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Upon completion of the chapter, the reader will be able to:
Explain the regulation and physiologic roles of hormones produced by the adrenal glands.
Recognize the clinical presentation of adrenal insufficiency.
Describe the pharmacologic management of acute and chronic adrenal insufficiency.
Recommend therapy monitoring parameters for adrenal insufficiency.
Recognize the clinical presentation of Cushing syndrome and the physiologic consequences of cortisol excess.
Describe the pharmacologic and nonpharmacologic management of Cushing syndrome.
Recommend strategies to prevent the development of hypercortisolism and hypocortisolism.
Recommend therapy monitoring parameters for Cushing syndrome.
The adrenal glands are important in the synthesis and regulation of key human hormones. They play a crucial role in water and electrolyte homeostasis, as well as regulation of blood pressure, carbohydrate and fat metabolism, physiologic response to stress, and sexual development and differentiation. This chapter focuses on pharmacologic and nonpharmacologic management of the two most common conditions associated with adrenal gland dysfunction: glucocorticoid insufficiency (eg, Addison disease) and glucocorticoid excess (Cushing syndrome). Other adrenal disorders such as congenital adrenal hyperplasia, pheochromocytoma, hypoaldosteronism, and hyperaldosteronism are beyond the scope of this chapter.
PHYSIOLOGY, ANATOMY, AND BIOCHEMISTRY OF THE ADRENAL GLAND
The adrenal gland is located on the upper segment of the kidney. It consists of an outer cortex and an inner medulla. The adrenal medulla secretes the catecholamines epinephrine (also called adrenaline) and norepineprhine (also called noradrenaline), which are involved in the regulation of the sympathetic nervous system. The adrenal cortex consists of three histologically distinct zones: the outer zona glomerulosa, the zona fasciculata, and an innermost layer called the zona reticularis. Each zone is responsible for production of different hormones (Figure 45–1).
The adrenal cortex consists of three histologically distinct zones: the outer zona glomerulosa, the middle zona fasciculata, and an innermost layer called the zona reticularis. Each zone is responsible for production of different hormones. The zona glomerulosa is responsible for the production of mineralocorticoids such as aldosterone. The zona fasciculata produces cortisol and the zona reticularis produces androgens. (ADX, adrenodoxin; CYP11A1, side chain cleavage enzyme; CYP17A1, 17-alpha-hydroxylase/17,20 lyase; CYP21A2, 21-hydroxylase; CYP11B1, 11-beta-hydroxylase; CYP11B2, aldosterone synthase; DHEA, dehydroepiandrosterone; DHEAS, dehydroepiandrosterone sulfate; H6PDH, hexose-6-phosphate dehydrogenase; HSD11B1, 11-beta-hydroxysteroid dehydrogenase type 1; HSD11B2, 11-beta-hydroxysteroid dehydrogenase type 2; HSD3B2, 3-beta-hydroxysteroid dehydrogenase type 2; HSD17B, 17-beta-hydroxysteroid dehydrogenase; PAPSS2, PAPS synthase type 2; POR, P450 oxidoreductase; SRD5A, 5-alpha-reductase; SULT2A1, DHEA sulfotransferase.) (Adapted, with permission, from Arlt W. Disorders of the adrenal cortex. In: Longo DL, Fauci AS, Kasper DL, et al., eds. Harrison’s Principles of Internal Medicine. New York City: McGraw-Hill, 2011.)
The zona glomerulosa is responsible for the production of the mineralocorticoids aldosterone, 18-hydroxy-corticosterone, corticosterone, and deoxycorticosterone. ...