Glucocorticoids insufficiency

Cortisol-Cortisone Conversion. Under normal conditions, this equilibrium slightly favors the oxidized compound. Similarly, the conversion of corticosterone to 11-deoxycorticosterone is also mediated by the liP-hydroxysteroid dehydrogenase enzyme system and requites NAD(P) /NAD(P)H. This conversion is especially important both in the protection of the human fetus from excessive glucocorticoid exposure, and in the protection of distal nephron mineral ocorticoid receptors from glucocorticoid exposure (14). The impairment of this conversion is thought to result in hypertension associated with renal insufficiency (15). 

Unfortunately steroids merely suppress the inflammation while the underlying cause of the disease remains. Another serious concern about steroids is that of toxicity. The abmpt withdrawal of glucocorticoid steroids results in acute adrenal insufficiency. Long term use may induce osteoporosis, peptidic ulcers, the retention of fluid, or an increased susceptibiUty to infections. Because of these problems, steroids are rarely the first line of treatment for any inflammatory condition, and their use in rheumatoid arthritis begins after more conservative therapies have failed. 

ADRENAL INSUFFICIENCY. Administration of the glucocorticoids poses the threat of adrenal gland insufficiency (particularly if the altemate-day therapy is not prescribed). Administration of glucocorticoids several times a day and during a short time (as little as 5-10 days) results in shutting off the pituitary release of ACTH... 

Lifelong glucocorticoid replacement therapy may be necessary for patients with adrenal insufficiency, and mineralocor-ticoid replacement therapy usually is required for those with Addison s disease. 

Fhtients may require a lower dose of glucocorticoid than those with primary adrenal insufficiency. Some patients will only require glucocorticoid replacement temporarily, which can be discontinued after recovery of the HPA axis (e.g., drug-induced adrenal insufficiency, adrenal insufficiency following treatment for Cushing s syndrome). 

TABLE 42-6. Glucocorticoid Treatment of Adrenal Insufficiency in Patients Undergoing Surgery... 

Evaluate patients at risk for adrenal insufficiency as a result of treatment(s) of Cushing s syndrome and initiate glucocorticoid and miner-alocorticoid replacement therapy as appropriate. 

Mitotane—if well-tolerated, dose may be doubled on day 3 then, from day 5 onwards, may increase dose by 500 mg every 2-3 days until maximum tolerated dose (8-12 grams daily) has been reached glucocorticoid and mineralocorticoid replacement necessary to prevent adrenal insufficiency increased steroid doses may be needed at times of physiologic stress... 

Mitotane (o,p-DDD) -adrenocortical cytotoxin -nausea and vomiting -CNS toxicity—lethargy, vertigo, sedation, dizziness -adrenal insufficiency—must use replacement doses of mineralocorticoids and glucocorticoids -diarrhea -fever -wheezing -flushing... 

The answer is e. (Katzung, p 672. Hardman, pp 1477—1978.) Fludrocortisone is a synthetic steroid compound that exhibits profound mineralo-corticoid activity and some glucocorticoid activity Electrolyte and water metabolisms are affected by the administration of this compound. Fludrocortisone promotes the reabsorption of Na and the urinary excretion of K and hydrogen ions in the collecting duct of the nephron. The drug is indicated for mineralocorticoid replacement therapy in primary" adrenal insufficiency... 

Patients with adrenal insufficiency should carry a card or wear a bracelet or necklace that contains information about their condition. They should also have easy access to injectable hydrocortisone or glucocorticoid suppositories in case of an emergency or during times of physical stress, such as febrile illness or injury. 

Corticosteroids are produced by the adrenal glands, and display two main types of biological activity. Glucocorticoids are concerned with the synthesis of carbohydrate from protein and the deposition of glycogen in the liver. They also play an important role in inflammatory processes. Mineralocorticoids are concerned with the control of electrolyte balance, promoting the retention of Na+ and CC, and the excretion of K+. Synthetic and semi-synthetic corticosteroid drugs are widely used in medicine. Glncocorticoids are primarily nsed for their antirhenmatic and anti-inflammatory activities, and mineralocorticoids are nsed to maintain electrolyte balance where there is adrenal insufficiency. 

Unlike glucocorticoids, mineralocorticoids have an insignificant effect on carbohydrate volume. They do not exhibit any anti-inflammatory or anti-aUergy properties. They are used for chronic adrenal insufficiency, as well as for raising tonicity and work capacity of muscles. 

Autoimmune polyglandular syndrome-Chron c autoimmune thyroiditis may occur in association with other autoimmune disorders. Treat patients with concomitant adrenal insufficiency with replacement glucocorticoids prior to initiation of treatment. Failure to do so may precipitate an acute adrenal crisis when thyroid hormone therapy is initiated. Patients with diabetes mellitus may require upward adjustments of their antidiabetic therapeutic regimens. Nontoxic diffuse goiter or nodular thyroid disease Use caution when administering levothyroxine to patients with nontoxic diffuse goiter or nodular thyroid disease in order to prevent precipitation of thyrotoxicosis. If the serum TSH is already suppressed, do not administer levothyroxine. 

Fludrocortisone acetate Synthetic corticosteroid with some glucocorticoid and potent mineralocorticoid activity Administered orally to treat primary adrenal insufficiency... 

The naturally occurring mineralocorticosteroid is aldosterone. Its release is not ACTH dependent but is stimulated under control of the renin-angiotensin system. Aldosteron is not in clinical use because of its short halflife (20 min). Fludrocortisone is a synthetic analogue with considerably more potent mineralocorticoid than glucocorticoid activity. It is used as substitution therapy in adrenocorticoid insufficiency and in low-renin hypoaldosteronism. It is well absorbed orally and its effects last 1-2 days. 

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