61. Corticosteroids

Page created on September 18, 2019. Last updated on February 22, 2022 at 14:02


The corticosteroids are hormones released from the adrenal cortex. We distinguish two types of corticosteroids, the glucocorticoids and the mineralocorticoids, although in clinical practice the term “corticosteroids” is often used to mean glucocorticoids only. The release of glucocorticoids is stimulated by ACTH. The level of ACTH, and therefore glucocorticoids, follows a diurnal rhythm, meaning that it is at its highest at 8:00 and at its lowest at midnight.

Effects of glucocorticoids

The effects of glucocorticoids on the body explains all pharmacological indications and possible side-effects of glucocorticoid therapy.

The metabolic effects involve decreased glucose uptake and utilization, decreased protein synthesis, increased protein breakdown, increased ketone body synthesis and increased lipolysis. In high, non-physiological doses glucocorticoids will have mineralocorticoid-like effects due to the spillover-mechanism, causing Na+ retention and K+ loss. There will also be a negative Ca2+ balance, causing osteoporosis.

Glucocorticoids elicit most of their effects by binding to the intracellular glucocorticoid receptor, which alters gene transcription and represses pro-inflammatory genes and induces anti-inflammatory genes. These genomic effects take long time to set in. However, glucocorticoids also have so-called non-genomic effects, which occur within minutes of administration. These non-genomic effects involve decreased leukocyte migration and decreased capillary permeability and vasodilation. The latter two have an anti-oedema effect.

By both genomic and non-genomic effects glucocorticoids increase the production and activation of lipocortin, a protein which inhibits phospholipase A2. By this mechanism will glucocorticoids decrease the production of thromboxanes, prostaglandins and leukotrienes.

Pharmacology of glucocorticoids

Many glucocorticoids are used pharmacologically, where they’re often called “steroids”. Most of them are synthetic. They differ in their potency in activating the glucocorticoid receptor, their degree of activating the mineralocorticoid receptor, their degree of systemic and local effectiveness and their duration of action.


The following glucocorticoids are used systemically:

Duration of action Name Relative potency Formulations
Short (~12h) Hydrocortisone (cortisol) 1 IM, IV, PO, topical
Cortisone 0,8 PO
Medium (~24 – 48h) Prednisolone 4 PO
Methylprednisolone 5 IM, IV, PO
Long (~36 – 72h) Dexamethasone 25 – 30 IM, IV, PO
Betamethasone 25 – 30 IM, topical

The potency is measured relative to the potency of cortisol. Hydrocortisone and cortisol are the same molecule, but in a pharmacological setting we use the name hydrocortisone.

The numbers of the above table aren’t that important to know, but it’s important to know the duration of action and the potency. The following brand names are not important for the exam but may be nice to know:

  • Hydrocortisone
    • In PO formulation: Cortef®
    • In IV formulation: Solu-Cortef®
  • Methylprednisolone
    • In PO formulation: Medrol®
    • In IV formulation: Solu-Medrol®

The following glucocorticoids are used locally, including topically, as an inhalation or as nasal spray:

  • Mild strength
    • Hydrocortisone – topical
  • Moderate strength
    • Desonide – topical
  • Strong
    • Momethasone – topical, inhalation, nasal spray
    • Fluticasone – topical, inhalation, nasal spray
    • Betamethasone – topical
    • Budesonide – oral, inhalation
    • Triamcinolon – intraarticular injection, topical, nasal spray
  • Extra strong
    • Clobetasol – topical


The list of indications for glucocorticoids is endless. It’s mostly used for symptomatic treatment, either locally or systemically. Here are some of the most important indications:

  • As substitution therapy (usually hydrocortisone)
    • In primary adrenal insufficiency (Addison’s disease)
    • In secondary adrenal insufficiency
    • In tertiary adrenal insufficiency
  • As systemic symptomatic therapy
    • Acute
      • Allergic reactions and anaphylactic shock
      • Asthma attack
      • Antiemetic treatment
      • Acute exacerbation of autoimmune diseases like MS, psoriasis
      • Acute exacerbation of COPD
      • Cerebral oedema – only dexamethasone
      • Pain (as adjuvant treatment)
    • Chronic
      • Asthma
      • COPD
      • Inflammatory bowel disease
      • Sarcoidosis
      • Rheumatological disorders (Sjögren, SLE, RA)
      • Kidney disorders
  • As local symptomatic treatment
    • Skin diseases
    • Ear diseases
    • Eye diseases
  • Organ transplant
  • To distinguish between different types of Cushing syndrome
    • As part of the dexamethasone suppression test
  • Preterm delivery
    • Glucocorticoids given to the mother induce foetal lung maturity

People who are on substitution therapy with glucocorticoids should increase their dose of glucocorticoids in cases of stress, like infections, surgery or trauma. These types of stress can increase the body’s need for cortisol by a factor of 10. If this demand is not met, the patient can develop an adrenal crisis due to relative lack of cortisol, which can be fatal.


Glucocorticoids are available in many different drug formulations. Local treatment is preferred over systemic treatment where possible, to prevent systemic side-effects. Drug formulations like ointments, creams, eye drops, ear drops, nasal sprays, intraarticular injections and inhalation aerosols all allow for local treatment. Some glucocorticoids which are not absorbed through the GI tract are administered orally to locally treat inflammations of the GI tract, like in Crohn disease.

Most glucocorticoids have good oral absorption, so for chronic systemic treatment oral preparations are often used. Long-term systemic steroid therapy causes atrophy of the adrenal cortex. If long-term (> 3 weeks) steroid therapy is discontinued suddenly the body will experience relative cortisol deficiency, potentially causing an adrenal crisis. Long-term steroid therapy should only be terminated gradually, to prevent this. Taking steroids every second day may help limit adrenal atrophy. We should always strive to find the lowest dose that is still effective, to limit side effects.


All glucocorticoids are small lipophilic molecules that easily penetrate through biological membranes.

Hydrocortisone is inactivated by the liver and then excreted by the kidneys. Cortisone is a prodrug which is converted into hydrocortisone in the liver.

90% of endogenous glucocorticoids are bound to a transport protein called corticosteroid-binding globulin (CBG). Synthetic glucocorticoids like dexamethasone and betamethasone don’t bind to CBG and therefore act more rapidly than non-synthetic glucocorticoids.

Side effects

Side effects usually develop during chronic treatment, and rarely during short-term treatment. The potential side effects of steroid treatment comprise Cushing syndrome and has been described many times before, but here are some of them:

  • Skin atrophy
  • Purple stretch marks
  • Hypertension
  • Central weight gain, buffalo hump, moon face
  • Hyperglycaemia/diabetes
  • Osteoporosis
  • Muscle weakness
  • Psychosis


There are no contraindications for people who require glucocorticoid as substitution therapy. These contraindications are for those that receive symptomatic steroid therapy.

  • Allergy
  • Systemic fungal infections
  • Concomitant live virus vaccination

Glucocorticoids should be used with care in people with psychosis, diabetes, ulcers, severe hypertension and pregnant women.

Pharmacology of mineralocorticoids

Mineralocorticoids are used pharmacologically only in substitution treatment of primary adrenal insufficiency (Addison disease) and the most common type of congenital adrenal hyperplasia (21β deficiency). Both conditions are treated with life-long substitution with cortisol and fludrocortisone, a synthetic corticosteroid with significant mineralocorticoid effect.

Drugs acting on corticosteroid synthesis

Metyrapone inhibits cortisol synthesis by inhibiting the enzyme 11β-hydroxylase, an enzyme involved in cortisol synthesis. It’s used to treat Cushing syndrome.

Ketoconazole is an antifungal drug which also inhibits 17α-hydroxylase, an enzyme involved in cortisol synthesis. It’s used to treat Cushing syndrome.

Aminoglutethimide decreases corticosteroid synthesis but is no longer available due to its toxicity.

4 thoughts on “61. Corticosteroids”

  1. hey greek.doctor
    should we learn the numbers in glucocorticoid table for final exam?

    thanks and as alway,you rock

    1. No, not at all. You should perhaps know that certain glucocorticoids, like dexamethasone, are much more potent than cortisol.

      You rock too 😉

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