There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport=
=====Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Pediatric Indications and Dosage-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed=
=====Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
<!--Off-Label Use and Dosage (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport=
=====Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport=
=====Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Contraindications-->
|contraindications=
* Condition1
<!--Warnings-->
|warnings=
* Description
====Precautions====
* Description
<!--Adverse Reactions-->
<!--Clinical Trials Experience-->
|clinicalTrials=
There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Postmarketing Experience-->
|postmarketing=
There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Drug Interactions-->
|drugInteractions=
* Drug
:* Description
<!--Use in Specific Populations-->
|useInPregnancyFDA=
* '''Pregnancy Category'''
|useInPregnancyAUS=
* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=
There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=
There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
|useInPed=
There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInGeri=
There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=
There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=
There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
<!--Administration and Monitoring-->
|administration=
* Oral
* Intravenous
|monitoring=
There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
* Description
<!--IV Compatibility-->
|IVCompat=
There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
<!--Overdosage-->
|overdose=
===Acute Overdose===
====Signs and Symptoms====
* Description
====Management====
* Description
===Chronic Overdose===
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
<!--Pharmacology-->
<!--Drug box 2-->
|drugBox=
<!--Mechanism of Action-->
'''Cortisol''' is a [[corticosteroid]] [[hormone]] produced by the [[adrenal cortex]] (in the adrenal gland). It is a vital hormone that is often referred to as the "stress hormone" as it is involved in the response to [[stress (medicine)|stress]]. It increases [[blood pressure]], [[blood sugar]] levels and has an [[immunosuppressive]] action. In [[pharmacology]], the synthetic form of cortisol is referred to as '''hydrocortisone''', and is used to treat [[allergy|allergies]] and [[inflammation]] as well as cortisol production deficiencies. When first introduced as a treatment for rheumatoid arthritis, it was referred to as '''Compound E'''.
|mechAction=
==Physiology==
*
===Diurnal variation===
The amount of cortisol present in the [[blood|serum]] undergoes diurnal variation, with the highest levels present in the early morning, and the lowest levels present around midnight, 3-5 hours after the onset of [[sleep]]. Information about the [[Circadian rhythm|light/dark cycle]] is transmitted from the [[retina]] to the paired [[suprachiasmatic nuclei]] in the [[hypothalamus]]. The pattern is not present at birth (estimates of when it starts vary from two weeks to 9 months.<ref>{{cite journal |author=de Weerth C, Zijl R, Buitelaar J |title=Development of cortisol circadian rhythm in infancy |journal=Early Hum Dev |volume=73 |issue=1-2 |pages=39-52 |year=2003 |pmid=12932892}}</ref>)
<!--Structure-->
Changed patterns of serum cortisol levels have been observed in connection with abnormal [[ACTH]] levels, [[clinical depression]], [[stress (psychology)|psychological stress]], and such physiological stressors as [[hypoglycemia]], illness, [[fever]], trauma, [[surgery]], [[fear]], [[Pain and nociception|pain]], physical exertion or extremes of temperature.
|structure=
There is also significant individual variation, although a given person tends to have consistent rhythms.
*
===Effects===
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
:''See also [[Glucocorticoid#Medical uses and effects of high dose glucocorticoids|Medical uses and effects of high dose glucocorticoids]]''
In normal release, cortisol (like other [[glucocorticoid]] agents) has widespread actions which help restore [[homeostasis]] after [[Stress (medicine)|stress]]. (These normal [[endogenous]] functions are the basis for the physiological consequences of chronic stress - prolonged cortisol secretion.)
<!--Pharmacodynamics-->
* It acts as a physiological [[Receptor antagonist|antagonist]] to [[insulin]] by promoting [[glycogenolysis]] (breakdown of [[glycogen]]), breakdown of [[lipid]]s ([[lipolysis]]), and [[protein]]s, and mobilization of extrahepatic amino acids and ketone bodies. This leads to increased circulating [[glucose]] concentrations (in the blood). There is a decreased [[glycogen]] formation in the [[liver]] . <ref>Freeman, Scott (2002). ''Biological Science''. Prentice Hall; 2nd Pkg edition (December 30, 2004). ISBN 0-13-218746-9.</ref> Prolonged cortisol secretion causes [[hyperglycemia]].
|PD=
* It can weaken the activity of the [[immune system]] . Cortisol prevents proliferation of T-cells by rendering the [[interleukin-2]] producer [[T-cell]]s unresponsive to [[interleukin-1]] (IL-1), and unable to produce the T-cell growth factor.<ref>{{cite journal |author=Palacios R., Sugawara I. |title=Hydrocortisone abrogates proliferation of T cells in autologous mixed lymphocyte reaction by rendering the interleukin-2 Producer T cells unresponsive to interleukin-1 and unable to synthesize the T-cell growth factor |journal=Scand J Immunol |volume=15 |issue=1 |pages=25-31 |year=1982 |pmid=6461917}}</ref> It reflects [[leukocyte]] redistribution to lymph nodes, [[bone marrow]], and [[skin]]. Acute administration of [[corticosterone]] (the endogenous Type I and Type II receptor agonist), or [[RU28362]] (a specific Type II receptor agonist), to adrenalectomized animals induced changes in leukocyte distribution.
There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
* It lowers [[bone]] formation thus favoring development of osteoporosis in the long term. Cortisol moves [[potassium]] into cells in exchange for an equal number of [[sodium]] ions.<ref>{{cite journal |author=Knight, R.P., Jr. Kornfield, D.S. Glaser, G.H. Bondy, P.K. |title=Effects of intravenous hydrocortisone on electrolytes of serum and urine in man |journal=J Clin Endocrinol Metab |volume=15 |issue=2 |pages=176-81 |year=1955 |pmid=13233328}}</ref> This can cause a major problem with the [[hyperkalemia]] of metabolic shock from surgery.
<!--Pharmacokinetics-->
* It may help to create [[memories]] when exposure is short-term; this is the proposed mechanism for storage of [[flash bulb memories]]. However, long-term exposure to cortisol results in damage to cells in the [[hippocampus]]. This damage results in impaired learning.
|PK=
* It increases [[blood pressure]] by increasing the sensitivity of the vasculature to epinephrine and norepinephrine. In the absence of cortisol, widespread [[vasodilation]] occurs.
There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
* It inhibits the secretion of [[corticotropin-releasing hormone]] (CRH), resulting in feedback inhibition of [[ACTH]] secretion. Some researchers believe that this normal feedback system may break down when animals are exposed to chronic stress.
<!--Nonclinical Toxicology-->
* It increases the effectiveness of [[catecholamine]]s.
|nonClinToxic=
* It allows for the kidneys to produce [[hypotonic]] urine.
There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
* It has anti-inflammatory effects by reducing [[histamine]] secretion and stabilizing [[lysosome|lysosomal]] membranes. The stabilization of lysosomal membranes prevents their rupture, thereby preventing damage to healthy tissues.
<!--Clinical Studies-->
* It stimulates hepatic [[detoxification]] by inducing tryptophan oxygenase (to reduce [[serotonin]] levels in the brain), glutamine synthase (reduce [[glutamate]] and [[ammonia]] levels in the brain), cytochrome P-450 hemoprotein (mobilizes [[arachidonic acid]]), and metallothionein (reduces [[heavy metals]] in the body).
|clinicalStudies=
In addition to the effects caused by cortisol binding to the [[glucocorticoid receptor]], because of its molecular similarity to [[aldosterone]], it also binds to the [[mineralocorticoid receptor]]. (It binds with less affinity to it than aldosterone does, but the concentration of blood cortisol is higher than that of blood aldosterone.)
There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
===Binding===
<!--How Supplied-->
Most serum cortisol, all but about 4%, is bound to proteins including [[Transcortin|corticosteroid binding globulin]] ('''CBG'''), and [[serum albumin]]. Only free cortisol is available to most receptors.
==Diseases and disorders==
|howSupplied=
* '''Hypercortisolism''': Excessive levels of cortisol in the blood result in [[Cushing's syndrome]].
*
* '''Hypocortisolism, or [[adrenal insufficiency]]''': If on the other hand the adrenal glands do not produce sufficient amounts of cortisol, [[Addison's disease]] is the consequence.
<!--Patient Counseling Information-->
The relationship between cortisol and ACTH is as follows:
|fdaPatientInfo=
{| class="wikitable"
There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
Hydrocortisone is the chemical form of cortisol used for oral administration or intravenous injection. It is used as an [[immunosuppressive drug]], given by injection in the treatment of severe allergic reactions such as [[anaphylaxis]] and [[angioedema]], in place of [[prednisolone]] in patients who need steroid treatment but cannot take oral medication, and peri-operatively in patients on long-term steroid treatment to prevent an [[Addison's disease|Addisonian crisis]].
It is given by topical application for its [[anti-inflammatory]] effect in allergic rashes, [[eczema]], [[psoriasis]] and certain other inflammatory conditions.
|alcohol=
It may also be injected into inflamed joints resulting from diseases such as [[gout]].
* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Compared to [[prednisolone]], hydrocortisone is about 1/4th the strength (for the [[anti-inflammatory]] effect only). [[Dexamethasone]] is about 40 times stronger than hydrocortisone. For side effects, see [[corticosteroid]] and [[prednisolone]]. Non prescription 1% hydrocortisone cream or ointment are available; stronger forms are prescription only.[http://www.drnase.com/Prescipt_ions_non.htm]
<!--Brand Names-->
==Biochemistry==
|brandNames=
===Biosynthesis===
Cortisol is synthesized from [[cholesterol]]. The synthesis takes place in the ''[[zona fasciculata]]'' of the [[adrenal cortex|cortex of the adrenal glands]]. (The name ''cortisol'' comes from ''cortex''.) While the adrenal cortex also produces [[aldosterone]] (in the ''zona glomerulosa'') and some [[sex hormone]]s (in the ''zona reticularis''), cortisol is its main secretion. The medulla of the adrenal gland lies under the cortex and mainly secretes the catecholamines, adrenaline (epinephrine) and noradrenaline (norepinephrine) under sympathetic stimulation (more epinephrine is produced than norepinephrine, in a ratio 4:1).
The synthesis of cortisol in the adrenal gland is stimulated by the [[anterior pituitary|anterior lobe]] of the [[pituitary gland]] with [[adrenocorticotropic hormone]] (ACTH); production of ACTH is in turn stimulated by [[corticotropin-releasing hormone]] (CRH), released by the [[hypothalamus]]. ACTH increases the concentration of cholesterol in the inner mitochondrial membrane (via regulation of STAR (steroidogenic acute regulatory) protein). The cholesterol is converted to pregnenolone, catalysed by Cytochrome P450SCC (side chain cleavage).
* ®<ref>{{Cite web | title = | url = }}</ref>
=== Metabolism ===
<!--Look-Alike Drug Names-->
Cortisol is metabolized by the [[11-beta hydroxysteroid dehydrogenase]] system (11-beta HSD), which consists of two enzymes: [[11-beta HSD1]] and [[11-beta HSD2]].
* ''11-beta HSD1'' utilizes the cofactor NADPH to convert biologically inert cortisone to biologically active cortisol.
* ''11-beta HSD2'' utilizes the cofactor NAD+ to convert cortisol to cortisone.
Overall the net effect is that 11-beta HSD1 serves to increase the local concentrations of biologically active cortisol in a given tissue, while 11-beta HSD2 serves to decrease the local concentrations of biologically active cortisol.
|lookAlike=
An alteration in 11-beta HSD1 has been suggested to play a role in the [[pathogenesis]] of [[obesity]], [[hypertension]], and [[insulin resistance]], sometimes referred to the [[metabolic syndrome]].
* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
An alteration in 11-beta HSD2 has been implicated in [[essential hypertension]] and is known to lead to the [[syndrome of apparent mineralocorticoid excess]] (SAME).
<!--Drug Shortage Status-->
== See also ==
|drugShortage=
* [[Cushing's syndrome]]
}}
* [[HPA axis]]
* [[Hypopituitarism]]
* [[Post-traumatic stress disorder]]
* [[Central serous retinopathy]]
* [[CortiSlim]]
* [[Relacore]], a pill which claims to reduce Cortisol.
==Additional images==
<!--Pill Image-->
<gallery>
Image:Steroidogenesis.gif|[[Steroidogenesis]]
Image:11-Deoxycortisol.png|[[11-Deoxycortisol]]
</gallery>
==References==
{{PillImage
<references/>
|fileName=No image.jpg|This image is provided by the National Library of Medicine.
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==External links==
<!--Label Display Image-->
{{Hormones}}
{{LabelImage
{{Corticosteroids}}
|fileName={{PAGENAME}}11.png|This image is provided by the National Library of Medicine.
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Black Box Warning
Title
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Overview
Cortisol is a that is FDA approved for the {{{indicationType}}} of . There is a Black Box Warning for this drug as shown here. Common adverse reactions include .
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Condition1
Dosing Information
Dosage
Condition2
Dosing Information
Dosage
Condition3
Dosing Information
Dosage
Condition4
Dosing Information
Dosage
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Cortisol in adult patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Cortisol in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Cortisol in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Cortisol in pediatric patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Cortisol in pediatric patients.
Contraindications
Condition1
Warnings
Title
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Description
Precautions
Description
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Cortisol in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Cortisol in the drug label.
