This article was automatically translated from the original Turkish version.
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Corticosteroids are synthetic analogs of naturally occurring steroid hormones produced by the adrenal cortex, including glucocorticoids and mineralocorticoids. Since their discovery, they have been used across nearly all fields of medicine and can be administered via various routes. These synthetic hormones possess varying degrees of glucocorticoid and mineralocorticoid activity. Glucocorticoids primarily participate in metabolism and exhibit immunosuppressive, anti-inflammatory, and vasoconstrictive effects. Mineralocorticoids regulate electrolyte and water balance by influencing ion transport in renal tubular epithelial cells. The effects of glucocorticoids are mediated by cortisol; pharmacologically, cortisol is known as hydrocortisone and is primarily responsible for maintaining blood glucose levels during the stress response. Glucocorticoid activity is evaluated relative to cortisol, and differences among corticosteroids are attributed to variations in their chemical structures. For example, prednisone and prednisolone exhibit 4 to 5 times greater anti-inflammatory and carbohydrate metabolism effects than cortisol but have lower potential for water and sodium retention. Halogenated derivatives such as betamethasone and dexamethasone possess 25 to 40 times greater glucocorticoid activity than cortisol with minimal mineralocorticoid effects. These structural differences enable a range of therapeutic options in clinical practice with varying potencies and durations of action.
Structures of Cortisone and Its Derivatives (ResearchGate)
Based on the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), the cost-effectiveness of four different treatment strategies was evaluated for patients with hypertension and three or more cardiovascular risk factors from the perspective of the United Kingdom (NHS) and Sweden (societal perspective). The compared strategies were: amlodipine-based therapy plus atorvastatin, atenolol-based therapy plus atorvastatin, amlodipine-based therapy alone, and atenolol-based therapy alone. Using a Markov model based on ASCOT data, long-term costs, mortality, and quality-of-life impacts of events such as myocardial infarction, stroke, and revascularization procedures were calculated. Patients were followed for life after a three-year treatment period. The combination of amlodipine and atorvastatin was the most effective and most expensive option. The incremental cost per quality-adjusted life year (QALY) gained with this combination was estimated at £11,965 in the United Kingdom and €8,591 in Sweden. Amlodipine-based therapy was found to be more cost-effective than atenolol-based therapy, while the atenolol plus atorvastatin combination was dominated. The results indicate that the use of amlodipine with atorvastatin represents a cost-effective approach for this patient group according to thresholds accepted by NICE and the Swedish Health Council.
In a retrospective analysis conducted in tertiary healthcare settings in Türkiye, the average direct cost per patient for asthma exacerbations was calculated at €214.90. The study evaluated costs associated with 294 emergency visits by patients with persistent asthma, including medication therapy, non-pharmacological interventions, healthcare utilization, emergency department visits, laboratory tests, and specialist consultations. Findings showed that costs increased significantly with the severity of exacerbations: average costs were €128.60 for mild attacks, €172.60 for moderate attacks, and up to €308.20 for severe attacks. Costs for patients admitted for inpatient care were nearly five times higher than for those managed as outpatients. Additionally, healthcare expenditures for patients with uncontrolled asthma were nearly double those for patients with controlled asthma. These data demonstrate that the economic burden of asthma in Türkiye is largely associated with the level of disease control and the severity of exacerbations. Insufficient use of inhaled corticosteroids in asthma treatment increases the frequency of exacerbations and emergency department visits, thereby raising direct costs. Therefore, implementing healthcare policies such as achieving disease control during stable periods, rational prescribing, and limiting hospital admissions to only necessary cases plays a critical role in reducing economic burden at both individual and societal levels.
In clinical practice, the term “corticosteroids” typically refers to glucocorticoid effects. Glucocorticoids are the primary stress hormones that regulate many physiological processes essential for life. Corticosteroids are among the most commonly prescribed drug classes worldwide, with an estimated annual market exceeding $10 billion USD. Approximately 1% of the adult population in the United Kingdom receives oral glucocorticoids at any given time. Indications for corticosteroid therapy are highly diverse and generally fall into categories such as infectious and inflammatory disorders, allergic and autoimmune diseases, shock, hypercalcemia treatment, diuresis enhancement, treatment of pathological hypoglycemia, suppression of excessive adrenal secretion, prevention of graft rejection, and management of neurological, hematological, dermatological conditions, and corticosteroid replacement therapy.
Over the past 20 years, long-term (≥3 months) oral glucocorticoid (GC) prescriptions in the United Kingdom have increased by 34%. Analysis of health data shows that approximately 0.75% of the general population receives long-term GC therapy, rising from 0.59% in 1989 to 0.79% in 2008. While long-term GC prescriptions have increased in patients with rheumatoid arthritis (RA) and polymyalgia rheumatica/giant cell arteritis (PMR/GCA), they have decreased in patients with asthma, COPD, and Crohn’s disease, and remained stable in ulcerative colitis. However, when only newly diagnosed patients were analyzed, a decline in long-term GC use was observed in RA and ulcerative colitis patients. This trend indicates evolving treatment approaches among physicians over time.
In a study conducted by Istanbul University on hospitalized patients in Türkiye, it was determined that 10.6% of patients used corticosteroids (CS). CS use was most concentrated in pulmonary diseases (47.6%), rheumatology (40.6%), and transplant units (38.5%). The mean age of patients receiving CS was 62.3 years, and 57.8% were male. However, only 43.9% of CS users underwent hepatitis B virus (HBV) screening. Among those screened, the rate of appropriate prophylaxis remained at 18.1%, and protective measures remained inadequate even in patients at high risk for HBV reactivation. Although long-term (4 weeks or longer) CS users include individuals at high risk for HBV reactivation, the number of patients undergoing regular HBV monitoring is very low. This study conducted by Istanbul University highlights significant gaps in HBV screening and prophylaxis despite widespread CS use. This underscores the importance of increasing HBV screening and implementing appropriate preventive measures to reduce infection risks in CS-treated patients.
Corticosteroids have both endocrine and non-endocrine applications. Endocrine use typically involves diagnosis of Cushing syndrome or treatment of adrenal insufficiency and congenital adrenal hyperplasia. Non-endocrine use exploits their potent anti-inflammatory and immunosuppressive effects in treating various immunological and inflammatory diseases. Physiological doses are used for replacement therapy in adrenal insufficiency, while supraphysiological doses are administered to achieve anti-inflammatory and immunosuppressive effects.
Daily doses used for glucocorticoid replacement therapy are often determined without adequately considering individual variables such as dose-conversion physiological ratio (DCPR), oral hydrocortisone bioavailability, body surface area, and age. Recent dose recommendations may exceed physiological requirements by up to 30% and have been associated with adverse outcomes in long-term use; however, the causality of these associations has not yet been definitively established.
The effects of glucocorticoids on the hematologic and immune systems are pronounced. They can increase red blood cell and hemoglobin levels by slowing erythrophagocytosis, manifesting clinically as polycythemia in Cushing disease and normochromic anemia in Addison disease. Additionally, glucocorticoids increase the number of circulating polymorphonuclear leukocytes while decreasing lymphocyte, eosinophil, monocyte, and basophil counts. Marked reductions of up to 70% in lymphocytes and 90% in monocytes can be observed 4–6 hours after cortisol administration, with effects lasting approximately 24 hours. These cellular changes are largely attributed to redistribution of cells, with apoptosis of certain lymphocyte subtypes also contributing. T lymphocytes are more susceptible to apoptosis than B lymphocytes, and sensitivity varies among T-cell subsets.
This study by the Adrenal Working Group of the Turkish Society of Pediatric Endocrinology and Diabetes provides evidence-based recommendations for the diagnosis, treatment, and monitoring of adrenal insufficiency (AI). The study emphasizes that AI, characterized by inadequate production of glucocorticoid and/or mineralocorticoid hormones by the adrenal cortex, is a serious and potentially life-threatening condition due to its vital role in water-salt balance and energy metabolism. In the Turkish context, particularly for pediatric primary adrenal insufficiency (PAI) cases, initiation of hydrocortisone in three to four daily doses tailored to individual needs is recommended. Use of long-acting glucocorticoids such as prednisolone and dexamethasone is not recommended for children. Mineralocorticoid and salt replacement are also required in cases with aldosterone deficiency. Clinical assessments covering growth, weight gain, blood pressure, and overall health status are recommended every three to four months. Special emphasis is placed on educating patients and families regarding dose adjustments during stress to reduce the risk of adrenal crisis. In long-term therapy, the lowest effective dose necessary to control the disease should be used to avoid side effects.
Meta-analyses and randomized controlled trials have demonstrated that inhaled corticosteroids (ICS) significantly reduce hospitalization rates during asthma exacerbations. Compared with placebo, ICS reduce hospitalization rates in the general population (odds ratio 0.63), with greater efficacy observed in the moderate-severe asthma subgroup (odds ratio 0.17). Compared with systemic corticosteroids (SC), ICS use results in lower hospitalization rates in both general and mild-moderate asthma patients. Furthermore, combination therapy with ICS and SC provides additional benefit over SC alone in moderate-severe asthma exacerbations. Studies in organ transplantation have shown that steroid-free immunosuppressive regimens reduce acute rejection without compromising patient or graft survival compared to steroid-containing regimens. Steroid use has been associated with certain side effects such as diabetes, hypercholesterolemia, and cytomegalovirus infection. These findings highlight the need for careful evaluation of the efficacy and side effect profiles of corticosteroids in both asthma treatment and organ transplant immunosuppression.
In a study conducted in Türkiye on the use of inhaled corticosteroids in childhood asthma management, significant improvements in lung function parameters (FEV₁, PEF, FEF25–75) and marked reductions in serum total IgE, eosinophil counts, eosinophil cationic protein, and cystatin C levels were observed over an eight-week treatment period in children with mild-moderate persistent asthma. Although no significant changes in daytime or nighttime symptoms were detected during treatment, the laboratory findings demonstrate that inhaled corticosteroids positively influence not only clinical symptoms but also immunological biomarkers. This treatment approach, applied in pediatric allergy clinics in Türkiye, provides scientific support for the efficacy of inhaled corticosteroids in childhood asthma and their association with measurable biological response indicators.
According to Ahmet Çayakar’s study “Steroid Use in Clinical Practice”, glucocorticoid use in rheumatology varies according to disease type, severity, and patient condition in terms of dose, duration, and route of administration. Dose categories based on prednisone equivalents include low (<7.5 mg/day), moderate (7.5–30 mg/day), high (30–100 mg/day), very high (>100 mg/day), and pulse therapy. Moderate dosing is most commonly used. Pulse therapy is preferred in severe vasculitides and serious SLE cases. Intra-articular injections are typically administered no more than three times per year.
Corticosteroid Administration via Injection (Generated with AI assistance)
Corticosteroids exert their effects through multiple pathways, influencing anti-inflammatory and immunosuppressive responses, protein and carbohydrate metabolism, water and electrolyte balance, the central nervous system, and blood cells. These effects occur via both genomic and non-genomic mechanisms.
The genomic mechanism involves intracellular glucocorticoid receptors. Upon activation, these receptors translocate to the nucleus and suppress gene expression and translation in inflammatory leukocytes and structural cells such as epithelial cells, thereby reducing the production of proinflammatory cytokines, chemokines, cell adhesion molecules, and enzymes involved in inflammation.
The non-genomic mechanism acts more rapidly and involves interactions with intracellular or membrane-bound glucocorticoid receptors. This pathway rapidly inhibits phospholipase A2, preventing arachidonic acid release, and regulates thymocyte apoptosis. High concentrations of corticosteroids also suppress B and T lymphocyte production.
A study conducted at Istanbul University examining activation-induced cytidine deaminase (AID) levels in patients with myelodysplastic syndrome (MDS) provides important insights into the immunomodulatory mechanisms of corticosteroids. AID plays a role in B-cell activation and regulation of the immune response, and its interaction with corticosteroid therapy reveals the biochemical basis of immunosuppression. Study results indicate that the response to immunosuppressive therapy varies between individuals and that corticosteroid effects may differ according to the molecular characteristics of the disease. This research conducted in Türkiye is one of the high-quality examples evaluating the pharmacological effects of corticosteroids at the clinical level.
The route of corticosteroid administration depends primarily on the condition being treated. Routes include parenteral, oral, inhaled, topical, injection (intramuscular, intra-articular, intraleSIONal, intradermal), and rectal. Parenteral administration is typically preferred in emergency settings or for patients unable to tolerate oral medications. Oral administration is more common in chronic therapy. Whenever possible, non-systemic (local) therapies are preferred to minimize systemic exposure.
Pulse therapy typically involves intravenous infusion of methylprednisolone at doses of 250 mg/day or higher for 1–3 days. This approach is preferred in rapidly progressive vasculitides and severe central nervous system or renal involvement in systemic lupus erythematosus. The effect of pulse therapy can last approximately six weeks.
Inhaled glucocorticosteroids are specifically formulated to minimize systemic effects. When used correctly, they can reduce systemic side effects by up to 95% compared to systemic corticosteroids. Due to these properties, they are recommended as first-line anti-inflammatory agents for long-term asthma control.
In a study conducted in Türkiye, adverse effects such as adrenal insufficiency, Cushing syndrome (CS), and osteoporosis were investigated in psoriasis patients receiving long-term topical corticosteroids (TCS). Forty-nine patients were included and divided into two groups based on the potency of their topical steroid. ACTH levels, cortisol levels, and bone density measurements were evaluated. No significant differences were found between the two groups regarding the development of adrenal insufficiency, CS, or osteoporosis. However, patients using superpotent topical steroids at doses exceeding 50 grams per week showed significantly reduced cortisol levels, with a negative correlation identified between steroid amount used and cortisol levels (p < 0.01). Osteoporosis was observed in a small number of patients, but insufficient sample size prevented statistical analysis of risk factors. The study demonstrates that adverse effects of long-term topical steroid use are dose-dependent and that risk increases with usage exceeding 50 grams. Therefore, avoidance of long-term use of superpotent topical steroids and preference for moderately potent topical steroids when necessary is recommended.
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Terminology and General Use
Endocrine and Non-Endocrine Indications
Common Indications by Medical Specialty
Mechanism of Action
Administration