Corticosteroid therapy adrenal insufficiency from

IV.a.1.9. Adrenal suppression. It results from inhibition of pituitary ACTH secretion, and some suppression of the normal adrenal response to stress may persist for years after stopping therapy. Rapid withdrawal of corticosteroid therapy can therefore precipitate dangerous acute adrenal insufficiency ( Addisonian crisis , with hypotension, vomiting, coma and ultimately death), and for this reason steroid treatment should always be reduced gradually, sometimes over many months, according to the dose and duration of therapy. 

In patients with longstanding hypothyroidism and those with ischemic heart disease, rapid correction of hypothyroidism may precipitate angina, cardiac arrhythmias, or other adverse effects. For these patients, replacement therapy should be started at low initial doses, followed by slow titration to full replacement as tolerated over several months. If hypothyroidism and some degree of adrenal insufficiency coexist, an appropriate adjustment of the corticosteroid replacement must be initiated prior to thyroid hormone replacement therapy. This prevents acute adrenocortical insufficiency that could otherwise arise from a thyroid hormone-induced increase in the metabolic clearance rate of adrenocortical hormones. 

Prednisolone - The stress of surgery causes an increase in plasma adrenocorticotrophic hormone and cortisol concentrations. Cortisol secretion can rise from 30 mg/day to 50 mg/day following minor surgery and 150 mg/day following major surgery. However, an abrupt withdrawal after a prolonged period may lead to acute adrenal insufficiency, hypotension or shock. Thus it is important to continue SC s corticosteroid therapy and additional intravenous hydrocortisone may be administered peri-operatively. 

Mitotane (lysodren) is administered in initial daily oral doses of 2-6 g, usually given in 3 or 4 divided portions, but the maximal tolerated dose may vary from 2 to 16 g/day. Treatment should be continued for at least 3 months if beneficial effects are observed, therapy should be maintained indefinitely. Spironolactone should not be administered concomitantly, since it interferes with the adrenal suppression produced by mitotane. Treatment with mitotane is indicated for the palliation of inoperable adrenocortical carcinoma, producing symptomatic benefit in 30—50% of such patients. Although the administration of mitotane produces anorexia and nausea in 80% of patients, somnolence and lethargy in 34%, and dermatitis in 15—20%, these effects do not contraindicate the use of the drug at lower doses. Since this drug damages the adrenal cortex, administration of corticosteroids is indicated, particularly in patients with evidence of adrenal insufficiency, shock, or severe trauma. 

WITHDRAWAL OE THERAPY The most frequent problem in steroid withdrawal is flare-up of the underlying disease for which steroids were prescribed. There are several other complications associated with steroid withdrawal. The most severe complication of steroid cessation, acute adrenal insufficiency, results from overly rapid withdrawal of corticosteroids after prolonged therapy has suppressed the HPA axis. Treatment with supraphysiological doses of glucocorticoids for 2-4 weeks may cause some degree of HPA impairment. The therapeutic approach to acute adrenal... 

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