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Chapter 77

Adrenal Gland

John A. Olson, Jr. and Douglas J. Turner

Key Points

1 Adrenocortical steroid hormones, glucocorticoids, mineralocorticoids, and androgenic steroids are all

synthetic derivatives of cholesterol that are either extracted from plasma or synthesized

intracellularly.

2 Catecholamines of the adrenal medulla include epinephrine, norepinephrine, and dopamine, the

vasoactive synthetic derivatives of the amino acid tyrosine.

3 Cushing syndrome is adrenocorticotropic hormone (ACTH) dependent in 80% to 90% of cases, most

often because of an ACTH-secreting pituitary adenoma, though ectopic ACTH-producing

nonendocrine tumors (mostly non–small-cell lung cancer and bronchial carcinoids) represent 10% to

20% of cases of ACTH-dependent Cushing syndrome; the remainder have a primary adrenal cause of

hypercortisolism.

4 An aldosterone-producing adrenal adenoma (Conn syndrome) is the source of primary

hyperaldosteronism in 60% to 70% of cases while idiopathic bilateral adrenal hyperplasia causes

most of the remaining cases of primary hyperaldosteronism; adrenocortical carcinoma is a rare cause

of primary hyperaldosteronism.

5 Surgical removal by laparoscopic adrenalectomy of an aldosterone-secreting adenoma results in

durable improvement of hypertension and hypokalemia in 70% to 90% of patients; management of

idiopathic adrenal hyperplasia is medical, because fewer than 20% to 30% of patients with this

disease are cured by adrenalectomy.

6 The congenital adrenal hyperplasias are autosomal recessive conditions resulting from inherited

defects of one or several of the enzymes necessary for cortisol biosynthesis leading to ACTH

overproduction and secondary hyperplasia of the adrenal cortex with shunting of cortisol precursors

into adrenal androgen pathways; peripheral conversion of the excess adrenal androgens to

testosterone causes virilization of the patient.

7 Adrenocortical carcinoma has an estimated incidence of 0.5 to 2 cases per million per year, is very

aggressive (most patients present with locoregionally advanced or distant disease), and hormone

overproduction syndromes are frequent including hypercortisolism, hyperaldosteronism, or

virilization.

8 The rule of tens is a useful way to characterize pheochromocytoma: tumors are bilateral in 10% of

cases, extraadrenal in 10%, familial in 10%, multicentric in 10%, and malignant in 10% and occur in

children in 10% of cases; determination of plasma-fractionated metanephrines is the best test for

diagnosis of pheochromocytoma.

9 Unsuspected adrenal masses are detected by computed tomography in between 0.6% and 1.9% of

healthy patients; the goal of evaluation is to distinguish and remove those adrenal masses that are

functioning or likely to be malignant versus those that are neither and can be observed.

ANATOMY

The adrenal glands are bilateral, retroperitoneal, endocrine organs located adjacent to the superior pole

of each kidney. These glands appear grossly as flat, triangular structures each weighing approximately 4

g. Each adrenal gland is composed of two distinct endocrine organs, the cortex and medulla. The outer

adrenal cortex is bright yellow and nodular, whereas the adrenal medulla is red-brown in color and is

sandwiched between the thin layers of the cortex. The adrenals are embedded in retroperitoneal

perinephric fat but can be identified as distinct structures by their golden brown, nodular appearance.

The right adrenal gland abuts the inferior vena cava medially and lies in close proximity to the

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diaphragmatic crus posteriorly and the liver anteriorly. The left adrenal gland resides between the

kidney and aorta, immediately deep to the tail of the pancreas and spleen.

Embryologically, fetal and definitive adrenal cortices arise from coelomic mesoderm near the

urogenital ridge during the fourth to sixth weeks of gestation. Postnatally, the fetal cortex involutes,

leaving only the definitive cortex to differentiate into the three adult zonae, the glomerulosa,

fasciculata, and reticularis. The adrenal medulla develops from the neural crest during the fifth

gestational week and migrates along paraaortic and paravertebral routes to join the developing cortex.

Ectopic adrenal cortex and medulla may be found anywhere along their respective paths of embryologic

migration. Most neural crest tissue regresses, however, extraadrenal neural crest derivatives may be

found along the retroperitoneum and at the aortic bifurcation (organ of Zuckerkandl).

The adrenal cortex is composed of three distinct zones. The outer zona glomerulosa, located just

beneath the fibrous gland capsule, is the site of mineralocorticoid production. The middle zona

fasciculata, composed of linear arrays of large, foamy cells with lipid inclusions, is the predominant site

of glucocorticoid and adrenal sex steroid biosynthesis. The inner zona reticularis is the primary location

of synthesis of adrenal androgens. Both the zona fasciculata and zona reticularis respond to stimulation

by adrenocorticotropic hormone (ACTH). The adrenal medulla is smaller than the cortex. Cells of the

adrenal medulla appear as homogeneous sheets, with large, irregular, atypical-looking nuclei. The

cytoplasm of these cells has numerous secretory granules containing catecholamines, neuron-specific

enolase, and chromogranin. Catecholamines in these granules precipitate chromium salts, which is the

basis for the term chromaffin cells.

Figure 77-1. A: Arterial (dark shaded) and venous (light shaded) anatomy of the adrenal glands. B: Schematic showing outer adrenal

cortex (light shaded) and inner adrenal medulla (dark shaded).

The adrenal glands have an extensive vascular supply derived from branches of the inferior phrenic

artery superiorly, the aorta medially, and the renal artery inferiorly. Venous return from the right

adrenal gland empties directly into the inferior vena cava through a wide but short central vein. Venous

drainage from the left adrenal gland empties into a smaller vein that shares a common trunk with the

left phrenic vein. Together they join the left renal vein (Fig. 77-1).

BIOCHEMISTRY AND PHYSIOLOGY

Adrenal Cortex

1 Adrenocortical steroid hormones, glucocorticoids, mineralocorticoids, and androgenic steroids are all

synthetic derivatives of cholesterol that are either extracted from plasma or synthesized intracellularly

(Fig. 77-2). In mitochondria of cells in the adrenal cortex, cholesterol is converted by desmolase

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