7. Hypoadrenal Disorders

Question 1

Types of reaction which occur in cholesterol steroid synthesis pathway

Answer 1

Oxidation or hydroxylation

Question 2

P450 scc

Answer 2

P450 enzyme that performs side chain cleavage

Question 3

Conversion of pregenalone to cortisol

Answer 3

Occurs in the adrenal cortex- fasciculata (first conversion of cholesterol to progenalone)

OH groups are added to positions 17, 21 and 11

Enzyme for conversion is the number-hydroxylase

Question 4

Conversion of cholesterol to aldosterone

Answer 4

Occurs in the adrenal medulla- glomerulosa

OH groups added to positions 21, 11 and 18

Enzyme for conversion is the number-hydroxylase

Question 5

Stimulation of the glucocorticoid (cortisol) producing pathway

Answer 5

Stimulated by ACTH- stimulated by STRESS

Question 6

Causes of adrenocortical failure (3)

Answer 6

THREE categories of causes:

• Tuberculous Addison’s Disease- MOST COMMON cause of AF worldwide- generally occurs when you stop a course of treatment to early
• Autoimmune Addison’s Disease- commonest in the UK- immune degredation of adrenal gland
• Congenital Adrenal Hyperplasia- born with big adrenals, stimulated since you are deficient in essential enzymes so cant produce hormones effectively

Question 7

Vitiligo

Answer 7

An autoimmune disease of the skin- antibodies produced against melanin so patches of white skin

Question 8

Features of addison’s disease

Answer 8

Darker hair, more pigmented skin, pigmentation in the mouth, vitiligo (associated with autoimmune disesae causing hypoadrenalism)

Very low blood pressure before death

Question 9

Consequences of Adrenal Failure

Answer 9

• Fall in blood pressure- no aldosterone
• Loss of salt in urine + rise in plasma potassium- no aldosterone
• Fall in glucose- glucocorticoid deficiency
• ACTH resulting in pigmentation
• Eventual hypotension- Addison’s Crisis

Question 10

How does adrenal failure cause increased pigmentation

Answer 10

Due to increase in ACTH and therfore POMC- proopiomelanocortin

ACTH is produced from POMC and MSH

Because there is adrenal failure there is not cortisol negative feedback= increased ACTH

POMC is produced due to breakdown of ACTH by endorphins and enkephalins

Question 11

Tests for Addison’s

Answer 11

1. Measure the hormones at 9am (cortisol should be high)- normal is 270-900mg, Addisons- 100mg
2. Could measure ACTH- should be high
3. Could give them a 250mg injection of synthetic ACTH (synacthen) then measure cortisol response

Question 12

Cause of congenital adrenal hyperplasia

Answer 12

21- hydoxylase deficiency is the most common

Can be complete or partial

complete loss means huge ACTH production and large but innefective adrenals.

testosterone will be in excess since you can still produce sex steroids- abnormality of genitals

Question 13

Immediate problem of congenital adrenal hyperplasia

Answer 13

Can still rely on maternal hormones pre birth but will have a salt losing Addisonian crisis on the first day- give saline

Question 15

later problems of congenital adrenal hyperplasia

Answer 15

• Hypotension
• Virilisation

Question 16

Effects of 11-beta hydroxylase deficiency

Answer 16

• Build up of 11-deoxycorticosterone
• Acts as an aldosterone receptor agonist- so no ADdisonian crisis- behave like they have aldosterone
• Hypertensive and hypokalaemic in childhood
• Virilised
• Also lacks cortisol so hypoglycaemia

Question 17

17-hydroxylase deficiency

Answer 17

They will have high levels of aldosterone (so they are hypertensive and hypokalaemic) But they are missing cortisol and sex steroids

• They will never go through puberty
• They will also be hypertensive
• They don’t have an Addisonian crisis because they have aldosterone
• But they do have borderline HYPOGLYCAEMIA
• They also have infections a lot because you need cortisol to cope with the stress of infection