Lecture 22 - 2018/2017

Question 1

What can you see in a glucocorticoid deficiency?

Answer 1

1. Low levels of cortisol, despite there being adequate ACTH.
2. Hyponatraemia.
3. Hypoglycaemia.
4. Hypotension.

Question 2

What can you see in a mineralocorticoid deficiency?

Answer 2

1. Low levels of aldosterone, there are no changes in cortisol.
2. Hyponatraemia.
3. Hyperkalaemia.
4. Hypotension.
5. Metabolic acidosis.

Question 3

What is the mechanism of glucocorticoid deficiency to cause hyponatraemia?

Answer 3

1. Unable to excrete a water load (reduced GFR) due to loss of cortisol inhibition of ADH.
2. Increase in ADH will cause more aquaporins inserted on the membrane so increase in water reabsorption.
3. Decrease in sodium in serum.

Question 4

What is the mechanism of glucocorticoid deficiency to cause hypoglycaemia?

Answer 4

There is reduced hepatic gluconeogenesis.

Question 5

What is the mechanism of glucocorticoid deficiency to cause hypotension?

Answer 5

Loss of cortisol effects on vascular tone.

Question 6

What is the mechanism of a mineralocorticoid deficiency to cause hyponatraemia?

Answer 6

There is urinary sodium loss with intravascular contraction (decrease in blood volume), and secondary increase in ADH - causes an increase in reabsorption of water so dilution of sodium.

Question 7

What is the mechanism of a mineralocorticoid deficiency to cause hyperkalaemia?

Answer 7

There is reduced renal potassium excretion.

Question 8

What is the mechanism of a mineralocorticoid deficiency to cause metabolic acidosis?

Answer 8

Reduced renal hydrogen excretion, so there is an increase in hydrogen ions in the body so there is a decrease in pH.

Question 9

What is primary adrenal failure?

Answer 9

Failure that stems from the adrenal gland.

Question 10

What is secondary adrenal failure?

Answer 10

Failure that stems from the pituitary.

Question 11

What is tertiary secondary adrenal failure?

Answer 11

Failure that stems from the hypothalamus.

Question 12

What is ACTH a product of?

Answer 12

POMC - proopiomelanocrtin.

Question 13

What else is a product of POMC?

Answer 13

3 MSH - melanocyte stimulating hormone.

Question 14

What does ACTH contain?

Answer 14

alpha-MSH.

Question 15

What happens if there is an increase in POMC?

Answer 15

Increase in ACTH so there is an increase in MSH - hence pigmentation (tan).

Question 16

What causes an increase in POMC?

Answer 16

Lack of feedback inhibition - decrease in cortisol due to primary adrenal failure.

Question 17

Where does pigmentation (due to primary adrenal failure) occur?

Answer 17

It occurs generally but it is more apparent in:

• Skin flexures (e.g. hand creases).
• Buccal mucosa (mouth).
• Old scars.
• Freckles.
• Nails.

Question 18

When does simple obesity become apparent?

Answer 18

3-4 years of age with progressive worsening.

Question 19

What does childhood glucocorticoid excess lead to?

Answer 19

Generalised obesity.

Question 20

What does adult glucocorticoid excess lead to?

Answer 20

Truncal obesity.

Question 21

What does simple obesity do?

Answer 21

Drives growth - fat kids are taller than you would expect from their genetic potential, however, they enter puberty earlier and end up at a height similar to their parents.

Question 22

How does glucocorticoid excess affect growth?

Answer 22

It can cause profound growth failure and a crossing of percentiles downwards.

Question 23

What are features of a glucocorticoid excess?

Answer 23

1. Moon face.
2. Thinning skin - violaceous striae, facial plethora, bruising.
3. Androgen excess - hirsutism, amenorrhoea/irregular period.
4. Myopathy - proximal weakness.
5. Glucose intolerance - diabetes mellitus.
6. Hypertension.
7. Osteoporosis.

Question 24

What happens in cortisol excess to aldosterone?

Answer 24

Cortisol has the same binding affinity to mineralocorticoid receptor and glucocorticoid receptor. With normal cortisol levels, cortisol usually will have no mineralocorticoid effects as it is rapidly metabolised to cortisone before it can bind to the mineralocorticoid receptors. However, with excess cortisol, cortisol can bind to the mineralocorticoid receptors - see an increase in aldosterone (see mineralocorticoid effects).

Question 25

What happens when there is a partial loss of function of the glucocorticoid receptor?

Answer 25

1. Increased cortisol.
2. Secondary mineralocorticoid effects - alkalosis, hypokalaemia, hypertension.
3. Hyper-androgenism.
4. Fatigue/tiredness.

Question 26

What happens when there is loss of function of the mineralocorticoid receptor?

Answer 26

1. High aldosterone and renin levels.
2. Depleted extracellular fluid space.
3. High serum (K+) and low sodium (Na+) concentrations.

Question 27

What happens when there is loss of ACTH receptor function (i.e. mutation)?

Answer 27

Severe cortisol deficiency:

1. Hypotension.
2. Hyponatraemia.
3. Hypoglycaemia.