CPT2: Corticosteriods

Question 1

1. What are steriods dervied from?
2. Where are endongenous steriods produced?
3. What are the classes of steriods?

Answer 1

1. Steroids are a series of structurally related compounds derived from cholesterol
2. Endogenous steroids are produced in the adrenal glands and gonads.
3. Steroid hormones may be divided into corticosteroids (glucocorticoid and mineralocorticoid) and sex steroids (androgens, oestrogens and progesterone).

Question 2

Cortisol vs aldoesterone

1. What activity do they each have?
2. What are they controlled by?
3. What effects do they both have?

Answer 2

Question 3

Describe and explain how the the activity of cortisol varies with concentration?

Answer 3

Mineralocorticoid effect of cortisol is limited due to presence of an enzyme in tissues with mineralocorticoid receptors which converts cortisol to its inactive form cortisone. However this enzyme can be saturated at high steroid concentrations, leading to mineralocorticoid effects.

Question 4

Describe the pathway of release of cortisol

The negative feedback pathway

The effects

Answer 4

1. Additional stressor e.g. physical exercise, illness, hypoglycaemia, hypotension, emotion triggers release of CRH (corticotrophin releasing hormone) from the hypothalamus
2. CRH acts on the pituitary to release ACTH (adrenocorticotropic hormone)
3. ACTH acts on the adrenal glands to release cortisol
4. Cortisol has a metabolic effect insuring enough glucose is available for the organs to deal with the stress

Negative feed back - increased cortisol supresses CRH and ACTH release

Question 5

Glucocoticoids have anti-inflammatory/immunomodulatory, anti-prolifferative effectas and metablic effects.

Explain the anti-inflammatory effects

Answer 5

• Inhibits phospholipase A2 resulting in reduction in arachadonic acid derivatives
• Reduced white cell penetration through endothelium of vessels
• Bind to glucocorticoid receptors which alter gene transcription
  
  • Turns on anti-inflammatory genes (e.g. IL10)
  • Turns off pro-inflammatory transcription factors (NF-KB)

Question 6

Glucocoticoids have anti-inflammatory/immunomodulatory, anti-prolifferative effectas and metablic effects.

Explain the anti-prolifferativ effects

Answer 6

• Reduces fibroblast activity
  
  • Important for healing activity
• Triggers cell apoptosis (lymphocytes, eosinophils)

Question 7

Glucocoticoids have anti-inflammatory/immunomodulatory, anti-prolifferative effectas and metablic effects.

Explain the metabolic/ endocrine effects

Answer 7

• Increased gluconeogenesis
• Protein breakdown
• Peripheral insulin resistance
• Lipolysis and redistribution of fat
• Reduce calcium absorption/increased osteoclast activity
• Leptin suppression
  
  • Important hormone in control of hunger. IF this is low then become hungry (therefore eat and gain energy)

Question 8

Describe the release of the mineralocorticoid aldosterone and the effects it can have

Answer 8

1. Dehydration, N+ defiency or haemorrhage leads to decreased blood volume
2. This leads to decreased BP
3. Decreased BP detected by juxtaglomerular cells in kidney which releases renin in response
4. Renin in cleaved by angiotensinogen released from the liver to Angiotensin I
5. Angiotensin I is converted to Angiotensin II by ACE
6. Angiotensin II has several effects - it is a potent vasoconstrictor so it constricts the arterioles leading to increased BP
7. Angiotensin II also acts on the adrenal cortex to release aldosterone
8. Aldosterone in kidneys increases Na+ and water reabsorption and increases K+ and H+ excretion into the urine (ATPase)
9. This leads to increased blood volume
10. Therefore increased BP to normal

Aldoseterone main effects:

• Na+ reabsorption
• Water reabsorption
• K+ excretion
• Expansion of blood volume

Question 9

symptoms of cushing syndrome - what is this caused by?

Answer 9

Hypercortisol

• Moon face
• Osteoporosis
  
  • Reduced calcium absorption and increased osteoclast activity
• Hyperglycaemia
  
  • Prolonged insulin resistance leads to Diabetes
• Hypertension
• Central obesity
• Poor wound healing
  
  • Reduced fibroblasts
• Immune suppression
• Thinning of the skin
• Muscle wasting
• Effects on sexual characteristics (hirsutism, gynecomastia)

Question 10

Treatment method for cushings disease?

Answer 10

remove cause e.g.if tumour causing excessive cortisol secretion (surgery/radiotherapy/reduce steroid dose OR cortisol blocking drugs

Question 11

What is important counselling point for patients taking steriods

Answer 11

Take in monring to try mimic natual endogenou steriod pattern and prevent 2 peaks

Question 12

What is Addison’s disease?

What is secondary Addison’s disease

Answer 12

1. Problem with adrenal gland where it is not producing enough or any cortisol (hypoadrenalism)
2. Patient on steriods for prolonged periods of time and this is suddenly stopped - as steriod supressing CRH and ACTH production therefore endongenous steriods suddenly stopping this medication leave the body without enough endogenous steriods and an adrenal crisis.

Aldosterone still produced in secondary Addisons

Question 13

Symptoms of Addison’s disease and Secondary Addison’s disease

Answer 13

Question 14

Treatment for Addison’s disease

Treatment for secondary Addisons diseae

Answer 14

1. Treatment: steroids – Hydrocortisone for Addison’s. +/- Fludrocortisone
2. Continue with prior steroid therapy if hypoadrenalism is due to exogenous steroid use

Question 16

Hydrocortisone, prednisolone, dexamethasone, fludrocortisone are all steriods used for treatment.

What is the differnece in potencys for gluco and miner receptors, half-lives and equivalent doses?

What migt each be used for?

Question 17

What are patient considerations for corticosteriods?

Answer 17

• History of peptic ulceration
  
  • Poor wound healing due to reduced fibroblasts therefore could effect healing if current ulcer or re-emerge a previous one
    
    • Use PPI to reduce risk
• Diabetes
  
  • Steriods increase glucose levels therefore could lead to uncontrolled diabetes. Does patient have risk factors for diabetes - prolongs insuline resistance so could lead to development of diabetes
    
    • Short course
    • Can steriods be avoided?
    • Weigh-loss?
    • Diabetes specialists?
• Osteoporosis
  
  • Reduce Ca2+ absorption and increases osteoclast activity.
    
    • Risk calculatior e.g. Qfracture
    • Vit D/calcium supplements needed?
• Psychiatric history
  
  • Steriods can cause insomnia or psychosis. Important to consider if any current/previous pyschiatric conditions
    
    • benefit vs risk
    • give in morning to avoid sleeping problems
    • Ask specialist
• Drug history (including live vaccines)
  
  • Interactions
  • Immunosupressed should not get live vaccines
• Dose tapering (adrenal insufficiency, disease flare)
• Infections (chickenpox, untreated bacterial/fungal infection)
• Age
  
  • Higher risk of osteoporosis as increases
• Cardiovascular disease

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Question 18

Withdrawl considerations

Answer 18

• Generally, courses of <3 weeks may be stopped abruptly.
• Gradual withdrawal should be considered for those who have:
• Taken >40mg of prednisolone (or equivalent) daily for >1 week.
• Take repeated evening doses.
• Received >3 weeks of treatment.
• Recently received repeated courses.
• A history of long-term therapy.
• Other possible causes of adrenal suppression (stress, alcoholism)

Question 19

Patient counselling points with steriods

Answer 19

• Advise the patient about:
• Carry a steroid card if on long-term treatment and know about what to do if unwell
• Avoid close contact with those who have chickenpox, shingles or measles if they have not had chickenpox or measles before, or seek urgent medical advice if they are exposed.
• Take in the morning to mimic the body’s natural variation in cortisol levels and minimise effect on sleep.
• Adverse effects (sleep, hunger, weight gain, mood changes, muscle weakness etc)
• Take with food to minimise the risk of gastrointestinal side effects.