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Cortisol is a steroid hormone that is normally secreted by the adrenal cortex in response to ACTH. It exerts its action by binding to nuclear receptors, which then act upon chromatin to regulate gene expression, producing effects throughout the body.


Hydrocortisone and cortisone acetate, like cortisol, have mineralocorticoid effects that become excessive at higher doses (eTable 26–3). Other synthetic corticosteroids such as prednisone, dexamethasone, and deflazacort (an oxazoline derivative of prednisolone) have minimal mineralocorticoid activity. Anticonvulsant drugs (eg, phenytoin, carbamazepine, phenobarbital) accelerate the metabolism of corticosteroids other than hydrocortisone, making them significantly less potent. Megestrol, a synthetic progestin, has slight corticosteroid activity that becomes significant when administered in high doses for appetite stimulation.

eTable 26–3.Systemic versus topical activity of corticosteroids.1


Prolonged treatment with high-dose corticosteroids causes toxic effects that can be life threatening. Besides oral and parenteral administration, transdermal and inhaled corticosteroids have some systemic absorption and can cause similar adverse effects. Patients should be thoroughly informed of the major possible side effects of treatment: insomnia, cognitive and personality changes, weight gain with central obesity, skin thinning and bruising, striae, muscle weakness, polyuria, renal calculi, diabetes mellitus, glaucoma, cataracts, sex hormone suppression, candidiasis, and opportunistic infections (Table 26–15). Prolonged high-dose corticosteroids also increase the risk of hypertension, dyslipidemia, myocardial infarction, stroke, atrial fibrillation or flutter, and heart failure. Gastric ulceration is more common with high-dose corticosteroids, particularly when patients take NSAIDs concurrently. High-dose inhaled corticosteroids predispose to oral thrush and pulmonary nontuberculous mycobacterial infection. To reduce risks, the dosage and duration of corticosteroid administration must be minimized. Immediately following inhaled corticosteroids, proper mouth-washing and gargling can reduce systemic absorption.

Table 26–15.Management of patients receiving systemic corticosteroids.

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