Corticosteroids, Systemic

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Corticosteroids, Systemic


Corticosteroids are a group of drugs which are chemically related to the hormones produced by the adrenal glands as a response to adrenocorticotropic hormone (ACTH), but excluding the sex hormones that are produced by this gland. The primary adrenal corticosteroids are cortisol and aldosterone. Cortisol is a glucocorticoid, responsible for influencing carbohydrate, fat, and protein metabolism. Aldosterone is a mineralocorticoid, responsible for regulating salt and water balance.

All corticosteroids, both natural ones and those which have been developed synthetically, share a similar chemical structure, which is based on the structure of cholesterol.


The primary purpose of corticosteroids is replacement of naturally occurring hormones when the adrenal glands do not make enough of the natural hormones. Known as Addison's disease, this deficit is marked by low blood pressure, weight loss, loss of appetite, weakness, and a bronze-like hyperpigmentation of the skin. Addison's disease requires both glucocorticoid and mineralocorticoid treatment.

Because the glucocorticoids inhibit some portions of the immune response, they are used in treatment of a large number of diseases. The following list includes some of the established uses of systemic corticosteroids.

  • acute, severe allergic reactions
  • arthritis, osteoarthritis, rheumatoid arthritis, psoriatic arthritis, and gouty arthritis
  • adrenocortical insufficiency
  • allergic conjunctivitis
  • allergic rhinitis
  • anemia
  • (acquired hemolytic and congenital hypoplastic)
  • ankylosing spondylitis
  • asthma
  • beryliosis
  • bursitis
  • corneal ulcers
  • Crohn's disease
  • dermatitis (atopic, contact, exfoliative, and seborrheic)
  • dermatomyositis
  • erythema multiforme
  • erythroblastopenia
  • herpes zoster of the eye
  • hypercalcemia secondary to cancer
  • hypersensitivity reactions
  • idiopathic thrombocytopenic purpura
  • leukemia
  • lupus erythematosis
  • lymphoma
  • multiple myeloma
  • multiple sclerosis, acute exacerbations
  • mycosis fungoides
  • optic neuritis
  • pemphigus
  • pneumonitis (aspiration)
  • rheumatic carditis
  • Stevens-Johnson syndrome
  • thrombocytopenia
  • trichinosis with nerve or heart involvement
  • tuberculosis, disseminated and fulminating
  • tuberculous meningitis
  • ulcerative colitis

Dexamethasone, a related corticosteroid, is widely used to prevent the nausea and vomiting associated with cancer therapy.

Glucocorticoid treatment is not a cure for any disease or condition, but it may be used as supportive therapy in addition to other treatments.


Because they both have mineralocorticoid and glucocorticoid effects, cortisone and hydrocortisone are preferred for use in treating adrenal insufficiency. When glucocorticoids are used for their anti-inflammatory and immunosuppressant properties and their effects on blood and lymphatic systems, synthetic compounds, which have increased glucocorticoid effects and minimal mineralocorticoid effects, are generally preferred.

A number of systemic corticosteroid compounds are commercially available. Although they are generally similar, they vary in their potency, sodium-retaining effects, and duration of action.

Short acting

Cortisone has both glucocorticoid and mineralocorticoid effects. It has the lowest potency of the commercially available corticosteroids and a short duration of action. It is appropriate for replacement therapy in patients with adrenal insufficiency.

Hydrocortisone has both glucocorticoid and mineralocorticoid effects. It is more potent than cortisone and has a somewhat longer duration of action. Although hydrocortisone may be used for its systemic effects, it is most commonly used in skin preparations.

Intermediate acting

Prednisone is probably the most widely used of the systemic steroids. It has about half the sodium-retaining effects of hydrocortisone but several times the anti-inflammatory effects. Because of the low level of mineralocorticoid effects, however, prednisone is not suitable for treatment of adrenal insufficiency unless it is used in combination with a mineralocorticoid drug. Prednisolone is very similar to prednisone. In addition to oral dosage form, it is available for subcutaneous, intramuscular, and intravenous injection.

Triamcinolone is slightly more potent than prednisone or prednisolone but has no sodium-retaining effects. It is administered various ways, including inhalation for respiratory problems and as ointments and creams for skin conditions. Methylprednisolone, which is similar to triamcinolone, is most commonly given by injection.

Long acting

Dexamethasone is a very potent glucocorticoid, with no mineralocorticoid activity. It is used in various forms, including tablets, injection, ointments, and eye and eardrops. In cancer treatment, dexamethasone is used both for its corticosteroid properties and as an antinauseant, to help control the side effects of other drugs. Betamethasone is similar to dexamethasone. Although the drug is available for systemic use, it is more commonly used in the form of inhalations and ointments. Other corticosteroids are available but are most often used in inhalation form, for asthma, allergic rhinitis, or other respiratory conditions.

Recommended dosage

Dosages of corticosteroids must be individualized based on the drug selected, the condition being treated, and the response of the patient. In adrenal insufficiency, a dose equivalent to 25 mg of cortisone or 20 mg of hydrocortisone is normally appropriate. In other conditions, a pharmacologic dose (any dose in excess of the replacement dose) is called for. The equivalent doses of corticosteroids are as follows:

  • cortisone: 25 mg
  • hydrocortisone: 20 mg
  • prednisolone: 5 mg
  • prednisone: 5 mg
  • methylprednisolone: 4 mg
  • triamcinolone: 4 mg
  • dexamethason: 0.75 mg
  • betamethasone: 0.6 mg

For short-term use, corticosteroids are normally administered in two or three doses each day. In most cases, an initial dose equivalent to 5 to 60 milligrams of prednisone per day is appropriate. Usually, a response will be seen within ten days. Once a response has been observed, the dose should be carefully reduced to the lowest dose that will provide adequate control. If no response is seen after a reasonable period of time, an alternative method of treatment should be considered. On rare occasions, patients will respond better to one corticosteroid than to others.

In the case of acute exacerbations of multiple sclerosis, doses as high as 200 milligrams of prednisone or prednisolone for a week followed by 80 mg every other day for one month have been used.

Because administration of corticosteroids reduces the output of cortisone from the adrenal glands, dosing should be designed to minimize the effects of corticosteroid therapy on the adrenal glands. For patients who will be taking corticosteroids for a long time, a single dose of the corticosteroid is taken every other morning. This regimen provides benefits for most conditions, while minimizing many adverse effects of long-term steroid administration, including adrenal suppression and protein breakdown. Although alternate day treatment is the preferred dosing schedule, it is not suited for treatment of rheumatoid arthritis or ulcerative colitis, for which daily doses are essential. Only the shorter acting corticosteroids such as prednisone or prednisolone should be used for alternate-day dosing.

When corticosteroid treatment is being discontinued, it is frequently useful to reduce the dose gradually, over several days. Many of these tapering schedules have been described. In one tapering schedule glucocorticoid dosage is reduced by the equivalent of 2.5-5 mg of prednisone every three to seven days until the physiologic dose (e.g., 5 mg of prednisone or prednisolone, 0.75 mg of dexamethasone, or 20 mg of hydrocortisone) is reached. Other schedules may call for slower dose adjustments. The dose may have to be increased if there is a flare-up of the condition being treated while the dose is being reduced. Then, tapering may begin again, but at a slower rate.


Because corticosteroids reduce the immune response, they should not be used in patients who have active fungal infections. Similarly, patients being treated with corticosteroids should avoid receiving live virus vaccines.

Corticosteroids may mask some signs of infection, and new infections may appear during their use. There may be decreased resistance and inability to localize infection. Any evidence of infection should be treated promptly with appropriate anti-infective therapy.

Corticosteroids may activate latent amebic infections. Therefore, it is recommended that latent or active amebiasis be ruled out before starting corticosteroid therapy in any patient who has spent time in the tropics or any patient with unexplained diarrhea.

Adequate human reproduction studies have not been done with corticosteroids. Use of these drugs in pregnancy or in women of childbearing potential requires that the anticipated benefits be weighed against the possible hazards to the mother and embryo or fetus. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

Corticosteroids have been associated with an increased risk of gastric ulcers, and patients are usually advised to take these drugs either with food or a drug which inhibits gastric acid. Those taking high dose steroids or on maintenance therapy should take the medication with meals or a gastric acid blocker to reduce the risk of gastric ulcers. However, these precautions are probably not needed for patients taking low doses for a short period of time.

Side effects

Corticosteroids are generally safe when used for a short period of time with appropriate monitoring. When used for longer periods, the frequency and severity of adverse effects increases dramatically. Many of these effects are the unavoidable results of the normal actions of the steroid drugs and must be considered when people decide on a course of long-term corticosteroid therapy.

Fluid and electrolyte disturbances

Sodium retention, fluid retention, congestive heart failure in susceptible patients, potassium loss, calcium loss, hypertension may result from long-term use.

Muscle and bone

Muscle weakness, loss of muscle mass, osteoporosis, compression fractures of the spine, aseptic necrosis of femoral and humeral heads, pathologic fracture of long bones, and tendon rupture are all possible effects from long-term use.

Gastrointestinal effects

Peptic ulcer with possible perforation and hemorrhage, perforation of the small and large bowel particularly in patients with inflammatory bowel disease, pancreatitis, abdominal distention, and ulcerative esophagitis can result from long-term use.

Skin reactions

Impaired wound healing, thin fragile skin, red spots, increased sweating, reduced reactions to skin tests, along with other reactions, including rashes, itching and swelling can all result from long-term use.

Nerves and central nervous system

Convulsions, increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment, dizziness and loss of balance, headache, and emotional disturbances can result from long-term use.

Endocrine gland system

Menstrual irregularities, development of cushingoid state, suppression of growth in children, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), decreased carbohydrate tolerance, manifestations of latent diabetes mellitus, hyperglycemia, increased requirements for insulin or oral hypoglycemic agents in diabetics, and increased hair growth can result from long-term use.

Eye problems

Cataracts, increased intraocular pressure, glaucoma, and bulging eyes can result from long-term use.

Other problems

Hypersensitivity, blood clotting problems, weight gain, increased appetite, nausea, and hiccups can result from long-term use.

In addition to this incomplete list of long-term effects, other serious effects have been associated with systemic corticosteroid treatment. The severity and likelihood of adverse effects increases both with dose and duration of treatment. Because of their greater effects on sodium and water, the natural corticosteroids, cortisone, and hydrocortisone are more likely to cause fluid and electrolyte problems than the pure glucocorticoids such as dexamethasone and betamethasone.


Drugs that stimulate liver enzymes such as phenobarbital, phenytoin, and rifampin may increase the rate of elimination of corticosteroids and may require increases in corticosteroid dose to achieve the desired response.

Drugs such as troleandomycin and ketoconazole may reduce the rate of metabolism of corticosteroids and decrease the rate of elimination. Therefore, the dose of corticosteroid should be lowered to avoid steroid toxicity.

Corticosteroids may increase the rate of elimination of chronic high dose aspirin. This effect could lead to decreased salicylate serum levels or increase the risk of salicylate toxicity when corticosteroid is withdrawn.

The effects of corticosteroid treatment on anticoagulants vary. There have been reports of both increased anticoagulant activity and decreased anticoagulant activity. Careful monitoring is essential when corticosteroids are used together with anticoagulants.


Crohn's disease A chronic inflammatory disease of unknown cause, involving any part of the gastrointestinal tract from mouth to anus, but commonly involving the large intestine, with scarring and thickening of the bowel wall. Crohn's disease frequently leads to intestinal obstruction and has a high rate of recurrence after treatment.

Erythema multiforme A type of hypersensitivity (allergic) reaction that occurs in response to medications, infections, or illness. Medications associated with erythema multiforme include sulfonamides, penicillins, barbiturates, and phenytoin. Associated infections include herpes simplex and mycoplasma infections. In severe cases, the condition is called Stevens-Johnson syndrome.

Erythroblastopenia A deficiency in the cells that create red blood cells. This condition may be severe and life-threatening, but there is a transient form, seen in young children, which resolves spontaneously and does not recur.

Hypercalcemia An excessive amount of calcium in the blood. The most common cause an excess hormone secretion from the parathyroid gland, but hypercalcemia may also be seen in some cancers (lung, breast, multiple myeloma), as a side effect of some drugs, or from excess calcium in the diet.

Mycosis fungoides The most common type of cutaneous T-cell lymphoma. This low-grade lymphoma primarily affects the skin. Generally, it has a slow course and often remains confined to the skin. Over time, in about 10% of cases, it can progress to the lymph nodes and internal organs.

Optic neuritis Inflammation of the optic nerve (cranial nerve II) which connects to the retina of the eye. This variable condition can be present with any of the following symptoms: blurred vision, loss of visual acuity, loss of some or all color vision, complete or partial blindness, and pain behind the eye.

Pemphigus An autoimmune disorder in which the immune system produces antibodies against specific proteins in the skin and mucous membrane. These antibodies produce a reaction that leads to a separation of skin cells.

Pneumonitis (aspiration) Inflammation of the lung caused by inhaling a liquid, usually carbon based.

Stevens-Johnson syndrome A severe form of erythema multiforme in which the systemic symptoms are severe and the lesions extensive, involving multiple body areas, especially the mucous membranes.

Trichinosis A roundworm infection, usually contracted by eating raw or undercooked meat. Trichinosis is rare in the United States but a common infection in some parts of the world.

Ulcerative colitis A chronic, episodic, inflammatory disease of the large intestine and rectum characterized by bloody diarrhea.



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American Association of Immunologists Inc. 9650 Rockville Pike, Bethesda, MD 20814. (301) 634-7178.

Arthritis National Research Foundation. 200 Oceangate, Suite 830, Long Beach, CA 90802. (800) 588-2873.