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Steroid Therapy in Adrenal Insufficiency - MedCrave online. |
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ANSWER : There are a few forms of adrenal insufficiency, which is an uncommon disorder caused by the adrenal glands not making enough of certain hormones. Your adrenal glands are located on the top of each kidney. Hormones secreted by the adrenal glands include cortisol and aldosterone. Cortisol helps your body respond to stress, such as from an injury or infection.
It also helps glucose metabolism and helps with proper cardiovascular function. Aldosterone helps maintain proper blood pressure through the balance of sodium, potassium and water in the body. There are two main categories of adrenal insufficiency: primary adrenal insufficiency and secondary adrenal insufficiency.
Primary adrenal insufficiency occurs when adrenal glands are diseased or damaged. If the pituitary gland somehow is damaged or altered, it can affect adrenal gland cortisol secretion, even if the adrenal glands are healthy. Secondary adrenal insufficiency is most commonly caused by medications, such as prednisone, intra-articular injections with steroids, or steroid creams.
In this situation, the adrenal glands may take days to months to recover function and restore proper cortisol production. Signs and symptoms of adrenal insufficiency often come on gradually and progressively worsen over months.
Diagnosis sometimes is delayed because early symptoms can easily be mistaken for something else. The most common signs and symptoms include muscle weakness and fatigue; muscle, joint or abdominal pains; and decreased appetite and weight loss.
In addition, signs and symptoms can include lightheadedness, feeling wiped out by an ordinary illness, depression, nausea, vomiting or diarrhea. Cravings for salt and darkening of skin, especially on the face and hands, or on moles, scars or skin folds, are seen only with primary adrenal insufficiency.
Symptoms of adrenal insufficiency can develop suddenly and rapidly into an adrenal crisis. This can occur in someone who has been diagnosed with adrenal insufficiency or in someone who has yet to be diagnosed. Often, an adrenal crisis is triggered by health-related stress, such as an illness, surgical procedure or serious injury. These are also the times that higher cortisol production usually would occur in someone without adrenal insufficiency.
As symptoms of adrenal crisis escalate, most people feel terrible — perhaps with severe abdominal pain, nausea, vomiting and lightheadedness — and realize that emergency care is required. Some people may pass out, requiring help from others. An adrenal crisis can result in death if not promptly treated.
Adrenal insufficiency can be confirmed or ruled out with blood tests. Treatment plans also involve preparing for the possibility of an adrenal crisis. If you have adrenal insufficiency, have an individualized, written action plan for times when you may be at heightened risk of adrenal crisis.
This includes periods of health stress and times when worsening symptoms indicate you may be headed toward an adrenal crisis. A chronic, progressive lung disease is attracting new global attention. Today marks the inaugural World Bronchiectasis Day, an awareness day set for July 1 each [ Phoenix, Arizona. Aunque los fibromas sean frecuentes, en algunas [ By Liza Torborg.
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Secondary adrenal insufficiency is most commonly caused by medications, such as prednisone, intra-articular injections with steroids. Use of exogenous glucocorticoids is known to cause suppression of the HPA axis. Secondary adrenal insufficiency may be noted with oral and. Use of exogenous glucocorticoids is known to cause suppression of the HPA axis. Secondary adrenal insufficiency may be noted with oral and. Prednisolone can be given mg/d. Secondary adrenal insufficiency is most commonly caused by medications, such as prednisone, intra-articular injections with steroids. Email alerts Article activity alert. The use of multiple administration forms of corticosteroids resulted in a pooled percentage of adrenal insufficiency of 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. Hormones secreted by the adrenal glands include cortisol and aldosterone. Permissions Icon Permissions. This includes periods of health stress and times when worsening symptoms indicate you may be headed toward an adrenal crisis.Leonie H. Broersen, Alberto M. Pereira, Jens Otto L. We aimed to estimate pooled percentages of patients with adrenal insufficiency after treatment with corticosteroids for various conditions in a meta-analysis. Secondly, we aimed to stratify the results by route of administration, disease, treatment dose, and duration. Original articles testing adult corticosteroid users for adrenal insufficiency were eligible. We included 74 articles with a total of participants.
Stratified by administration form, percentages of patients with adrenal insufficiency ranged from 4. Stratified by disease, percentages ranged from 6. The risk also varied according to dose from 2. This is the first meta-analysis providing a broad view on the risk of adrenal insufficiency after use of various types of corticosteroids in several underlying diseases.
Studies displayed heterogeneity in the type of corticosteroid used, underlying condition, treatment dose, treatment duration, and route of administration, thereby reflecting clinical practice. Our results were stratified by these factors. Because no individual data were available, risk stratification at the level of the individual patient was not possible. Many articles with high levels of bias were included in this meta-analysis because there were only a few articles with low levels of bias available.
This may have affected the results. Corticosteroids are widely used for the treatment of various inflammatory conditions and malignancies and after organ transplantation.
Therapy with corticosteroids is targeted toward inhibition of an inflammatory response 1 — 3. However, the use of corticosteroids is associated with numerous side effects and is considered to be the most common cause of adrenal insufficiency 4 , 5.
Chronic use of corticosteroids inhibits the function of the hypothalamic-pituitary-adrenal axis by negative feedback, which may cause adrenal insufficiency also after the cessation of corticosteroid treatment 4 , 6.
Adrenal insufficiency is a serious, potentially life-threatening side effect of corticosteroid use. Therefore, patients may require glucocorticoid replacement therapy after chronic use of corticosteroids in periods of stress, such as trauma, surgery, or acute illness, until full recovery of adrenal function.
In some cases, chronic replacement with physiological doses of glucocorticoid therapy is indicated 7 — 9. Neither treatment dose and duration, nor administration form, nor random serum cortisol measurements seem to accurately predict the development of adrenal insufficiency after the use of corticosteroids 10 , The magnitude of the risk of developing this side effect is unclear. Given the high prevalence of corticosteroid users, it is of great clinical relevance to try to obtain knowledge about the risk of developing adrenal insufficiency.
The aim of this study is to perform a systematic review and meta-analysis of the percentage of patients that develops adrenal insufficiency after the use of corticosteroids.
Secondary aims are to stratify the results by route of administration, underlying disease, treatment dose, and duration, and to perform a separate analysis for the studies that repeated the test for adrenal insufficiency.
Original studies assessing adrenal insufficiency in adult human corticosteroid users were eligible for inclusion. The diagnosis of adrenal insufficiency had to be established by one of the following tests: the insulin tolerance test, ACTH stimulation tests 0. There were no restrictions in dose, duration, or type of corticosteroid therapy.
Eligible administration forms of corticosteroids were oral, inhalation, topical, nasal, intra-articular injection, and im injection. Articles were excluded if the examined population was not at risk of adrenal insufficiency secondary to the use of corticosteroids eg, corticosteroid replacement therapy for primary or secondary adrenocortical failure, if not all patients used corticosteroids, or if patients included in the study were selected on the basis of having adrenal insufficiency.
Articles were also excluded if no data or insufficient data were presented to analyze adrenal insufficiency after corticosteroid use. Inclusion of articles was restricted to those in English and to articles that included at least 10 subjects to minimize the risk of selection bias.
Articles containing the following populations were excluded: pregnant women, intensive care patients, and patients receiving corticosteroids perioperatively. 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.
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