- ACE Angiotensin-converting enzyme
- ACTH Adrenocorticotropic hormone
- AM Adrenomedullin
- APMO Adnexal cystadenomas of probable mesonephric origin
- ARDS Acute respiratory distress syndrome
- ATP Adenosine triphosphate
- cAMP Cyclic adenosine monophosphate
- CgA Chromogramin A
- CGRP Calcitonin gene–related peptide
- COMT Catecholamine-O-methyltransferase
- DBH Dopamine-β-hydroxylase
- FDG Fluorodeoxyglucose
- DHMA Dihydroxymandelic acid
- DHPG Dihydroxyphenylglycol
- ECD Electrochemical detection
- HIF Hypoxia-inducible factor
- HPLC High-pressure liquid chromatography
- IP3 Inositol triphosphate
- MAO Monoamine oxidase
- MEN Multiple endocrine neoplasia
- MHBA 3-methoxy-4-hydroxybenzylamine
- MIBG Metaiodobenzylguanidine
- NF-1 Neurofibromatosis type 1
- NSE Neuron-specific enolase
- PBSC Peripheral blood stem cell
- PNMT Phenylethanolamine- N-methyltransferase
- PTHrP Parathyroid hormone–related peptide
- RECIST Response evaluation criteria in solid tumors
- SDH Succinate dehydrogenase
- SDHB Succinate dehydrogenase subunit B
- SDHC Succinate dehydrogenase subunit C
- SDHD Succinate dehydrogenase subunit D
- SPECT Single photon emission computed tomography
- SRI Somatostatin receptor imaging
- VEGF Vascular endothelial growth factor
- VHL Von Hippel-Lindau
- VIP Vasoactive intestinal polypeptide
- VMA Vanillylmandelic acid (3-methoxy-4-hydroxymandelic acid)
The adrenal medulla and paraganglia are part of the autonomic/sympathetic nervous system. The endocrine and nervous systems are alike in that they exert their actions by releasing hormones/neurotransmitters that bind to cell surface receptors in the target tissue, thereby inducing an effect.
Autonomic nerves are not under conscious control. They innervate the heart, adrenal medulla, vascular smooth muscle, and smooth muscle in visceral organs, thereby controlling cardiac rate and output, adrenal medullary secretion of catecholamines, blood pressure, the genitourinary tract, and intestinal motility. Autonomic nerves originate within the central nervous system and have two major divisions according to their anatomic locations:
- (1) Parasympathetic preganglionic nerves exit the central nervous system via the cranial nerves and sacral spinal nerves. They terminate in nonchromaffin paraganglia that are most numerous in the neck and associated with the glossopharyngeal and vagus nerves. These ganglia serve as chemoreceptors that are involved in the control of respiration. An important paraganglion at the carotid bifurcation is known as the carotid body. They are also found along the jugular vein and in the jugulo-tympanic region. Head-neck paragangliomas are tumors that arise from these parasympathetic paraganglia.
- (2) Sympathetic preganglionic nerves exit the central nervous system via the thoracic and lumbar spinal nerves. The sympathetic nervous system coordinates the body's automatic fight-flight response by stimulating the adrenal medulla to secrete catecholamines and by directly stimulating cardiac output and blood flow to muscles while diverting blood flow away from visceral organs.
Sympathetic preganglionic nerves terminate mainly in paravertebral and prevertebral nerve ganglia where they secrete acetylcholine as their neurotransmitter; they are, therefore, known as cholinergic nerves. These nerve ganglia are collectively known as paraganglia and contain neuroendocrine cells that are similar to adrenal medullary cells on light microscopy by chromaffin and immunohistochemical staining. Paraganglia are also found in the mediastinum, particularly adjacent to the cardiac atria, and in the abdomen along the sympathetic nerve chains in paravertebral and prevertebral positions. Paraganglia are plentiful along the aorta, particularly around the celiac axis, adrenal glands, renal medullae, and aortic bifurcation (organ of Zuckerkandl). Paraganglia are also abundant in the pelvis, particularly adjacent to the bladder. Preganglionic nerves also terminate in the adrenal medulla, which is basically a sympathetic ganglion that is surrounded by adrenal cortex.
Sympathetic postganglionic nerve fibers originate from the paraganglia and run to the tissues being innervated. They secrete norepinephrine as their neurotransmitter at synaptic junctions. Adrenal medullary cells are basically modified postganglionic nerves that lack axons and secrete their neurotransmitter (mainly epinephrine) directly into the blood; thus, the bloodstream acts like a giant synapse, carrying epinephrine to receptors throughout the body. Synonyms for epinephrine and norepinephrine are adrenalin and noradrenaline, respectively (see later).
Although the adrenal medulla is not essential for survival, its secretion of epinephrine and other compounds helps maintain the body's homeostasis during stress. Investigations of the adrenal medulla and the sympathetic nervous system have led to the discovery of different catecholamine receptors and the production of a wide variety of sympathetic agonists and antagonists with diverse clinical applications.
Pheochromocytomas are tumors that arise from the adrenal medulla, whereas non–head-neck paragangliomas arise from extra-adrenal sympathetic ganglia. Pheochromocytomas can secrete excessive amounts of both epinephrine and norepinephrine, whereas paragangliomas secrete only norepinephrine. The excessive secretion of catecholamines can result in a dangerous exaggeration of the stress response.
The embryonic development of adrenergic cells and tumors that develop from them (in parentheses). Sympathogonia are primitive cells derived from the neural crest. Neuroblasts are also called sympathoblasts; ganglion cells are the same as sympathocytes; and pheochromocytes are mature chromaffin cells.
The sympathetic nervous system arises in the fetus from the primitive cells of the neural crest (sympathogonia). At about the fifth week of gestation, these cells migrate from the spinal ganglia in the thoracic region to form the sympathetic chain posterior to the dorsal aorta. They then begin to migrate anteriorly to form the remaining ganglia.
At 6 weeks of gestation, groups of these primitive cells migrate along the central vein and enter the fetal adrenal cortex to form the adrenal medulla, which is detectable by the eighth week. The adrenal medulla at this time is composed of sympathogonia and pheochromoblasts, which then mature into pheochromocytes. The cells appear in rosette-like structures, with the more primitive cells occupying a central position. Storage granules can be found in these cells at 12 weeks. The adrenal medullas are very small and amorphous at birth but develop into recognizable adult form by the sixth month of postnatal life.
Pheochromoblasts and pheochromocytes also collect on both sides of the aorta to form the paraganglia. These cells collect principally at the origin of the mesenteric arteries and at the aortic bifurcation where they fuse anteriorly to form the organ ...