Corticosteroid responsive conditions

Question 1

Corticosteroids can be used for

Answer 1

replacement therapy when there is an insufficiency or they can be used in the treatment of disease.

Question 2

The adrenal cortex (in healthy individuals) secretes

Answer 2

• CORTISOL (glucocorticoid) and ALDOSTERONE (mineralocorticoid).

Question 3

In replacement therapy,

Answer 3

•hydrocortisone is used to replace cortisol and fludrocortisone is used to replace aldosterone.

Question 4

In glucocorticoid therapy of other diseases, hydrocortisone is

Answer 4

• rarely used since it also has mineralocorticoid activity which can lead to fluid retention. However, it is still useful for topical treatments.

Question 5

Betamethasone and Dexamethasone have

Answer 5

• HIGHER GLUCOCORTICOID (=anti-inflammatory) and lower mineralocorticoid activity than Prednisolone making them a better drug for high-dose therapy. However, Prednisolone remains the drug of choice for most oral corticosteroid treatments since it has a larger margin of safety.

Question 6

If oral corticosteroids are used, they should be

Answer 6

taken in the morning, so they don’t suppress the natural adrenal activity which is most active at NIGHT. (corticosteroids supress cortisol secretion).

Question 7

Long-term treatment can lead to

Answer 7

• adrenal atrophy, abrupt withdrawal can lead to adrenal deficiency which may lead to hypotension or death. Withdrawal is also linked with cold and flu-like symptoms, itching and weight loss.

Question 8

Patients should also be advised to

Answer 8

• stay clear of people with chickenpox, shingles or measles due to immunosuppression.

Question 9

Steroids should also be used in caution in children due to

Answer 9

• possible growth restrictions.

Question 10

Corticosteroids and anticoagulants

Answer 10

Corticosteroids may enhance the anticoagulant effects of warfarin at high doses; they may reduce anticoagulant effects at lower doses.

Question 11

Mineralocorticoid side-effects

Answer 11

(most likely with fludrocortisone – most potent) include hypertension, sodium + water retention, and the loss of potassium and calcium. Aldosterone is a mineralocorticoid involved in the rennin- angiotensin system – hence increased sodium and decreased potassium and hydrogen ions

Question 12

Glucocorticoid side-effects

Answer 12

include diabetes, osteoporosis (>3m use: prophylaxis with bisphosphonate), muscle wasting, psychiatric reactions; also, potentially peptic ulceration (take with/after food). High doses cause avascular necrosis of femoral head. Hydrocortisone is a glucocorticoid; it has anti- inflammatory + immunosuppressive effects (hence ulceration); they increase blood glucose levels (hence diabetes) and mobilise calcium (hence osteoporosis).

Question 13

Side effects can be minimised by

Answer 13

using the lowest effective dose for the minimum time period.

Question 14

Glucocorticoid and Mineralocorticoid activity

Answer 14

When comparing the potencies of corticosteroids in terms of their anti-inflammatory (glucocorticoid) effects it should be noted that high glucocorticoid activity in itself is of no advantage unless it is accompanied by relatively low mineralocorticoid activity.

Question 15

• The high mineralocorticoid activity of Hydrocortisone

Answer 15

resulting in fluid retention, makes it unsuitable for long-term use. Thus, it is used on a short-term basis by I.V. injection for the emergency management of some conditions. The relatively moderate anti-inflammatory potency of hydrocortisone makes it a useful topical corticosteroid for inflammatory skin conditions because side effects are less marked.

Question 16

Prednisolone and Prednisone have

Answer 16

• predominantly glucocorticoid activity. Prednisolone is the corticosteroid most commonly used by mouth for long-term disease suppression.

Question 17

Betamethasone and Dexamethasone have

Answer 17

• a long duration of action and along with their lack of mineralocorticoid activity, they are suitable for conditions which require suppression of corticotropin secretion (e.g. congenital adrenal hyperplasia)

Question 18

MHRA: Corticosteroids

Answer 18

Rare risk of central serous chorioretinopathy with local + systemic use. Report any blurred vision or other visual disturbances.

Question 19

Adrenal suppression

Answer 19

• During prolonged therapy with corticosteroids, particularly with systemic use, adrenal atrophy (wasting) develops and can persist for years after stopping.
• Abrupt withdrawal after a prolonged period can lead to acute adrenal insuffiency, hypotension or death.
• To compensate for adrenal suppression caused by prolonged treatment… any significant intercurrent illness, trauma or surgical procedure requires a temporary increase in corticosteroid dose (or if already stopped, a temporary reintroduction of corticosteroid treatment).

Question 20

Corticosteroids (systemic) Side effects mnemonic

Answer 20

ACHING BOSOM:
Adrenal suppression/appetite larger, 
Cushing’s syndrome/cataracts, Hyperglycaemia/ Hyperlipidaemia, 
Infections/ insomnia, 
Nervous system (psychiatric reactions), 
Glaucoma/GI ulcers, 

BP increased, 
Osteoporosis, 
Skin thinning, 
Obesity, 
Muscle wasting

Question 21

Psychiatric reactions with Corticosteroids (systemic)

Answer 21

• High doses can cause psychiatric reactions (glucocorticoid side effect) including euphoria, insomnia nightmares, irritability and behavioural changes. These reactions frequently subside on reducing the dose or discontinuing the corticosteroid, but they may also require specific management.
• Thus, they should be used in caution in patients with a history of psychiatric problems.
• Patients should seek medical attention if they become depressed or have suicidal thoughts.

Question 22

Abrupt withdrawal can lead to

Answer 22

to adrenal deficiency which may lead to hypotension or death. Withdrawal is also linked with cold and flu-like symptoms, itching and weight loss.

• However, systemic corticosteroids can be abruptly stopped in those whose disease is unlikely to relapse and have received treatment for 3 weeks or less and who are not included in the patient groups above.
• High-dose steroid treatment can suddenly be brought down to 7.5 mg prednisolone daily (or equivalent), as this is equal to the natural adrenal levels, and then decreased gradually

Question 23

Gradual withdrawal by titration is needed if patients have any one of the following:

Answer 23

1. Taking more than 40mg prednisolone for more than a week
2. Taking evening doses
3. Received more than 3 weeks treatment at any dose.

Question 24

MHRA: Methylprednisolone (Solu-Medrone 40mg):

Answer 24

Contains lactose: DO NOT use is patients with cow’s milk allergy

Question 25

Patient and Carer advice

Answer 25

1. Immunosuppression: prolonged courses of corticosteroids can increase susceptibility to infection and serious infections can go unrecognised. Unless already immune, patients are at risk of severe chicken pox and should avoid close contact with people who have chickenpox or shingles.
2. Adrenal suppression: if the corticosteroid is given for longer than 3 weeks, treatment must not be stopped abruptly.
3. Mood and behaviour changes: corticosteroid treatment, especially with high doses, can alter mood and behaviour early in treatment – the patient can become confused, irritable and suffer from delusions + suicidal thoughts. These effects can also occur when corticosteroid treatment is being withdrawn

Question 26

Adrenal replacement therapy:

Answer 26

HC + Fludrocortisone

Used in: Adrenalectomy, Addison’s Disease

 Low Cortisol (natural glucocorticoid)
 Low Aldosterone (natural mineralocorticoid)

Fludrocortisone is added because hydrocortisone alone is too weak to provide
sufficient mineralocorticoid activity for complete replacement. In Addison’s a
large dose in given in the morning and a small dose in the evening to mimic
physiological cortisol secretion.
 Relatively high mineralocorticoid activity of hydrocortisone and resulting fluid
retention makes it unsuitable for long term disease management – but can be
used for adrenal replacement therapy

Question 27

Hypopituitarism replacement therapy:

Answer 27

HC only

Question 28

Most potent topical steroid

Answer 28

Clobetasol

Question 29

Least potent topical steroid

Answer 29

Hydrocortisone

Question 30

Cushing’s Syndrome & Disease symptoms

Answer 30

Skin thinning, hirsutism, striae, reddish-purple stretch marks, moon face, acne, easy bruising

Question 31

Cushing’s Syndrome causes

Answer 31

Corticosteroids (reduce dose or withdraw), tumour (surgery or cortisol-inhibiting drugs: Metyrapone or Ketoconazole)

Question 32

Cushing’s Syndrome & Disease treatment

Answer 32

 Metyrapone is useful in controlling symptoms (low dose tailored to cortisol production OR high dose corticosteroid replacement therapy is also needed)

 Ketoconazole

Question 33

Ketoconazole (potent)

Answer 33

 Can be used under specialist supervision to treat endogenous Cushing’s syndrome which has a direct effect on corticotropic tumour cells.
 Avoid in pregnancy + breastfeeding
 CHMP: Risk of hepatotoxicity associated with oral ketoconazole is greater than the benefit in treating fungal infections. Oral Ketoconazole for Cushing’s syndrome & topical ketoconazole are not affected.
 Report signs of liver toxicity: anorexia, nausea, vomiting, fatigue, jaundice, abdominal pain or dark urine
 Adrenal insufficiency: Report fatigue anorexia, nausea + vomiting, hypotension.
 Adrenal suppression causes hyponatremia, hyperkalaemia + hypoglycaemia
 Monitor: ECG before and one week after initiation, Adrenal function (symptoms of adrenal insufficiency: fatigue, anorexia, nausea, vomiting, hypotension, hyponatraemia, hyperkalaemia and/or hypoglycaemia  discontinue treatment), Hepatotoxicity.
 Do not take indigestion remedies 2h before or after taking ketoconazole.