Adrenal disorders

Question 1

What is made in the adrenal cortex?

Answer 1

Corticosteroids

Mineralocorticoids (Aldosterone)
Glucocorticoids (Cortisol)
Sex steroids (Androgens, oestrogens)

Question 2

What does angiotensin II do on the adrenals?

Answer 2

Bind to receptors on the zona glomorulosa

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

Makes aldosterone

Question 3

What does aldosterone do?

Answer 3

Controls blood pressure, retains sodium and lower potassium

Question 4

What does ACTH do on the adrenals? (During stress/ pneumonia…etc)

Answer 4

Binds to zona fasciculata

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

Makes cortisol

Question 5

What rhythm does cortisol have

Answer 5

diurnal

Question 6

What is Addison’s disease

Answer 6

Primary adrenal failure
Autoimmune disease where the immune system decides to destroy the adrenal cortex (UK)
Tuberculosis of the adrenal glands (commonest cause worldwide)

Pituitary starts secreting lots of ACTH and hence MSH

Question 7

What happens in an adrenal crisis?

Answer 7

Fever
Syncope
Convulsions
Hypoglycaemia
Hyponatremia
Severe vomiting
Diarrhoea

Question 8

What are some of the main symptoms of Addisons:

Answer 8

Weight loss
Increased pigmentation
Autoimmune vitiligo
No cortisol or aldosterone, so low blood pressure

Question 9

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

Answer 9

POMC is a large precursor protein that is cleaved to form a number of smaller peptides, including ACTH, MSH and endorphins
Thus people who have pathologically high levels of ACTH may become tanned

Question 10

What are 2 causes of adrenal destruction?

Answer 10

Tuberculosis
Autoimmune disease
Congenital adrenal hyperplasia - born with huge adrenal glands as they were not making enough cortisol before you were born so pituitary made lots of ACTH but born with a missive enzyme

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 - due to no negative feedback
Eventual death due to severe hypotension

Question 12

What is POMC

Answer 12

Pro-opio melanocortin

Synthesised in pituitary and broken down to ACTH and MSH and endorphins and enkephalins and other peptides

Question 13

What are the test for Addison’s?

Answer 13

9am cortisol = low
ACTH = high

Short synACTHen test
Give 250 ug synacthen IM
Measure cortisol response

Question 14

What would cortisol be like in a typical Addison’s patient compared to normal?

Answer 14

Cortisol at 9am = 100 (270-900)
Administer injection IM of synacthen
Cortisol at 9.30 = 150 (>600)nM

Question 15

How do you treat adrenal failure?

Answer 15

Fludrocortisone-50-100mcg daily

Fluorine does not exist in natural steroids, so its presence slows metabolism substantially.
Binds to both MR and GR
Fludrocortisone half life 3.5h and
effects seen for 18h.

Half life of aldosterone is too short for safe once daily administration

Question 16

How do you increase cortisol?

Answer 16

Hydrocortisone by injections but half life too short - need to take it thrice a day
1-2 dehydro-hydrocortisone - longer half life - aka prednisolone - only need to take it once a day

2-4mg prednisolone = 15-25mg hydrocortisone

Question 17

What is congenital adrenal hyperplasia

Answer 17

Usually caused by 21-hydroxylase deficiency

Either complete or partial deficiency

Question 18

What hormones absent in complete 21-hydroxylase deficieny?

Answer 18

Aldosterone and cortisol

Can survive for less than 24 hours

Excess 17-OH progesterone in blood so excess sex steroids and testosterone

Question 19

How does congenital adrenal hyperplasia present?

Answer 19

As a neonate with a salt losing Addisonian crisis

Before birth, (while in utero), foetus gets steroids across placenta

Girls might have ambiguous genitalia (virilised by adrenal testo)

Question 20

What happens in partial 21 hydroxylase deficiency

What hormones are deficient

What hormones are in excess

What age will they present

Answer 20

There will be a bit of aldosterone and cortisol to get by with

Not enough cortisol to inhibit ACTH from pituitary

Cortisol and aldosterone

Sex steroids and testosterone

Any age as they survive

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

Question 21

What happens with 11 hydroxylase deficiency?

Answer 21

There is an excess of 11 deoxycorticosterone

11 deoxycorticosterone behaves like aldosterone

In excess it can cause hypertension and hypokalaemia

Question 22

What hormones are deficient in 11 hydroxylase deficiency?

What hormones are in excess

Associated problems?

Answer 22

Which hormones are deficient ?
Cortisol and aldosterone

Which hormones are in excess ?
Sex steroids and testosterone and 11-deoxycorticosterone

Problems :
Virilisation, hypertension and low K

Question 23

What hormones are deficient in 17 hydroxylase deficiency?

What hormones are in excess

Associated problems?

Answer 23

Which hormones are deficient ?
Cortisol and sex steroids

Which hormones are in excess ?
11-deoxycorticosterone and aldosterone (mineralocorticoids)

Problems :
Hypertension, low K, sex steroid deficiency and glucocorticoid deficiency (low glucose).