Adrenocortical hormones metabolic effects

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. 

The metabolic effects of exogenous cortisone are similar to the sequence of events following injury. A close correlation was found between urinary cortisol excretion and nitrogen losses in surreal patients (MIO). For these reasons it was considered that the adrenocortical hormones initiated and controlled the metabolic response to injury. There are serious objections, however, to this hypothesis, as the complete interdependence of the responses has been demonstrated in man and animals. 

The question of the effect of ascorbic acid on adrenocortical hormone production has proved hard enough (see Section XI) the question of the influence of adrenocortical hormones on ascorbic acid metabolism seems likely to be still more difficult. 

The exact role of the adrenocortical hormones in intermediary metabolism is still amost completely obscure. Hormones may exert their effects through their influence on the rates of enzymatic reactions. If such enzymatic reactions also require some nutritional factor as part of a coenzyme, altered nutritional requirements as a consequence of changes in hormone levels might be anticipated. 

Anatomical Considerations 458 Histophysiology 459 Adrenocortical Hormones 460 Steroid Hormone Biosynthesis Metabolic Effects of Corticoid Hormones Properties of ACTH Cushing s Syndrome... 

Biologic Significance of the Adrenal Cortex. The adrenocortical hormones constitute some of the most vital substances. Extirpation of the adrenal gland in experimental animals is followed by most serious disturbances and, in a few days, by death. Among other things, the metabolism of electrolytes is unbalanced (increased Na+ excretion). This effect can be reversed by administration of adrenocortical hormones, some of which (especially aldosterone) effect the retention of sodium and excretion of potassium (cf. Chapt. XXI-5). 

Besides the mineralcorticoid effect on the electrolyte metabolism, the adrenocortical hormones also influence the metabolism of glucose by promoting glycogen formation in the liver, especially from protein. This effect is termed the glucocorticoid effect and is manifested especially by the 11/3-hydroxy compounds. Emphasizing the breakdown of protein, this effect is also called the catabolic effect. The mechanism of this hormone action seems to involve the de novo formation of more enzymes of amino acid metabolism, e.g., tyrosine a-ketoglutarate transaminase, tr5rptophan pyrrolase, etc. (cf. Enzyme Induction, Chapt. VII-7). 

Mitotane, or o,p -DDD, is an oral medication used in the treatment of adrenocortical carcinoma. Chemically it is an isomere of DDT. Following its metabolism in the adrenal cortex to a reactive acyl chloride intermediate, mitotane covalently binds to adrenal proteins, specitically inhibiting adrenal cortical hormone production. The drug accumulates in fat tissue. It is eliminated mainly by the kidneys with a half-life of 18-159 days. Common side effects include anorexia, nausea, lethargy, sleepiness and skin problems. 

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