Primary Adrenal Failure

Question 1

What is a steroid?

Answer 1

Comes from Cholesterol

Question 2

What is the effect of Angiotensin 2?

Answer 2

Stimulates production of Aldosterone in the Adrenal gland. Controls blood pressure, sodium and potassium.

Question 3

What is the mechanism of action of Angiotensin 2?

Answer 3

Activation of the following enzymes in the zona glomerulosa
Side Chain Cleavage
3 Hydroxysteroid dehydrogenase
21 hydroxylase
11 hydroxylase
18 hydroxylase

Question 4

What is the mechanism of action of ACTH on the Adrenal glands?

Answer 4

Activation of the following enzymes in the zona fesiculata
Side Chain Cleavage
3 Hydroxysteroid dehydrogenase
21 hydroxylase
11 hydroxylase
17 hydroxylase

Question 5

What is cortisols rhythm?

Answer 5

Diurnal, best time to test in in the morning when it should be the highest.

Question 6

What is Primary adrenal failure?

Answer 6

Autoimmune disease where the immune system decides to destroy the adrenal cortex (UK)
TB is still the commonest cause worldwise.

Question 7

What happens in Primary adrenal failure?

Answer 7

Not enough steroids produced

Not enough cortisol or aldosterone

Question 8

How does Addison’s present?

Answer 8

Increased pigmentation
Autoimmune vitiligo may coexist
No cortisol or aldosterone, so low blood pressure

Question 9

Why do patients with Addison’s disease have a good tan?

Answer 9

High MSH due to Pro-opio-melanocortin POMC cleaved to form many smaller peptides, including ACTH, MSH.
High ACTH means high MSH.

Question 10

What is the third possible cause of Primary Adrenal failure?

Answer 10

Congenital adrenal hyperplasia

Question 11

What are the consequences of adrenocortical failure?

Answer 11

Fall in blood pressure
Loss of salt in the urine
Increased plasma potassium
Fall in glucose due to glucocorticoid deficiency
High ACTH resulting in increased pigmentation
Eventual death due to severe hypotension

Question 12

What are the tests for Addison’s disease?

Answer 12

9am cortisol = low
ACTH = high
Short synACTHen test
Give 250 ug synacthen IM
Measure cortisol response

Question 13

Why is Fludrocortisone 50-100mcg daily used instead of Aldosterone?

Answer 13

Aldosterone has a very short half life, not safe for once daily administration. Fluorine takes longer to be metabolised as it is not present naturally. It has a longer half life and binds to both MR & GR.

Question 14

What is the problem with giving aldosterone multiple times a day?

Answer 14

Multiple peaks can be harmful.

Question 15

Why is 2-4mg of prednisolone once daily used instead of 12-15mg of hydrocortisone split throughout the day?

Answer 15

Prednisolone has a longer half life and is more potent than cortisol
2.3x binding affinity than cortisol

Replacement dose 3-4mg ONCE daily

Question 16

What is the problem with higher doses of Prednisolone?

Answer 16

Increased mortality due to adrenal insufficiency, steroid exposure.

Question 17

What is the treatment for a patient with Adrenal failure?

Answer 17

Hydrocortisone three times daily (10 + 5 + 2.5)
Prednisolone 3mg daily

Fludrocortisone 50 to 100 mcg daily

Question 18

What happens in complete Congenital Adrenal Hyperplasia?

Answer 18

21-hydroxylase deficiency. Aldosterone and Cortisol will be absent. You cannot survive more than a few hours. you can have a salt losing adddisonian crisis when you’re less than a day old. Can be treated with saline + hydrocortisone as a neonate. In utero foetus gets steroids across the placenta.
Enlarged Adrenal glands

Question 19

Why do you have increased sex steroids & testosterone in utero in Congenital Adrenal Hyperplasia?

Answer 19

Increased ACTH production. Girls might have ambiguous gentialia.

Question 20

What happens in partial Congenital Adrenal Hyperplasia?

Answer 20

Partial 21 hydroxylase deficiency means that there will be a bit of aldosterone and cortisol to get by with. Low in aldosterone and cortisol. High testosterone. Can present at any age, but may have facial hair as a child.
Enlarged Adrenal glands

Question 21

What is the main problem later on in life for someone with partial congenital adrenal hyperplasia?

Answer 21

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

Question 22

What is the most common defficiency?

Answer 22

21 - 90%
11 - 10%
17

Question 23

What happens if you have 11-hydroxylase deficiency ?

Answer 23

11 deoxycorticosterone behaves like aldosterone

In excess it can cause hypertension and hypokalaemia

Question 24

What are the features of 11-hydroxylase deficiency?

Answer 24

Cortisol and Aldosterone deficient.
Sex steroids, testosterone & 11-deoxycorticosterone are in excess.
Main problems are virilisation, hypertension and low Potassium

Question 25

What happens in 17-hydroxylase deficiency?

Answer 25

Deficiency of cortisol and sex steroids, but an excess of aldosterone and 11-deoxycorticosterone.
Hypertension, low K, sex steroid deficiency means they will not go through puberty, and glucocorticoid deficiency (low glucose).