The adrenal gland is located on the upper segment of the kidney (Fig. 45-1).1 It consists of an outer cortex and an inner medulla. The adrenal medulla secretes the catecholamines epinephrine (also called adrenaline) and norepinephrine (also called noradrenaline), which are involved in the regulation of the sympathetic nervous system. The adrenal cortex consists of three histologically distinct zones: the zona glom-erulosa, zona fasciculata, and an innermost layer called the zona reticularis. Each zone is responsible for production of different hormones (Fig. 45-2).
The zona glomerulosa is responsible for the production of the mineralocorticoids aldosterone, deoxycorticosterone, and 18-hydroxy-deoxycorticosterone. Aldosterone promotes renal sodium retention and potassium excretion. Its synthesis and release are regulated by renin in response to decreased vascular volume and renal perfusion. Adrenal aldosterone production is regulated by the renin-angiotensin-aldosterone system.
The zona fasciculata produces the glucocorticoid hormone cortisol. Cortisol is responsible for maintaining homeostasis of carbohydrate, protein, and fat metabolism. Its secretion follows a circadian rhythm, generally beginning to rise at approximately 4 am and peaking around 6 to 8 am. Thereafter, cortisol levels decrease throughout the day, approach 50% of the peak value by 4 pm, and reach their nadir around midnight. The normal rate of cortisol production is approximately 8 to 15 mg/day. Cortisol plays a key role in the body's response to stress. Its production increases markedly during physiologic stress such as during acute illness, surgery, or trauma. In addition, certain conditions such as alcoholism, depression, anxiety disorder, obsessive-compulsive disorder, poorly controlled diabetes, morbid obesity, starvation, anorexia nervosa, and chronic renal failure are associated with increased cortisol levels. High total cortisol levels are also observed in the presence of increased cortisol binding globulin (the carrier protein for 80% of circulating cortisol molecules), which is seen in pregnancy or other high-estrogen states (e.g., exogenous estrogen administration). Cortisol is converted in the liver to an inactive metabolite known as cortisone.
The zona reticularis produces the androgens andro-stenedione, dehydroepiandros-terone (DHEA), and the sulfated form of dehydroepiandrosterone (DHEA-S). Only a small amount of testosterone and estrogen are produced in the adrenal glands. Androstenedione and DHEA are converted in the periphery, largely to testosterone and estrogen.
Adrenal hormone production is controlled by the hypothalamus and pituitary. Corticotropin-releasing hormone (CRH) is secreted by the hypothalamus and stimulates secretion of adrenocorticotropic hormone (ACTH; also known as corticotropin) from the anterior pituitary. ACTH in turn stimulates the adrenal cortex to produce cortisol. When sufficient or excessive cortisol levels are reached, a negative feedback is exerted on the secretion of CRH and ACTH, thereby decreasing overall cortisol production. The control of adrenal androgen synthesis also follows a similar negative feedback mechanism. Figure 46-1 in the Pituitary Gland Disorders chapter depicts the hormonal regulation with the hypothalamic-pituitary-adrenal axis.
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