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. Where the tenancy is a short SST on any of the antisocial behaviour grounds and the landlord has served a notice of proceedings for recovery of possession of the tenancy on the tenant within 12 months of creation of the tenancy (or 18 months in cases where an extension notice has been served following creation of the short SST), [42] and either the notice: 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

A binomial logistic regression was performed on the whole cohort to ascertain the effects of selected variables on the likelihood that participants will show recovery at the subsequent test. Six variables were inserted into the model: age, sex, 30-minute cortisol, basal cortisol of the subsequent test, use of steroid medication, and different assay used. Linearity of the continuous variables with respect to the logit of the dependent variable was assessed via the Box-Tidwell (1962) procedure. A Bonferroni correction was applied using all six terms in the model resulting in statistical significance being accepted when P< 0.008. Based on this assessment, all continuous independent variables were found to be linearly related to the logit of the dependent variable. Data are expressed as median with 95% CI assuming a normal distribution.Setting the baseline cortisol threshold: We clarified the correlation between the baseline cortisol level and the final SST results. 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 The test does not require hospital admission but please note the contraindications and precautions. No dietary preparation is required. Current or recent steroid therapy may make result interpretation difficult. At our institution, we measure the serum ACTH levels before ACTH administration. This later helps to differentiate between primary and secondary adrenal insufficiency in those who show insufficient cortisol response. The objective of this study was to determine the current clinical practice involved in performing SST and to establish a standardized test protocol. 2 Objectives

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. In the pituitary disease group of patients with SAI, 57% of patients with nonfunctioning pituitary tumors and 44% of patients who underwent pituitary surgery subsequently passed the SST. This is significantly higher than one would have expected and has major potential implications for clinical practice. Although untreated or unrecognized AI confers the risk of adrenal crisis and increased morbidity and mortality, it has also become increasingly evident that morbidity and mortality are increased in patients with AI taking replacement GC ( 10–16). The mortality excess is largely due to increased cardiovascular deaths ( 15), most likely from subtle but prolonged increase in either dose of GC replacement and/or a noncircadian mode of replacement, effectively leading to mild Cushing syndrome ( 17). Impaired quality of life is a further major issue that again appears to be related to AI but also GC exposure ( 18, 19). The realization that many patients with established SAI might recover endogenous adrenal function and thereby avoid lifelong GC replacement is clearly important. The binomial logistic regression model was statistically significant ( χ 2 = 143.8, P< 0.0001) and explained 47.9% of the variance in adrenal recovery, correctly classifying 88.6% of cases. Sensitivity was 72%, specificity was 94.7%, positive predictive value was 83.2%, and negative predictive value was 90.0%. Of the six predictor variables incorporated into the model, two were statistically significant: 30-minute cortisol ( P< 0.0001) and the basal cortisol of the subsequent test ( P< 0.0001). Lower 30-minute cortisol and basal cortisol of the subsequent test were associated with an increased likelihood of failing the subsequent test. HPA axis recovery Proposed flow chart for the use of SST in patients with potentially reversible causes of AI. *Random morning cortisol was measured between 9 and 12 am and at least 18 h after the last dose of glucocorticoid.the expiry of the 12 month period from the creation of the tenancy (or the expiry of 18 months from the creation of the tenancy in cases where an extension notice has been served), whichever is the later.

A normal response does not exclude ACTH deficiency which requires an endocrine referral if suspected. We reminded the clinicians of their responses to the standard dose SST (250 mcg cosyntropin injection) to enable comparison with our previous study. 1 We excluded pediatric clinicians from the survey. 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. Ensure that you have read the contraindications and precautions as given in the Synacthen product information sheet. Having done so it is the responsibility of the investigating medical officer to decide whether it is safe to proceed with this investigation. It remains unclear why no records were kept for a majority of our patients on the indications for performing the test in the medical notes. As this test is associated with a risk of allergic reaction and is expensive to run, the justification of performing it is crucial from a clinical, medicolegal, economical and insurance coverage perspective. The UK wide national audit of SST outcomes showed that 47% of the respondents did not record indications for the test. [18] This reflects poor medical documentation and the need for effective medical documentation. We plan to disseminate these results to our medical colleagues through the institutional quality management team.AI has classically been subdivided into primary (conditions directly impacting upon adrenal function, such as Addison disease) and secondary AI (diseases limiting pituitary ACTH synthesis and secretion). Although many of these underlying conditions are believed to be irreversible, for example, the impact of pituitary radiotherapy, there are many situations in which recovery of hypothalamo-pituitary-adrenal (HPA) axis function may occur. As a specific example, the widespread use of glucocorticoid therapy ( 5, 6), largely for its anti-inflammatory actions, is associated with many adverse effects, including AI as a result of ACTH suppression ( 7, 8). Indeed, this is probably the commonest form of AI, although almost certainly underrecognized ( 1).

Abbreviations: ACTH = adrenocorticotropic hormone, ANOVA = analysis of variance, HPA = hypothalamic-pituitary-adrenal, ITT = insulin tolerance test, SST = short Synacthen test.

We have therefore undertaken a retrospective analysis of repeat SSTs performed in patients with potentially reversible causes of AI to determine if there are features of the SST results (basal, 30-minute, or delta cortisol) that might both guide a strategy for repeat testing and in addition help to identify groups of patients in whom HPA axis function is likely (or unlikely) to be restored. Materials and Methods Patient selection Data collection and curation: Hadeel Aljamei, Lama Amer, Muhammad Sohaib Khan, Eman Alrajhi, Anhar Alnassar, Reem Alahmed, Mohammed Abufarhaneh, Fayha Farraj Abothenain, Dina Mahmoud Ahmad Aljayar. Overall, 37% of patients of the whole cohort who initially failed the SST eventually went on to pass, and 57% of those with nonfunctioning pituitary tumors and 44% of those patients who underwent pituitary surgery eventually passed the SST. Logistic regression modeling