See question 2.

The adrenal gland represents the union of two functionally distinct organs: the adrenal medulla and adrenal cortex. The adrenal medulla is derived from the neural crest and produces catecholamines that mediate the fight-or-flight response. The adrenal cortex is derived from the mesoderm and is responsible for producing steroid hormones that regulate electrolyte balance (aldosterone), the stress response (cortisol), and to a lesser extent sexual differentiation (adrenal androgens). Production of these three hormones is anatomically compartmentalized within the cortex into the zona glomerulosa, fasciculata, and reticularis, respectively [1].

The adrenal cortex and gonads share a common origin in the mesodermal adrenogonadal primordium. As the adrenal and gonadal primordia separate, the adrenal becomes encapsulated and differentiates into the fetal cortex which will later become the zona fasciculata and reticularis. The zona glomerulosa develops later and may be distinguished at birth.

As the adrenal cortex develops, it is invaded by neural crest-derived cells (T6–T12) during the third month of gestation. These cells will form the adrenal medulla. However, not all cells may reach the developing adrenal and may become extra-adrenal medullary tissue, found along the distal aorta in perivertebral location (organ of Zuckerkandl), kidneys, broad ligament, and spermatic cord. This ectopic tissue may give rise to symptomatic adenomas or malignant tumors [2, 3] (Figs. 22.1 and 22.2).

Interestingly, there is interdependence between the adrenal cortex and the adrenal medulla. Cortisol stimulates epinephrine synthesis by increasing the activity of phenylethanolamine N-methyltransferase, the enzyme responsible for synthesizing epinephrine, using norepinephrine as a substrate. The sympathetic system also modulates the activity of the hypothalamus–pituitary–adrenal axis. Norepinephrine produced in the locus coeruleus induces hypothalamic release of corticotrophin-releasing hormone [4].

Development of the adrenal glands is not complete at birth. In the newborn, the adrenal cortex is proportionally 20 times larger than that of the adult, and the medulla is scarcely developed, perhaps reflecting underdeveloped fight-or-flight responses. Through childhood, the cortex becomes smaller and more clearly differentiates into three distinct zones, reaching complete development around the time of puberty, in which the adrenal cortex is also thought to play an important role [5].

Reflecting their common origin, ectopic adrenal cortical tissue may be found in relation to the gonads or associated structures. Ectopic adrenal tissue along the spermatic cord is a fairly frequent finding during the course of pediatric groin explorations, with an incidence of 1–2 %. It is recommended that this tissue be excised [6, 7]. With less frequency, ectopic adrenal cortical tissue in the renal parenchyma has been described [8].

Extra-adrenal medullary tissue is often located along the distal aorta, particularly below the inferior mesenteric artery (organs of Zuckerkandl). They are prominent in the fetus and infant and serve as the main source of epinephrine. As the adrenal medulla develops, these aggregations of tissue involute and are usually absent by puberty. While the majority of neuroblastomas and pheochromocytomas arise from the adrenal medulla proper, extra-adrenal medullary tissue may also be affected [3, 9].

The urinary bladder is a rare site of pheochromocytoma, accounting for 0.06 % of all bladder tumors and 1 % of all pheochromocytomas. Bladder pheochromocytomas are thought to arise from chromaffin cells in the sympathetic plexus of the bladder wall. Bladder pheochromocytomas are most often located in the trigone of the bladder, which is the area with the richest sympathetic innervation. These tumors produce a unique clinical syndrome characterized by catecholamine release crisis triggered by micturition. Diagnosis is made on a biochemical basis, and localization can be made through cross-sectional imaging and cystoscopy. Similar to adrenal pheochromocytomas, bladder pheochromocytomas are hyperintense in MRI T2-weighted imaging. Like with all extra-adrenal pheochromocytomas, metaiodobenzylguanidine (MIBG) scans may be useful to localize an otherwise occult lesion. Surgical excision is the treatment of choice. It must be preceded by pharmacologic adrenergic blockade [10, 11].