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A 19-year-old man complains of anorexia, fatigue, dizziness, and weight loss of 8 months’ duration. The examining physician discovers postural hypotension and moderate vitiligo (depigmented areas of skin) and obtains routine blood tests. She finds hyponatremia, hyperkalemia, and acidosis and suspects Addison disease. She performs a standard ACTH 1–24 stimulation test, which reveals an insufficient plasma cortisol response, which is compatible with primary adrenal insufficiency. The diagnosis of autoimmune Addison disease is made, and the patient must start replacement of the hormones he cannot produce himself. How should this patient be treated? What precautions should he take?

The natural adrenocortical hormones are steroid molecules produced and released by the adrenal cortex. Deficiency of the adrenocortical hormones results in the signs and symptoms of Addison disease. Excess production causes Cushing syndrome. Both natural and synthetic corticosteroids are used for the diagnosis and treatment of disorders of adrenal function. They are also used—more often and in much larger doses—for treatment of a variety of inflammatory, immunologic, and hematologic disorders.

Secretion of adrenocortical steroids, especially the glucocorticoids, is controlled by the pituitary release of corticotropin (ACTH) (see Chapter 37). Corticotropin is derived from a larger protein synthesized in the pituitary, pro-opiomelanocortin (POMC). Secretion of the salt-retaining hormone aldosterone is primarily under the influence of circulating angiotensin and potassium. Corticotropin has some actions that do not depend on its effect on adrenocortical secretion. However, its pharmacologic value as an anti-inflammatory agent and its use in testing adrenal function depend on its secretory action. Its pharmacology is reviewed only briefly here.

Inhibitors of the synthesis or antagonists of the action of the adrenocortical steroids are important in the treatment of several conditions. These agents are described at the end of this chapter.


The adrenal cortex releases a large number of steroids into the circulation. Some have minimal biologic activity and function primarily as precursors, and there are some for which no function has been established. The hormonal steroids may be classified as those having important effects on intermediary metabolism and immune function (glucocorticoids), those having principally salt-retaining activity (mineralocorticoids), and those having androgenic or estrogenic activity (see Chapter 40). In humans, the major glucocorticoid is cortisol and the most important mineralocorticoid is aldosterone. Quantitatively, dehydroepiandrosterone (DHEA) in its sulfated form (DHEAS) is the major adrenal androgen. However, DHEA and two other adrenal androgens, androstenedione and androstenediol, are weak androgens and androstenediol is a potent estrogen. Androstenedione can be converted to testosterone and estradiol in extra-adrenal tissues (Figure 39–1). Adrenal androgens constitute the major endogenous precursors of estrogen in women after menopause and in younger patients in whom ovarian function is deficient or absent.


Outline of major pathways in adrenocortical hormone biosynthesis. The major secretory products are underlined. Pregnenolone is the major precursor of corticosterone and aldosterone, and ...

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