Corticosteroids
On this page
Corticosteroids are synthetic analogues of hormones produced by the adrenal cortex. Corticosteroids can have glucocorticoid or mineralocorticoid properties and different corticosteroids have varying ratios of these properties.
Glucocorticoids affect cells by binding to the glucocorticoid receptors of cells and up-regulating the expression of anti-inflammatory proteins in the nucleus whilst inhibiting the expression of pro-inflammatory proteins. Mineralocorticoids bind to the mineralocorticoid receptor in cells and regulate gene transcription (aldosterone is the main endogenous mineralocorticoid and up-regulates renal sodium influx through the epithelial sodium channel).
Mineralocorticoid effects include:
Mineralocorticoid side effects:
Mineralocorticoid side effects are most marked with fludrocortisone, but are significant with hydrocortisone, corticotropin, and tetracosactide. Mineralocorticoid actions are negligible with the high potency glucocorticoids, betamethasone and dexamethasone, and occur only slightly with methylprednisolone, prednisolone, and triamcinolone.
Glucocorticoid side effects:
Managing side-effects:
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 (pituitary-adrenal suppression) may be mitigated by using local rather thena systemic therapy when possible and when systemic therapy is used intermittent therapy with short courses is sometimes used (this isn't appropriate in the management of asthma).
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.
Corticosteroid potency
In comparing the relative potencies of corticosteroids in terms of their anti-inflammatory (glucocorticoid) effects it should be borne in mind that high glucocorticoid activity in itself is of no advantage unless it is accompanied by relatively low mineralocorticoid activity. The mineralocorticoid activity of fludrocortisone acetate is so high that its anti-inflammatory activity is of no clinical relevance.
Dexamethasone (and betamethasone) also have a long duration of action and this, coupled with lack of mineralocorticoid action makes them particularly suitable for conditions which require suppression of corticotropin (corticotrophin) secretion (e.g. congenital adrenal hyperplasia). In common with all glucocorticoids their suppressive action on the hypothalamic-pituitary-adrenal axis is greatest and most prolonged when they are given at night. In most individuals a single dose of dexamethasone at night, is sufficient to inhibit corticotropin secretion for 24 hours. This is the basis of the ‘overnight dexamethasone suppression test’ for diagnosing Cushing’s syndrome.
Mineralocorticoid and glucocorticoid
Corticosteroids have mineralocorticoid and glucocorticoid properties with different corticosteroids varying in their mineralocorticoid and glucocorticoid effect.Glucocorticoids affect cells by binding to the glucocorticoid receptors of cells and up-regulating the expression of anti-inflammatory proteins in the nucleus whilst inhibiting the expression of pro-inflammatory proteins. Mineralocorticoids bind to the mineralocorticoid receptor in cells and regulate gene transcription (aldosterone is the main endogenous mineralocorticoid and up-regulates renal sodium influx through the epithelial sodium channel).
Mineralocorticoid effects include:
- Increased sodium and water retention (increased blood pressure)
- Increased potassium and hydrogen ion loss.
- Metabolic actions: decreased uptake and utilisation of glucose and increased gluconeogenesis, decreased protein synthesis and increased protein breakdown, a permissive effect on lipolytic hormones and a redistribution of fat (observed in Cushing's syndrome) and decreased calcium stores.
- Regulatory actions (anti-inflammatory and immunosuppressive): decreased production of inflammatory mediators (such as prostaglandins and cytokines), decreased production of histamine and other mediators from basophils and mast cells, decreased production of immunoglobulin G (IgG), decreased egress of neutrophils from blood vessels and reduced activation, and decreased activation of T-lymphocytes.
- Cardiovascular: reduced vasodilation, decreased fluid exudation.
- Musculoskeletal: decreased osteoblast and increased osteoclast activity
Corticosteroids in respiratory conditions
Corticosteroids are preferably used by inhalation in the management of asthma and chronic obstructive pulmonary disease (COPD). Systemic therapy along with bronchodilators is required for treatment of acute asthma attacks, in some very severe cases of chronic asthma, and exacerbations of COPD.
Corticosteroids are preferably used by inhalation in the management of asthma and chronic obstructive pulmonary disease (COPD). Systemic therapy along with bronchodilators is required for treatment of acute asthma attacks, in some very severe cases of chronic asthma, and exacerbations of COPD.
Side effects
Mineralocorticoid side effects:
- Hypertension
- Sodium retention
- Water retention (oedema)
- Potassium loss (hypokalaemia)
- Calcium loss (hypocalcaemia)
Mineralocorticoid side effects are most marked with fludrocortisone, but are significant with hydrocortisone, corticotropin, and tetracosactide. Mineralocorticoid actions are negligible with the high potency glucocorticoids, betamethasone and dexamethasone, and occur only slightly with methylprednisolone, prednisolone, and triamcinolone.
Glucocorticoid side effects:
- Diabetes
- Osteoporosis
- Avascular necrosis of the femoral head (high doses)
- Muscle wasting (proximal myopathy)
- Peptic ulceration and perforation
- Psychiatric reactions including psychosis
Managing side-effects:
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 (pituitary-adrenal suppression) may be mitigated by using local rather thena systemic therapy when possible and when systemic therapy is used intermittent therapy with short courses is sometimes used (this isn't appropriate in the management of asthma).
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.
Steroid withdrawal:
As a general principle, short courses of oral corticosteroids (less than 3 weeks) can be stopped abruptly. Gradual withdrawal should be considered for people whose disease is unlikely to relapse and who have:- Taken more than 40 mg oral prednisolone daily or equivalent for more than 1 week.
- Taken repeated evening doses of corticosteroids.
- Received more than 3 weeks of corticosteroid treatment.
- Recently received repeated courses of corticosteroids (especially if taken for longer than 3 weeks), such as short courses repeatedly prescribed for the treatment of acute exacerbations of asthma.
- A history of previous long-term therapy (months or years).
- Other possible causes of adrenal suppression, such as excessive alcohol consumption or stress.
Corticosteroid potency
In comparing the relative potencies of corticosteroids in terms of their anti-inflammatory (glucocorticoid) effects it should be borne in mind that high glucocorticoid activity in itself is of no advantage unless it is accompanied by relatively low mineralocorticoid activity. The mineralocorticoid activity of fludrocortisone acetate is so high that its anti-inflammatory activity is of no clinical relevance.
Hydrocortisone
The relatively high mineralocorticoid activity of hydrocortisone, and the resulting fluid retention, makes it unsuitable for disease suppression on a long-term basis. However, hydrocortisone can be used for adrenal replacement therapy. Hydrocortisone is used on a short-term basis by intravenous injection for the emergency management of some conditions. The relatively moderate anti-inflammatory potency of hydrocortisone also makes it a useful topical corticosteroid for the management of inflammatory skin conditions because side-effects (both topical and systemic) are less marked.Dexamethasone
Dexamethasone (and betamethasone) have very high glucocorticoid activity in conjunction with insignificant mineralocorticoid activity. This makes them particularly suitable for high-dose therapy in conditions where fluid retention would be a disadvantage.Dexamethasone (and betamethasone) also have a long duration of action and this, coupled with lack of mineralocorticoid action makes them particularly suitable for conditions which require suppression of corticotropin (corticotrophin) secretion (e.g. congenital adrenal hyperplasia). In common with all glucocorticoids their suppressive action on the hypothalamic-pituitary-adrenal axis is greatest and most prolonged when they are given at night. In most individuals a single dose of dexamethasone at night, is sufficient to inhibit corticotropin secretion for 24 hours. This is the basis of the ‘overnight dexamethasone suppression test’ for diagnosing Cushing’s syndrome.