Corticosteroids are a class of
steroid hormones that are produced in the
adrenal cortex of
vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids,
glucocorticoids and
mineralocorticoid
Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances ( electrolyte balance and fluid balance). The primary ...
s, are involved in a wide range of
physiological
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemica ...
processes, including
stress response,
immune response
An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which coul ...
, and regulation of
inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
,
carbohydrate
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may o ...
metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...
,
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
catabolism, blood
electrolyte levels, and behavior.
Some common naturally occurring steroid hormones are
cortisol (),
corticosterone
Corticosterone, also known as 17-deoxycortisol and 11β,21-dihydroxyprogesterone, is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands. It is of minor importance in humans, except in the very rar ...
(),
cortisone () and
aldosterone (). (Note that cortisone and aldosterone are
isomers
In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. ...
.) The main corticosteroids produced by the adrenal cortex are cortisol and aldosterone.
Classes
*
Glucocorticoids such as
cortisol affect carbohydrate, fat, and protein metabolism, and have
anti-inflammatory,
immunosuppressive,
anti-proliferative, and
vasoconstrictive effects.
Anti-inflammatory effects are mediated by blocking the action of
inflammatory mediators (
transrepression In the field of molecular biology, transrepression is a process whereby one protein represses (i.e., inhibits) the activity of a second protein through a protein-protein interaction. Since this repression occurs between two different protein mole ...
) and inducing anti-inflammatory mediators (
transactivation).
Immunosuppressive effects are mediated by suppressing
delayed hypersensitivity reactions by direct action on
T-lymphocytes.
Anti-proliferative effects are mediated by inhibition of
DNA synthesis and
epidermal cell turnover.
Vasoconstrictive effects are mediated by inhibiting the action of inflammatory mediators such as
histamine
Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discover ...
.
*
Mineralocorticoid
Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances ( electrolyte balance and fluid balance). The primary ...
s such as
aldosterone are primarily involved in the regulation of
electrolyte and water balance by modulating
ion transport
In biology, a transporter is a transmembrane protein that moves ions (or other small molecules) across a biological membrane to accomplish many different biological functions including, cellular communication, maintaining homeostasis, energy produc ...
in the
epithelial cells
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...
of the
renal tubules of the
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
.
Medical uses
Synthetic
pharmaceutical drug
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...
s with corticosteroid-like effects are used in a variety of conditions, ranging from
brain tumor
A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and seco ...
s to
skin diseases.
Dexamethasone
Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ...
and its derivatives are almost pure glucocorticoids, while
prednisone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect.
Fludrocortisone
Fludrocortisone, sold under the brand name Florinef, among others, is a corticosteroid used to treat adrenogenital syndrome, postural hypotension, and adrenal insufficiency. In adrenal insufficiency, it is generally taken together with hydroco ...
(Florinef) is a synthetic mineralocorticoid.
Hydrocortisone (cortisol) is typically used for replacement therapy, ''e.g.'' for
adrenal insufficiency
Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal gland normally secretes glucocorticoids (primarily cortisol), mineralocorticoids (primarily aldosterone), and andro ...
and
congenital adrenal hyperplasia
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex ...
.
Medical conditions treated with systemic corticosteroids:
*
Allergy
Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...
and
respirology
Pulmonology (, , from Latin ''pulmō, -ōnis'' "lung" and the Greek suffix "study of"), pneumology (, built on Greek πνεύμων "lung") or pneumonology () is a medical specialty that deals with diseases involving the respiratory tra ...
medicine
**
Asthma
Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
(severe exacerbations)
**
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...
(COPD)
**
Allergic rhinitis
Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, ...
**
Atopic dermatitis
**
Hives
**
Angioedema
**
Anaphylaxis
Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...
**
Food allergies
**
Drug allergies
A drug allergy is an allergy to a drug, most commonly a medication, and is a form of adverse drug reaction. Medical attention should be sought immediately if an allergic reaction is suspected.
An allergic reaction will not occur on the first exp ...
**
Nasal polyps
**
Hypersensitivity pneumonitis
**
Sarcoidosis
Sarcoidosis (also known as ''Besnier-Boeck-Schaumann disease'') is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly af ...
**
Eosinophilic pneumonia
** Some other types of
pneumonia
Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severit ...
(in addition to the traditional
antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
treatment protocols)
**
Interstitial lung disease
*
Dermatology
Dermatology is the branch of medicine dealing with the skin.''Random House Webster's Unabridged Dictionary.'' Random House, Inc. 2001. Page 537. . It is a speciality with both medical and surgical aspects. A dermatologist is a specialist medica ...
**
Pemphigus vulgaris
**
Contact dermatitis
*
Endocrinology
Endocrinology (from '' endocrine'' + '' -ology'') is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions known as hormones. It is also concerned with the integration of developmental event ...
(usually at physiologic doses)
**
Addison's disease
Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrena ...
**
Adrenal insufficiency
Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal gland normally secretes glucocorticoids (primarily cortisol), mineralocorticoids (primarily aldosterone), and andro ...
**
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex ...
*
Gastroenterology
Gastroenterology (from the Greek gastḗr- “belly”, -énteron “intestine”, and -logía "study of") is the branch of medicine focused on the digestive system and its disorders. The digestive system consists of the gastrointestinal tract ...
**
Ulcerative colitis
**
Crohn's disease
**
Autoimmune hepatitis
Autoimmune hepatitis, formerly known as lupoid hepatitis, plasma cell hepatitis, or autoimmune chronic active hepatitis, is a chronic, autoimmune disease of the liver that occurs when the body's immune system attacks liver cells, causing the live ...
*
Hematology
Hematology ( always spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to blood. It involves treating diseases that affect the produc ...
**
Lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include en ...
**
Leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
**
Hemolytic anemia
**
Idiopathic thrombocytopenic purpura
Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is a type of thrombocytopenic purpura defined as an isolated low platelet count with a normal bone marrow in the absence of oth ...
**
Multiple Myeloma
Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, ...
*
Rheumatology
Rheumatology (Greek ''ῥεῦμα'', ''rheûma'', flowing current) is a branch of medicine devoted to the diagnosis and management of disorders whose common feature is inflammation in the bones, muscles, joints, and internal organs. Rheumatolog ...
/
Immunology
Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see ther ...
**
Rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are inv ...
eas
**
Systemic lupus erythematosus
**
Polymyalgia rheumatica
Polymyalgia rheumatica (PMR) is a syndrome experienced as pain or stiffness, usually in the neck, shoulders, upper arms, and hips, but which may occur all over the body. The pain can be sudden or can occur gradually over a period. Most people wi ...
**
Polymyositis
Polymyositis (PM) is a type of chronic inflammation of the muscles (inflammatory myopathy) related to dermatomyositis and inclusion body myositis. Its name means "inflammation of many muscles" ('' poly-'' + '' myos-'' + '' -itis''). The inflam ...
**
Dermatomyositis
Dermatomyositis (DM) is a long-term inflammatory disorder which affects skin and the muscles. Its symptoms are generally a skin rash and worsening muscle weakness over time. These may occur suddenly or develop over months. Other symptoms may inc ...
**
Polyarteritis
Polyarteritis nodosa (PAN) is a systemic necrotizing inflammation of blood vessels (vasculitis) affecting medium-sized muscular arteries, typically involving the arteries of the kidneys and other internal organs but generally sparing the lungs' ...
**
Vasculitis
Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused ...
*
Ophthalmology
Ophthalmology ( ) is a surgical subspecialty within medicine that deals with the diagnosis and treatment of eye disorders.
An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Following a me ...
**
Uveitis
**
Optic neuritis
**
Keratoconjunctivitis
Keratoconjunctivitis is inflammation ("-itis") of the cornea and conjunctiva.
When only the cornea is inflamed, it is called '' keratitis''; when only the conjunctiva is inflamed, it is called ''conjunctivitis''.
Causes
There are several potent ...
* Other conditions
**
Multiple sclerosis relapses
**
Organ transplantation
**
Nephrotic syndrome
**
Chronic hepatitis (
flare ups)
**
Cerebral edema
**
IgG4-related disease
**
Prostate cancer
**
Tendinosis
**
Lichen planus
Topical formulations are also available for the
skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other animal coverings, such as the arthropod exoskeleton, have different ...
, eyes (
uveitis), lungs (
asthma
Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
), nose (
rhinitis), and
bowels. Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists (''e.g.''
ondansetron).
Typical
undesired effects of glucocorticoids present quite uniformly as drug-induced
Cushing's syndrome. Typical mineralocorticoid side-effects are
hypertension (abnormally high blood pressure), steroid induced diabetes mellitus, psychosis, poor sleep,
hypokalemia (low potassium levels in the blood),
hypernatremia (high sodium levels in the blood) without causing
peripheral edema,
metabolic alkalosis
Metabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range (7.35–7.45). This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct resu ...
and connective tissue weakness. Wound healing or ulcer formation may be inhibited by the immunosuppressive effects.
Clinical and experimental evidence indicates that corticosteroids can cause permanent eye damage by inducing
central serous retinopathy
Central serous chorioretinopathy (CSC or CSCR), also known as central serous retinopathy (CSR), is an eye disease that causes visual impairment, often temporary, usually in one eye. When the disorder is active it is characterized by leakage of f ...
(CSR, also known as central serous chorioretinopathy, CSC). This should be borne in mind when treating patients with
optic neuritis. There is experimental and clinical evidence that, at least in
optic neuritis speed of treatment initiation is important.
A variety of steroid medications, from anti-allergy nasal sprays (
Nasonex
Mometasone, also known as mometasone y 3 s, is a steroid medication used to treat certain skin conditions, hay fever, and asthma. Specifically it is used to prevent rather than treat asthma attacks. It can be applied to the skin, inhaled, or use ...
,
Flonase) to topical skin creams, to eye drops (
Tobradex), to prednisone have been implicated in the development of CSR.
Corticosteroids have been widely used in treating people with
traumatic brain injury. A
systematic review
A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on t ...
identified 20 randomised controlled trials and included 12,303 participants, then compared patients who received corticosteroids with patients who received no treatment. The authors recommended people with traumatic head injury should not be routinely treated with corticosteroids.
Pharmacology
Corticosteroids act as
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...
s of the
glucocorticoid receptor and/or the
mineralocorticoid receptor.
In addition to their corticosteroid activity, some corticosteroids may have some
progestogenic activity and may produce sex-related side effects.
Pharmacogenetics
Asthma
Patients' response to inhaled corticosteroids has some basis in genetic variations. Two genes of interest are CHRH1 (
corticotropin-releasing hormone receptor 1
Corticotropin-releasing hormone receptor 1 (CRHR1) is a protein, also known as CRF1, with the latter (CRF1) now being the IUPHAR-recommended name. In humans, CRF1 is encoded by the ''CRHR1'' gene at region 17q21.31, beside micrototubule-associa ...
) and TBX21 (
transcription factor T-bet
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
). Both genes display some degree of polymorphic variation in humans, which may explain how some patients respond better to inhaled corticosteroid therapy than others. However, not all asthma patients respond to corticosteroids and large sub groups of asthma patients are corticosteroid resistant.
A study funded by the Patient-Centered Outcomes Research Institute of children and teens with mild persistent asthma found that using the control inhaler as needed worked the same as daily use in improving asthma control, number of asthma flares, how well the lungs work, and quality of life. Children and teens using the inhaler as needed used about one-fourth the amount of corticosteroid medicine as children and teens using it daily.
Adverse effects
Use of corticosteroids has numerous side-effects, some of which may be severe:
* Severe amebic colitis: Fulminant amebic colitis is associated with high case fatality and can occur in patients infected with the parasite ''
Entamoeba histolytica'' after exposure to corticosteroid medications.
* Neuropsychiatric:
steroid psychosis,
and
anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
,
depression. Therapeutic doses may cause a feeling of artificial well-being ("steroid euphoria"). The neuropsychiatric effects are partly mediated by sensitization of the body to the actions of adrenaline. Therapeutically, the bulk of corticosteroid dose is given in the morning to mimic the body's diurnal rhythm; if given at night, the feeling of being energized will interfere with sleep. An extensive review is provided by Flores and Gumina.
* Cardiovascular: Corticosteroids can cause sodium retention through a direct action on the kidney, in a manner analogous to the mineralocorticoid
aldosterone. This can result in fluid retention and
hypertension.
* Metabolic: Corticosteroids cause a movement of body fat to the face and torso, resulting in "
moon face", "buffalo hump", and "pot belly" or "beer belly", and cause movement of body fat away from the limbs. This has been termed
corticosteroid-induced lipodystrophy
Corticosteroid-induced lipodystrophy (CIL) is a condition of abnormal fat deposition caused by corticosteroid medications. Fat accumulates in the facial area ("moon face"), dorsocervical region ("buffalo hump"), and abdominal area ("pot belly" or ...
. Due to the diversion of amino-acids to glucose, they are considered anti-anabolic, and long term therapy can cause muscle wasting.
* Endocrine: By increasing the production of glucose from amino-acid breakdown and opposing the action of insulin, corticosteroids can cause
hyperglycemia,
insulin resistance and
diabetes mellitus
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
.
* Skeletal:
Steroid-induced osteoporosis may be a side-effect of long-term corticosteroid use. Use of inhaled corticosteroids among children with asthma may result in decreased height.
* Gastro-intestinal: While cases of
colitis have been reported, corticosteroids are often prescribed when the colitis, although due to suppression of the immune response to pathogens, should be considered only after ruling out infection or microbe/fungal overgrowth in the gastrointestinal tract. While the evidence for corticosteroids causing
peptic ulceration is relatively poor except for high doses taken for over a month,
the majority of doctors still believe this is the case, and would consider protective prophylactic measures.
* Eyes: chronic use may predispose to
cataract and
glaucoma
Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for aqueous humor, fluid withi ...
.
* Vulnerability to infection: By suppressing immune reactions (which is one of the main reasons for their use in allergies), steroids may cause infections to flare up, notably
candidiasis.
* Pregnancy: Corticosteroids have a low but significant
teratogenic
Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The related ...
effect, causing a few birth defects per 1,000 pregnant women treated. Corticosteroids are therefore
contraindicated in pregnancy.
* Habituation: Topical steroid addiction (TSA) or
red burning skin
Topical steroid withdrawal, also known as red burning skin and steroid dermatitis, has been reported in people who apply topical steroids for 2 weeks or longer and then discontinue use. Symptoms affect the skin and include redness, a burning sen ...
has been reported in long-term users of topical steroids (users who applied topical steroids to their skin over a period of weeks, months, or years).
TSA is characterised by uncontrollable, spreading dermatitis and worsening skin inflammation which requires a stronger topical steroid to get the same result as the first prescription. When topical steroid medication is lost, the skin experiences redness, burning, itching, hot skin, swelling, and/or oozing for a length of time. This is also called 'red skin syndrome' or 'topical steroid withdrawal' (TSW). After the withdrawal period is over the atopic dermatitis can cease or is less severe than it was before.
* In children the short term use of steroids by mouth increases the risk of vomiting, behavioral changes, and sleeping problems.
Biosynthesis
The corticosteroids are synthesized from
cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell memb ...
within the
adrenal cortex.
Most steroidogenic reactions are catalysed by
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s of the
cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
family. They are located within the
mitochondria
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
and require
adrenodoxin as a cofactor (except
21-hydroxylase and
17α-hydroxylase).
Aldosterone and
corticosterone
Corticosterone, also known as 17-deoxycortisol and 11β,21-dihydroxyprogesterone, is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands. It is of minor importance in humans, except in the very rar ...
share the first part of their biosynthetic pathway. The last part is mediated either by the
aldosterone synthase (for
aldosterone) or by the
11β-hydroxylase (for
corticosterone
Corticosterone, also known as 17-deoxycortisol and 11β,21-dihydroxyprogesterone, is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands. It is of minor importance in humans, except in the very rar ...
). These enzymes are nearly identical (they share 11β-hydroxylation and 18-hydroxylation functions), but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the
zona glomerulosa
The ''zona glomerulosa'' (sometimes, glomerular zone) of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the renal capsule. Its cells are ovoid and arranged in clusters or arches (''glomus'' is Latin ...
at the outer edge of the
adrenal cortex; 11β-hydroxylase is found in the
zona fasciculata and
zona glomerulosa
The ''zona glomerulosa'' (sometimes, glomerular zone) of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the renal capsule. Its cells are ovoid and arranged in clusters or arches (''glomus'' is Latin ...
.
Classification of corticosteroids
By chemical structure
In general, corticosteroids are grouped into four classes, based on chemical structure. Allergic reactions to one member of a class typically indicate an intolerance of all members of the class. This is known as the "Coopman classification".
The highlighted steroids are often used in the screening of allergies to topical steroids.
Group A – Hydrocortisone type
Hydrocortisone,
hydrocortisone acetate,
cortisone acetate
Cortisone acetate (brand names Adreson, Cortison, Cortisone, Cortisone Acetate, Cortone, Cortistab, Cortisyl, others) is a synthetic glucocorticoid corticosteroid and corticosteroid ester which is marketed (under prescription) in many countries ...
,
tixocortol pivalate
Tixocortol pivalate is a corticosteroid. It has anti-inflammatory properties similar to hydrocortisone. It is marketed under the brand name Pivalone.
It is sometimes used in patch testing in atopic dermatitis.
See also
* Tixocortol
Tixocor ...
,
prednisolone
Prednisolone is a steroid medication used to treat certain types of allergies, inflammatory conditions, autoimmune disorders, and cancers. Some of these conditions include adrenocortical insufficiency, high blood calcium, rheumatoid arth ...
,
methylprednisolone, and
prednisone.
Group B – Acetonides (and related substances)
Amcinonide
Amcinonide (trade name Cyclocort) is a topical glucocorticoid used to treat itching, redness and swelling associated with several dermatologic conditions such as atopic dermatitis and allergic contact dermatitis.
Amcinonide can also be classifie ...
,
budesonide,
desonide,
fluocinolone acetonide,
fluocinonide,
halcinonide
Halcinonide is a high potency corticosteroid, in group II (second most potent group) under US classification. It is used topical
A topical medication is a medication that is applied to a particular place on or in the body. Most often topica ...
, and
triamcinolone acetonide.
Group C – Betamethasone type
Beclometasone,
betamethasone
Betamethasone is a steroid medication. It is used for a number of diseases including rheumatic disorders such as rheumatoid arthritis and systemic lupus erythematosus, skin diseases such as dermatitis and psoriasis, allergic conditions such ...
,
dexamethasone
Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ...
,
fluocortolone,
halometasone, and
mometasone.
Group D – Esters
=Group D1 – Halogenated (less labile)
=
Alclometasone dipropionate,
betamethasone dipropionate
Betamethasone dipropionate is a glucocorticoid steroid with anti-inflammatory and immunosuppressant, immunosuppressive abilities. It is applied as a topical cream, ointment, lotion or gel (Diprolene) to treat pruritus, itching and other skin cond ...
,
betamethasone valerate
Betamethasone valerate is a synthetic glucocorticoid ester. It is the 17-valerate ester of betamethasone
Betamethasone is a steroid medication. It is used for a number of diseases including rheumatic disorders such as rheumatoid arthritis ...
,
clobetasol propionate,
clobetasone butyrate,
fluprednidene acetate, and
mometasone furoate.
=Group D2 – Labile prodrug esters
=
Ciclesonide,
cortisone acetate
Cortisone acetate (brand names Adreson, Cortison, Cortisone, Cortisone Acetate, Cortone, Cortistab, Cortisyl, others) is a synthetic glucocorticoid corticosteroid and corticosteroid ester which is marketed (under prescription) in many countries ...
,
hydrocortisone aceponate,
hydrocortisone acetate,
hydrocortisone buteprate,
hydrocortisone butyrate
Hydrocortisone butyrate is a corticosteroid that comes in one of the following forms:
* '' Hydrocortisone-17-butyrate'' —
* '' Hydrocortisone-21-butyrate'' —
It is a group IV corticosteroid under US classification.
See also
* Cortisol
...
,
hydrocortisone valerate
Hydrocortisone valerate is a synthetic glucocorticoid corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main class ...
,
prednicarbate, and
tixocortol pivalate
Tixocortol pivalate is a corticosteroid. It has anti-inflammatory properties similar to hydrocortisone. It is marketed under the brand name Pivalone.
It is sometimes used in patch testing in atopic dermatitis.
See also
* Tixocortol
Tixocor ...
.
By route of administration
Topical steroids
For use topically on the skin, eye, and
mucous membranes.
Topical corticosteroids are divided in potency classes I to IV in most countries (A to D in Japan). Seven categories are used in the United States to determine the level of potency of any given topical corticosteroid.
Inhaled steroids
For nasal mucosa, sinuses, bronchi, and lungs.
This group includes:
*
Flunisolide
*
Fluticasone furoate
Fluticasone furoate, sold under the brand name Flonase Sensimist and formerly Veramyst, among others, is a corticosteroid for the treatment of non-allergic and allergic rhinitis administered by a nasal spray. It is also available as an inhaled ...
[
* Fluticasone propionate][
* Triamcinolone acetonide][
* Beclomethasone dipropionate][
* Budesonide][
* Mometasone furoate
* Ciclesonide
There also exist certain combination preparations such as Advair Diskus in the United States, containing fluticasone propionate and salmeterol (a long-acting bronchodilator), and ]Symbicort
Budesonide/formoterol, sold under the brand name Symbicort among others, is a fixed-dose combination medication used in the management of asthma or chronic obstructive pulmonary disease (COPD). It contains budesonide, a steroid and formoterol, ...
, containing budesonide and formoterol fumarate dihydrate (another long-acting bronchodilator).[ They are both approved for use in children over 12 years old.
]
Oral forms
Such as prednisone, prednisolone, methylprednisolone, or dexamethasone
Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ...
.
Systemic forms
Available in injectables for intravenous and parenteral routes.
History
Tadeusz Reichstein, Edward Calvin Kendall. and Philip Showalter Hench
Philip Showalter Hench (February 28, 1896 – March 30, 1965) was an American physician. Hench, along with his Mayo Clinic co-worker Edward Calvin Kendall and Swiss chemist Tadeus Reichstein was awarded the Nobel Prize for Physiology or Medicine ...
were awarded the Nobel Prize
The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...
for Physiology
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemic ...
and Medicine
Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pr ...
in 1950 for their work on hormones of the adrenal cortex, which culminated in the isolation of cortisone.
Initially hailed as a miracle
A miracle is an event that is inexplicable by natural or scientific lawsOne dictionary define"Miracle"as: "A surprising and welcome event that is not explicable by natural or scientific laws and is therefore considered to be the work of a divi ...
cure and liberally prescribed during the 1950s, steroid treatment brought about adverse events of such a magnitude that the next major category of anti-inflammatory drugs, the nonsteroidal anti-inflammatory drugs (NSAIDs), was so named in order to demarcate from the opprobrium. Corticosteroids were voted Allergen of the Year Allergen of the Year is an annual award voted upon by the American Contact Dermatitis Society. This is "designed to draw attention to allergens that are very common, under-recognized, merit more attention because they are causing significant allergi ...
in 2005 by the American Contact Dermatitis Society.
Lewis Sarett of Merck & Co. was the first to synthesize cortisone, using a 36-step process that started with deoxycholic acid, which was extracted from ox bile
Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bi ...
. The low efficiency of converting deoxycholic acid into cortisone led to a cost of US$200 per gram. Russell Marker, at Syntex, discovered a much cheaper and more convenient starting material, diosgenin
Diosgenin, a phytosteroid sapogenin, is the product of hydrolysis by acids, strong bases, or enzymes of saponins, extracted from the tubers of '' Dioscorea'' wild yam species, such as the Kokoro. The sugar-free ( aglycone) product of such hy ...
from wild Mexican yams. His conversion of diosgenin into progesterone by a four-step process now known as Marker degradation was an important step in mass production of all steroidal hormones, including cortisone and chemicals used in hormonal contraception.
In 1952, D.H. Peterson and H.C. Murray of Upjohn
The Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 in Hastings, Michigan, by Dr. William E. Upjohn who was an 1875 graduate of the University of Michigan medical school. The company was originally formed to make ''fria ...
developed a process that used '' Rhizopus'' mold to oxidize progesterone into a compound that was readily converted to cortisone. The ability to cheaply synthesize large quantities of cortisone from the diosgenin in yams resulted in a rapid drop in price to US$6 per gram, falling to $0.46 per gram by 1980. Percy Julian's research also aided progress in the field.[Julian, Percy L., Cole, John Wayne, Meyer, Edwin W., and Karpel, William J. (1956) "Preparation of Cortisone". U. S. Patent 2,752,339] The exact nature of cortisone's anti-inflammatory action remained a mystery for years after, however, until the leukocyte adhesion cascade and the role of phospholipase A2 in the production of prostaglandins and leukotrienes was fully understood in the early 1980s.
Etymology
The '' cortico-'' part of the name refers to the adrenal cortex, which makes these steroid hormones. Thus a corticosteroid is a "cortex steroid".
See also
* List of corticosteroids
This is a list of corticosteroids (glucocorticoids and mineralocorticoids) or derivatives of cortisol (hydrocortisone). Most esters of these corticosteroids are not included in this list; for esters, see here instead.
The most common structural ...
* List of corticosteroid cyclic ketals
This is a list of corticosteroid cyclic ketals, including cyclic ketals (cyclic acetals) of steroidal glucocorticoids and mineralocorticoids. They are almost all C16α,17α cyclic ketals of corticosteroids. One of the most widely used corticoster ...
* List of corticosteroid esters
* List of steroid abbreviations
The steroid hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hor ...
References
{{Authority control
Corticosteroids
Endocrinology
Hormones
Steroid hormones
Steroids
World Anti-Doping Agency prohibited substances