Editing Adrenal gland

{{Short description|Endocrine gland}}
{{Good article}}
{{Use dmy dates|date=April 2017}}
{{Infobox anatomy
| Name        = Adrenal gland
| Latin       = glandula suprarenalis
| Image       = Adrenal Gland detail - English.png
| Caption     = Detailed animation of the adrenal gland
| Image2      = Diagram showing the position of the adrenal glands CRUK 343.svg
| Caption2    = Position of adrenal gland
| System      = [[Endocrine system]]
| Artery      = [[Superior suprarenal artery|Superior]], [[middle suprarenal artery|middle]] and [[inferior suprarenal artery|inferior suprarenal arteries]]
| Vein        = [[Suprarenal veins]]
| Nerve       = [[Celiac plexus|Celiac]] and [[renal plexus]]
| Lymph       = [[Lumbar lymph nodes]]
| Precursor   = [[Mesoderm]] and [[neural crest]]
}}

The '''adrenal glands''' (also known as '''suprarenal glands''') are [[endocrine gland]]s that produce a variety of hormones including [[adrenaline]] and the steroids [[aldosterone]] and [[cortisol]].<ref name="Columbia2015">{{cite book|author=Santulli G. MD|title=Adrenal Glands: From Pathophysiology to Clinical Evidence|url=https://books.google.com/books?id=J5pcjwEACAAJ|date=2015|publisher=Nova Science Publishers, New York, NY |isbn=978-1-63483-570-1}}</ref><ref name=dictionary>{{cite web|title=Adrenal gland|url=http://www.merriam-webster.com/medlineplus/adrenal%20gland|website=Medline Plus/Merriam-Webster Dictionary|access-date=11 February 2015}}</ref> They are found above the [[kidneys]]. Each gland has an outer [[adrenal cortex|cortex]] which produces [[steroid hormone]]s and an inner [[Adrenal medulla|medulla]]. The [[adrenal cortex]] itself is divided into three main zones: the [[zona glomerulosa]], the [[zona fasciculata]] and the [[zona reticularis]].<ref name=ross />

The adrenal cortex produces three main types of [[steroid hormone]]s: [[mineralocorticoid]]s, [[glucocorticoid]]s, and [[androgen]]s. Mineralocorticoids (such as [[aldosterone]]) produced in the zona glomerulosa help in the regulation of blood pressure and [[osmoregulation|electrolyte balance]]. The glucocorticoids [[cortisol]] and [[cortisone]] are synthesized in the zona fasciculata; their functions include the regulation of [[metabolism]] and [[immune system]] suppression. The innermost layer of the cortex, the zona reticularis, produces androgens that are converted to fully functional sex hormones in the [[gonad]]s and other target organs.<ref name=williams /> The production of steroid hormones is called [[Steroid#Steroidogenesis|steroidogenesis]], and involves a number of reactions and processes that take place in cortical cells.<ref name="miller auchus" /> The medulla produces the [[catecholamine]]s, which function to produce a [[Fight-or-flight response (in humans)|rapid response]] throughout the body in [[Stress (biology)|stress]] situations.<ref name=williams />

A number of [[endocrine disease]]s involve dysfunctions of the adrenal gland. Overproduction of cortisol leads to [[Cushing's syndrome]], whereas insufficient production is associated with [[Addison's disease]]. [[Congenital adrenal hyperplasia]] is a genetic disease produced by dysregulation of endocrine control mechanisms.<ref name=williams /><ref name="harrison's" /> A variety of [[neoplasm|tumors]] can arise from adrenal tissue and are commonly found in [[medical imaging]] when searching for other diseases.<ref name=nieman />
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==Structure==
[[File:Adrenal glands.jpg|thumb|Adrenal glands, anterior (left) and posterior (right) surface]]
The adrenal glands are located on both sides of the body in the [[retroperitoneum]], above and slightly [[Anatomical terms of location#Medial and lateral|medial]] to the [[kidney]]s. In humans, the right adrenal gland is pyramidal in shape, whereas the left is semilunar or crescent shaped and somewhat larger.<ref name=Thomas2013 /> The adrenal glands measure approximately 5&nbsp;cm in length, 3&nbsp;cm in width, and up to 1&nbsp;cm in thickness.<ref>{{cite journal|url=http://www.medscape.com/viewarticle/543510_2|title=CT and MRI of Adrenal Masses|author=Antonio Carlos A. Westphalen and Bonnie N. Joe|journal=Appl Radiol|year=2006|volume=35|issue=8|pages=10–26}}</ref> Their combined  weight in an adult human ranges from 7 to 10 grams.<ref>{{cite book|last1=O'Hare|first1=A. Munro Neville, Michael J.|title=The Human Adrenal Cortex Pathology and Biology – An Integrated Approach|date=1982|publisher=Springer London|isbn=9781447113171|pages=Chapter 4: Structure of the adult cortex}}</ref> The glands are yellowish in colour.<ref name=Thomas2013>{{cite book|editor=Thomas, Paul|title=Endocrine Gland Development and Disease|date=2013|publisher=Elsevier Science|location=Burlington|isbn=9780123914545|pages=241}}</ref>

The adrenal glands are surrounded by a [[adipose capsule of kidney|fatty capsule]] and lie within the [[renal fascia]], which also surrounds the kidneys. A weak [[septum]] (wall) of [[connective tissue]] separates the glands from the kidneys.<ref name=Moore>{{cite book |vauthors=Moore KL, Dalley AF, Agur AM |date=2013 |title=Clinically Oriented Anatomy, 7th ed. |publisher=Lippincott Williams & Wilkins |pages=294, 298|isbn=978-1-4511-8447-1 }}</ref> The adrenal glands are directly below the [[thoracic diaphragm|diaphragm]], and are attached to the [[crura of the diaphragm]] by the renal fascia.<ref name=Moore />

Each adrenal gland has two distinct parts, each with a unique function, the outer [[adrenal cortex]] and the inner [[adrenal medulla|medulla]], both of which produce hormones.<ref name=Kay2015>{{cite web|last1=Kay|first1=Saundra|title=Adrenal Glands|url=http://emedicine.medscape.com/article/940347-overview|website=Medscape|access-date=1 August 2015}}</ref>

===Adrenal cortex===
{{Main|Adrenal cortex}}
[[File:Adrenal cortex labelled.jpg|thumb|right|Section of human adrenal gland [[histology|under the microscope]], showing its different layers. From the surface to the center: zona glomerulosa, zona fasciculata, zona reticularis, medulla. In the medulla, the central adrenomedullary vein is visible.]]
The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones.
The adrenal cortex is the outermost layer of the adrenal gland. Within the cortex are three layers, called "zones". When [[Histology|viewed under a microscope]] each layer has a distinct appearance, and each has a different function.<ref name="whitehead">{{cite book |author1=Whitehead, Saffron A. |author2=Nussey, Stephen |title=Endocrinology: an integrated approach |publisher=BIOS |location=Oxford |year=2001 |pages=122 |isbn=978-1-85996-252-7 }}</ref> The [[adrenal cortex]] is devoted to production of [[hormone]]s, namely [[aldosterone]], [[cortisol]], and [[androgen]]s.<ref name="safeuses">{{cite book |author=Jefferies, William McK |title=Safe uses of cortisol |publisher=Charles C. Thomas |location=Springfield, Ill |year=2004 |isbn=978-0-398-07500-2 }}</ref>

====Zona glomerulosa====
The outermost zone of the adrenal cortex is the [[zona glomerulosa]]. It lies immediately under the fibrous capsule of the gland. Cells in this layer form oval groups, separated by [[trabeculae|thin strands]] of connective tissue from the fibrous capsule of the gland and carry wide [[capillary|capillaries]].<ref name="wheater">{{cite book | title=Wheater's Functional Histology: A Text and Colour Atlas | publisher=Elsevier |vauthors=Young B, Woodford P, O'Dowd G | year=2013 | isbn=978-0702047473 | page=329 | edition=6th}}</ref>

This layer is the main site for production of [[aldosterone]], a [[mineralocorticoid]], by the action of the enzyme [[aldosterone synthase]].<ref name="pmid1775135">{{cite journal |vauthors=Curnow KM, Tusie-Luna MT, Pascoe L, Natarajan R, Gu JL, Nadler JL, White PC |title=The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex. |journal=Mol. Endocrinol. |volume=5 |issue=10 |pages=1513–1522 |date=October 1991 |pmid=1775135 |doi= 10.1210/mend-5-10-1513 |url=https://academic.oup.com/mend/article-pdf/5/10/1513/10490358/mend1513.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://academic.oup.com/mend/article-pdf/5/10/1513/10490358/mend1513.pdf |archive-date=2022-10-09 |url-status=live |doi-access=free }}</ref><ref name="pmid8333830">{{cite journal |vauthors=Zhou M, Gomez-Sanchez CE |title=Cloning and expression of a rat cytochrome P-450 11 beta-hydroxylase/aldosterone synthase (CYP11B2) cDNA variant. |journal=Biochem Biophys Res Commun |volume=194 |issue=1 |pages=112–117 |date=July 1993 |pmid=8333830 |doi= 10.1006/bbrc.1993.1792 }}</ref> Aldosterone plays an important role in the long-term [[regulation of blood pressure]].<ref name=marieb>{{cite book|last1=Marieb|first1=EN|last2=Hoehn|first2=K|title=Human anatomy & physiology|date=2012|publisher=Pearson|isbn=978-0321743268|pages=629|edition=9th}}</ref>

====Zona fasciculata====
The [[zona fasciculata]] is situated between the zona glomerulosa and zona reticularis. Cells in this layer are responsible for producing [[glucocorticoid]]s such as [[cortisol]].<ref name=Kaplan.Physio>{{cite book|title=Kaplan USMLE Step 1 Physiology Lecture Notes|year=2011|author=Dunn R. B.|author2=Kudrath W.|author3=Passo S.S.|author4=Wilson L.B.|pages=263–289|chapter=10}}</ref> It is the largest of the three layers, accounting for nearly 80% of the volume of the cortex.<ref name="ross">{{cite book | title=Histology: A Text and Atlas | url=https://archive.org/details/histologytextatl00ross | url-access=limited | publisher=Lippincott Williams & Wilkins |vauthors=Ross M, Pawlina W | year=2011 | isbn=978-0-7817-7200-6 | pages=[https://archive.org/details/histologytextatl00ross/page/n727 708], 780| edition=6th}}</ref> In the zona fasciculata, cells are arranged in columns radially oriented towards the medulla. Cells contain numerous lipid droplets, abundant [[Mitochondrion|mitochondria]] and a complex [[endoplasmic reticulum#smooth endoplasmic reticulum|smooth endoplasmic reticulum]].<ref name="wheater" />

====Zona reticularis====
The innermost cortical layer, the [[zona reticularis]], lies directly adjacent to the medulla. It produces [[androgen]]s, mainly [[dehydroepiandrosterone]] (DHEA), [[DHEA sulfate]] (DHEA-S), and [[androstenedione]] (the precursor to [[testosterone]]) in humans.<ref name=Kaplan.Physio /> Its small cells form irregular cords and clusters, separated by capillaries and connective tissue. The cells contain relatively small quantities of cytoplasm and lipid droplets, and sometimes display brown [[lipofuscin]] pigment.<ref name="wheater" />

===Medulla===
{{Main|Adrenal medulla}}
The [[adrenal medulla]] is at the center of each adrenal gland, and is surrounded by the adrenal cortex. The [[chromaffin cell]]s of the medulla are the body's main source of the [[catecholamine]]s, such as adrenaline and noradrenaline, released by the medulla. Approximately 20% noradrenaline (norepinephrine) and 80% adrenaline (epinephrine) are secreted here.<ref name=Kaplan.Physio />

The adrenal medulla is driven by the [[sympathetic nervous system]] via [[preganglionic fiber]]s originating in the [[thoracic spinal cord]], from vertebrae T5–T11.<ref name="essentialneuroscience">{{cite book |author1=Sapru, Hreday N. |author2=Siegel, Allan |title=Essential Neuroscience |publisher=Lippincott Williams & Wilkins |location=Hagerstown, MD |year=2007 |isbn=978-0-7817-9121-2 |url-access=registration |url=https://archive.org/details/essentialneurosc0000sieg }}</ref> Because it is innervated by [[preganglionic nerve fibers]], the adrenal medulla can be considered as a specialized [[sympathetic ganglion]].<ref name="essentialneuroscience"/> Unlike other sympathetic ganglia, however, the adrenal medulla lacks distinct synapses and releases its secretions directly into the blood.

===Blood supply===
The adrenal glands have one of the greatest blood supply rates per gram of tissue of any organ: up to 60 [[arteriole|small arteries]] may enter each gland.<ref name="isbn960-399-074-4">{{cite book |vauthors=Mirilas P, Skandalakis JE, Colborn GL, Weidman TA, Foster RS, Kingsnorth A, Skandalakis LJ, Skandalakis PN |title=Surgical Anatomy: The Embryologic And Anatomic Basis Of Modern Surgery |publisher=McGraw-Hill Professional Publishing |year=2004 |isbn=978-960-399-074-1 }}</ref> Three arteries usually supply each adrenal gland:<ref name=Thomas2013 />
* The [[superior suprarenal artery]], a branch of the [[inferior phrenic arteries|inferior phrenic artery]]
* The [[middle suprarenal artery]], a direct branch of the [[abdominal aorta]]
* The [[inferior suprarenal artery]], a branch of the [[renal artery]]
These blood vessels supply a network of small arteries within the capsule of the adrenal glands. Thin strands of the capsule enter the glands, carrying blood to them.<ref name=Thomas2013 />

[[Vein|Venous blood]] is drained from the glands by the [[suprarenal veins]], usually one for each gland:<ref name=Thomas2013 />
* The [[right suprarenal vein]] drains into the [[inferior vena cava]].
* The [[left suprarenal vein]] drains into the left [[renal vein]] or the left [[inferior phrenic vein]].

The central adrenomedullary vein, in the adrenal medulla, is an unusual type of blood vessel. Its structure is different from the other veins in that the [[smooth muscle]] in its [[tunica media]] (the middle layer of the vessel) is arranged in conspicuous, longitudinally oriented bundles.<ref name=ross />

===Variability===
The adrenal glands may not develop at all, or may be fused in the midline behind the [[aorta]].<ref name=Kay2015 /> These are associated with other [[congenital abnormality|congenital abnormalities]], such as failure of the kidneys to develop, or fused kidneys.<ref name=Kay2015 /> The gland may develop with a partial or complete absence of the cortex, or may develop in an unusual location.<ref name=Kay2015 />

==Function==
[[File:1818 The Adrenal Glands.jpg|thumb|center|600px|Different hormones are produced in different zones of the cortex and medulla of the gland. Light microscopy at magnification × 204.<ref>{{Cite web|title = OpenStax CNX|url = http://cnx.org/contents/14fb4ad7-39a1-4eee-ab6e-3ef2482e3e22@7.28:112/Anatomy-&-Physiology|website = cnx.org| date=25 April 2013 |access-date = 2015-08-01}}</ref>]]

The adrenal gland secretes a number of different hormones which are metabolised by [[enzyme]]s either within the gland or in other parts of the body. These hormones are involved in a number of essential biological functions.<ref name=DAVIDSONS2010>{{cite book|editor1-first=Nicki R.|editor1-last=Colledge|editor2-first=Brian R.|editor2-last=Walker|editor3-first=Stuart H.|editor3-last=Ralston|title=Davidson's principles and practice of medicine.|date=2010|publisher=Churchill Livingstone/Elsevier|location=Edinburgh|isbn=978-0-7020-3085-7|pages=768–778|edition=21st}}</ref>

===Corticosteroids===
[[Corticosteroid]]s are a group of steroid hormones produced from the cortex of the adrenal gland, from which they are named.<ref>{{cite web|title=Corticosteroid|url=http://medical-dictionary.thefreedictionary.com/corticosteroid|website=TheFreeDictionary|access-date=23 September 2015}}</ref>
* Mineralocorticoids such as [[aldosterone]] regulate salt ("mineral") balance and blood pressure<ref name=Marieb>Marieb Human Anatomy & Physiology 9th edition, chapter:16, page:629, question number:14</ref>
* Glucocorticoids such as [[cortisol]] influence metabolism rates of proteins, fats and sugars ("glucose").<ref>{{cite web|title=Corticosteroid|url=http://medical-dictionary.thefreedictionary.com/glucocorticoid|website=TheFreeDictionary|access-date=23 September 2015}}</ref>
* Androgens such as [[dehydroepiandrosterone]].

;Mineralocorticoids
The adrenal gland produces [[aldosterone]], a [[mineralocorticoid]], which is important in the regulation of salt ("mineral") balance and [[blood volume]]. In the kidneys, aldosterone acts on the [[distal convoluted tubule]]s and the [[Collecting duct system|collecting ducts]] by increasing the reabsorption of [[Sodium in biology|sodium]] and the excretion of both potassium and hydrogen ions.<ref name="marieb" /> Aldosterone is responsible for the reabsorption of about 2% of filtered [[glomerular filtrate]].<ref>{{cite book |author=Sherwood, Lauralee |title=Human physiology: from cells to systems |publisher=Brooks/Cole |location=Pacific Grove, CA |year=2001 |isbn=978-0-534-56826-9 |oclc= 43702042}}</ref> Sodium retention is also a response of the distal colon and sweat glands to aldosterone receptor stimulation. [[Angiotensin II]] and extracellular [[potassium]] are the two main regulators of aldosterone production.<ref name="Kaplan.Physio"/> The amount of sodium present in the body affects the extracellular volume, which in turn influences [[blood pressure]]. Therefore, the effects of aldosterone in sodium retention are important for the regulation of blood pressure.<ref name=boron />

;Glucocorticoids
[[Cortisol]] is the main [[glucocorticoid]] in humans. In species that do not create cortisol, this role is played by [[corticosterone]] instead. Glucocorticoids have many effects on [[metabolism]]. As their name suggests, they increase the circulating level of [[glucose]]. This is the result of an increase in the mobilization of [[amino acids]] from protein and the stimulation of [[Gluconeogenesis|synthesis of glucose]] from these amino acids in the liver. In addition, they increase the levels of [[free fatty acids]], which cells can use as an alternative to glucose to obtain energy. Glucocorticoids also have effects unrelated to the regulation of blood sugar levels, including the suppression of the immune system and a potent [[anti-inflammatory]] effect. Cortisol reduces the capacity of [[osteoblast]]s to produce new bone tissue and decreases the absorption of calcium in the [[Human gastrointestinal tract|gastrointestinal tract]].<ref name=boron />

The adrenal gland secretes a basal level of cortisol but can also produce bursts of the hormone in response to [[adrenocorticotropic hormone]] (ACTH) from the [[anterior pituitary]]. Cortisol is not evenly released during the day – its concentrations in the blood are highest in the early morning and lowest in the evening as a result of the [[circadian rhythm]] of ACTH secretion.<ref name=boron /> [[Cortisone]] is an inactive product of the action of the enzyme [[11β-Hydroxysteroid dehydrogenase|11β-HSD]] on cortisol. The reaction catalyzed by 11β-HSD is reversible, which means that it can turn administered cortisone into cortisol, the biologically active hormone.<ref name=boron />

;Formation
[[File:Adrenal Steroids Pathways.svg|thumb|right|Steroidogenesis in the adrenal glands – different steps occur in different layers of the gland]]
All [[corticosteroid]] hormones share [[cholesterol]] as a common precursor. Therefore, the first step in [[Steroid#Steroidogenesis|steroidogenesis]] is cholesterol uptake or synthesis. Cells that produce steroid hormones can acquire cholesterol through two paths. The main source is through dietary cholesterol transported via the blood as [[cholesterol esters]] within [[low density lipoprotein]]s (LDL). LDL enters the cells through [[receptor-mediated endocytosis]]. The other source of cholesterol is synthesis in the cell's [[endoplasmic reticulum]]. Synthesis can compensate when LDL levels are abnormally low.<ref name=williams>{{cite book|last1=Melmed|first1=S|last2=Polonsky|first2=KS|last3=Larsen|first3=PR|last4=Kronenberg|first4=HM|title=Williams Textbook of Endocrinology|date=2011|publisher=Saunders|isbn=978-1437703245|edition=12th}}</ref> In the [[lysosome]], cholesterol esters are converted to free cholesterol, which is then used for steroidogenesis or stored in the cell.<ref name="miller bose">{{cite journal|last1=Miller|first1=WL|last2=Bose|first2=HS|title=Early steps in steroidogenesis: intracellular cholesterol trafficking|journal=Journal of Lipid Research|date=2011|volume=52|issue=12|pages=2111–2135|doi=10.1194/jlr.R016675 |doi-access=free |pmid=21976778|pmc=3283258}}</ref>

The initial part of conversion of cholesterol into steroid hormones involves a number of enzymes of the [[cytochrome P450]] family that are located in the inner membrane of [[mitochondrion|mitochondria]]. Transport of cholesterol from the outer to the inner membrane is facilitated by [[steroidogenic acute regulatory protein]] and is the rate-limiting step of steroid synthesis.<ref name="miller bose"/>

The layers of the adrenal gland differ by function, with each layer having distinct enzymes that produce different hormones from a common precursor.<ref name=williams/> The first enzymatic step in the production of all steroid hormones is cleavage of the cholesterol side chain, a reaction that forms [[pregnenolone]] as a product and is catalyzed by the enzyme [[P450scc]], also known as ''cholesterol desmolase''. After the production of pregnenolone, specific enzymes of each cortical layer further modify it. Enzymes involved in this process include both mitochondrial and [[Microsome|microsomal]] P450s and [[hydroxysteroid dehydrogenase]]s. Usually a number of intermediate steps in which pregnenolone is modified several times are required to form the functional hormones.<ref name="miller auchus">{{cite journal|last1=Miller|first1=WL|last2=Auchus|first2=RJ|title=The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.|journal=Endocrine Reviews|date=2011|volume=32|issue=1|pages=81–151|pmid=21051590|pmc=3365799|doi=10.1210/er.2010-0013}}</ref> Enzymes that catalyze reactions in these metabolic pathways are involved in a number of endocrine diseases. For example, the most common form of [[congenital adrenal hyperplasia]] develops as a result of deficiency of [[21-hydroxylase]], an enzyme involved in an intermediate step of cortisol production.<ref name=charmandari>{{cite journal|last1=Charmandari |first1=E |last2=Brook |first2=CG |last3=Hindmarsh |first3=PC |title=Classic congenital adrenal hyperplasia and puberty. |url=http://eje-online.org/content/151/Suppl_3/U77.long |archive-url=https://archive.today/20150204104659/http://eje-online.org/content/151/Suppl_3/U77.long |url-status=dead |archive-date=2015-02-04 |journal=European Journal of Endocrinology |date=2004 |volume=151 |issue=Suppl 3 |pages=77–82 |doi=10.1530/eje.0.151U077 |pmid=15554890 |citeseerx=10.1.1.613.6853 |s2cid=27083986 }}</ref>

;Regulation
[[File:ACTH Negative Feedback.svg|thumb|right|Negative feedback in the [[hypothalamic–pituitary–adrenal axis|HPA axis]]]]
Glucocorticoids are under the regulatory influence of the [[hypothalamic–pituitary–adrenal axis|hypothalamic–pituitary–adrenal axis (HPA) axis]]. Glucocorticoid synthesis is stimulated by [[adrenocorticotropic hormone]] (ACTH), a hormone released into the bloodstream by the [[anterior pituitary]]. In turn, production of ACTH is stimulated by the presence of [[corticotropin-releasing hormone]] (CRH), which is released by neurons of the [[hypothalamus]]. ACTH acts on the adrenal cells first by increasing the levels of StAR within the cells, and then of all steroidogenic P450 enzymes. The HPA axis is an example of a negative [[feedback]] system, in which cortisol itself acts as a direct inhibitor of both CRH and ACTH synthesis. The HPA axis also interacts with the immune system through increased secretion of ACTH at the presence of certain molecules of the [[inflammatory response]].<ref name="williams" />

Mineralocorticoid secretion is regulated mainly by the [[renin–angiotensin–aldosterone system]] (RAAS), the concentration of [[potassium]], and to a lesser extent the concentration of ACTH.<ref name="williams" /> Sensors of blood pressure in the [[juxtaglomerular apparatus]] of the kidneys release the enzyme [[renin]] into the blood, which starts a cascade of reactions that lead to formation of [[angiotensin II]]. [[Angiotensin receptor]]s in cells of the zona glomerulosa recognize the substance, and upon binding they stimulate the release of [[aldosterone]].<ref name=crowley>{{cite journal|last1=Crowley|first1=SD|last2=Coffman|first2=TM|title=Recent advances involving the renin–angiotensin system|journal=Experimental Cell Research|date=2012|volume=318|issue=9|pages=1049–1056|doi=10.1016/j.yexcr.2012.02.023|pmid=22410251|pmc=3625040}}</ref>

===Androgens===
Cells in [[zona reticularis]] of the adrenal glands produce male sex hormones, or [[androgen]]s, the most important of which is [[Dehydroepiandrosterone|DHEA]]. In general, these hormones do not have an overall effect in the male body, and are converted to more potent androgens such as [[testosterone]] and [[Dihydrotestosterone|DHT]] or to [[estrogen]]s (female sex hormones) in the [[gonad]]s, acting in this way as a [[metabolic intermediate]].<ref name="guyton">{{cite book|title=Guyton and Hall Textbook of Medical Physiology, 12th edition|vauthors=Hall JE, [[Arthur Guyton|Guyton AC]]|publisher=Saunders|year=2010|isbn=978-1416045748}}</ref>

===Catecholamines===
Also called [[epinephrine]] and [[norepinephrine]], [[adrenaline]] and [[noradrenaline]], respectively, are [[catecholamine]]s &ndash; water-soluble [[organic compound|compounds]] that have a structure made of a [[catechol]] group and an [[amine group]].<ref name="statp">{{cite web |vauthors=Khalil B, Rosani A, Warrington SJ |title=Physiology, catecholamines |url=https://www.ncbi.nlm.nih.gov/books/NBK507716/ |publisher=StatPearls, US National Library of Medicine |access-date=8 March 2025 |date=11 December 2024|pmid=29939538 }}</ref> The adrenal glands are responsible for most of the adrenaline that circulates in the body, but only for a small amount of circulating noradrenaline.<ref name=DAVIDSONS2010 /> These hormones are released by the adrenal medulla, which contains a dense network of blood vessels. Adrenaline and noradrenaline act by binding to [[adrenoreceptor]]s throughout the body, with effects that include an increase in blood pressure and heart rate.<ref name=statp/> Actions of adrenaline and noradrenaline are responsible for the [[fight or flight response]], characterised by a quickening of breathing and heart rate, an increase in blood pressure, and constriction of blood vessels in many parts of the body.<ref name=statp/>

====Formation====
Catecholamines are produced in chromaffin cells in the medulla of the adrenal gland, from [[tyrosine]], a non-essential amino acid derived from food or produced from [[phenylalanine]] in the liver.<ref name=statp/> The enzyme [[tyrosine hydroxylase]] converts tyrosine to [[L-DOPA]] in the first step of catecholamine synthesis. L-DOPA is then converted to [[dopamine]] before it can be turned into noradrenaline. In the [[cytosol]], noradrenaline is converted to epinephrine by the enzyme [[phenylethanolamine N-methyltransferase]] (PNMT) and stored in granules. Glucocorticoids produced in the adrenal cortex stimulate the synthesis of catecholamines by increasing the levels of tyrosine hydroxylase and PNMT.<ref name=williams /><ref name="whitehead"/>

Catecholamine release is stimulated by the activation of the [[sympathetic nervous system]].<ref name=statp/> [[Splanchnic nerves]] of the [[sympathetic nervous system]] innervate the medulla of the adrenal gland. When activated, it evokes the release of catecholamines from the storage granules by stimulating the opening of [[calcium channel]]s in the cell membrane.<ref name=statp/><ref name=garcia>{{cite journal|last1=García|first1=AG|last2=García de Diego|first2=AM|last3=Gandía|first3=L|last4=Borges|first4=R|last5=García Sancho|first5=J|title=Calcium signaling and exocytosis in adrenal chromaffin cells.|journal=Physiological Reviews|date=2006|volume=86|issue=4|pages=1093–1131|doi=10.1152/physrev.00039.2005|pmid=17015485}}</ref>

==Gene and protein expression==
{{Further |Bioinformatics#Gene and protein expression}}
The&nbsp;[[human genome]]&nbsp;includes approximately 20,000 protein coding genes and 70% of these&nbsp;[[Gene expression|genes are expressed]]&nbsp;in the normal adult adrenal glands.<ref>{{Cite web|url=https://www.proteinatlas.org/humanproteome/adrenal+gland|title=The human proteome in adrenal gland – The Human Protein Atlas|website=www.proteinatlas.org|access-date=2017-09-21}}</ref><ref>{{Cite journal|last1=Uhlén|first1=Mathias|last2=Fagerberg|first2=Linn|last3=Hallström|first3=Björn M.|last4=Lindskog|first4=Cecilia|last5=Oksvold|first5=Per|last6=Mardinoglu|first6=Adil|last7=Sivertsson|first7=Åsa|last8=Kampf|first8=Caroline|last9=Sjöstedt|first9=Evelina|date=2015-01-23|title=Tissue-based map of the human proteome|journal=Science|language=en|volume=347|issue=6220|pages=1260419|doi=10.1126/science.1260419|issn=0036-8075|pmid=25613900|s2cid=802377}}</ref>&nbsp;Only some 250 genes are more specifically expressed in the adrenal glands compared to other organs and tissues.&nbsp;The adrenal-gland-specific genes with the highest level of expression include members of the [[cytochrome P450]] superfamily of enzymes. Corresponding proteins are expressed in the different compartments of the adrenal gland, such as [[CYP11A1]], [[HSD3B2]] and [[FDX1]] involved in [[steroid hormone]] synthesis and expressed in cortical cell layers, and [[Phenylethanolamine N-methyltransferase|PNMT]] and [[Dopamine beta-hydroxylase|DBH]] involved in [[Norepinephrine|noradrenaline]] and [[Epinephrine|adrenaline]] synthesis and expressed in the medulla.<ref>{{Cite journal|last1=Bergman|first1=Julia|last2=Botling|first2=Johan|last3=Fagerberg|first3=Linn|last4=Hallström|first4=Björn M.|last5=Djureinovic|first5=Dijana|last6=Uhlén|first6=Mathias|last7=Pontén|first7=Fredrik|date=2017-02-01|title=The Human Adrenal Gland Proteome Defined by Transcriptomics and Antibody-Based Profiling|journal=Endocrinology|volume=158|issue=2|pages=239–251|doi=10.1210/en.2016-1758|pmid=27901589|issn=0013-7227|doi-access=free}}</ref>

==Development==
The adrenal glands are composed of two heterogenous types of tissue. In the center is the [[adrenal medulla]], which produces [[adrenaline]] and [[noradrenaline]] and releases them into the bloodstream, as part of the [[sympathetic nervous system]]. Surrounding the medulla is the [[adrenal cortex|cortex]], which produces a variety of [[steroid hormone]]s. These tissues come from different [[Human embryogenesis|embryological]] precursors and have distinct [[prenatal development]] paths. The cortex of the adrenal gland is derived from [[mesoderm]], whereas the medulla is derived from the [[neural crest]], which is of [[ectoderm]]al origin.<ref name=Kay2015 />

The adrenal glands in a newborn baby are much larger as a proportion of the body size than in an adult.<ref name=Barwick2005>{{cite journal |last1=Barwick |first1=T.D. |last2=Malhotra |first2=A. |last3=Webb |first3=J.A.W. |last4=Savage |first4=M.O. |last5=Reznek |first5=R.H. |title=Embryology of the adrenal glands and its relevance to diagnostic imaging |journal=Clinical Radiology |date=September 2005 |volume=60 |issue=9 |pages=953–959 |doi=10.1016/j.crad.2005.04.006|pmid=16124976 }}</ref> For example, at age three months the glands are four times the size of the kidneys. The size of the glands decreases relatively after birth, mainly because of shrinkage of the cortex. The cortex, which almost completely disappears by age 1, develops again from age 4–5. The glands weigh about {{Value|1|u=gram}} at birth<ref name=Kay2015 /> and develop to an adult weight of about {{Value|4|u=grams}} each.<ref name=boron>{{cite book|last1=Boron|first1=WF.|last2=Boulapep|first2=EL.|title=Medical Physiology|date=2012|publisher=Saunders|location=Philadelphia|isbn=978-1437717532|edition=2nd}}</ref> In a fetus the glands are first detectable after the sixth week of development.<ref name=Kay2015/>

===Cortex===
Adrenal cortex tissue is derived from the [[intermediate mesoderm]]. It first appears 33 days after [[fertilisation]], shows [[Steroid#Steroidogenesis|steroid hormone production]] capabilities by the eighth week and undergoes rapid growth during the first trimester of pregnancy. The fetal adrenal cortex is different from its adult counterpart, as it is composed of two distinct zones: the inner "fetal" zone, which carries most of the hormone-producing activity, and the outer "definitive" zone, which is in a [[cell proliferation|proliferative]] phase. The fetal zone produces large amounts of adrenal [[androgen]]s (male sex hormones) that are used by the [[placenta]] for [[estrogen]] biosynthesis.<ref name="ishimoto">{{cite journal | title=Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit |vauthors=Ishimoto H, Jaffe RB | journal=Endocrine Reviews | year=2011 | volume=32 | issue=3 | pages=317–355 | doi=10.1210/er.2010-0001 | pmid=21051591 | pmc=3365797 }}</ref> Cortical development of the adrenal gland is regulated mostly by [[Adrenocorticotropic hormone|ACTH]], a hormone produced by the [[pituitary gland]] that stimulates [[cortisol]] synthesis.<ref name="hoeflich">{{cite journal | title=Mechanisms of adrenal gland growth: signal integration by extracellular signal regulated kinases1/2 |vauthors=Hoeflich A, Bielohuby M | journal=Journal of Molecular Endocrinology | year=2009 | volume=42 | issue=3 | pages=191–203 | doi=10.1677/JME-08-0160 | pmid=19052254 | doi-access=free }}</ref> During midgestation, the fetal zone occupies most of the cortical volume and produces 100–200&nbsp;mg/day of [[DHEA-S]], an [[androgen]] and precursor of both androgens and [[estrogen]]s (female sex hormones).<ref name="messiano">{{cite journal | title=Developmental and Functional Biology of the Primate Fetal Adrenal Cortex |vauthors=Mesiano S, Jaffe RB | journal=Endocrine Reviews | year=1997 | volume=18 | issue=3 | pages=378–403 | doi=10.1210/edrv.18.3.0304 | pmid=9183569 | doi-access=free }}</ref> Adrenal hormones, especially [[glucocorticoid]]s such as cortisol, are essential for prenatal development of organs, particularly for the maturation of the [[lung]]s. The adrenal gland decreases in size after birth because of the rapid disappearance of the fetal zone, with a corresponding decrease in androgen secretion.<ref name="ishimoto" />

====Adrenarche====
{{Main|Adrenarche}}
During early childhood androgen synthesis and secretion remain low, but several years before puberty (from 6–8 years of age) changes occur in both anatomical and functional aspects of cortical androgen production that lead to increased secretion of the steroids [[dehydroepiandrosterone|DHEA]] and [[dehydroepiandrosterone sulfate|DHEA-S]]. These changes are part of a process called [[adrenarche]], which has only been described in humans and some other primates. Adrenarche is independent of [[Adrenocorticotropic hormone|ACTH]] or [[gonadotropin]]s and correlates with a progressive thickening of the [[zona reticularis]] layer of the cortex. Functionally, adrenarche provides a source of androgens for the development of axillary and pubic hair before the beginning of puberty.<ref name=hornsby>{{cite journal|last1=Hornsby|first1=PJ|title=Adrenarche: a cell biological perspective.|journal=The Journal of Endocrinology|date=2012|volume=214|issue=2|pages=113–119|doi=10.1530/JOE-12-0022|pmid=22573830|doi-access=free}}</ref><ref name=rege>{{cite journal|last1=Rege|first1=J|last2=Rainey|first2=WE|title=The steroid metabolome of adrenarche.|journal=The Journal of Endocrinology|date=2012|volume=214|issue=2|pages=133–143|doi=10.1530/JOE-12-0183|pmid=22715193|pmc=4041616}}</ref>

===Medulla===
The adrenal medulla is derived from [[neural crest|neural crest cells]], which come from the [[ectoderm]] layer of the [[embryo]]. These cells [[cell migration|migrate]] from their initial position and aggregate in the vicinity of the [[dorsal aorta]], a primitive blood vessel, which activates the differentiation of these cells through the release of proteins known as [[Bone morphogenetic protein|BMP]]s. These cells then undergo a second migration from the dorsal aorta to form the adrenal medulla and other organs of the [[sympathetic nervous system]].<ref name="huber">{{cite journal | title=The sympathoadrenal cell lineage: Specification, diversification, and new perspectives | author=Huber K | journal=Developmental Biology | year=2006 | volume=298 | issue=2 | pages=335–343 | doi=10.1016/j.ydbio.2006.07.010 | pmid=16928368 | doi-access=free }}</ref> Cells of the adrenal medulla are called [[chromaffin cells]] because they contain granules that stain with [[chromium]] salts, a characteristic not present in all sympathetic organs. [[Glucocorticoid]]s produced in the adrenal cortex were once thought to be responsible for the differentiation of chromaffin cells. More recent research suggests that [[Bone morphogenetic protein 4|BMP-4]] secreted in adrenal tissue is the main responsible for this, and that glucocorticoids only play a role in the subsequent development of the cells.<ref name="unsicker">{{cite journal | title=Resolved and open issues in chromaffin cell development |vauthors=Unsicker K, Huber K, Schober A, Kalcheim C | journal=Mechanisms of Development | year=2013 | volume=130 | issue=6–8 | pages=324–329 | doi=10.1016/j.mod.2012.11.004 | pmid=23220335 | doi-access=free }}</ref>

==Clinical significance==
{{Main|Adrenal gland disorder}}

The normal function of the adrenal gland may be impaired by conditions such as infections, tumors, genetic disorders and [[autoimmune disease]]s, or as a [[side effect]] of medical therapy. These disorders affect the gland either directly (as with infections or autoimmune diseases) or as a result of the dysregulation of hormone production (as in some types of [[Cushing's syndrome]]) leading to an excess or insufficiency of adrenal hormones and the related symptoms.

===Corticosteroid overproduction===
====Cushing's syndrome====
[[Cushing's syndrome]] is the manifestation of glucocorticoid excess. It can be the result of a prolonged treatment with glucocorticoids or be caused by an underlying disease which produces alterations in the [[HPA axis]] or the production of cortisol. Causes can be further classified into [[Adrenocorticotropic hormone|ACTH]]-dependent or ACTH-independent. The most common cause of [[endogeny|endogenous]] Cushing's syndrome is a [[pituitary adenoma]] which causes an excessive production of ACTH. The disease produces a wide variety of signs and symptoms which include obesity, diabetes, increased blood pressure, excessive body hair ([[hirsutism]]), [[osteoporosis]], depression, and most distinctively, [[striae|stretch marks]] in the skin, caused by its progressive thinning.<ref name=williams /><ref name="harrison's">{{cite book|last1=Longo|first1=D|last2=Fauci|first2=A|author-link2=Anthony Fauci|last3=Kasper|first3=D|author-link3=Dennis Kasper|last4=Hauser|first4=S|last5=Jameson|first5=J|last6=Loscalzo|first6=J|title=Harrison's Principles of Internal Medicine|date=2012|publisher=McGraw-Hill|location=New York|isbn=978-0071748896|edition=18th}}</ref>

====Primary aldosteronism====
When the zona glomerulosa produces excess [[aldosterone]], the result is [[primary aldosteronism]]. Causes for this condition are bilateral [[hyperplasia]] (excessive tissue growth) of the glands, or aldosterone-producing [[adenoma]]s (a condition called [[Conn's syndrome]]). Primary aldosteronism produces hypertension and [[electrolyte]] imbalance, increasing [[potassium]] depletion sodium retention.<ref name="harrison's" />

===Adrenal insufficiency===
Adrenal insufficiency (the deficiency of [[glucocorticoid]]s) occurs in about 5 in 10,000 in the general population.<ref name="harrison's" /> Diseases classified as ''primary adrenal insufficiency'' (including [[Addison's disease]] and genetic causes) directly affect the adrenal cortex. If a problem that affects the [[hypothalamic–pituitary–adrenal axis]] arises outside the gland, it is a ''secondary adrenal insufficiency''.<ref>{{cite web | url=https://www.ncbi.nlm.nih.gov/books/NBK279083/ | pmid=25905309 | date=2000 | last1=Feingold | first1=K. R. | last2=Ahmed | first2=S. F. | last3=Anawalt | first3=B. | last4=Blackman | first4=M. R. | last5=Boyce | first5=A. | last6=Chrousos | first6=G. | last7=Corpas | first7=E. | last8=De Herder | first8=W. W. | last9=Dhatariya | first9=K. | last10=Dungan | first10=K. | last11=Hofland | first11=J. | last12=Kalra | first12=S. | last13=Kaltsas | first13=G. | last14=Kapoor | first14=N. | last15=Koch | first15=C. | last16=Kopp | first16=P. | last17=Korbonits | first17=M. | last18=Kovacs | first18=C. S. | last19=Kuohung | first19=W. | last20=Laferrère | first20=B. | last21=Levy | first21=M. | last22=McGee | first22=E. A. | last23=McLachlan | first23=R. | last24=Muzumdar | first24=R. | last25=Purnell | first25=J. | last26=Rey | first26=R. | last27=Sahay | first27=R. | last28=Shah | first28=A. S. | last29=Singer | first29=F. | last30=Sperling | first30=M. A. | title=Adrenal Insufficiency | publisher=MDText.com | display-authors=1 }}</ref>

====Addison's disease====
[[File:T. Addison; On...supra-renal capsules Wellcome L0018484.jpg|thumb|right|Characteristic skin [[hyperpigmentation]] in [[Addison's disease]]]]
Addison's disease refers to primary hypoadrenalism, which is a deficiency in glucocorticoid and mineralocorticoid production by the adrenal gland. In the Western world, Addison's disease is most commonly an [[autoimmunity|autoimmune]] condition, in which the body produces [[Antibody|antibodies]] against cells of the adrenal cortex. Worldwide, the disease is more frequently caused by infection, especially from [[tuberculosis]]. A distinctive feature of Addison's disease is [[hyperpigmentation]] of the skin, which presents with other nonspecific symptoms such as fatigue.<ref name=williams />

A complication seen in untreated Addison's disease and other types of primary adrenal insufficiency is the [[adrenal crisis]], a [[medical emergency]] in which low glucocorticoid and mineralocorticoid levels result in [[hypovolemic shock]] and symptoms such as vomiting and fever. An adrenal crisis can progressively lead to [[stupor]] and [[coma]].<ref name=williams /> The management of adrenal crises includes the application of [[hydrocortisone]] injections.<ref>[http://www.pituitary.org.uk/media/134894/Factsheet-for-Ambulance-Personnel.pdf Hydrocortisone Emergency Factsheet for Ambulance Personnel] {{Webarchive|url=https://web.archive.org/web/20150924073703/http://www.pituitary.org.uk/media/134894/Factsheet-for-Ambulance-Personnel.pdf |date=24 September 2015 }} The Pituitary Foundation</ref>

====Secondary adrenal insufficiency====
In secondary adrenal insufficiency, a dysfunction of the [[hypothalamic–pituitary–adrenal axis]] leads to decreased stimulation of the adrenal cortex. Apart from suppression of the axis by glucocorticoid therapy, the most common cause of secondary adrenal insufficiency are tumors that affect the production of [[adrenocorticotropic hormone]] (ACTH) by the [[pituitary gland]].<ref name="harrison's" /> This type of adrenal insufficiency usually does not affect the production of [[mineralocorticoid]]s, which are under regulation of the [[renin–angiotensin system]] instead.<ref name=williams />

====Congenital adrenal hyperplasia====
[[Congenital adrenal hyperplasia]] is a family of [[congenital diseases]] in which [[mutation]]s of enzymes that produce steroid hormones result in a [[glucocorticoid deficiency]] and malfunction of the negative feedback loop of the [[HPA axis]]. In the HPA axis, cortisol (a glucocorticoid) inhibits the release of [[corticotropin-releasing hormone|CRH]] and [[Adrenocorticotropic hormone|ACTH]], hormones that in turn stimulate corticosteroid synthesis. As cortisol cannot be synthesized, these hormones are released in high quantities and stimulate production of other adrenal steroids instead. The most common form of congenital adrenal hyperplasia is due to [[21-hydroxylase]] deficiency. 21-hydroxylase is necessary for production of both mineralocorticoids and glucocorticoids, but not [[androgen]]s. Therefore, ACTH stimulation of the adrenal cortex induces the release of excessive amounts of [[adrenal androgen]]s, which can lead to the development of ambiguous [[genitalia]] and [[secondary sex characteristic]]s.<ref name=charmandari />

===Adrenal tumors===
[[File:Incidences and prognoses of adrenal tumors.png|thumb|240px|Incidences and prognoses of adrenal tumors.<ref>Data and references for pie chart are located at [[Commons:File:Incidences and prognoses of adrenal tumors.png|file description page in Wikimedia Commons.]]</ref>]]
{{Main|Adrenal tumor}}
Adrenal tumors are commonly found as [[incidentaloma]]s, unexpected [[asymptomatic]] tumors [[incidental findings|found]] during [[medical imaging]]. They are seen in around 3.4% of [[X-ray computed tomography|CT scans]],<ref name=nieman>{{cite journal|last1=Nieman|first1=LK|title=Approach to the patient with an adrenal incidentaloma.|journal=The Journal of Clinical Endocrinology and Metabolism|date=2010|volume=95|issue=9|pages=4106–13|doi=10.1210/jc.2010-0457|pmid=20823463|pmc=2936073}}</ref> and in most cases they are benign [[Adrenocortical adenoma|adenoma]]s.<ref name=mantero>{{cite journal|last1=Mantero|first1=F|last2=Terzolo|first2=M|last3=Arnaldi|first3=G|last4=Osella|first4=G|last5=Masini|first5=AM|last6=Alì|first6=A|last7=Giovagnetti|first7=M|last8=Opocher|first8=G|last9=Angeli|first9=A|title=A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology.|journal=The Journal of Clinical Endocrinology and Metabolism|date=2000|volume=85|issue=2|pages=637–644|doi=10.1210/jcem.85.2.6372|pmid=10690869|doi-access=free}}</ref> [[Adrenal carcinoma]]s are very rare, with an [[incidence (epidemiology)|incidence]] of 1 case per million per year.<ref name=williams />

[[Pheochromocytomas]] are tumors of the adrenal medulla that arise from [[chromaffin cell]]s. They can produce a variety of nonspecific symptoms, which include headaches, sweating, anxiety and [[palpitation]]s. Common signs include [[hypertension]] and [[tachycardia]]. Surgery, especially adrenal [[laparoscopy]], is the most common treatment for small pheochromocytomas.<ref name=martucci>{{cite journal|last1=Martucci|first1=VL|last2=Pacak|first2=K|title=Pheochromocytoma and paraganglioma: diagnosis, genetics, management, and treatment.|journal=Current Problems in Cancer|date=2014|volume=38|issue=1|pages=7–41|doi=10.1016/j.currproblcancer.2014.01.001|pmid=24636754|url=http://www.cpcancer.com/article/S0147-0272%2814%2900002-6/fulltext|pmc=3992879}}</ref>

==History==
[[Bartolomeo Eustachi]], an Italian anatomist, is credited with the first description of the adrenal glands in 1563–4.<ref name=schmidt>{{cite book|last1=Schmidt|first1=JE|title=Medical Discoveries: Who and When|date=1959|publisher=Thomas|url=http://catalog.hathitrust.org/Record/001557037|pages=9–10}}</ref><ref name=OHARE2012 /><ref>{{cite journal|url=https://www.hormones.gr/pdf/Hormones_2016-136.pdf|author=Papadakis, Marios|author2=Manios, Andreas|author3=Schoretsanitis, Georgios|author4=Trompoukis, Constantinos|title=Landmarks in the history of adrenal surgery|journal=Hormones|volume=15|issue=1|year=2016|pages=136–141|doi=10.1007/BF03401414 |pmid=26732166 |s2cid=195290802 }}</ref> However, these publications were part of the [[papal library]] and did not receive public attention, which was first received with [[Caspar Bartholin the Elder]]'s illustrations in 1611.<ref name=OHARE2012 >{{cite book|last1=O'Hare|first1=A. Munro Neville, Michael J.|title=The Human Adrenal Cortex Pathology and Biology – An Integrated Approach|date=2012|publisher=Springer London|location=London|isbn=978-1447113171|pages=Chapter 2: Historical Aspects}}</ref>

The adrenal glands are named for their location relative to the kidneys. The term "adrenal" comes from [[Latin]] ''[[wikt:ad-|ad]]'', "near", and ''[[:wikt:ren|ren]]'', "kidney".<ref>{{cite web|url=http://psychology.about.com/od/aindex/g/adrenal-glands.htm|title=What Are The Adrenal Glands?|access-date=18 September 2013|publisher=About.com|archive-date=29 October 2013|archive-url=https://web.archive.org/web/20131029203616/http://psychology.about.com/od/aindex/g/adrenal-glands.htm|url-status=dead}}</ref> Similarly, "suprarenal", as termed by [[Jean Riolan the Younger]] in 1629, is derived from the [[Latin]] ''[[:wikt:supra-|supra]]'', "above", and ''ren'', "kidney", as well. The suprarenal nature of the glands was not truly accepted until the 19th century, as anatomists clarified the ductless nature of the glands and their likely secretory role – prior to this, there was some debate as to whether the glands were indeed suprarenal or part of the kidney.<ref name=OHARE2012 />

One of the most recognized works on the adrenal glands came in 1855 with the publication of ''On the Constitutional and Local Effects of Disease of the Suprarenal Capsule'', by the English physician [[Thomas Addison]]. In his monography, Addison described what the French physician [[Georges Phillipe Trousseau|George Trousseau]] would later name [[Addison's disease]], an eponym still used today for a condition of [[adrenal insufficiency]] and its related clinical manifestations.<ref name=pearce>{{cite journal|last1=Pearce|first1=JM|title=Thomas Addison (1793–1860)|journal=Journal of the Royal Society of Medicine|date=2004|volume=97|issue=6|pages=297–300|doi=10.1177/014107680409700615|pmid=15173338|url= |pmc=1079500}}</ref> In 1894, English physiologists [[George Oliver (physician)|George Oliver]] and [[Edward Albert Sharpey-Schafer|Edward Schafer]] studied the action of adrenal extracts and observed their [[antihypotensive agent|pressor]] effects. In the following decades several physicians experimented with extracts from the adrenal cortex to treat Addison's disease.<ref name=schmidt /> [[Edward Calvin Kendall]], [[Philip Hench]] and [[Tadeusz Reichstein]] were then awarded the 1950 [[Nobel Prize in Physiology or Medicine]] for their discoveries on the structure and effects of the adrenal hormones.<ref name="nobel-1950">{{cite web|url=http://nobelprize.org/nobel_prizes/medicine/laureates/1950/index.html|title=The Nobel Prize in Physiology or Medicine 1950|access-date=10 February 2015|publisher=Nobel Foundation}}</ref>

==See also==
* [[Adrenopause]]
* [[Adrenochrome]]
* [[List of distinct cell types in the adult human body]]
* [[Adrenal insufficiency]]
* [[Adrenal gland disorder]]

==References==
{{Reflist|30em}}

==External links==
{{Commons category}}
* [https://www.proteinatlas.org/humanproteome/adrenal+gland Adrenal gland at the Human Protein Atlas]
* {{MedlinePlusEncyclopedia|002219}}
* [http://www.proteinatlas.org/learn/dictionary/normal/adrenal+gland Adrenal gland histology]
* {{AnatomyAtlasesMicroscopic|15|292}} – "Adrenal Gland"
* {{BUHistology|14501loa}}
* {{SUNYAnatomyLabs|40|03|01|05}} – "Posterior Abdominal Wall: The Retroperitoneal Fat and Suprarenal Glands"
* [https://web.archive.org/web/20040404014307/http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/adrenal/index.html Adrenal Gland], from Colorado State University
* {{ViennaCrossSection|pembody/body8a}}

{{Endocrine system}}
{{Human system and organs}}

{{Authority control}}

{{DEFAULTSORT:Adrenal Gland}}
[[Category:Adrenal gland| ]]
[[Category:Adrenaline]]
[[Category:Endocrine system anatomy]]