-deoxycorticosterone are in XS

Question 25

what do patients with 17 hydroxylase deficiency present with?

Answer 25

- hypertension - hypokalaemia - don't go through puberty (sex steroid deficient) - borderline hypoglycaemia (lack of glucocorticoid stimulation) - susceptible to infection (cortisol deficient)