72 - Iatrogenic Complications of Steroid Treatments

Question 1

Diurnal pattern of cortisol

Answer 1

Three peaks at breakfast, lunch and dinner (opposes the action of insulin).
Between 10pm and 2am is a trough of lowest concentration.

Question 2

What causes the pigmentation of the skin in Addison’s disease?

Answer 2

Melanocortin release

Question 3

How does cortisol deficiency present?

Answer 3

Cortisol deficiency presents with weakness, fatigue,

anorexia, nausea, vomiting, hypotension and hypoglycaemia.

Question 4

Symptoms of primary adrenal hypofunction

Answer 4

In primary adrenal hypofunction, cortisol deficiency is
combined with mineralocorticoid deficiency to cause
hyperkalaemia and hyponatraemia, acidosis and
dehydration

Question 5

Administration of cortisol replacement therapy
1
2
3

Answer 5

1) Divide dose to mimic the physiological time-course
2) Extra doses for infections and periods of stress
3) Add fludrocortisone if needed

Question 6

Side effects of cortisone replacement therapy

Answer 6

None, if managed correctly

Question 7

Some iatrogenic complications of glucocorticoid therapy
1
2
3
4
5
6

Answer 7

1) Cushingoid syndrome
2) Adrenal suppression
3) Immunosuppression (reactivation of latent
tuberculosis)
4) Peptic ulcers
5) Osteoporosis
6) Inhibition of linear growth in children

Question 8

Two things suppressed by cortisol

Answer 8

Immune system and adrenal gland

Question 9

Effect of excessive cortisol

1-5

Answer 9

1) Weight gain
2) Wasting of muscle, skin and bone
3) Hyperglycaemia (muscle amino acid for gluconeogenesis)
4) Hypertension (from salt retention)
5) Inhibition of linear growth

Question 10

Why doesn’t cortisone stimulate aldosterone receptors?

Answer 10

Equal affinity for mineralocorticoid receptors as aldosterone.
Normally, kidney converts cortisol to cortisone (inactive), preventing stimulation of aldosterone receptors by cortisol.
Liver reconstructs cortisol from cortisone.

Question 11

Cortisol half life

Answer 11

Short half life of cortisol (60-90 minutes).

Longer half life of reconstructed cortisol (reconstructed by liver)

Question 12

Relative affinity of dexamethasone and cortisone for cortisol receptor

Answer 12

Dexamethasone has 75 times the affinity.

Question 13

Aldosterone replacement hormone

Answer 13

Fludrocortisone.

Mineralocorticoid-selective exogenous steroid.

Question 14

How can cortisol stimulate aldosterone receptors in kidney?

Answer 14

Equal affinity for mineralocorticoid receptors as aldosterone.
Normally, kidney converts cortisol to cortisone (inactive), preventing stimulation of aldosterone receptors by cortisol.
Liver reconstructs cortisol from cortisone.
If there is too much cortisol, it overwhelms the ability of the kidneys to convert cortisol, and stimulates aldosterone receptors.

Question 15

Dissociated selectivity of steroids

Answer 15

Better at either doing:
Transactivation (activation of gene transcription via GREs)
or
Transrepression (reduction of gene transcription via inhibition of AP-1 and NFkB).

Question 16

Gross morphological effect of long-term glucocorticoid therapy on adrenal glands

Answer 16

Atrophy (as not being stimulated by ACTH for a long time).

Question 17

Strategies for minimising adrenal suppression with steroid therapy 
1 a, b, c
2
3
4

Answer 17

1) Allow for ACTH secretion if possible
- Avoid long-lasting drugs
- Alternate day dosing
- Morning dosing
2) Minimise systemic absorption of steroids
3) Inhaled or topical (but note: still absorbed!)
4) Third generation glucocorticoid drugs

Question 18

Example of a third-generation glucocotricoid

Answer 18

Ciclesonide

Question 19

Ciclesonide

1-4

Answer 19

Third-generation glucocorticoid
Reduced systemic effects after inhalation because:
1) Pro-drug, activated in lungs (not in mouth or larynx)
2) Lipophilic: retained in tissue
3) Low oral bioavailability (hepatic first pass)
4) Highly protein bound in plasma

Question 20

Relationship between glucocorticoids and peptic ulcers
1
2
3

Answer 20

1) Causal role is debatable
2) Mostly occur in patients who are also taking NSADS, which are implicated in stomach ulcers.
3) Could be a synergistic effect

Question 21

Effect of higher doses of glucocorticoids on bones

Answer 21

Osteoclast precursor has RANK (a receptor for RANKL).
OPG is a soluble RANK, which mops up RANKL.
These oppose each other in osteoclast activation.
Glucocorticoids decrease OPG, increase RANKL, leading to more osteoclasts, leading to increased bone resorption.

Question 22

Effect of inhaled glucocorticoids on bone density

Answer 22

Increases risk of fracture, but not hugely.

Question 23

Effect of inhaled glucocorticoids on childhood growth

Answer 23

Untreated asthma reduces growth, so can increase hight in severe asthmatics, as reduces effect of illness.

Glucocorticoids can decrease growth, but not to the point that it would offset the effect of untreated asthma.