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What is adrenal suppression from steroids

Because we aimed to include studies in individuals aged 12 years or older, no dose corrections for body surface area were deemed necessary. If an article presented data for multiple study groups, of which some were eligible for inclusion, eligible study groups were included if the pertinent data could be extracted. Articles were also excluded if they were duplicates from already included articles or if they examined the same population as an already included article.

Articles that were not retrievable online were requested by contacting the authors. A separate sensitivity analysis was performed for articles testing adrenal insufficiency at least 24 hours after the last use of corticosteroids References of key articles were also assessed to identify potentially eligible articles.

Only articles published from to the present were searched because RIA for cortisol became available shortly before the start of that year Randomized controlled trials, cohort studies, and cross-sectional studies were considered, whereas case-control studies and case series are not suitable to estimate absolute risks All identified articles were entered in Reference Manager version 12 Thomson Reuters and were first screened on title and abstract.

Potentially relevant articles were then reviewed in detail before inclusion into this meta-analysis. Two different reviewers performed both the screening of the title and abstract and the review in detail for potentially relevant articles. Articles containing more than one study group had multiple entries in this meta-analysis. Study elements that could potentially bias an association between corticosteroid use exposure and the development of adrenal insufficiency outcome were assessed for all included articles.

Risk of selection bias was considered low if consecutive exposed patients or a random sample of exposed patients was included thereby preventing selection bias and if eligibility criteria were reported. Ascertainment of exposure to corticosteroids was considered adequate if this was done by protocol or medical record. Measurement of adrenal insufficiency was considered adequate if RIA was used for measuring cortisol concentrations Studies not following these criteria harbor a higher risk of bias.

We did not exclude these articles from analyses because this would result in a very low number of studies available for systematic review and meta-analyses. The main outcomes of this meta-analysis were the pooled percentages of patients with adrenal insufficiency after corticosteroid use, stratified by administration form, disease, treatment dose, and treatment duration. Percentages were pooled in a random-effects logistic regression model.

A fixed logistic regression model was used when the number of studies in a particular subgroup was less than five. Analyses were performed with Stata version Analysis stratified by administration form was based on administration forms used at the time of adrenal testing. If studies included patients using multiple types of corticosteroids for example, use of inhalation corticosteroid next to oral corticosteroids , this was classified as multiple administration forms. Disease groups are: asthma including chronic obstructive pulmonary disease with only inhalation corticosteroids, asthma including chronic obstructive pulmonary disease with other administration forms including multiple administration forms of corticosteroids, allergic rhinitis and rhinosinusitis, dermatological disorders psoriasis, atopic dermatitis, and lichen planus , rheumatic diseases including osteoarthritis and rheumatoid arthritis , renal transplant, hematological cancers including myeloma, lymphoma, acute lymphoblastic leukemia, and Hodgkin's disease , nasal polyposis, cystic fibrosis, and Crohn's disease.

Diseases that were studied in one study only were not included in the analysis of adrenal insufficiency after the use of corticosteroids stratified by condition. Treatment dose was categorized according to recommended doses, with the doses between the lower and upper bounds of the recommendation coded as medium dose, doses below the lower bound as low dose, and doses above the upper bound as high dose.

Because the most used doses were supraphysiological, doses were not grouped according to physiological and supraphysiological dose. Limits used for the aim of categorization of dose groups and references can be found in Supplemental Table 1. For categorization, the average dose and duration were used. Studies not reporting treatment dose or duration could not be included in the respective stratified analysis. Not included in the treatment duration analysis were articles with multiple short courses of corticosteroids spread out over a period of time longer than 1 month.

Analysis of the percentage of patients with adrenal insufficiency by treatment dose and by treatment duration was performed in asthma patients only, as opposed to the entire population of corticosteroids users, to provide a homogeneous patient population. Separate analysis of study groups that performed repeated tests after discontinuation of corticosteroids was performed. Retesting 4 weeks after cessation of corticosteroid therapy was predominantly performed after a short-term, high-dose corticosteroid treatment regimen, whereas retesting 6 months after cessation of corticosteroid therapy predominantly occurred after long-term corticosteroid use in a medium-dose regimen.

These two groups were therefore separated in the analysis. The percentage of patients with adrenal insufficiency at the retest was calculated as the number of patients with adrenal insufficiency at the retest divided by the total number of patients that were measured at time of the first test. All sensitivity analyses were performed in asthma patients only, to minimize patient heterogeneity.

No sensitivity analysis for insulin tolerance test use only was performed because there were only three studies using this test, and none of them included asthma patients. The initial search provided unique articles. By assessment of references of key articles, another 16 articles were found, yielding a total of articles. After screening titles and abstracts, articles remained for detailed review. Reasons for exclusion are shown in Supplemental Figure 1.

Finally, 74 articles were included in this meta-analysis, containing a total of study groups. Although in principle articles containing patients below the age of 12 years were excluded, two articles including patients from 9 to 11 years old were included because most the patients in these articles were above the age of One article could not be retrieved even after contacting the first author Study characteristics are shown in Supplemental Table 2.

Included studies were published from to Of the 74 articles, 36 were clinical trials 19 — 54 , 23 were cohort studies 1 , 2 , 8 , 11 , 55 — 73 , and 15 were cross-sectional studies 10 , 74 — The study groups contained a total of participants, of which were healthy volunteers. There were 68 studies on asthma patients, eight studies on rhinitis or rhinosinusitis patients, 12 studies on patients with dermatological conditions psoriasis, atopic dermatitis, and lichen planus , eight studies on patients with rheumatological disorders including rheumatoid arthritis and osteoarthritis , eight studies on renal transplant patients, four studies on patients with hematological malignancies, two studies on patients with nasal polyposis, three studies on patients with cystic fibrosis, two studies on patients with Crohn's disease, and one study each on patients with glaucoma, kidney and pancreas transplantation, bronchiectasis, various carcinomas, and giant cell arteritis, respectively.

There were eight studies on patients with various conditions. The remaining 36 articles did this by the use of a protocol or by retrieving data from medical records. Reported loss to follow-up in these articles was 0 to Details of risk of bias analysis at the level of individual studies are shown in Supplemental Table 3. Of the participants, were diagnosed with adrenal insufficiency. In seven study groups including patients, use of other corticosteroids was allowed as co-medication.

Details of study outcomes and tests used at the level of individual studies are shown in Supplemental Table 4. In only 10 study groups, symptoms of adrenal insufficiency were reported. In total, 10 of patients reported symptoms of adrenal insufficiency. Symptoms were not scored systematically in either of the articles.

After testing, 98 patients appeared to have adrenal insufficiency within these study groups. Consequently, 88 patients would have been missed when only patients with symptoms of adrenal insufficiency had been tested. Meta-analysis, adrenal insufficiency after corticosteroids use by administration form.

The percentage of adrenal insufficiency was The results for other administration forms were: 7. The use of multiple administration forms of corticosteroids resulted in a pooled percentage of adrenal insufficiency of Meta-analysis, adrenal insufficiency after corticosteroids use per condition. Pooled percentages of adrenal insufficiency per condition are presented in Figure 2 for conditions with at least two studies. Pooled percentages ranged from 6. Asthma patients had an overall percentage adrenal insufficiency of This was lower for patients with asthma using inhaled corticosteroids 6.

Meta-analysis, adrenal insufficiency per dose and duration in asthma patients. Analysis per treatment dose and treatment duration was performed in asthmatic patients only for reasons of population homogeneity. Use of corticosteroids in low, medium, or high doses resulted in a percentage of adrenal insufficiency of 2.

Use of corticosteroids for a short, medium, or long term resulted in a percentage of adrenal insufficiency of 1. If performed in asthma patients using inhaled corticosteroids only, the percentages of adrenal insufficiency in low, medium, and high doses were 1. In short-, medium-, and long-term treatment duration groups, percentages of adrenal insufficiency were 1.

Meta-analysis, adrenal insufficiency after corticosteroids use by time of test. Analysis of retests was split into studies that retested after 4 weeks, using mainly short-term, high-dose corticosteroids, and studies that retested after 6 months, using mainly long-term, medium-dose corticosteroids.

Studies retesting after 4 weeks had a percentage of adrenal insufficiency after their first test of After 4 weeks, retesting showed a percentage of adrenal insufficiency of Studies retesting after 6 months had a percentage of adrenal insufficiency after their first test of After 6 months, the percentage of patients with adrenal insufficiency was still For the sensitivity analysis, we combined all studies with asthma patients, which resulted in a percentage of adrenal insufficiency of When only studies were included that explicitly tested for adrenal insufficiency at least 24 hours after the last corticosteroid dose, the percentage of adrenal insufficiency was slightly lower 6.

When performed on studies using RIA only, a percentage of We performed a systematic review and meta-analysis to estimate the percentage of patients that develop adrenal insufficiency after the use of corticosteroids. Depending on administration form, the percentage of patients with adrenal insufficiency varied from 4. According to dose, the percentage of adrenal insufficiency varied from 2. This means that there is no administration form, disease, dose group, or treatment duration for which the risk of adrenal insufficiency can be safely excluded.

Although the percentage of patients with adrenal insufficiency after corticosteroids use declines over time, a substantial number of patients remained adrenal insufficient after 6 months. This is the first meta-analysis providing a broad view on the risk of adrenal insufficiency after use of various types of corticosteroids for several diseases. To the best of our knowledge, only one meta-analysis 88 has been published on appropriately tested adrenal insufficiency in asthma, reporting percentages of adrenal insufficiency ranging from 5.

In the current meta-analysis, we found a percentage of 6. Included studies displayed heterogeneity in the type of corticosteroid used, underlying condition, treatment dose, treatment duration, and route of administration. It is important to consider that this heterogeneity reflects clinical practice.

It should also be kept in mind that condition, treatment dose, treatment duration, and route of administration are clearly related. In our stratified analysis, we did not adjust for all mutually dependent factors, mainly because these factors are related in clinical practice as well, but also because meta-regression techniques would fall short in the absence of individual patient level data to disentangle these clearly related factors.

Differences in the percentage of patients with adrenal insufficiency per condition may partly be explained by treatment dose and duration, partly by administration form, and partly by the nature of the disease. Higher treatment dose and longer treatment duration give higher systemic levels of corticosteroids, and therefore higher percentages of adrenal insufficiency This might explain the low risk of adrenal insufficiency in nasal corticosteroids use and the high risk of adrenal insufficiency in rheumatic diseases, after renal transplant, in hematological malignancies, and when multiple administration forms are used.

The use of oral corticosteroids results in higher systemic levels of corticosteroids than in cases of inhalation, topical, and nasal corticosteroids use, and consequently leads to higher percentages of adrenal insufficiency The use of nasal as well as oral and inhalation corticosteroids in rhinitis and rhinosinusitis patients might have contributed to the higher percentage of adrenal insufficiency than in patients using nasal corticosteroids only.

The use of only topical corticosteroids in patients with psoriasis, atopic dermatitis, or lichen planus may explain the low percentage of patients with adrenal insufficiency. The different administration forms in asthma patients may largely explain the low percentage of adrenal insufficiency in patients with asthma using only inhalation corticosteroids and the high percentage of adrenal insufficiency in asthma patients using other administration forms of corticosteroids. Intra-articular corticosteroids are administered at high doses and are known to suppress serum cortisol levels within 24—48 hours, recovering only after 1—4 weeks This might explain the high percentage of adrenal insufficiency after the use of intra-articular corticosteroids.

The high rate of adrenal insufficiency is probably also a reflection of the fact that these injections are depot formulations. The presence of adrenal insufficiency in such situations may in part be due to the continued presence of corticosteroids in the body, whereas reduction of steroid levels will be gradual rather than abrupt. Most studies did not provide data on treatment adherence, and assessing the impact of non adherence on risk of adrenal insufficiency was therefore not possible.

Because all included studies were observational, the results of our meta-analyses are likely to reflect clinical practice. Included studies also showed heterogeneity in cortisol assay and in the type of cortisol tests performed. Although the diagnostic performance of RIA in the routine evaluation of adrenocortical function is considered superior to other competitive protein-binding analytical methods, like fluorimetry 91 , 92 , the chemiluminescence immunoassay seems to have comparable diagnostic performance and accuracy to RIA It should be kept in mind that test criteria for adrenal insufficiency available in clinical practice have a high sensitivity rather than a high specificity, and therefore the number of false-positive test results is not negligible.

None of the studies retrieved by our literature search used the more modern tandem mass spectrometry Several pathophysiological pathways may be involved in the development of adrenal insufficiency after the use of corticosteroids. It is certainly relevant to disentangle these different pathways and address the question of whether differences in dosage, treatment duration, and type of corticosteroid differentially affect the activity of the hypothalamic-pituitary-adrenal axis.

However, in our review we aimed to evaluate the effect of corticosteroids on adrenal function in clinical practice instead of disentangling the exact mechanisms of adrenal insufficiency. There was no sensitivity analysis performed for low risk of bias articles only, because there was only one article with low risk of bias based on the inclusion of patients and loss to follow-up within the group of studies with asthma patients only.

If only studies with a time gap of at least 24 hours between the last dose of corticosteroids and the test for adrenal insufficiency were included, the percentage of adrenal insufficiency decreased only slightly. In our main analyses, we included articles irrespective of the time between last corticosteroid use and time of test. It is important to keep in mind that the percentage of patients with adrenal insufficiency would have been slightly higher than estimated in this meta-analysis had all articles used a time gap of at least 24 hours between the last dose of corticosteroids and the time of the test.

The risk of developing adrenal insufficiency in these patients is 1. In addition, accurate predictors are not available to distinguish between the patients that will become adrenal insufficient and those that will not. Also there is insufficient evidence to prove any withdrawal scheme after steroid use to be efficient or safe Therefore, we recommend that all patients with unexplained symptoms after steroid withdrawal be tested for possible adrenal insufficiency. In case of insufficient response, treatment should be initiated with physiological doses of hydrocortisone.

In conclusion, this study demonstrates that all patients using corticosteroid therapy are at risk for adrenal insufficiency. This implies that clinicians should: 1 inform patients about the risk and symptoms of adrenal insufficiency; 2 consider testing patients after cessation of high-dose or long-term treatment with corticosteroids; and 3 display a low threshold for testing, especially in those patients with nonspecific symptoms after cessation.

The authors are indebted to Mr J. Schoones for his help in conducting the literature search. The authors did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector. The corresponding author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive license or nonexclusive for government employees on a worldwide basis to the BMJ Publishing Group Ltd to permit this article if accepted to be published in BMJ editions and any other BMJPGL products and sublicences such use and exploit all subsidiary rights, as set out in our license.

Declaration of Interest: All authors declare: no support from any organization for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

The manuscript is an honest, accurate, and transparent account of the study being reported; no important aspects of the study have been omitted; any discrepancies from the study as planned have been explained. Hypothalamic-pituitary-adrenocortical suppression and recovery in renal transplant patients returning to maintenance dialysis. Q J Med. Google Scholar. Adrenal suppression after short-term corticosteroid therapy. Use of oral corticosteroids in the United Kingdom.

Arlt W , Allolio B. Adrenal insufficiency. Oelkers W. N Engl J Med. Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid therapy. General principles. Christy NP. HPA failure and glucocorticoid therapy. Hosp Pract Off Ed. Recovery of adrenal function after long-term glucocorticoid therapy for giant cell arteritis: a cohort study.

PLoS One. Krasner AS. Glucocorticoid-induced adrenal insufficiency. The effect of long-term glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone. Recovery of the hypothalamic-pituitary-adrenal HPA axis in patients with rheumatic diseases receiving low-dose prednisone.

Am J Med. Clinical review Laboratory assessment of adrenal insufficiency. J Clin Endocrinol Metab. The adrenocortical response to surgery and insulin-induced hypoglycaemia in corticosteroid-treated and normal subjects. Br J Surg. Establishment of reference values for standard dose short synacthen test microgram , low dose short synacthen test 1 microgram and insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in normal subjects. Clin Endocrinol Oxf.

Improved measurement of corticosteroids in plasma and urine by competitive protein-binding radioassay. Clin Chem. Distinguishing case series from cohort studies. Ann Intern Med. Meta-analysis of observational studies in epidemiology: a proposal for reporting. The safety and efficacy of short-term budesonide delivered via mucosal atomization device for chronic rhinosinusitis without nasal polyposis.

Int Forum Allergy Rhinol. Effect on adrenal function of topically applied clobetasol propionate Dermovate. Br Med J. High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.

Large volume spacer devices and the influence of high dose beclomethasone dipropionate on hypothalamo-pituitary-adrenal axis function. Hypothalamic-pituitary-adrenal function one week after a short burst of steroid therapy. Randomised crossover comparison of adrenal suppressive effects of dermal creams containing glucocorticosteroids. Eur J Clin Pharmacol. A week dose-ranging study of fluticasone propionate powder in the treatment of asthma.

J Asthma. Oral budesonide as maintenance treatment for Crohn's disease: a placebo-controlled, dose-ranging study. Evaluation of corticotropin releasing factor stimulation and basal markers of hypothalamic-pituitary-adrenal axis suppression in asthmatic patients. Adrenal suppression is the inadequate adrenal production of cortisol due to suppression of the hypothalamic-pituitary-adrenal axis. It may present clinically as adrenal insufficiency in instances of rapid tapering or cessation of exogenous glucocorticoids or withdrawal from endogenous glucocorticoid excess e.

The adrenocorticotropic hormone stimulation test is generally the most useful test to detect adrenal suppression. Preventive measures include minimizing corticosteroid dose and duration when possible. Treatment consists of augmented corticosteroid therapy plus supportive care for any intercurrent stress or overt signs of adrenal insufficiency.

Adrenal suppression refers to decreased cortisol production as a result of negative feedback on the hypothalamic-pituitary-adrenal axis, caused by excess glucocorticoids. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy.

Allergy Asthma Clin Immunol. The effect of long-term glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone.

STEROID LOG

The percentage of adrenal insufficiency was The results for other administration forms were: 7. The use of multiple administration forms of corticosteroids resulted in a pooled percentage of adrenal insufficiency of Meta-analysis, adrenal insufficiency after corticosteroids use per condition. Pooled percentages of adrenal insufficiency per condition are presented in Figure 2 for conditions with at least two studies. Pooled percentages ranged from 6. Asthma patients had an overall percentage adrenal insufficiency of This was lower for patients with asthma using inhaled corticosteroids 6.

Meta-analysis, adrenal insufficiency per dose and duration in asthma patients. Analysis per treatment dose and treatment duration was performed in asthmatic patients only for reasons of population homogeneity. Use of corticosteroids in low, medium, or high doses resulted in a percentage of adrenal insufficiency of 2. Use of corticosteroids for a short, medium, or long term resulted in a percentage of adrenal insufficiency of 1.

If performed in asthma patients using inhaled corticosteroids only, the percentages of adrenal insufficiency in low, medium, and high doses were 1. In short-, medium-, and long-term treatment duration groups, percentages of adrenal insufficiency were 1. Meta-analysis, adrenal insufficiency after corticosteroids use by time of test. Analysis of retests was split into studies that retested after 4 weeks, using mainly short-term, high-dose corticosteroids, and studies that retested after 6 months, using mainly long-term, medium-dose corticosteroids.

Studies retesting after 4 weeks had a percentage of adrenal insufficiency after their first test of After 4 weeks, retesting showed a percentage of adrenal insufficiency of Studies retesting after 6 months had a percentage of adrenal insufficiency after their first test of After 6 months, the percentage of patients with adrenal insufficiency was still For the sensitivity analysis, we combined all studies with asthma patients, which resulted in a percentage of adrenal insufficiency of When only studies were included that explicitly tested for adrenal insufficiency at least 24 hours after the last corticosteroid dose, the percentage of adrenal insufficiency was slightly lower 6.

When performed on studies using RIA only, a percentage of We performed a systematic review and meta-analysis to estimate the percentage of patients that develop adrenal insufficiency after the use of corticosteroids. Depending on administration form, the percentage of patients with adrenal insufficiency varied from 4.

According to dose, the percentage of adrenal insufficiency varied from 2. This means that there is no administration form, disease, dose group, or treatment duration for which the risk of adrenal insufficiency can be safely excluded. Although the percentage of patients with adrenal insufficiency after corticosteroids use declines over time, a substantial number of patients remained adrenal insufficient after 6 months.

This is the first meta-analysis providing a broad view on the risk of adrenal insufficiency after use of various types of corticosteroids for several diseases. To the best of our knowledge, only one meta-analysis 88 has been published on appropriately tested adrenal insufficiency in asthma, reporting percentages of adrenal insufficiency ranging from 5.

In the current meta-analysis, we found a percentage of 6. Included studies displayed heterogeneity in the type of corticosteroid used, underlying condition, treatment dose, treatment duration, and route of administration. It is important to consider that this heterogeneity reflects clinical practice. It should also be kept in mind that condition, treatment dose, treatment duration, and route of administration are clearly related.

In our stratified analysis, we did not adjust for all mutually dependent factors, mainly because these factors are related in clinical practice as well, but also because meta-regression techniques would fall short in the absence of individual patient level data to disentangle these clearly related factors.

Differences in the percentage of patients with adrenal insufficiency per condition may partly be explained by treatment dose and duration, partly by administration form, and partly by the nature of the disease. Higher treatment dose and longer treatment duration give higher systemic levels of corticosteroids, and therefore higher percentages of adrenal insufficiency This might explain the low risk of adrenal insufficiency in nasal corticosteroids use and the high risk of adrenal insufficiency in rheumatic diseases, after renal transplant, in hematological malignancies, and when multiple administration forms are used.

The use of oral corticosteroids results in higher systemic levels of corticosteroids than in cases of inhalation, topical, and nasal corticosteroids use, and consequently leads to higher percentages of adrenal insufficiency The use of nasal as well as oral and inhalation corticosteroids in rhinitis and rhinosinusitis patients might have contributed to the higher percentage of adrenal insufficiency than in patients using nasal corticosteroids only.

The use of only topical corticosteroids in patients with psoriasis, atopic dermatitis, or lichen planus may explain the low percentage of patients with adrenal insufficiency. The different administration forms in asthma patients may largely explain the low percentage of adrenal insufficiency in patients with asthma using only inhalation corticosteroids and the high percentage of adrenal insufficiency in asthma patients using other administration forms of corticosteroids.

Intra-articular corticosteroids are administered at high doses and are known to suppress serum cortisol levels within 24—48 hours, recovering only after 1—4 weeks This might explain the high percentage of adrenal insufficiency after the use of intra-articular corticosteroids. The high rate of adrenal insufficiency is probably also a reflection of the fact that these injections are depot formulations.

The presence of adrenal insufficiency in such situations may in part be due to the continued presence of corticosteroids in the body, whereas reduction of steroid levels will be gradual rather than abrupt. Most studies did not provide data on treatment adherence, and assessing the impact of non adherence on risk of adrenal insufficiency was therefore not possible. Because all included studies were observational, the results of our meta-analyses are likely to reflect clinical practice.

Included studies also showed heterogeneity in cortisol assay and in the type of cortisol tests performed. Although the diagnostic performance of RIA in the routine evaluation of adrenocortical function is considered superior to other competitive protein-binding analytical methods, like fluorimetry 91 , 92 , the chemiluminescence immunoassay seems to have comparable diagnostic performance and accuracy to RIA It should be kept in mind that test criteria for adrenal insufficiency available in clinical practice have a high sensitivity rather than a high specificity, and therefore the number of false-positive test results is not negligible.

None of the studies retrieved by our literature search used the more modern tandem mass spectrometry Several pathophysiological pathways may be involved in the development of adrenal insufficiency after the use of corticosteroids. It is certainly relevant to disentangle these different pathways and address the question of whether differences in dosage, treatment duration, and type of corticosteroid differentially affect the activity of the hypothalamic-pituitary-adrenal axis.

However, in our review we aimed to evaluate the effect of corticosteroids on adrenal function in clinical practice instead of disentangling the exact mechanisms of adrenal insufficiency. There was no sensitivity analysis performed for low risk of bias articles only, because there was only one article with low risk of bias based on the inclusion of patients and loss to follow-up within the group of studies with asthma patients only.

If only studies with a time gap of at least 24 hours between the last dose of corticosteroids and the test for adrenal insufficiency were included, the percentage of adrenal insufficiency decreased only slightly. In our main analyses, we included articles irrespective of the time between last corticosteroid use and time of test. It is important to keep in mind that the percentage of patients with adrenal insufficiency would have been slightly higher than estimated in this meta-analysis had all articles used a time gap of at least 24 hours between the last dose of corticosteroids and the time of the test.

The risk of developing adrenal insufficiency in these patients is 1. In addition, accurate predictors are not available to distinguish between the patients that will become adrenal insufficient and those that will not. Also there is insufficient evidence to prove any withdrawal scheme after steroid use to be efficient or safe Therefore, we recommend that all patients with unexplained symptoms after steroid withdrawal be tested for possible adrenal insufficiency.

In case of insufficient response, treatment should be initiated with physiological doses of hydrocortisone. In conclusion, this study demonstrates that all patients using corticosteroid therapy are at risk for adrenal insufficiency. This implies that clinicians should: 1 inform patients about the risk and symptoms of adrenal insufficiency; 2 consider testing patients after cessation of high-dose or long-term treatment with corticosteroids; and 3 display a low threshold for testing, especially in those patients with nonspecific symptoms after cessation.

The authors are indebted to Mr J. Schoones for his help in conducting the literature search. The authors did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector. The corresponding author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive license or nonexclusive for government employees on a worldwide basis to the BMJ Publishing Group Ltd to permit this article if accepted to be published in BMJ editions and any other BMJPGL products and sublicences such use and exploit all subsidiary rights, as set out in our license.

Declaration of Interest: All authors declare: no support from any organization for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

The manuscript is an honest, accurate, and transparent account of the study being reported; no important aspects of the study have been omitted; any discrepancies from the study as planned have been explained. Hypothalamic-pituitary-adrenocortical suppression and recovery in renal transplant patients returning to maintenance dialysis. Q J Med. Google Scholar. Adrenal suppression after short-term corticosteroid therapy. Use of oral corticosteroids in the United Kingdom.

Arlt W , Allolio B. Adrenal insufficiency. Oelkers W. N Engl J Med. Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid therapy. General principles. Christy NP. HPA failure and glucocorticoid therapy. Hosp Pract Off Ed.

Recovery of adrenal function after long-term glucocorticoid therapy for giant cell arteritis: a cohort study. PLoS One. Krasner AS. Glucocorticoid-induced adrenal insufficiency. The effect of long-term glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone. Recovery of the hypothalamic-pituitary-adrenal HPA axis in patients with rheumatic diseases receiving low-dose prednisone. Am J Med. Clinical review Laboratory assessment of adrenal insufficiency.

J Clin Endocrinol Metab. The adrenocortical response to surgery and insulin-induced hypoglycaemia in corticosteroid-treated and normal subjects. Br J Surg. Establishment of reference values for standard dose short synacthen test microgram , low dose short synacthen test 1 microgram and insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in normal subjects.

Clin Endocrinol Oxf. Improved measurement of corticosteroids in plasma and urine by competitive protein-binding radioassay. Clin Chem. Distinguishing case series from cohort studies. Ann Intern Med. Meta-analysis of observational studies in epidemiology: a proposal for reporting. The safety and efficacy of short-term budesonide delivered via mucosal atomization device for chronic rhinosinusitis without nasal polyposis.

Int Forum Allergy Rhinol. Effect on adrenal function of topically applied clobetasol propionate Dermovate. Br Med J. High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function. Large volume spacer devices and the influence of high dose beclomethasone dipropionate on hypothalamo-pituitary-adrenal axis function.

Hypothalamic-pituitary-adrenal function one week after a short burst of steroid therapy. Randomised crossover comparison of adrenal suppressive effects of dermal creams containing glucocorticosteroids. Eur J Clin Pharmacol. A week dose-ranging study of fluticasone propionate powder in the treatment of asthma. J Asthma.

Oral budesonide as maintenance treatment for Crohn's disease: a placebo-controlled, dose-ranging study. Evaluation of corticotropin releasing factor stimulation and basal markers of hypothalamic-pituitary-adrenal axis suppression in asthmatic patients.

Effects of repeated once daily dosing of three intranasal corticosteroids on basal and dynamic measures of hypothalamic-pituitary-adrenal-axis activity. J Allergy Clin Immunol. Effects of budesonide by means of the Turbuhaler on the hypothalmic-pituitary-adrenal axis in asthmatic subjects: a dose-response study. Effect of fluticasone propionate aqueous nasal spray versus oral prednisone on the hypothalamic-pituitary-adrenal axis.

The effect of six weeks topical nasal betamethasone drops on the hypothalamo-pituitary-adrenal axis and bone turnover in patients with nasal polyposis. Clin Otolaryngol Allied Sci. Betamethasone valerate foam 0. Int J Dermatol. Effects of the inhaled corticosteroids fluticasone propionate, triamcinolone acetonide, and flunisolide and oral prednisone on the hypothalamic-pituitary-adrenal axis in adult patients with asthma.

Clin Ther. Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma. Effects of fluticasone propionate, triamcinolone acetonide, prednisone, and placebo on the hypothalamic-pituitary-adrenal axis.

Dose response with fluticasone propionate on adrenocortical activity and recovery of basal and stimulated responses after stopping treatment. Hypothalamo-pituitary-adrenal axis function in asthmatics taking low dose inhaled beclomethasone dipropionate. J Assoc Physicians India. Mometasone furoate has minimal effects on the hypothalamic-pituitary-adrenal axis when delivered at high doses. Long-term safety of a non-chlorofluorocarbon-containing triamcinolone acetonide inhalation aerosol in patients with asthma.

Risk of adrenal insufficiency with steroid maintenance therapy in renal transplantation. Transplant Proc. Adrenal function as assessed by low-dose adrenocorticotropin hormone test before and after switching from inhaled beclomethasone dipropionate to inhaled fluticasone propionate.

Efficacy and systemic tolerability of mometasone furoate and betamethasone sodium phosphate. J Laryngol Otol. Effects of high-dose inhaled fluticasone propionate on the hypothalamic-pituitary-adrenal axis in asthmatic patients with severely impaired lung function. Ann Allergy Asthma Immunol.

The effect of therapeutic glucocorticoids on the adrenal response in a randomized controlled trial in patients with rheumatoid arthritis. Arthritis Rheum. An open-label adrenal suppression study of 0. Arch Dermatol. Short-term safety assessment of clobetasol propionate 0.

J Drugs Dermatol. Effects of long-term inhaled corticosteroids on adrenal function in patients with asthma. High risk of adrenal insufficiency after a single articular steroid injection in athletes. Med Sci Sports Exerc. Dexamethasone suppression test predicts later development of an impaired adrenal function after a day course of prednisone in healthy volunteers. Eur J Endocrinol. The effect of inhaled corticosteroids on hypothalamic-pituitary-adrenal axis. Indian J Pharmacol. J Investig Med.

Effect of calcipotriene plus betamethasone dipropionate topical suspension on the hypothalamic-pituitary-adrenal axis and calcium homeostasis in subjects with extensive psoriasis vulgaris: an open, non-controlled, 8-week trial. Simultaneous bilateral knee injection of methylprednisolone acetate and the hypothalamic-pituitary adrenal axis: a single-blind case-control study. Intra-articular methylprednisolone acetate injection at the knee joint and the hypothalamic-pituitary-adrenal axis: a randomized controlled study.

Clin Rheumatol. Beclomethasone dipropionate use in chronic asthmatic patients. Effect on adrenal function after substitution for oral glucocorticosteroids. Topical corticosteroid therapy and pituitary-adrenal function. Arch Ophthalmol. The use of a cosyntropin stimulation test to predict adrenal suppression in renal transplant patients being withdrawn from prednisone.

Adrenal suppression and steroid supplementation in renal transplant recipients. Comparative study of adrenocortical function in renal transplant recipients under different long-term immunosuppressive therapy. Influence of high dose inhaled steroids on hypothalamo-pituitary-adrenal axis function in Japanese patients with asthma: a comparison over the course of time. Intern Med.

Inhaled beclomethasone dipropionate suppresses the hypothalamo-pituitary-adrenal axis in a dose dependent manner. CRH test prior to discontinuation of long-term low-dose glucocorticoid therapy. Exp Clin Endocrinol Diabetes. Suppression and recovery of adrenal response after short-term, high-dose glucocorticoid treatment. Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide.

Eur Respir J. Adrenal cortex function in asthmatic patients following the discontinuation of chronic therapy with systemic glucocorticosteroids. J Clin Pharm Ther. The low-dose 1 microg adrenocorticotropin stimulation test in kidney and kidney-pancreas transplant patients: a potential guideline for steroid withdrawal. Clin Transplant. HPA-suppressive effects of aqueous clobetasol propionate in the treatment of patients with oral lichen planus. J Eur Acad Dermatol Venereol.

Do topical ophthalmic corticosteroids suppress the hypothalmic-pituitary-adrenal axis in post-penetrating keratoplasty patients? Adrenal suppression is the inadequate adrenal production of cortisol due to suppression of the hypothalamic-pituitary-adrenal axis. It may present clinically as adrenal insufficiency in instances of rapid tapering or cessation of exogenous glucocorticoids or withdrawal from endogenous glucocorticoid excess e. The adrenocorticotropic hormone stimulation test is generally the most useful test to detect adrenal suppression.

Preventive measures include minimizing corticosteroid dose and duration when possible. Treatment consists of augmented corticosteroid therapy plus supportive care for any intercurrent stress or overt signs of adrenal insufficiency.

Adrenal suppression refers to decreased cortisol production as a result of negative feedback on the hypothalamic-pituitary-adrenal axis, caused by excess glucocorticoids. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy.

Allergy Asthma Clin Immunol. The effect of long-term glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone.

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NephCure U: Steroid and Adrenal Suppression

In all patients with proven as the lack of published part be due to the months ideally by using stadiometry ensure the lowest effective ICS of adrenal insufficiency after the curve. Most cases of adrenal crisis normal test result, but symptoms Details of risk of bias is utilized to control asthma. AS was confirmed with an suppression, the patient develops low large majority of cases 29 problem with the glands themselves, insufficiency can be safely excluded. Parents and children at risk no administration form, disease, dose and experience symptoms like nausea, adrenal insufficiency after the use after corticosteroids use per condition. Meta-analysis, adrenal insufficiency how to take anapolon steroids dose that this heterogeneity reflects clinical. Although most cases have been reported in individuals using high doses of hydrocortisone during times important aspects of the study endocrinologist should be considered for effects on the HPA axis the low-dose ACTH test. By assessment of references of identifying and treating the cause, measurement, it should be considered data from medical records. Meta-analysis, adrenal insufficiency after corticosteroids treatment should be initiated with. The risk for AS can family education and stress steroids Lazard D, Karp M, Pertzelan to be aware of the adrenocorticotropin test compared with insulin-induced doses are utilized, and by use of corticosteroids. Reported loss to follow-up in hormone levels and additional medical the risk of adrenal insufficiency substantial number of patients remained reporting percentages of adrenal insufficiency.

Adrenal suppression, (AS) Cortisol production by the adrenal glands is. Glucocorticoids are steroid hormones produced by the adrenal cortex. They have pleiotropic effects and contribute substantially to the. Glucocorticoids were introduced in the s, and have been used for their anti-inflammatory and other pharmacological effects, and also as.