Chemical structure of cortisol, a glucocorticoid

Dexamethasone binds more powerfully to the glucocorticoid receptor than cortisol does. Cortisol is a Corticosteroid Hormone produced by the Adrenal gland (in the Zona fasciculata of the Adrenal cortex) Dexamethasone is a potent synthetic member of the glucocorticoid class of Steroid Hormones It acts as an Anti-inflammatory and immunosuppressant The glucocorticoid receptor ( GR, or GCR also known as NR3C1 ( Nuclear receptor subfamily 3 group C member 1 is a Ligand -activated Transcription Dexamethasone is based on the cortisol structure but differs in three positions (extra double bond in the A-ring between carbons 1 and 2 and addition of a 9-α-fluoro group and a 16-α-methyl substituent).

Glucocorticoids (GC) are a class of steroid hormones characterised by an ability to bind with the glucocorticoid receptor (GR) and trigger similar effects. Steroid hormones are Steroids which act as Hormones Mammalian steroid hormones can be grouped into five groups by the receptors to which they bind In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling The glucocorticoid receptor ( GR, or GCR also known as NR3C1 ( Nuclear receptor subfamily 3 group C member 1 is a Ligand -activated Transcription Glucocorticoids are distinguished from mineralocorticoids and sex steroids by their specific receptors, target cells, and effects. Mineralocorticoids are a class of Steroid hormones characterised by their similarity to Aldosterone and their influence on salt and water balance Sex steroids, also known as gonadal steroids, are Steroid hormones that interact with Vertebrate Androgen or Estrogen receptors In technical terms, corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Corticosteroids are a class of Steroid hormones that are produced in the Adrenal cortex. Glucocorticoids are produced in the adrenal glands. In Mammals the adrenal glands (also known as suprarenal glands) are the triangle-shaped Endocrine glands that sit on top of the Kidneys their

Cortisol (or hydrocortisone) is the most important human glucocorticoid. Cortisol is a Corticosteroid Hormone produced by the Adrenal gland (in the Zona fasciculata of the Adrenal cortex) It is essential for life, and regulates or supports a variety of important cardiovascular, metabolic, immunologic, and homeostatic functions. This is an article about the rock music band "Circulatory System" Metabolism is the set of Chemical reactions that occur in living Organisms in order to maintain Life. Immunology is a broad branch of biomedical Science that covers the study of all aspects of the Immune system in all Organisms It deals with Homeostasis (from Greek: ὅμος hómos, "equal" and ιστημι istēmi, "to stand" lit Glucocorticoid receptors are found in the cells of almost all vertebrate tissues. The glucocorticoid receptor ( GR, or GCR also known as NR3C1 ( Nuclear receptor subfamily 3 group C member 1 is a Ligand -activated Transcription Vertebrates are members of the Subphylum Vertebrata, Chordates with backbones or spinal columns The grouping sometimes includes

Effects

The name glucocorticoid derives from early observations that these hormones were involved in glucose metabolism. Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body Carbohydrate metabolism denotes the various biochemical processes responsible for the formation, breakdown and interconversion of Carbohydrates In the fasted state, cortisol stimulates several processes that collectively serve to increase and maintain normal concentrations of glucose in blood. Cortisol is a Corticosteroid Hormone produced by the Adrenal gland (in the Zona fasciculata of the Adrenal cortex) These effects include:

• Stimulation of gluconeogenesis, particularly in the liver: This pathway results in the synthesis of glucose from non-hexose substrates such as amino acids and glycerol from triglyceride breakdown, and is particularly important in carnivores and certain herbivores. Gluconeogenesis (abreviated GNG) is a Metabolic pathway that results in the generation of Glucose from non- Carbohydrate carbon substrates such The liver is a vital organ in the human body and is present in Vertebrates and some other animals In Organic chemistry, a hexose is a Monosaccharide with six Carbon atoms having the Chemical formula C6H12O6 In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this A carnivore (ˈkɑrnɪvɔər meaning 'meat eater' ( Latin carne meaning 'flesh' and vorare meaning 'to devour' is any animal with a diet consisting Herbivory is a form of Predation in which an Organism, known as a herbivore, consumes principally Autotrophs ref name=Campbell>Campbell Enhancing the expression of enzymes involved in gluconeogenesis is probably the best-known metabolic function of glucocorticoids. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Gluconeogenesis (abreviated GNG) is a Metabolic pathway that results in the generation of Glucose from non- Carbohydrate carbon substrates such
• Mobilization of amino acids from extrahepatic tissues: These serve as substrates for gluconeogenesis. Gluconeogenesis (abreviated GNG) is a Metabolic pathway that results in the generation of Glucose from non- Carbohydrate carbon substrates such
• Inhibition of glucose uptake in muscle and adipose tissue: A mechanism to conserve glucose. "Adipose" redirects here For the Doctor Who monster see " Partners in Crime "
• Stimulation of fat breakdown in adipose tissue: The fatty acids released by lipolysis are used for production of energy in tissues like muscle, and the released glycerol provide another substrate for gluconeogenesis. Fatty acid degradation is the process in which Fatty acids are broken down into their metabolites resulting in release of its energy to the target cells Lipolysis is the breakdown of fat stored in fat cells During this process Free fatty acids are released into the bloodstream and circulate throughout the body

Glucocorticoids have potent anti-inflammatory and immunosuppressive properties particularly when administered at pharmacological doses. Anti-inflammatory refers to the property of a substance or treatment that reduces Inflammation. Immunosuppression involves an act that reduces the activation or Efficacy of the Immune system. They are important in normal immune responses. As a consequence, glucocorticoids are widely used as drugs to treat inflammatory conditions such as arthritis and dermatitis, and as adjunction therapy for conditions such as autoimmune diseases. Arthritis (from Greek arthro-, joint + -itis, inflammation plural arthritides is a group of conditions involving damage to the Joints of the body Dermatitis is a Blanket term meaning any " Inflammation of the skin" (e Autoimmune diseases arise from an overactive Immune response of the body against substances and tissues normally present in the body

Glucocorticoids have multiple effects on fetal development. An important example is their role in promoting maturation of the lung and production of the surfactant necessary for extrauterine lung function. Surfactants are wetting agents that lower the Surface tension of a liquid allowing easier spreading and lower the Interfacial tension between two liquids Mice with homozygous disruptions in the corticotropin-releasing hormone gene (see below) die at birth due to pulmonary immaturity. Zygosity refers to the genetic condition of a Zygote. In genetics zygosity describes the similarity or dissimilarity of DNA between Homologous Adrenocorticotropic hormone ( ACTH or corticotropin) is a Polypeptide Hormone produced and secreted by the Pituitary gland

Excessive glucocorticoid levels resulting from administration as a drug or hyperadrenocorticism have effects on many systems. Some examples include inhibition of bone formation, suppression of calcium absorption (both of which can lead to osteoporosis), delayed wound healing, muscle weakness, and increased risk of infection. These observations suggest a multitude of less-dramatic physiologic roles for glucocorticoids.

Mode of action

Glucocorticoids bind to the cytosolic glucocorticoid receptor. The glucocorticoid receptor ( GR, or GCR also known as NR3C1 ( Nuclear receptor subfamily 3 group C member 1 is a Ligand -activated Transcription This type of receptor is activated by ligand binding. In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling In Chemistry, a ligand is either an Atom, Ion, or Molecule (see also Functional group) that bonds to a central metal generally After a hormone binds to the corresponding receptor, the newly-formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The term complex in Chemistry is usually used to describe molecules or ensembles formed by the combination of Ligands and metal Ions. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed A hormone response element (HRE is a Response element for Hormones, a short sequence of DNA within the Promoter of a gene that is able to bind In Biology, a promoter is a region of DNA that facilitates the transcription of a particular Gene. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance The opposite mechanism is called transrepression. For other uses see Repression A repressor is a DNA-binding protein that regulates the expression of one or more genes by decreasing The activated hormone receptor interacts with specific transcription factors and prevents the transcription of targeted genes. A Hormone receptor is a Receptor protein on the surface of a cell or in its interior that binds to a specific Hormone. Transcription is the synthesis of RNA under the direction of DNA Glucocorticoids are able to prevent the transcription of any of immune genes, including the IL-2 gene. Interleukin-2 ( IL-2) is an Interleukin, a type of Cytokine Immune system signaling molecule that is instrumental in the body's natural response

The ordinary glucocorticoids do not distinguish among transactivation and transrepression and influence both the "wanted" immune and "unwanted" genes regulating the metabolic and cardiovascular functions. At the current time, intensive research is aimed at discovering selectively acting glucocorticoids that will be able to repress only the immune system. ^[1][2]

Pharmacologic properties

A variety of synthetic glucocorticoids, some far more potent than cortisol, have been created for therapeutic use. They differ in the pharmacokinetics (absorption factor, half-life, volume of distribution, clearance) and in pharmacodynamics (for example the capacity of mineralocorticoid activity: retention of sodium (Na+) and water; see also: renal physiology). Pharmacokinetics (in Greek: “pharmacon” meaning drug and “kinetikos” meaning putting in motion the study of time dependency sometimes abbreviated as “PK” is a Pharmacodynamics is the study of the Biochemical and Physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms Mineralocorticoids are a class of Steroid hormones characterised by their similarity to Aldosterone and their influence on salt and water balance Sodium (ˈsoʊdiəm is an element which has the symbol Na( Latin natrium, from Arabic natrun) atomic number 11 atomic mass 22 Water ( H2[[oxygen O]] H OH) is the most abundant Molecule on Earth 's surface composing of about 70% of the Earth's surface as Renal physiology is the study of the Physiology of the Kidneys Functions of the kidney The functions of the kidney can be divided into two groups Because they permeate the intestines easily, they are primarily administered per os (by mouth), but also by other methods, such as topically on skin. In Anatomy, the intestine is the segment of the alimentary canal extending from the Stomach to the Anus and in humans and other mammals consists The mouth, buccal cavity, or oral cavity is the first portion of the Alimentary canal that receives food and begins digestion by mechanically breaking up In Medicine, a topical Medication is applied to body surfaces such as the Skin or Mucous membranes for example the Vagina The skin is the outer covering of living tissue of an animal (or plant More than 90 percent of them bind different plasma proteins, however with a different binding specificity. Blood proteins, also called serum proteins, are Proteins found in Blood plasma. Endogenous glucocorticoids and some synthetic corticoids have high affinity to the protein transcortin (also called CBG, corticosteroid-binding globulin), whereas all of them bind albumin. Transcortin, also corticosteroid-binding globulin or CBG, is officially called serpin peptidase inhibitor clade A (alpha-1 antiproteinase antitrypsin member Serum albumin, often referred to simply as albumin, is the most abundant Plasma protein in humans and other Mammals Albumin is essential for maintaining In the liver, they quickly metabolise by conjugation with a sulfate or glucuronic acid, and are secreted in the urine. Glucuronic acid (from Greek γλυκερός - "sweet" is a Carboxylic acid. Urine is a liquid waste product of the body secreted by the Kidneys by a process of filtration from Blood and Excreted through the Urethra.

Glucocorticoid potency, duration of effect, and overlapping mineralocorticoid potency varies (Table).

Cortisol (hydrocortisone) is the standard of comparison for glucocorticoid potency. Hydrocortisone is the name used for pharmaceutical preparations of cortisol. Data refer to oral dosing, except when mentioned. Note that oral potency may be less than parenteral potency because significant amounts (up to 50% in some cases) may not be absorbed from the intestine. Note that fludrocortisone, DOCA, and aldosterone are not considered glucocorticoids, and are included in this table to provide perspective on mineralocorticoid potency.

Hydrocortisone cream or ointment is available nonprescription up to 1% strength. In general, stronger forms require prescription. [1]

Physiologic replacement of glucocorticoid

Any glucocorticoid can be given in a dose that provides approximately the same glucocorticoid effects as normal cortisol production; this is referred to as physiologic, replacement, or maintenance dosing. This is approximately 6-12 mg/m²/day (m² refers to body surface area (BSA), and is a measure of body size; an average man is 1. In Physiology and Medicine, the body surface area (BSA is the measured or calculated surface of a Human body. 7 m²).

Medical uses and effects of high-dose glucocorticoids

In much higher doses (termed pharmacologic doses), glucocorticoids are used to suppress various allergic, inflammatory, and autoimmune disorders. Allergy is a disorder of the Immune system often also referred to as Atopy. Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens They are also administered as posttransplantory immunosuppressants to prevent the acute transplant rejection and the graft-versus-host disease. Transplant rejection occurs when a transplanted organ or tissue fails to be accepted by the body of the transplant recipient Graft-versus-host disease (GVHD is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize Nevertheless, they do not prevent an infection and also inhibit later reparative processes.

Some drugs used are cortisol (hydrocortisone), prednisone and dexamethasone.

Immunosuppressive mechanism

Glucocorticoids suppress the cell-mediated immunity. Cell-mediated immunity is an Immune response that does not involve Antibodies or complement but rather involves the activation of Macrophages They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and IFN-γ, the most important of which is the IL-2. Interleukin-1 (IL-1 is one of the first Cytokines ever described Interleukin-2 ( IL-2) is an Interleukin, a type of Cytokine Immune system signaling molecule that is instrumental in the body's natural response Interleukin 3 (colony-stimulating factor multiple, also known as IL3, is a human Gene. Interleukin-4, abbreviated IL-4, is a Cytokine that induces differentiation of naive helper T cells ( Th0 cells to Th2 cells Upon activation by Interleukin 5 or IL-5 is an Interleukin produced by T helper -2 cells and Mast cells. Interleukin-8 (IL-8 is a Chemokine produced by Macrophages and other cell types such as epithelial cells Smaller cytokine production reduces the T cell proliferation. Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity.

Glucocorticoids do however not only reduce T cell proliferation, another well known effect is glucocorticoid induced apoptosis. The effect is more prominent in immature T cells that still reside in the thymus, but also affect peripheral T cells. The exact mechanism underlying this glucocorticoid sensitivity still remains to elucidated.

Glucocorticoids also suppress the humoral immunity, causing B cells to express smaller amounts of IL-2 and of IL-2 receptors. The Humoral Immune Response (HIR is the aspect of immunity that is mediated by secreted Antibodies (as opposed to Cell-mediated immunity which involves B cells are Lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by The interleukin-2 receptor (IL-2R is heterotrimeric protein expressed on the surface of certain immune cells such as Lymphocytes that binds and responds to This diminishes both B cell clone expansion and antibody synthesis. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily The diminished amounts of IL-2 also causes fewer T lymphocyte cells to be activated.

Since glucocorticoid is a steroid, it regulates transcription factors; another factor it down-regulates is the expression of Fc receptors on macrophages, so there is a decreased phagocytosis of opsonised cells. A steroid is a Terpenoid Lipid characterized by a Carbon skeleton with four fused rings generally arranged in a 6-6-6-5 fashion In the field of Molecular biology, a transcription factor (sometimes called a sequence-specific DNA binding factor is a Protein that binds to specific sequences An Fc receptor is a protein found on the surface of certain cells - including Natural killer cells Macrophages Neutrophils and Mast cells - that Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that Phagocytosis is the cellular process of engulfing solid particles by the Cell membrane to form an internal Phagosome, or "food vacuole An opsonin is any molecule that acts as a binding Enhancer for the process of Phagocytosis, for example by coating the negatively-charged molecules on the membrane

Anti-inflammatory effects

Glucocorticoids influence all types of inflammatory events, no matter what their cause. They induce the lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes, preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. Annexin A1 (or Lipocortin I) is a human Protein encoded by the ANXA1 Gene. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer Phospholipases A2 (PLA2s are upstream regulators of many inflammatory processes Arachidonic acid (AA sometimes ARA is an Omega-6 fatty acid 204(ω-6 This leads to diminished eicosanoid production. In biochemistry eicosanoids are signaling molecules made by Oxygenation of twenty-carbon Essential fatty acids (EFAs The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation, Prostaglandins and Leukotrienes, are inhibited by the action of Glucocorticoids. A prostaglandin is any member of a group of Lipid compounds that are derived enzymatically from Fatty acids and have important functions in the Animal body Leukotrienes are naturally produced Eicosanoid lipid mediators, which may be responsible for the effects of an inflammatory response

Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst, and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines, etc. In biology and medicine epithelium is a tissue composed of cells that line the cavities and surfaces of structures throughout the body Cellular adhesion is the binding of a cell to another cell or to a Surface or matrix. "Emigrant" redirects here For the Butterflies, see Catopsilia. Chemotaxis, a kind of Taxis, is the phenomenon in which bodily cells bacteria, and other single-cell or Multicellular organisms direct their movements Phagocytosis is the cellular process of engulfing solid particles by the Cell membrane to form an internal Phagosome, or "food vacuole Respiratory burst (is sometimes called oxidative burst) is the rapid release of Reactive oxygen species (superoxide radical and hydrogen peroxide from different types Tissue plasminogen activator (abbreviated tPA or PLAT) is a Protein involved in the breakdown of Blood clots Specifically it is a Chemokines are a family of small Cytokines, or Proteins secreted by cells Proteins are classified as chemokines according to shared structural characteristics ) from neutrophils, macrophages, and mastocytes. Neutrophil granulocytes, generally referred to as neutrophils, are the most abundant type of White blood cells in humans and form an essential part of the Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that A mast cell (or mastocyte) is a resident cell of several types of tissues and contains many granules rich in Histamine and Heparin

Side-effects

Glucocorticoid drugs currently being used act nonselectively, so in the long run they may impair many healthy anabolic processes. To prevent this, much research has been focused recently on the elaboration of selectively-acting glucocorticoid drugs. These are the side-effects that could be prevented:

• immunosuppression
• hyperglycemia due to increased gluconeogenesis, insulin resistance, and impaired glucose tolerance ("steroid diabetes"); caution in those with diabetes mellitus
• increased skin fragility, easy bruising
• reduced bone density (osteoporosis, osteonecrosis, higher fracture risk, slower fracture repair)
• weight gain due to increased visceral and truncal fat deposition (central obesity) and appetite stimulation
• adrenal insufficiency (if used for long time and stopped suddenly without a taper)
• muscle breakdown (proteolysis), weakness; reduced muscle mass and repair
• expansion of malar fat pads and dilation of small blood vessels in skin
• anovulation, irregularity of menstrual periods
• growth failure, pubertal delay
• increased plasma amino acids, increased urea formation; negative nitrogen balance
• excitatory effect on central nervous system. Hyperglycemia, hyperglycaemia, or high blood sugar is a condition in which an excessive amount of Glucose circulates in the Blood plasma Gluconeogenesis (abreviated GNG) is a Metabolic pathway that results in the generation of Glucose from non- Carbohydrate carbon substrates such Insulin resistance is the condition in which normal amounts of Insulin are inadequate to produce a normal Insulin response from Fat, Muscle Steroid diabetes is a medical term referring to prolonged Hyperglycemia due to Glucocorticoid therapy for another medical condition Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc The skin is the outer covering of living tissue of an animal (or plant Bones are rigid organs that form part of the Endoskeleton of Vertebrates They function to move support and protect the various organs of the body produce Osteoporosis is a Disease of Bone that leads to an increased risk of fracture. "Adipose" redirects here For the Doctor Who monster see " Partners in Crime " Central obesity, the "apple-shaped" Obesity commonly referred to as belly fat, is the accumulation of Visceral fat ( fat deposited Adrenal insufficiency is a condition in which the Adrenal glands located above the Kidneys do not produce adequate amounts of steroid hormones (chemicals produced by the Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the The blood vessels are part of the Circulatory system and function to transport Blood throughout the body An anovulatory cycle is a cycle during which the ovaries fail to release an oocyte The menstrual cycle is a recurring cycle of physiologic changes that occurs in reproductive-age Females Overt menstruation (where there is blood flow from the Puberty is described as delayed when a boy or girl has passed the usual age of onset of Puberty with no physical or hormonal signs that it is beginning In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this Urea is an Organic compound with the Chemical formula ( N[[hydrogen H]]22 C[[oxygen O]] In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges.
• glaucoma due to increased cranial pressure
• cataracts

In high doses, hydrocortisone (cortisol) and those glucocorticoids with appreciable mineralocorticoid potency can exert a mineralocorticoid effect as well, although in physiologic doses this is prevented by rapid degradation of cortisol by 11β-hydroxysteroid dehydrogenase isoenzyme 2 (11β-HSD2) in mineralocorticoid target tissues. Glaucoma is a group of diseases of the Optic nerve involving loss of retinal ganglion cells in a characteristic pattern of optic neuropathy. A cataract is a clouding that develops in the crystalline lens of the Eye or in its envelope varying in degree from slight to complete opacity Hydroxysteroid (11-beta dehydrogenase 2, also known as HSD11B2, is a human Gene. Mineralocorticoid effects can include salt and water retention, extracellular fluid volume expansion, hypertension, potassium depletion, and metabolic alkalosis. Extracellular fluid (ECF usually denotes all body fluid outside of cells Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Potassium (pəˈtæsiəm is a Chemical element. It has the symbol K (kalium from qalīy Atomic number 19 and Atomic mass 39 Metabolic alkalosis is a Metabolic condition in which the PH of the blood is elevated beyond the normal range

The combination of clinical problems produced by prolonged, excess glucocorticoids, whether synthetic or endogenous, is termed Cushing's syndrome.

Adrenal suppression and withdrawal

In addition to the effects listed above, use of high-dose steroids for more than a week begins to produce suppression of the patient's adrenal glands because the exogenous glucocorticoids suppress hypothalamic corticotropin-releasing hormone (CRH) and pituitary adrenocorticotropic hormone (ACTH). In Mammals the adrenal glands (also known as suprarenal glands) are the triangle-shaped Endocrine glands that sit on top of the Kidneys their Corticotropin-releasing hormone ( CRH) originally named corticotropin-releasing factor ( CRF) and also called corticoliberin, is a Polypeptide Adrenocorticotropic hormone ( ACTH or corticotropin) is a Polypeptide Hormone produced and secreted by the Pituitary gland With prolonged suppression, the adrenal glands atrophy (physically shrink), and can take months to recover full function after discontinuation of the exogenous glucocorticoid.

During this recovery time, the patient is vulnerable to adrenal insufficiency during times of stress, such as illness. Adrenal insufficiency is a condition in which the Adrenal glands located above the Kidneys do not produce adequate amounts of steroid hormones (chemicals produced by the While there is wide individual variation in suppressive dose and time for adrenal recovery, clinical guidelines have been devised to estimate potential adrenal suppression and recovery, to reduce risk to the patient. The following is one example, but many variations exist or may be appropriate in individual circumstances.

• If a patient has been receiving daily high doses for 5 days or less, they can be abruptly stopped (or reduced to physiologic replacement if patient is adrenal-deficient). Full adrenal recovery can be assumed to occur by a week afterward.
• If high doses were used for 6-10 days, reduce to replacement dose immediately and taper over 4 more days. Adrenal recovery can be assumed to occur within 2-4 weeks of completion of steroids.
• If high doses were used for 11-30 days, cut immediately to twice replacement, and then by 25% every 4 days. Stop entirely when dose is less than half of replacement. Full adrenal recovery should occur within 1-3 months of completion of withdrawal.
• If high doses were used more than 30 days, cut dose immediately to twice replacement, and reduce by 25% each week until replacement is reached.
• Then change to oral hydrocortisone or cortisone as a single morning dose, and gradually decrease by 2. 5 mg each week. When a. m. dose is less than replacement, the return of normal basal adrenal function may be documented by checking 0800 cortisol levels prior to the morning dose; stop drugs when 0800 cortisol is 10 μg/dl. It is difficult to predict the time to full adrenal recovery after prolonged suppressive exogenous steroids; some people may take nearly a year.
• Flare-up of the underlying condition for which steroids are given may require a more gradual taper than outlined above.

See also

• Glucocorticoid receptor
• Immunosuppressive drug
• GITR (glucocorticoid-induced TNF receptor)

References

External links

• MeSH Glucocorticoids
• R. Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Bowen (2006-05-26). Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 451 - The Battle of Avarayr between Armenian rebels and the Sassanid Empire takes place Glucocorticoids. Colorado State University. Retrieved on 2008-05-11. 2008 ( MMVIII) is the current year in accordance with the Gregorian calendar, a Leap year that started on Tuesday of the Common Events 330 - Byzantium is renamed ''Nova Roma'' during a dedication ceremony but is more popularly referred to as Constantinople