Some common naturally occurring steroid hormones arecortisol (C 21H 30O 5),corticosterone (C 21H 30O 4),cortisone (C 21H 28O 5) andaldosterone (C 21H 28O 5) (cortisone andaldosterone areisomers). The main corticosteroids produced by the adrenal cortex are cortisol and aldosterone.[1]
The etymology of thecortico- part of the name refers to theadrenal cortex, which makes these steroid hormones. Thus a corticosteroid is a "cortex steroid".[citation needed]
Topical formulations are also available for theskin, eyes (uveitis), lungs (asthma), nose (rhinitis), andbowels. Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists (e.g.,ondansetron).[citation needed]
Typicalundesired effects of glucocorticoids present quite uniformly as drug-inducedCushing's syndrome. Typical mineralocorticoid side-effects arehypertension (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 causingperipheral edema,metabolic alkalosis and connective tissue weakness.[5] Wound healing or ulcer formation may be inhibited by the immunosuppressive effects.
A variety of steroid medications, from anti-allergy nasal sprays (Nasonex,Flonase) to topical skin creams, to eye drops (Tobradex), to prednisone have been implicated in the development ofcentral serous retinopathy (CSR).[6][7]
Corticosteroids have been widely used in treating people withtraumatic brain injury.[8] Asystematic review 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.[9]
In addition to their corticosteroid activity, some corticosteroids may have someprogestogenic activity and may produce sex-related side effects.[10][11][12][13]
Patients' response to inhaled corticosteroids has some basis in genetic variations. Two genes of interest are CHRH1 (corticotropin-releasing hormone receptor 1) and TBX21 (transcription factor T-bet). Both genes display some degree of polymorphic variation in humans, which may explain how some patients respond better to inhaled corticosteroid therapy than others.[14][15] However, not all asthma patients respond to corticosteroids and large sub groups of asthma patients are corticosteroid resistant.[16]
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.[17][18]
Lower arm of a 47-year-old female showing skin damage caused by topical corticosteroid use.
Use of corticosteroids has numerous side-effects, some of which may be severe:
Severeamoebic colitis:Fulminant amoebic colitis is associated with high case fatality and can occur in patients infected with the parasiteEntamoeba histolytica after exposure to corticosteroid medications.[19]
Neuropsychiatric:steroid psychosis,[20] andanxiety,[21]depression. Therapeutic doses may cause a feeling of artificial well-being ("steroid euphoria").[22] 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.[23]
Cardiovascular: Corticosteroids can cause sodium retention through a direct action on the kidney, in a manner analogous to the mineralocorticoidaldosterone. This can result in fluid retention andhypertension.
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 termedcorticosteroid-induced lipodystrophy. Due to the diversion of amino-acids to glucose, they are considered anti-anabolic, and long term therapy can cause muscle wasting (muscle atrophy).[24] Besides muscle atrophy, steroid myopathy includes muscle pains (myalgias), muscle weakness (typically of the proximal muscles), serum creatine kinase normal, EMG myopathic, and some have type II (fast-twitch/glycolytic) fibre atrophy.[25]
Skeletal:Steroid-induced osteoporosis may be a side-effect of long-term corticosteroid use.[28][29][30] Use of inhaled corticosteroids among children with asthma may result in decreased height.[31]
Gastro-intestinal: While cases ofcolitis 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 causingpeptic ulceration is relatively poor except for high doses taken for over a month,[32] the majority of doctors as of 2010[update] still believe this is the case, and would consider protective prophylactic measures.[33]
Eyes: chronic use may predispose tocataract andglaucoma. Clinical and experimental evidence indicates that corticosteroids can cause permanent eye damage by inducing central serous retinopathy (CSR, also known as central serous chorioretinopathy, CSC).[34] This should be borne in mind when treating patients withoptic neuritis. There is experimental and clinical evidence that, at least inoptic neuritis speed of treatment initiation is important.[35]
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, notablycandidiasis.[36]
Pregnancy: Corticosteroids have a low but significantteratogenic effect, causing a few birth defects per 1,000 pregnant women treated. Corticosteroids are thereforecontraindicated in pregnancy.[37]
Habituation: Topical steroid addiction (TSA) orred burning skin 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).[38][39] 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.[40]
In children the short term use of steroids by mouth increases the risk of vomiting, behavioral changes, and sleeping problems.[41]
Dysphonia: Inhaled corticosteroids are used for treatment of asthma as a standard treatment. This can cause local adverse effects like vocal cord dysfunction.[42]
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".[43][44]
The highlighted steroids are often used in the screening of allergies to topical steroids.[45]
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.
Initially hailed as amiracle cure and liberally prescribed during the 1950s, steroid treatment brought aboutadverse events of such a magnitude that the next major category of anti-inflammatory drugs, thenonsteroidal anti-inflammatory drugs (NSAIDs), was so named in order to demarcate from the opprobrium.[56]
Lewis Sarett ofMerck & Co. was the first to synthesize cortisone, using a 36-step process that started with deoxycholic acid, which was extracted fromoxbile.[57] The low efficiency of converting deoxycholic acid into cortisone led to a cost of US$200 per gram in 1947.Russell Marker, atSyntex, discovered a much cheaper and more convenient starting material,diosgenin from wildMexican yams. His conversion of diosgenin intoprogesterone by a four-step process now known asMarker degradation was an important step in mass production of all steroidal hormones, including cortisone and chemicals used inhormonal contraception.[58]
In 1952, D.H. Peterson and H.C. Murray ofUpjohn developed a process that usedRhizopus mold to oxidize progesterone into a compound that was readily converted to cortisone.[59] 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[when?], falling to $0.46 per gram by 1980.Percy Julian's research also aided progress in the field.[60] The exact nature of cortisone's anti-inflammatory action remained a mystery for years after, however, until theleukocyte adhesion cascade and the role ofphospholipase A2 in the production ofprostaglandins andleukotrienes was fully understood in the early 1980s.[citation needed]
Corticosteroids were votedAllergen of the Year in 2005 by the American Contact Dermatitis Society.[61]
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^Brook EM, Hu CH, Kingston KA, Matzkin EG (March 2017). "Corticosteroid Injections: A Review of Sex-Related Side Effects".Orthopedics.40 (2):e211 –e215.doi:10.3928/01477447-20161116-07.PMID27874912.
^Luzzani F, Gallico L, Glässer A (1982). "In vitro and ex vivo binding to uterine progestin receptors of the rat as a tool to assay progestational activity of glucocorticoids".Methods and Findings in Experimental and Clinical Pharmacology.4 (4):237–242.PMID7121132.
^Cunningham GR, Goldzieher JW, de la Pena A, Oliver M (January 1978). "The mechanism of ovulation inhibition by triamcinolone acetonide".The Journal of Clinical Endocrinology and Metabolism.46 (1):8–14.doi:10.1210/jcem-46-1-8.PMID376542.
^Sumino K, Bacharier LB, Taylor J, Chadwick-Mansker K, Curtis V, Nash A, et al. (January 2020). "A Pragmatic Trial of Symptom-Based Inhaled Corticosteroid Use in African-American Children with Mild Asthma".The Journal of Allergy and Clinical Immunology. In Practice.8 (1): 176–185.e2.doi:10.1016/j.jaip.2019.06.030.PMID31371165.S2CID199380330.
^Donihi AC, Raval D, Saul M, Korytkowski MT, DeVita MA (2006). "Prevalence and predictors of corticosteroid-related hyperglycemia in hospitalized patients".Endocrine Practice.12 (4):358–362.doi:10.4158/ep.12.4.358.PMID16901792.
^Martínek J, Hlavova K, Zavada F, Seifert B, Rejchrt S, Urban O, Zavoral M (October 2010). ""A surviving myth"--corticosteroids are still considered ulcerogenic by a majority of physicians".Scandinavian Journal of Gastroenterology.45 (10):1156–1161.doi:10.3109/00365521.2010.497935.PMID20569095.S2CID5140517.
^Fukushima C, Matsuse H, Tomari S, Obase Y, Miyazaki Y, Shimoda T, Kohno S (June 2003). "Oral candidiasis associated with inhaled corticosteroid use: comparison of fluticasone and beclomethasone".Annals of Allergy, Asthma & Immunology.90 (6):646–651.doi:10.1016/S1081-1206(10)61870-4.PMID12839324.
^Shepard TH, Brent RL, Friedman JM, Jones KL, Miller RK, Moore CA, Polifka JE (April 2002). "Update on new developments in the study of human teratogens".Teratology.65 (4):153–161.doi:10.1002/tera.10032.PMID11948561.
^Rietschel RL (2007).Fisher's Contact Dermatitis, 6/e. Hamilton, Ont: BC Decker Inc. p. 256.ISBN978-1-55009-378-0.
^Coopman S, Degreef H, Dooms-Goossens A (July 1989). "Identification of cross-reaction patterns in allergic contact dermatitis from topical corticosteroids".The British Journal of Dermatology.121 (1):27–34.doi:10.1111/j.1365-2133.1989.tb01396.x.PMID2757954.S2CID40425526.
^Wolverton SE (2001).Comprehensive Dermatologic Drug Therapy. WB Saunders. p. 562.
^Khan MO, Park KK, Lee HJ (2005). "Antedrugs: an approach to safer drugs".Current Medicinal Chemistry.12 (19):2227–2239.doi:10.2174/0929867054864840.PMID16178782.
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