W5 Corticosteroid Disorders (GM)

Question 1

Corticosteroids in the body:

Answer 1

Corticosteroids (adrenal cortical steroids) are natural hormones made by the adrenal cortex

Adrenal cortex secretes:
* Glucocorticoids - cortisol (hydrocortisone)
* Mineralocorticoids – aldosterone

HPA Axis: Negative feedback mechanism
Hypothalamus secretes CRH
Anterior pituitary secretes ACTH
Adrenal cortex secretes Cortisol (also aldosterone and weak androgens)

Question 2

Corticosteroid medications:
Routes of administration? (3)

Answer 2

Dosages vary widely in different diseases and in different patients.
Route:
- orally as a systemic treatment
- locally applied to the affected area via creams, inhalations, nasal sprays, eye drops,
ear drops or injections.

Question 3

Corticosteroid therapy have varying ratios of mineralocorticoid to glucocorticoid
activity, and these ratios determine their potency, efficacy, and therapeutic use, which
must be borne in mind during selection.

Which have high mineralocorticoid activity? (4)
Which have high glucocorticoid activity? (3)

Answer 3

High Mineralocorticoid Activity:
Fludrocortisone
Hydrocortisone
Corticotropin
Tetracosactide

High Glucocorticoid Activity:
Betamethasone
Dexamethasone
Prednisolone

Question 4

Actions of cortisol (glucocorticoid) in the body? (3 main)

Answer 4

• Metabolic effects
• Role in adaptation to stress
• Anti-inflammatory/ immunosuppressive effects
• Permissive role in action of other endocrine hormones
• Actions on other tissues

Question 5

What are the Clinical uses of glucocorticoid analogues? (e.g. prednisolone, dexamethasone)

Answer 5

Anti-inflammatory:
* Asthma, COPD
* Ulcerative colitis, Crohn’s disease
* Rheumatoid arthritis
* Skin conditions, e.g. eczema, psoriasis
* Others, inc. rhinitis, conjunctivitis, local injections (joints/ soft tissue)….
Immunosuppression:
* Organ transplantation
Replacement therapy:
* Addison’s disease
Others:
* Pre-term labour (enhance foetal lung maturation)

Question 6

Actions of aldosterone (mineralocorticoids) in the body?

Answer 6

Mineralocorticoids e.g. aldosterone are necessary for regulation of salt and water in the body. (RAAS)
* Aldosterone helps regulate blood pressure by managing the levels of sodium and potassium in your blood.
* Aldosterone also helps control the amount of water your
kidneys reabsorb; this increases blood volume and also impacts blood pressure.
* Indirectly, aldosterone also helps maintain your blood’s pH (acid-base balance) and electrolyte levels

Question 7

Clinical uses of mineralocorticoid analogues (e.g. fludrocortisone)

Answer 7

• Use can be made of the mineralocorticoid activity of fludrocortisone acetate to treat postural hypotension in autonomic neuropathy.
• High-dose corticosteroids should be avoided for the management of septic shock.
• However, there is evidence that administration of lower doses of hydrocortisone and fludrocortisone acetate is of benefit in adrenal insufficiency resulting from septic shock.

Question 8

Cautions of mineralocorticoid analogues (e.g. fludrocortisone) ?
Contraindications?
S/E of mineralocorticoids? glucocorticoids?

Answer 8

• congestive heart failure,
• diabetes (including history of),
• epilepsy,
• glaucoma,
• hypertension,
• osteoporosis
  Cautions Contraindications
• Avoid injections containing benzyl
  alcohol in neonates
• Avoid live virus vaccine in
  immunosuppressive doses
• systemic infection
• Avoid injections containing benzyl alcohol in neonates
• Avoid live virus vaccine in
  immunosuppressive doses
• systemic infection

Mineralocorticoid side effects
*hypertension
*sodium retention
*water retention
*potassium loss
*calcium loss
Most marked with fludrocortisone, but are
significant with hydrocortisone, corticotropin,
and tetracosactide

Glucocorticoid side effects
* diabetes
* osteoporosis – caution elderly
* high doses are associated with avascular
necrosis of the femoral head
* muscle wasting (proximal myopathy) can
also occur
* weakly linked with peptic ulceration and
perforation
* psychiatric reactions may also occur

Question 9

Side effects – All Corticosteroids

Answer 9

• MHRA/CHM advice: Corticosteroids: rare risk of central serous chorioretinopathy (CSC) with local as well as systemic administration - patients should be advised to report any blurred vision or other visual disturbances with corticosteroid treatment.
• MHRA/CHM advice: Topical corticosteroids: risk of topical steroid withdrawal reactions

Adrenal suppression:
* Prolonged systemic corticosteroids- adrenal atrophy develops and persists years after stopping.
Abrupt withdrawal can lead to acute adrenal insufficiency, hypotension or death.
Cushing’s syndrome – resulting from prolonged exposure to excess cortisol, often caused by exogenous corticosteroid use.
Infections:
* Prolonged use can increase susceptibility to infections

Question 10

Cushing’s Syndrome
Causes?
Signs & Symptoms?

Answer 10

Glucocorticoid excess

Causes:
* Long term use of glucocorticoid medications
* Pituitary tumour- cushing disease
* Ectopic ACTH-Producing tumour
* Adrenal tumour

S/S:
* Personality changes
* Hyperglycaemia
* Red face
* CNS Irritability
* Fat round ‘moon’ face
* Thin extremities
* Fat deposition on back of Neck (Buffalo hump)
* Males: Gynecomastia
* Females: Amenorrhea, Hirsutism
* Thin extremities
* GI Distress - Inc Acid
* Purple striae
* Thin skin
* Bruises and petechiae
* Osteoporosis (inc risk of fractures)

Question 11

Cushing’s syndrome diagnosis – overnight dexamethasone suppression test

Answer 11

• Failure to suppress cortisol output will NOT diagnose Cushing’s but cortisol suppression will exclude the majority of patients thought
  to have the disease.
• Diurnal rhythym is lost
• High cortisol throughout day
• The overnight dexamethasone
  suppression test can be used as a screening
  procedure for Cushing’s syndrome, but may not be appropriate in all patients.

Question 12

Cushing’s syndrome diagnosis tests? (4)

Answer 12

1. Cortisol measurements - Loss of diurnal
   rhythm of cortisol release
2. 24-h urine free cortisol
3. ACTH measurements
4. Dynamic tests – dexamethasone
   (DEX) and CRH stimulation test

Question 13

Cushing’s syndrome treatment:

Answer 13

• Decrease and eventually stop taking any corticosteroids.
• Slowly tapering the medicine that is causing the condition can help reverse the effects
  of adrenal gland atrophy
• May not be possible if steroid benefit for disease outweighs complications of therapy.

If withdrawal not possible, symptom management suggested:
* Treating high blood sugar with diet, oral medicines, or insulin.
* Treating high cholesterol with diet or medicines.
* Taking medicines to prevent bone loss. This can help reduce the risk for fractures if you develop osteoporosis.
* Taking other medicines to decrease the amount of glucocorticoid medicine that you need.

Question 14

Adrenal insufficiency
what is it?
symptoms?

Answer 14

• Adrenal insufficiency is a disorder that occurs when the adrenal glands cannot make enough cortisol
• Tertiary adrenal insufficiency can be caused by abrupt withdrawal of corticosteroids following prolonged treatment.

Symptoms:
* Headache
* Dizziness
* Joint pain
* Emotional changes
* Weakness
* May be fatal

• Diagnosis – can be detected from ACTH stimulation test.
• Treatment – hormone replacement, using hydrocortisone and fludrocortisone.
  The goal of treatment is to relieve the symptoms of hormone deficiency without
  causing signs of hormone excess

Key point: Only cortisol/ glucocorticoids involve in feedback control

Question 15

When to use corticosteroids?

Answer 15

• If the use of a corticosteroid can save or prolong life, high doses may need to be given,
  because the complications of therapy are likely to be less serious than the effects of the
  disease itself.
• When long-term corticosteroid therapy is used in some chronic diseases, the adverse
  effects of treatment may become greater than the disabilities caused by the disease.
• When potentially less harmful measures are ineffective, corticosteroids are used
  topically for the treatment of inflammatory conditions of the skin

Question 16

Managing side effects:

Answer 16

• Side-effects can be minimised by using the lowest effective dose for the minimum
  period possible.
• The suppressive action of a corticosteroid on cortisol secretion is least when it is given
  as a single dose in the morning.
• Plasma [cortisol] shows a diurnal
  variation.
• Peak in the early morning trough in
  the late evening

Administration of exogenous steroid:
Limit suppressive action of steroid on
cortisol secretion by mimicking normal
cortisol hormone levels:
- as single dose in morning
(e.g. oral in asthma (acute/ chronic (step 5))
- high dose AM, low dose PM
(Addison’s disease

Question 17

Managing side effects cont..

Answer 17

• In an attempt to reduce pituitary-adrenal suppression further, the total dose for two days can sometimes be taken as a single dose on alternate days; alternate-day administration has not been very successful in the management of asthma.
• Pituitary-adrenal suppression can also be reduced by means of intermittent therapy with short courses.
• In some conditions it may be possible to reduce the dose of corticosteroid by adding a small dose of an immunosuppressive drug.
• Whenever possible local treatment with creams, intra-articular injections, inhalations, eye-drops, or enemas should be used in preference to systemic treatment.
• Inhaled corticosteroids have considerably fewer systemic effects than oral corticosteroids, but adverse effects including adrenal suppression have been reported.
• Use of other corticosteroid therapy (including topical) or concurrent use of drugs which inhibit corticosteroid metabolism should be taken into account when assessing systemic risk.

Question 18

Monitoring for long-term treatment
What should be monitored?

Answer 18

• BP, body weight, BMI, height (children and adolescents), HbA1c, triglycerides,
  potassium, eye examination (for glaucoma & cataract).
• Osteoporosis risk, falls risk assessment and adrenal suppression

Question 19

Counselling Points

Answer 19

Chicken pox:
Unless they have had chickenpox. Patients receiving corticosteroids at risk of severe chickenpox.

In children:
* The height and weight of children receiving prolonged treatment with corticosteroids should be monitored
annually - if growth is slowed, referral to paediatrician

Measles:
Patients should avoid exposure to measles and to seek medical advice if exposure occurs.
Psychiatric reactions:
High doses are linked to psychiatric reactions
including euphoria, insomnia, irritability, mood lability, suicidal thoughts, psychotic reactions and behavioural disturbances.

Withdrawal:
Patients should be advised that adrenal suppression can occur if stopped suddenly before natural production of cortisol is restored.

Directions for administration:
* Topical: once or twice daily max. quantity required is measured using a fingertip unit (the distance from the
tip of the adult index finger to the first crease) approx. 500 mg is sufficient to cover an area that is twice that of the flat adult handprint

• Steroid treatment cards should be issued to
  communicate risks and record details of treatment.
• Steroid emergency cards should be issued to patients with adrenal insufficiency and steroid dependence

Question 20

Treatment Cessation:
What requirements means that the pt requires gradual withdrawal of systemic corticosteroids?

Answer 20

• Abrupt withdrawal after a prolonged period can lead to acute adrenal insufficiency, hypotension or death.
• Withdrawal can be associated with fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and weight loss.

Gradual withdrawal of systemic corticosteroids should be considered in those whose disease is unlikely to relapse and have
* received more than 40 mg prednisolone (or equivalent) daily for more
than 1 week;
* been given repeat doses in the evening;
* received more than 3 weeks’ treatment;
* recently received repeated courses (particularly if taken for longer than 3
weeks);
* taken a short course within 1 year of stopping long-term therapy;
* other possible causes of adrenal suppression.

During corticosteroid withdrawal the dose may be reduced rapidly down to physiological doses (equivalent to prednisolone 7.5 mg daily) and then reduced more slowly.

Question 21

Steroid Cards

Answer 21

1. A Steroid Treatment Card (blue) carries
   patient instructions and informs
   healthcare professionals of the details
   of the steroids prescribed. Used by patients not needing emergency card.
2. NHS Steroid Emergency Card (Red)
   New card to help healthcare staff to identify
   appropriate patients and gives information on the emergency treatment to start if they are acutely ill, or experience trauma, surgery or other major stressors.
   The card should be issued by the prescriber to all patients with primary adrenal insufficiency and those who are steroid dependent i.e. on long-term steroid treatment(s).

Question 22

Steroid Emergency card – NPSA alert

Answer 22

New card issued for patients at risk of adrenal insufficiency:
* those with primary adrenal insufficiency
* Those with adrenal insufficiency due to hypopituitarism requiring corticosteroid replacement
* Those taking corticosteroids at doses equivalent to or exceeding, prednisolone 5 mg OD for 4 weeks or longer across all administration routes
* received more than 40 mg prednisolone (or equivalent) daily for more than 1 week or repeated short courses;
* taken a short course within 1 year of stopping long-term therapy;

Question 23

A corticosteroid produced naturally by the body is:

a) Betamethasone
b) Hydrocortisone
c) Dexamethasone
d) Deflazacort

Answer 23

=B (cortisol)

Question 24

A gradual withdrawal is needed for a patient who has taken hydrocortisone 100 mg PO for 1 week:
a) Yes
b) No
TOP TIP: see Glucocorticoid therapy
treatment summary BNF online!

Answer 24

=B
- No as hydrocortison 100mg PO although systemic is only equivalent to 25mg (less than 40mg) of prednisolone and the patient has not recieved more than 3 weeks of treatment