<h4>Objectives</h4>The aim of this systematic literature review was to summarize the current knowledge regarding the prevalence of, time to recovery from, and influence of glucocorticoid dose and duration on glucocorticoid-induced adrenal insufficiency (AI).<h4>Methods</h4>Eligible studies were original research articles, which included adult patients with an indication for glucocorticoids and measured adrenal function following exposure to systemic glucocorticoids. Searches were performed in Web of Science and MEDLINE, with further articles identified from reference lists. Screening was performed in duplicate. Data were extracted for each group of glucocorticoid-exposed patients within eligible studies. The reported proportion of patients with AI was summarized as median and inter-quartile range. Results were then stratified by daily dose, cumulative dose, duration of exposure and time since last glucocorticoid use. The risk of bias within and across studies was considered: for randomised controlled trials risk of bias was assessed using the tool developed by the Cochrane Collaboration.<h4>Results</h4>Overall, 73 eligible studies were identified out of 673 screened. The percentage of patients with AI ranged from 0% to 100% with a median (IQR) = 37.4% (13-63%). Studies were small-median (IQR) group size 16 (9-38)-and heterogeneous in methodology. AI persisted in 15% of patients retested 3 years after glucocorticoid withdrawal. Results remained widely distributed following stratification. AI was demonstrated at <5mg prednisolone equivalent dose/day, <4 weeks of exposure, cumulative dose <0.5g, and following tapered withdrawal.<h4>Conclusions</h4>The heterogeneity of studies and variability in results make it difficult to answer the research questions with confidence based on the current literature. There is evidence of AI following low doses and short durations of glucocorticoids. Hence, clinicians should be vigilant for adrenal insufficiency at all degrees of glucocorticoid exposure.

Glucocorticoids are widely prescribed as anti-inflammatory and immunosuppressive agents. This results in at least 1% of the population using chronic glucocorticoid therapy, being at risk for glucocorticoid-induced adrenal insufficiency. This risk is dependent on the dose, duration and potency of the glucocorticoid, route of administration, and individual susceptibility. Once glucocorticoid-induced adrenal insufficiency develops or is suspected, it necessitates careful education and management of affected patients. Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency. In general, tapering of glucocorticoids can be more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing. The degree and persistence of HPA axis suppression after cessation of glucocorticoid therapy are dependent on overall exposure and recovery of adrenal function varies greatly amongst individuals. This first European Society of Endocrinology/Endocrine Society joint clinical practice guideline provides guidance on this clinically relevant condition to aid clinicians involved in the care of patients on chronic glucocorticoid therapy.

Systemic glucocorticoid therapy is used worldwide by one to three percent of the general population and 0.5-1.8% on long-term oral glucocorticoid use. It is widely used in conditions such as inflammation, autoimmune diseases, and cancer to inhibit inflammatory responses. One of the possible undesirable side effects of exogenous corticosteroid treatment is adrenal suppression upon discontinuation of the medication and adrenal insufficiency after utilizing the supraphysiologic doses for more than one month. To prevent patients from the unwanted signs and symptoms of adrenal insufficiency, including fatigue, gastrointestinal upset, anorexia/weight loss, etc., better management of the quantity and frequency of exogenous corticosteroid use, as well as better education before starting its use, is needed. For patients actively on exogenous corticosteroids, a close follow-up must be in place to avoid adrenal suppression after the eventual discontinuation of their use. This review article summarizes the important studies to date on this subject, especially oral glucocorticoid use, and analyzes risks such as dose, duration of exposure, and comorbidities of adrenal insufficiency associated with oral glucocorticoid use. We comprehensively include information on those with primary adrenal insufficiency and pediatric patients, hoping to provide better insight and clinical reference.

Glucocorticoids are widely prescribed as anti-inflammatory and immunosuppressive agents. This results in at least 1% of the population using chronic glucocorticoid therapy, being at risk for glucocorticoid-induced adrenal insufficiency. This risk is dependent on the dose, duration and potency of the glucocorticoid, route of administration, and individual susceptibility. Once glucocorticoid-induced adrenal insufficiency develops or is suspected, it necessitates careful education and management of affected patients. Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency. In general, tapering of glucocorticoids can be more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing. The degree and persistence of HPA axis suppression after cessation of glucocorticoid therapy are dependent on overall exposure and recovery of adrenal function varies greatly amongst individuals. This first European Society of Endocrinology/Endocrine Society joint clinical practice guideline provides guidance on this clinically relevant condition to aid clinicians involved in the care of patients on chronic glucocorticoid therapy.

breaks down steroids. There is a greater risk for adrenal suppression with longer durations, greater doses, and oral and intraarticular preparations Adrenal crisis, also known as Addisonian crisis or acute adrenal insufficiency, is a life-threatening complication of adrenal insufficiency. Hypotension and hypovolemic shock are the main symptoms of an adrenal crisis. Other symptoms include weakness, anorexia, nausea, vomiting, fever, fatigue, abnormal electrolytes, confusion, and coma. Laboratory testing may detect low sodium, high potassium, hi Although the exact dosage has been debated, it is generally agreed upon that anyone with proven adrenal insufficiency receives glucocorticoid replacement during stressful times. The recommended amounts of glucocorticoid replacement are dependent on the anticipated stress, and the current guidelines depend on expert opinion. Though there may be variations in specific regimens, most agree that stress doses for simple surgery is quickly tapered and does not last longer than three days. This is because unneeded steroid excess can lead to infections, poor wound healing, and hyperglycemia. In those who are unable to tolerate oral medication or do not respond to stress doses, a low threshold to initiate parenteral hydrocortisone management can be used to guarantee adequate systemic absorption, since gastroenteritis frequently precedes an adrenal crisis and stress dose glucocorticoids may not always avoid an adrenal crisis. Those experiencing vomiting, chronic diarrhea, or an imminent adrenal crisis receive intramuscular hydrocortisone. Individuals must be prepared to administer it themselves because they can rapidly deteriorate. Those with adrenal insufficiency may own a hydrocortisone ampoule, but not all have practiced the injection, and most will depend on medical professionals to give it to them in the event of an adrenal crisis episode. Individuals may experience significant physical as well as cognitive impairment during their illness, which may impair their capacity to make wise decisions or administer medicine. Therefore, everyone with adrenal insufficiency can receive training on intramuscular hydrocortisone use and education on how to recognize an adrenal crisis, as well as assistance from a close family member or friend. In case an individual suffering from adrenal insufficiency loses consciousness, they must receive the necessary medical attention. A survey of 46 people with adrenal insufficiency revealed that some medical professionals are reluctant to medicate the condition even when it is brought to their attention. Only 54% of those with adrenal insufficiency got glucocorticoid administration within 30 minutes of arrival, even though 86% of those with…