adrenal pathway dysfunction

Question 1

What biochemical molecule are steroid hormones made from?

Answer 1

cholesterol

Question 2

which steroid hormones are produced in the adrenal cortex?

Answer 2

1. mineralocorticoids (aldosterone)
2. Glucocorticoids (cortisol)
3. Sex steroids (androgens, oestrogens)

Question 3

Angiotensin 2 activates which enzymes and produces which hormone?

Answer 3

• side chain cleavage
• 3 hydroxysteroid dehydrogenase

1. 21 hydroxylase
2. 11 hydroxylase
3. 18 hydroxylase

aldosterone

Question 4

ACTH activates which enzymes in the adrenal, producing which hormone?

Answer 4

cortisol

• side-chain cleavage
• 3 hydroxysteroid dehydrogenase

1. 17 hydroxylase
2. 21 hydroxylase
3. 11 hydroxylase

Question 5

what does aldosterone do?

Answer 5

stimulates sodium reabsorption in distal convoluted tubule and collecting duct, stimulates potassium and H+ secretion into urine

causes water to follow sodium back into blood by osmosis, increasing blood volume

therefore

increases blood pressure, sodium and lowers potassium

Question 6

Addison’s disease is what kind of adrenal failure?

Answer 6

primary adrenal failure

Question 7

what is the most common cause of addison’s disease in the UK?

Answer 7

Autoimmune destroying adrenals

Question 8

What is the most common cause of Addison’s disease worldwide?

Answer 8

tuberculosis of adrenal glands

Question 9

These are a symptom of what disease:

• hyperpigmentation
• low BP
• weakness
• weight loss
• nausea and GI problems
• vitiligo

Answer 9

Addison’s disease (primary adrenal failure)

Question 10

Why is there increased pigmentation in Addison’s disease?

Answer 10

Lack of negative feedback of cortisol to the anterior pituitary, driving ACTH upwards.

pro-opio melanocortin is the precursor of ACTH and is broken down to ACTH and MSH (melanocyte-stimulating hormone)

Therefore increased production of ACTH also results in equally increased production of MSH

Question 11

Why do people with addison’s disease have low blood pressure?

Answer 11

no cortisol or aldosterone

Question 12

what are the consequences of adrenocortical failure?

Answer 12

• fall in BP
• loss of salt in urine
• increased plasma potassium
• fall in glucose due to glucocorticoid deficiency
• eventual death due to hypotension if untreated

Question 14

What is the test for Addison’s?

Answer 14

1. 9am cortisol
2. Gie 250micrograms synacthen (synthetic ACTH) and measure cortisol response - will be low-zero

Question 15

What will be the levels of ACTH and cortisol in the 9am cortisol test in Addison’s?

Answer 15

low cortisol

high ACTH

Question 16

why do we give fludrocortisone instead of aldosterone when treating Addison’s disease?

Answer 16

fludrocortisone has a long enough half-life to be given once daily

Question 17

what are the drugs that can be given for Addison’s disease and why?

Answer 17

1. Fludrocortisone to replace aldosterone
2. Prednisolone once daily or hydrocortisone 3x daily

Question 18

What does of fludrocortisone should be given once daily?

Answer 18

50-100mg

Question 19

Which drug: prednisolone or hydrocortisone, has a suitable half-life to mimic cortisol?

Answer 19

prednisolone

Question 20

What dose should hydrocortisone be given at, and why?

Answer 20

3x daily 10 + 5 + 2.5mg to mimic diurnal rhythm

Question 21

What does of prednisolone should be given?

Answer 21

3mg daily

Question 22

What is the downside of using hydrocortisone 3x daily?

Answer 22

produces peaks which are unnatural and can affect metabolism and sleep

Question 23

Congenital 21 hydroxylase deficiency causes an increase in which hormones?

Answer 23

sex steroids

Question 24

why do people with congenital 21 hydroxylase deficiency have adrenal hyperplasia?

Answer 24

large amount of ACTH produced to try and stimulate hormone release

Question 25

what sexual/reproductive implications does 21 hydroxylase deficiency/congenital adrenal hyperplasia cause in girls?

Answer 25

• cliteromegaly
• labial fusion
• ambiguous genitalia

Question 26

Which hormones are absent in 21 hydroxylase deficiency?

Answer 26

aldosterone and cortisol

Question 27

what happens after birth in a baby with undiagnosed 21 hydroxylase deficiency?

Answer 27

salt losing addisonian crisis

Question 28

why does a baby with 21 hydroxylase deficiency not have problems while in utero?

Answer 28

foetus gets steroids across the placenta

Question 29

what problems arise later in life with partial 21 hydroxylase deficiency in girls and in boys?

Answer 29

girls - hirsutism, virilisation

boys - early puberty due to adrenal testosterone

Question 30

11 hydroxylase deficiency causes excess production of what?

Why?

Answer 30

11 deoxycortisone

because no cortisol or aldosterone are made due to the deficiency, so instead their precursors are made in excess, and the precursor of aldosterone, 11 deoxycortisone, has a similar effect to aldosterone

Question 31

Excess deoxycortisone and sex steroids/testosterone is caused by?

What 3 things does it cause, when in excess?

Answer 31

11 hydroxylase deficiency

hypertension, hypokalaemia, virilisation in females

Question 32

17- hydroxylase deficiency results in a lack of?

Answer 32

sex steroids and cortisol

Question 33

17-hydroxylase deficiency causes?

Answer 33

feminisation (no testosterone)

hypoglycaemia (no cortisol)

hypertension and hyperkalaemia (excess aldosterone)

never go through puberty

Question 34

what are the metabolic effects of cortisol?

Answer 34

peripheral protein catabolism

hepatic gluconeogenesis

increased blood glucose concentration

fat metabolism

enhanced effects of glucagon