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The patients’ characteristics are presented in Table 1, including the relevant clinical indications as well as the number and timing of the SSTs performed. A total of 776 subjects were recruited, all with potentially reversible causes of AI. A subgroup analysis was performed in 110 patients with AI secondary to treatment with suppressive doses of glucocorticoids. Here the study by Pofi et al. ( 9) is a useful addition to the literature reporting results of synacthen testing from a large retrospectively studied cohort of patients with central AI, comprising both SAI (n = 776) and TAI (n = 110), from three academic endocrine centers. It is important to make the distinction between patients with SAI and TAI in this study as the potential for recovery of adrenal function (and thus pre-test probability of recovery) are significantly different in each group but overall across the entire cohort of 886 patients, 37% of patients who initially failed an SST eventually went on to subsequently pass an SST. the expiry of the 12 months from the creation of the short SST for antisocial behaviour (18 months in cases where an extension notice has been served following the creation of the short SST), Proceedings are finally determined when the appeal period has expired without an appeal being lodged, or where an appeal is lodged the appeal is withdrawn or finally determined. All SSTs were performed between 9 and 12 am, at least 18 hours after the most recent dose of glucocorticoids. Individual clinicians determined the frequency of repeat testing on a case-by-case basis. Patients taking the oral contraceptive pill or other estrogen replacement were required to stop the treatment at least 6 weeks before the test. Blood was sampled for serum cortisol at baseline and after 30 minutes: baseline serum cortisol levels were measured prior to injection of 250 μg Synacthen (Questcor Operations Limited, Dublin, Ireland, for Siemens assays; Alliance Pharmaceuticals, Chippenham, United Kingdom, and Sigma-tau Pharmaceutical, Rome, Italy, for Roche assays) intramuscularly or intravenously. The 30-minute response to intramuscular or intravenous Synacthen has been shown to be equivalent ( 18). After administration of Synacthen, the patients were observed for 15 minutes for signs of any allergic reaction. The interpretation of the SST is based on the 30-minute serum cortisol where an adequate response to Synacthen was defined as >450 nmol/L for Siemens ADVIA Centaur ( 19), as >550 nmol/L for the Roche Generation I Modular System (tests done before February 2016) ( 19), and as >450 nmol/L for the Roche Generation II Modular System (tests done after February 2016). The incremental response to Synacthen was calculated as: delta cortisol = [30-minute – 0-minute cortisol]. Statistical methods

Patients >14 years who underwent SST from January 2010 to December 2017 were included. Pearson's chi-square cross-tabulation was used to identify individuals with inconsistent 30- and 60-minute serum cortisol test results. Logistic regression analysis was performed to predict normal responses based on the baseline cortisol value. Clinicians have been using SST with increasing frequency because of its ease; it is now replacing ITT for the assessment of adrenal reserve. Approximately 50% of surveyed clinicians were using SST to assess the HPA axis in 1996, which was in sharp contrast to only 25% in 1988. [5,9] SST provides an excellent clinical tool to test the HPA axis and has several advantages including relative ease and simplicity, lower cost, and accurate assessment of cortisol secretion. However, a wide variation occurs with the time points used for measuring cortisol levels after ACTH injection. For instance, some clinicians use the 30- and 60-minute serum cortisol level measurements, while some prefer either the 30-minute or the 60-minute serum cortisol measurements alone. Further, some clinicians measure the baseline serum cortisol before ACTH injection while others omit it. The insulin tolerance test (ITT) has been historically been used for evaluating the integrity of the hypothalamic-pituitary-adrenal (HPA) axis. Although both the ITT and short Synacthen test (SST) are useful in detecting secondary adrenal insufficiency, ITT is labor intensive and requires medical and nursing supervision. Performing this in children and patients with seizures, cardiovascular, and cerebrovascular diseases also has its limitations. http://www.pathology.leedsth.nhs.uk/dnn_bilm/Misc/Syntheticglucocorticoidsandcortisolassays.aspx Further informationA 30-minute serum cortisol level following ACTH injection might lead to a false positive diagnosis of adrenal insufficiency as some patients cross the threshold cortisol levels only at 60 minutes. This practice can lead to a lifelong exposure to unnecessary treatment with exogenous steroids that can have harmful effects, including increased healthcare costs related to over-prescribing, monitoring, physician time, and enormous emotional and psychological impacts on patients. With patients in the 30-minute SST only protocol for cortisol measurement with an inadequate response, a repeat test should be done for up to 60 minutes if a robust basal to 30-minute cortisol change was observed. A total of 13% of the clinicians reported encountering cortisol levels below the pass threshold and peak cortisol levels being reached only 60min after the ACTH injection. Other studies have reported similar results and have suggested that 60-min cortisol measurement is integral to the SST protocol. 4, 5, 6, 7, 8 Section 37 of the 2001 Act sets out the circumstances when a short SST given on any of the antisocial behaviour grounds is automatically converted to an SST. Short Synacthen test (SST) involves measuring the baseline, 30-, and 60-minute serum cortisol levels, after injecting 250 μg of synthetic adrenocorticotropic hormone or Synacthen (ACTH). This study aimed to review the current clinical practice of performing SST to establish a standardized test protocol and to additionally test the hypothesis regarding performing the 60-minute cortisol test alone and the dependence of overall SST result on baseline cortisol level. Our survey did not indicate any baseline morning cortisol levels that most clinicians considered adequate for the integrity of the HPA axis and will refrain from conducting SST. In contrast to this observation, we have previously shown 1 that a baseline morning cortisol threshold of 226nmol/L has a 93% positive predictive value for a normal SST. Yip etal. 2 and Watts etal. 3 have reported identical results. The SST involves extensive planning and time for clinicians, patients, and nursing staff. Furthermore, the pharmacy and the laboratory costs are high. Therefore, clinicians should use targeted testing of SST in patients with a high pretest probability of HPA axis abnormality or with low baseline serum cortisol results.

A variety of SST protocols are used. Some protocols involve the measurement of serum cortisol at 30 and 60min after ACTH injection, whereas others involve just a 30- or 60-min cortisol measurement after the injection. Likewise, some protocols include baseline serum cortisol and ACTH measurement before the ACTH injection, whereas other protocols do not require this step. Cho et al. investigated [4] over 200 healthy individuals to define the normal thresholds for serum cortisol levels upon stimulation in dynamic studies; however, they used an RIA instead of the traditional fluorometric assay, used in earlier studies. [1] Following an ITT, the 95 th percentile of the peak serum cortisol was 15 μg/dL (414 nmol/L), which was proposed to be the reference level for healthy volunteers. The study participants also underwent either a low dose (1 μg) or standard dose (250 μg) SST. All those who underwent the low dose SST had serum cortisol level >18 μg/dL (497 nmol/L) while those who underwent the standard-dose SST had serum cortisol ≥20 μg/dL (550 nmol/L). The use of this threshold as the standard dose SST was therefore suggested. [4] They also measured cortisol levels with 2 different RIAs and found that the results correlated with each other. Abbreviations: ACTH = adrenocorticotropic hormone, ANOVA = analysis of variance, HPA = hypothalamic-pituitary-adrenal, ITT = insulin tolerance test, SST = short Synacthen test. Other indications (autoimmune disease, hyponatremia, vomiting, weight loss, hyperkalemia, hypoglycemia, hypotension, collapse, fatigue)Kaplan-Meier plots estimating time to recovery of HPA axis function in 110 patients with AI due to exposure to suppressive doses of glucocorticoid therapy stratified by (a) basal (0-min) cortisol of the same test, (b) 30-min cortisol, and (c) delta cortisol (30-min – basal cortisol) of their initial SST. (d) ROC curve analysis to determine the ability of the characteristics of the initial SST to predict eventual recovery of adrenal function. Our study has several strengths. The participation of clinicians from a wide range of specialties and grades increased the power of our survey data. This survey, the first from our region, provides insight into the different SST protocols used in our area and the variations in practice among different grades and specialties. Therefore, this survey adds invaluable information to the literature.