Synthetic glucocorticoids are a group of drugs with antiinflammatory, immunosuppressant, metabolic, and endocrine effects. These drugs are structurally and functionally similar to the endogenous glucocorticoid hormone cortisol. Glucocorticoids have immediate effects (e.g., vasoconstriction) that do not depend on DNA interaction. However, they exert their main antiinflammatory and immunosuppressive actions by binding to glucocorticoid receptors, which causes complex changes in gene transcription. These genomic effects only begin to manifest after several hours. Similarly, glucocorticoids bind to mineralocorticoid receptors, but, for most glucocorticoid drugs, high doses are required for a significant mineralocorticoid effect. Systemic glucocorticoids are used for hormone replacement therapy (e.g., in Addison disease), for acute or chronic inflammatory diseases (e.g., rheumatoid arthritis), and for immunosuppression (e.g., after organ transplants). Local glucocorticoids are used to treat conditions like dermatoses, asthma, and anterior uveitis. Adverse effects include metabolic and endocrine disturbances, weight gain, skin reactions, hypertension, and psychiatric disorders; using the lowest dose possible for the shortest period of time, patient education, and regular screening can help lower the incidence of adverse effects and ensure early detection if they do occur. Contraindications for systemic glucocorticoids include systemic fungal infections and, in the case of dexamethasone, cerebral malaria. Status asthmaticus is a contraindication for inhaled glucocorticoids. Topical and ophthalmic glucocorticoids are usually contraindicated if there are preexisting local infections.
- Corticosteroids: a class of steroid hormones that includes glucocorticoids and mineralocorticoids 
Endogenous corticosteroids: hormones synthesized from cholesterol in the adrenal cortex 
- Endogenous glucocorticoids (e.g., cortisol): synthesized in the zona fasciculata with antiinflammatory, immunosuppressant, metabolic, and endocrine effects
- Endogenous (i.e., aldosterone): synthesized in the zona glomerulosa and primarily functions to regulate the renin-angiotensin system and maintain electrolyte and water balance
- Synthetic corticosteroids: structural and functional analogs of endogenous corticosteroids that are used in the treatment of a variety of conditions 
- Corticosteroids that are administered orally, intravenously, or intramuscularly
- Act systemically as they are distributed throughout the body
- Examples: See table below.
- Local corticosteroids (local glucocorticoids)
systemic corticosteroids  of
- Hydrocortisone is the synthetic equivalent of endogenous cortisol and its glucocorticoid and mineralocorticoid potency is considered to be “1” (see table below).
- Relative to hydrocortisone, systemic corticosteroids differ in potency of their glucocorticoid effects (relative glucocorticoid potency) and mineralocorticoid effects (relative mineralocorticoid potency) for a given dose.
|Relative potency of systemic corticosteroids |
|Duration of action|| |
| Common routes |
| Short-acting |
|Hydrocortisone|| || || || |
|Cortisone|| || || || |
| Intermediate-acting |
| || || |
|Methylprednisolone|| || || || |
|Triamcinolone|| || || || |
| Long-acting |
| || || || |
|Betamethasone|| || || || |
|Fludrocortisone|| || || || |
- Summary of effects of systemic corticosteroids
Antiinflammatory and immunosuppressive
- Acute effects (within minutes)
Long-term effects (within hours) : Glucocorticoids bind to cytoplasmic glucocorticoid receptors (GRs)
- Inhibition of neutrophil apoptosis and demargination (loss of neutrophil binding to adhesive endothelial integrin molecules) → neutrophilic leukocytosis
- Promotion of sequestration and apoptosis of eosinophils, monocytes, and lymphocytes → lymphopenia and eosinopenia
- ↑ Inhibition of phospholipase A2, which decreases the production of arachidonic acid derivatives → ↓ production of leukotrienes and prostaglandins
- ↑ Inhibition of transcription factors (e.g., NF-κB) → ↓ expression of pro-inflammatory genes (e.g., TNF-α gene, interleukin-2 gene)
- Translocation to the cell nucleus and binding to glucocorticoid responsive elements (GREs) within the promoters of antiinflammatory genes (e.g., interleukin-10 gene) → ↑ expression of antiinflammatory genes
- Suppression of B cells and T cells (T cell apoptosis)
- Inhibition of histamine release from mast cells
- Permissive effect on epinephrine and norepinephrine via upregulation of α1-adrenergic receptors on arterioles
- Mineralocorticoid properties
- Antiproliferative: triggers cell apoptosis, and inhibits fibroblast proliferation 
- Anabolic-androgenic effects with steroid abuse: : increase in muscle mass and strength
Both acute and long-term effects of glucocorticoids lead to inhibition of inflammatory processes and to immunosuppression.
Glucocorticoid toxicity depends on the dose that is administered over a certain period of time. Therefore, even low doses can have toxic effects if administered long-term. If glucocorticoids are administered once or only briefly (e.g., for treatment of anaphylactic shock), there are usually no significant adverse effects even at high doses.
|Organ/System of organs||Effects|
|Metabolism, electrolytes and endocrine system|| |
|CNS and psyche|
Many of the adverse effects listed above are also features of iatrogenic .
|Topical glucocorticoids||Inhaled glucocorticoids|
|Eyes|| || |
Local side-effects of inhaled glucocorticoids can be avoided by reducing the dose to the lowest effective amount, rinsing with mouthwash after each puff, improving the inhalation technique and compliance, and keeping vaccinations up to date.
We list the most important adverse effects. The selection is not exhaustive.
- Adrenocortical insufficiency ()
Systemic symptomatic treatment
- Antiemetic treatment (e.g., nausea due to cytostatic treatment)
- Toxic 
- Acute exacerbation of autoimmune diseases (e.g., , )
- Acute exacerbation of COPD
- Gout, calcium pyrophosphate deposition disease
- Thyroid storm:cortisol inhibits the peripheral conversion of T4 to T3 (the inactive byproduct of T4, rT3, increases)
- Acute pericarditis
- Local symptomatic treatment: anterior uveitis; , dermatoses; , ; , and osteoarthritis or juvenile idiopathic arthritis
- General: hypersensitivity
- Dermatological: bacterial, viral or fungal infection of the mouth or throat (triamcinolone)
- Inhalation: status asthmaticus or acute asthma episode requiring intensive measures (beclomethasone, budesonide)
- Relative contraindications: Glucocorticoids should be avoided in certain conditions due to increased risk of toxicity.
We list the most important contraindications. The selection is not exhaustive.
Tapering to avoid toxicity
- Short-term administration (≤ 3 weeks): usually no tapering necessary
- Long-term administration (> 3 weeks): tapering regimen based on patient age and condition and on duration/dose of prior glucocorticoid administration → e.g., tapering over 2 months
- Sudden discontinuation after chronic use should be avoided because of the risk of adrenal insufficiency (adrenal crisis) secondary to long-term hypothalamic-pituitary-adrenal axis suppression.
- Tapering to avoid toxicity
- IM application
If the Cushing threshold is exceeded over a longer period of treatment, the glucocorticoid dose should be gradually decreased to minimize the risk of adrenocortical insufficiency.
Complications are most common with long-term systemic treatment but can also occur with higher-dose topical and inhaled steroids. The risk of complications can be reduced by keeping treatment durations short or doses low. 
- Choose short-term higher-dose pulse therapy if possible.
- If continuous treatment is necessary, aim for the lowest possible daily dose. 
- Assess risk factors for complications of glucocorticoid therapy.
- Initiate measures to prevent complications of glucocorticoid therapy.
- When discontinuing long-term steroid regimens:
- Advise patients not to stop the medication suddenly because of the risk of adrenal suppression.
- Taper under medical supervision in courses lasting > 3 weeks. 
|Risk factors for complications of glucocorticoid therapy|
|Adrenal suppression and adrenal insufficiency || |
|Osteoporosis || |
|Peptic ulcer disease || |
|Diabetes and hyperglycemia || |
|Infections || |
|Cardiovascular disease |
|Ocular disease |
|Psychiatric complications || |
Measures to prevent complications
|Measures to prevent complications of glucocorticoid therapy|
|Complication to prevent||Before therapy||During therapy|
|Adrenal suppression and adrenal insufficiency |
|Peptic ulcer disease || |
|Diabetes and hyperglycemia |
|Cardiovascular disease |
|Ocular disease |
|Psychiatric disease || |