Hypoadrenal disorders

Question 1

What is:

CRH, ACTH, POMC, MSH?

Answer 1

CRH - corticoptrophin releasing hormones

ACTH - adrenocorticotrophin hormone

POMC - proopiomelanocortin

MSH - melanocyte stimulating hormone

Question 2

What are the three main steroid synthesis pathways?

Answer 2

cortisol, aldosterone and sex steroids

Question 3

Describe the pathway converting progesterone to cortisol and enzymes

Answer 3

progesterone -> 17 OH progestrone -> 11 deoxycortisol -> cortisol

enzymes: 17, 21 and 11 hydroxylase

Question 4

Describe the pathway converting progesterone to aldosterone including the enzymes

Answer 4

progestrone, 11 deoxycorticosterone, corticosterone, aldosterone

enzymes: 21, 11 and 18 hydroxylase

Question 5

What are the causes of adrenal failure?

Answer 5

Adrenal glands destroyed:

• TB Addison’s disease (most common worldwide)
• Autoimmune Addison’s disease (most common in UK)
• Congenital adrenal hyperplasia (gland overgrows but does not function properly)

Enzymes in the steroid synthetic pathway not working

Question 6

What are the signs and symptoms of adrenocortical failure?

Answer 6

• Hypotension
• Loss of salt in the urine
• Hyperkalaemia (caused by loss of aldosterone)
• Hypoglycaemia (due to glucocorticoid deficiency)
• High ACTH -> hyperpigmentation
• Eventual death due to severe hypotension

Question 7

Why does high ACTH occur in Addison’s and how does this cause hyperpigmentation?

Answer 7

High ACTH due to loss of negative feedback by cortisol on the pituitary

POMC -> ACTH + MSH (leading to hyperpigmentation)

Question 8

What would a blood test for Addison’s disease show?

Answer 8

9am Cortisol = 100 (normal range: 270-900)

ACTH = high

Question 9

Which test can be used for Addison’s?

Answer 9

Short synacthen test

• Give 250 micrograms of synacthen (synthetic ACTH )– this is a large dose of ACTH and should induce a large response in a healthy individual
• Measure the cortisol response
• If the cortisol response barely changes (e.g. goes from 100 to 150) they have Addison’s

Question 10

What is congenital adrenal hyperplasia?

Answer 10

CAH are inherited conditions that are congenital where the adrenal gland is hyperplastic. There is a missing enzyme that normally stimulates the adrenal glands to release the cortisol hormone

Question 11

What are the four types of CAH?

Answer 11

Complete 21-hydroxylase deficiency

Partial 21-hydroxylase deficiency

11-hyroxylase deficiency

17-hydroxylase deficiency

Question 12

What is the most common cause of CAH?

Answer 12

complete 21 hydroxylase deficiency

Question 13

What happens in complete 21 hydroxylase deficiency?

Answer 13

Leads to noproduction of aldosterone or cortisol but excess of sex steroids

Question 14

What is the presentation of individuals with complete 21 hydroxylase deficiency?

Answer 14

• This will usually be in the form of a salt losing Addisonian crisis
• In-utero the child will be fine as they receive steroids from the mother
• Girls present more obviously than boys due to ambiguous genitalia (virilisation) and may have clitoromegaly

Question 15

What hormones are deficient in partial 21 hydroxylase deficiency?

Answer 15

Cortisol and aldosterone

Question 16

What hormones are in excess in partial 21 hydroxylase deficiency?

Answer 16

Sex steroids: testosterone

Question 17

What is the age of presentation for partial 21 hydroxylase deficiency?

Answer 17

Any age (as they survive)

The main problem is in later life with hirsutism and virilisation in girls and precocious puberty in boys

Question 18

What are the signs and symptoms of partial 21 hydroxylase deficiency??

Answer 18

Acne, facial hirsutism, small breasts, clitoral enlargement, heavy arms/legs

Question 19

What is the age of presentation for complete 21 hydroxylase deficiency?

Answer 19

Children with this will present at 1 week-old

Question 20

What does 11- deoxycorticosterone behave like and what does this mean?

Answer 20

Behaves like aldosterone and so in excess (accumulation in zona glomerulosa) it can cause hypertension and hypokalaemia

Question 21

What hormones are deficient in 11- hydroxylase deficiency?

Answer 21

Cortisol and aldosterone

Question 22

What hormones are in excess in 11- hydroxylase deficiency?

Answer 22

Sex steroids and testosterone and 11-deoxycorticosterone

Question 23

What are the signs and symptoms of 11 hydroxylase deficiency?

Answer 23

Virilisation, hypertension, hypokalaemia

Question 24

What hormones are deficient in 17 hydroxylase deficiency?

Answer 24

Cortisol and sex steroids

Question 25

What hormones are in excess in 17 hydroxylase deficiency?

Answer 25

11-deoxy corticosterone and aldosterone (the mineralocorticoids)

Question 26

What are the signs and symptoms of 17 hydroxylase deficiency?

Answer 26

Hypertension, hypokalaemia, sex steroid deficiency and glucocorticoid deficiency (leading to hypoglycaemia)

Question 27

Give an example of a glucocorticoid and a mineralocorticoid

Answer 27

GC - cortisol

MC - aldosterone

Question 28

Signs of Addison’s disease

Answer 28

vitiligo (autoimmune disease of the skin – there are antibodies against melanin)
darkening of hair
darkening of mucous membranes
freckling
hyperpigmentation
muscular weakness
weight loss, diarrhoea, vomiting
hypotension