26 Adrenal corticosteroids
Corticosteroids are synthesized in the adrenal cortex under the control of the hypothalamic–pituitary axis (Fig. 3.26.1); and play an important role in carbohydrate and protein metabolism (glucocorticosteroids) and electrolyte balance (mineralcorticosteroids). The endogenous corticosteroid hydrocortisone (cortisol) demonstrates potency for both these activities and greater selectivity for glucocorticosteroid activity has been achieved with a variety of synthetic analogues, which are utilized clinically to treat inflammatory conditions. Aldosterone (mineralcorticosteroid) is secreted from the adrenal cortex following activation of the renin–angiotensin system and promotes Na+ reabsorption, water retention and K+ excretion (see Fig. 3.17.1). Corticosteroids bind to intracellular receptors that translocate to the nucleus of cells and bind to corticosteroid response elements (CRE) upstream of promoter region of genes, thereby influencing their rateof transcription.
Fig. 3.26.1 Regulation of adrenal corticosteroids. (A) Release; (B) synthesis in the adrenal glands.
Glucocorticosteroids
Glucocorticosteroids mainly affect the metabolism of carbohydrates (promote gluconeogenesis in the liver), lipids (enhance lipolysis by lipolytic agents) and protein (increase protein breakdown).
Impaired production
Deficiencies in the synthesis of hydrocortisone (e.g. Addison’s disease) give rise to a number of life-threatening symptoms including weakness, lethargy, susceptibility to infection (lack of glucocorticosteroid activity), hypotension, dehydration and excessive loss of Na+ (lack of mineralcorticosteroid activity). Impairment of the hypothalamic–pituitary axis also gives rise to these symptoms. In defective adrenocorticothalamic hormone (ACTH) secretion, the body can still synthesize aldosterone as this is under the control of the renin–angiotensin system. Deficiency disorders are treated with replacement therapy consisting of hydrocortisone (cortisol) or a synthetic glucocorticosteroid together with a mineralcorticosteroid twice daily in order to mimic the physiological rhythm of hormone release.
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