- Your Surgery
- Our Team
- Adrenal Surgery
- Location and Directions
- Patient Comments
- Anatomy and Function
- Adrenal Incidentaloma
- Primary Hyperaldosteronism (Aldosterone-Producing Tumor)
- Cushing's Syndrome
- Sex-Hormone Producing Tumor
- Adrenocortical Carcinoma
- Metastases to Adrenal Gland
- Other Benign Adrenal Gland Tumors
- Clinical Guidelines
- Genetic Counseling
- Adrenal Program at Jersey Shore University Medical Center
- Endocrinology Center of New Jersey
- Alexander L. Shifrin, MD
Anatomy and Function of Adrenal Glands
ANATOMY AND FUNCTION OF ADRENAL GLANDS
Embryology of the Adrenal Glands
The adrenal cortex is of mesodermal origin. It arises during the fifth gestation week from mesenchymal cells between the root of the mesentery and the urogenital ridge. The cortex is formed of two parts: a thick fetal cortex surrounded by a second thin layer of cells that will later form the adult cortex. After birth, the fetal cortex undergoes rapid degeneration and the adult cortex starts to proliferate. The fetal cortex vanishes totally during the first year of life, and the adult cortex becomes fully differentiated by the 12th year. Ectopic adrenocortical tissue is common in newborn infants, and is situated near the adrenal glands or in relation to the structures formed from the urogenital ridge. This tissue usually atrophies and disappears after a few weeks of life, but in adrenogenital syndrome or any form of adrenocorticotropic hormone (ACTH) stimulation it persists.5 The chromaffin cells of adrenal medulla originate from the neuroectoderm. Cells from the neural crest migrate and invade the fetal cortex during the second month of gestation. Sympathetic neurons are formed from the same precursors, which migrate to their destinations adjacent to the arterial vessels and cranial nerves of the head and neck, and sympathetic plexus and chains in the neck, thorax, abdomen and pelvis. In fact, some cells in the abdominal preaortic sympathetic plexus and paravertebral sympathetic chain differentiate to primitive adrenal medullary cells. Most of them degenerate after birth, but ectopic medullary tissue, so-called cromaffin bodies or paraganglia, is not uncommon . The organs of Zuckerkandl  are small collections of medullary tissue between the root of the inferior mesenteric artery and the aortic bifurcation. This collection is prominent at birth, and enlarges up to the third year after birth before it starts to degenerate. Ten to twenty per cent of pheochromocytomas develop in these  ectopic sites , the organs of Zuckerkandl being one of the most frequent sites. These cells of neural crest origin can also develop into malignant neuroblastomas or ganglioneuroblastomas (partly differentiated neuroblastomas) and benign ganglioneurinomas. The incidence of all these tumors of neural crest origin is higher in children than adults.
Anatomy of the Adrenal Glands
The adrenal glands lie retroperitoneally on each side of the vertebral column at the level of 11th - 12th thoracal vertebrae. They are in close contact with the superior poles of the kidneys and surrounded by perirenal fat and Gerota’s fascia. The normal adrenal gland weighs about 6 g and is 5 cm long, 2.5 cm wide and 1 cm thick. The right adrenal is pyramidal in shape with the base embracing the right kidney. It is situated anterior to the diapraghm and the right kidney and posterior to the vena cava and liver. The medial border lies towards the right celiac ganglion and the right inferior phrenic artery. The anterior surface is medially posterior to the inferior vena cava and laterally in contact with the right lobe of the liver. Sometimes the lateral part of the anterior surface is covered by peritoneum, but usually it is situated behind the liver. The posterior surface is in contact with the diaphragm and superior pole of the right kidney [4, 5]. The left adrenal is semilunar in shape. The medial border lies towards the left celiac ganglion, left inferior phrenic artery and left gastric artery. The anterior surface is covered with the peritoneum of the omental bursa and is superomedially near the spleen, the splenic artery, and the tail of the pancreas. The posterior surface is medially in contact with the left crus of the diaphragm and laterally with the medial aspect of the superior pole of the kidney [4, 5]. The rich arterial supply comes from small branches from three main sources: superior suprarenal arteries from the inferior phrenic artery, middle suprarenal arteries from the aorta and inferior suprarenal arteries from the renal artery. Additional small branches  may come from intercostal arteries, the left ovarian or left internal spermatic arteries. Some small branches supply the medulla directly, but most of them form a network of sinusoidal capillaries at the cortex and pass as small venules through the medulla to the medullary veins [4, 5]. The venous drainage mainly takes place into a single suprarenal vein leaving the gland through the hilum. On the left side, the hilum is situated at the inferior medial corner of the gland and on the right side at the medial border of the gland. The right adrenal vein is only 5 mm long and drains directly to the vena cava, whereas on the left side the vein is longer, usually joins the inferior phrenic vein near the gland and drains to the left renal vein. Small accessory veins are not uncommon, and may drain into the inferior phrenic, renal, and portal veins . The lymphatic drainage is mainly through the para-aortic and paracaval lymph nodes to the lumbar trunks and thoracic duct. The sympathetic nerve supply is rich. It originates at the spinal medulla between T-3 and L-3 and passes through the hilus to the adrenal medulla. These preganglionic sympatethic fibres terminate in synapses to the pheochromocytes and regulate the secretion of epinephrine. Parasympathetic nerves from vagal nerve through the celiac ganglion also enter the medulla. The adrenal cortex has only a vasomotor nerve supply. On section, the gland consists of a golden yellow thicker cortical layer, constituting about 85% of the gland, and a thinner reddish-brown medulla. The microscopic examination shows a thin capsule, a cortex comprising three concentric layers: zona glomerulosa, zona fasciculata and zona reticularis, and a well-vascularized medulla .
The adrenal cortex synthesizes three types of steroid hormones from plasma cholesterol:glucocorticoids, mineralocorticoids, and sex steroids. Glucocorticoids have widespread  effects on the metabolism of carbohydrate, protein, and fat. Mineralocorticoids are essential to the maintenance of sodium balance and extracellular fluid volume. Sex steroids have only minor effects on normal subjects, and can be considered as side products in steroidogenesis. There are two structural types of adrenocortical steroids: C 21 steroids, which have a 2- carbon side chain attached at position 17 of the 19 carbon cyclopentanoperhydrophenanthrene nucleus, and C 19 steroids that have a keto or hydroxyl group at position . C 19 steroids have androgenic activity and C 21 steroids have both glucocorticoid and mineralocorticoid activity. The C 21 steroids are classified as glucocorticoids or mineralocorticoids, depending on which effect predominates. The hormones secreted in physiologically significant amounts are the glucocorticoids cortisol and corticosterone, the mineralocorticoid aldosterone and the androgen dehydroepiandrosterone (DHEA). Aldosterone is synthesized in the zona glomerulosa, cortisol in zona fasciculata, and sex steroids in zona fasciculata and zona reticularis. The steroid synthesis takes place in mitochondrios and endoplasmic reticulum . The first step in steroid synthesis is the conversion of cholesterol into pregnenolone. Pregnenolone is further converted in three main pathways into aldosterone, cortisone and DHEA. Cortisone is secreted, and bound with high affinity to corticosteroid-binding globulin. Aldosterone is mostly secreted in its free form. The weak androgen DHEA is secreted mainly as DHEA-sulphate, and is converted in peripheral tissues into testosterone and estrogens . The glucocorticoid secretion is principally regulated by hormonal interactions among the hypothalamus, pituitary, and adrenal glands. Neural stimuli, as in the response to stress, cause the release of corticotropin-releasing hormone (CRH), and other agents from hypothalamic neurons. This stimulates ACTH secretion from the pituitary gland. ACTH acts on the adrenal cortex and increases the secretion of corticosteroids. Glucocorticoids have a negative feed-back effect on synthesis and secretion of CRH and ACTH. ACTH is secreted in brief episodic bursts of varying amplitude at different times of the day. The timing of this circadian rhythm is synchronized with the solar day by dark-light shifts. Plasma ACTH and cortisol levels are highest at the time of waking in the morning, low in the evening, and almost undetectable a few hours after the beginning of sleep . The physiological effects of cortisol are mediated by its binding to a glucocorticoid receptor. This complex principally inducts or inhibits the transcription of many different genes. Glucocorticoids have various effects on: 1) the metabolism (glycogen metabolism, gluconeogenesis, peripheral glucose utilization, and lipid metabolism), 2) immunologic function and inflammatory process (lymphocyte apoptosis, T- and B-cell function, monocyte and macrophage function, and mediators of inflammation), 3) musculoskeletal and connective tissue metabolism, 4) fluid and electrolyte homeostasis, 5) the central nervous system and behavior, and 6) the gastrointestinal system . The renin-angiotensin system and serum potassium concentration directly are the major regulators of aldosterone secretion, although various other minor modulators, including ACTH, exist. Changes in the circulating blood volume and sodium and potassium concentrations regulate the renin synthesis and release by the juxtaglomerular cells in the renal cortex. Renin levels increase when renal blood flow decreases, or in hypernatremia or hypokalemia. Renin cleaves angiotensin I from angiotensinogen in the liver. Angiotensin-converting enzyme, mainly in the lung, converts angiotensin I into biologically active angiotensin II, which in turn increases both peripheric vascular resistance by vasoconstricion and aldosterone production. Aldosterone mediates its physiological effects by binding in mineralocorticoid receptors in tubules of the kidney, which increases the number of open sodium and potassium channels. This leads to increased potassium excretion to and increased sodium and water resorption from the urine. The renin secretion is suppressed by the result of increased intravascular volume and decreased serum potassium concentration [9, 10].
Adrenal medulla functions under direct control of the central nervous system (CNS) and synthesizes catecholamines along the sympathetic nervous system. In this sympathoadrenal system the catecholamines are synthesized from tyrosine. The limiting 17 step of the synthesis is hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase. DOPA is further converted into dopamine, and dopamine into norepinephrine. This synthesis takes place throughout the sympathoadrenal system. In the adrenal medulla norepinephrine may further be converted into epinephrine by the action of phenylethanolamine n-methyltransferase. This enzyme is induced by glucocorticoids, and the major source of epinephrine are chromaffin cells next to the adrenal cortex where high concentrations of glucocorticoids are present [9, 11]. The function of the sympathoadrenal system is regulated by CNS, and different components of the system are affected differently by physiological stimuli. The adrenal medulla and sympathetic nervous system usually function in tandem, but sometimes the sympathetic nervous system is suppressed while the adrenal medulla is stimulated. This suggests that circulating and locally-released cathecolamines serve different functions. The physiological effects of catecholamines are mediated through different types of α- and β-adrenergic, and dopaminergic receptors. The principal effects are: 1) cardiovascular (effects on cardiac output and vascular resistance), 2) visceral (vegetative functions), and 3) metabolic effects (mobilization of energy reserves from storage depots, regulation of oxygen uptake, and maintenance of the constancy of extracellular fluid) .
1. Coupland, R. E. Observations on the size distribution of chromaffine granules and on the identity of adrenaline- and noradrenaline-storing chromaffine cells in vertebrates and man. In: Heller, H.; Lederis, K. eds. Subcellular organization and function in endocrine tissues - Proceedings of a symposium held at the University of Bristol. Society for Endocrinology memoirs, vol 19. Bristol, England: Society for Endocrinology; 1971:611-635.
2. Ober, W.B. Emil Zuckerkandl and his delightful little organ. Path. Ann. 18:103, 1983
3. Stenstrom, G., Svardsudd, K. Pheochromocytoma in Sweden 1958-1981, An Analysis of the National Cancer Registry Data. Acta Med. Scand. 220:225, 1986
4. Williams, P. L.; Warwick, R. W.; Dyson, M.; Bannister, L. H. eds. Gray's anatomy. New York: Churchill Livingstone; 1989:1468-1472.
5. Waldayer, A.; Mayet, A. eds. Anatomie des Menschen. Berlin: de Gruyter; 1976:257-264.
6. Monkhouse, W.S., Khalique, A. The adrenal and renal veins of man and their connections with azygos veins. J. Anat. 146:105, 1986
7. Bloom, W.; Fawcett, D. W. Adrenal Glands and Paraganglia. In: Anonymous A Textbook of Histology. 1975:540-555.
8. Ganong, W. F. The Adrenal Medulla & Adrenal Cortex. In: Anonymous Review of Medical Physiology. 1987:270-300.
9. Gröndal, S.; Hamberger, B. Adrenal Physiology. In: Clark, O. H.; Duh, Q. eds. Textbook of Endocrine Surgery. Philadelphia: W.B. Saunders; 1997:461-465. 66
10. Orth, D. N.; Kovacs, W. J. The Adrenal Cortex. In: Wilson, J. D.; Foster, D. W.; Kronenberg, H. M.; Larsen, P. R. eds. Williams Textbook of Endocrinology. Philadelphia: W.B. Saunders; 1998:517-664.
11. Young, J. B.; Landsberg, L. Catecholamines and the Adrenal Medulla. In: Wilson, J. D.; Foster, D. W.; Kronenberg, H. M.; Larsen, P. R. eds. Williams Textbook of Endocrinology. Philadelphia: W.B. Saunders; 1998:665-728