hypoadrenal disorders

Question 1

What is the precursor of adrenal steroids?

Answer 1

cholesterol

Question 2

How many carbons are in cholesterol?

Answer 2

27.

Question 3

Outline diagram showing synthesis pathways of mineralocorticoid and glucocorticoid steroids.

Answer 3

Question 4

What is synthesised in the medulla vs cortex of the adrenal glands?

Answer 4

medulla - catecholamines

cortex - adrenal steroids

Question 5

Diagram showing synthesis of adrenal steroids.

Answer 5

Question 6

Which enzyme numbers catalyse which reactions?

(11, 17, 18, 21).

Answer 6

11 - 11-deoxy-corticosterone –> corticosterone, 11-deoxycortisol –>cortisol.

17 - progesterone –> 17OH-progesterone.

18 - corticosterone –> aldosterone.

21 - progesterone –> 21-deoxy-corticosterone, 17OH-progesterone –> 11-deoxycortisol.

Question 7

What are the precursors for sex steroids?

Answer 7

Progesterone and 17-OH-progesterone.

Question 8

Give the rough pathology of causes of adrenocortical failure?

Answer 8

adrenal gland destruction, enzymes in steroid synthesis pathway not working.

Question 9

Give some causes of adrenocortical failure.

Answer 9

Tuberculous Addison’s disease (commonest worldwide)

Autoimmune Addison’s disease (commonest in UK)

Congenital adrenal hyperplasia.

Question 10

Give some signs and symptoms of Addison’s disease.

Answer 10

Mucous membrane pigmentation.

Skin pigmentation (especially around creases)

Freckling

Hypotension

Muscular weakness.

Loss of weight.
vomiting.

Diarrhea
anorexia.

Vitiligo.

Question 11

Give the consequences of adrenocortical failure.

Answer 11

BP fall.

Lost of salt in urine.

Increased plasma potassium.

Fall in glucose due to glucocorticooid deficiency.

Pigmentation - high ACTH

Eventually - death due to hypotension.

Question 12

Explain the increased pigmentation associated with Addison’s.

Answer 12

More ACTH needed due to low cortisol (stimulate adrenal gland). POMC (pro-opio melanocortin) is synthesised in pituitary and broken down to yield ACTH. Another product of this is MSH which causes pigmentation.

(also endorphins and enkephalins).

Question 13

Give a potential indicator for Addison’s that might feature in a blood test.

Answer 13

Low Na high K.

Low aldosterone - losing Na in urine, cannot excrete K.

Question 14

How can an Addison’s diagnosis be confirmed?

Answer 14

1. Measure cortisol. Diurnal variation - high in morning, decrease throughout day.

Low 9am cortisol indicative of Addison’s.

2. measure ACTH - should be very high (all the time).
3. Short synACTHen test. Give 250micrograms, cortisol remaining low indicative of Addison’s

Question 15

What is the commnest cause of congenital adrenal hyperplasia?

Answer 15

21-hydrpxylase deficiency.

Question 16

In complete 21-hydroxylase deficiency which hormones are absent?

How long can you survive?

Which hormones will be in excess?

Answer 16

1. cortisol, aldosterone.
2. less than 24 hours
3. sex steroids and testosterone.

Question 17

When does complete 21-hydroxylase deficiency present?

Answer 17

At birth - neonatal losing salt in an Addisonian crisis.

(before birth foetus gets steroids across placenta)

(girls may have ambiguou genitalia, virilised by adrenal testosterone).

Question 18

In partial 21-hydroxylase deficiency which hormones are deficient?

Which hormones are in excess?

When do patients present?

Answer 18

1. cortisol and aldosterone.
2. sex steroids and testosterone.
3. any age because it isn’t a fatal condition.

Question 19

What problems arise from partial 21-hydroxylase deficiency?

Answer 19

hirsutism and virilisation in girls, precocious puberty due to adrenal testosterone.

Question 20

Give some symptoms and signs of hirsutism and virilisation.

Answer 20

receding hairline.

baldness.

acne.

facial hirsutism.

androgenic flush.

variable pigmentation.

small breasts.

heavy, muscular arms and legs.

generalised hirsutism.

clitoral enlargement.

Question 21

Why can 11-hydroxylase deficiency cause hypertension and hypokalaemia?

Answer 21

11-deoxycorticosterone behaves like aldosterone.

Question 22

In 11-hydroxylase deficiency which hormones are deficient, which hormones are in excess, what problems arise?

Answer 22

1. cortisol and aldosterone.
2. sex steroids, 11-deoxycorticosterone.
3. virilisation, hypertension, low K

Question 23

In 17-hydroxylase deficiency which hormones are deficient, which hormones are in excess, what problems arise?

Answer 23

1. cortisol and sex steroids.
2. 11-deoxycorticosterone and aldosterone.
3. hypertension, low K, sex steroid deficieny, glucocorticoid deficiency (low glucose).