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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. 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

Other indications (autoimmune disease, hyponatremia, vomiting, weight loss, hyperkalemia, hypoglycemia, hypotension, collapse, fatigue) Preparations should be made in advance to combat any anaphylactic reaction that may occur after the injection of Synacthen. As well as the utility of the peak cortisol value post-SST, the authors highlight the importance of the delta cortisol to predict future recovery of AI. It is perhaps not surprising that in a group of patients with suppressed adrenal function post exogenous GC therapy as opposed to a “normal” population being evaluated for adrenal sufficiency, the incremental change in cortisol was clinically useful. However, it is important to stress that the SST in this context has yet to be validated against the ITT; Kane et al. ( 25) in a small series of GC treated rheumatology patients highlighted differences between the performance of the SST and ITT in patients with TAI; 8/22 patients failing the SST but passed the ITT. Abbreviations: ACTH = adrenocorticotropic hormone, ANOVA = analysis of variance, HPA = hypothalamic-pituitary-adrenal, ITT = insulin tolerance test, SST = short Synacthen test.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 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 Notably, 57% of our patients with nonfunctioning pituitary tumors and 44% of those patients who underwent pituitary surgery recovered HPA axis function at subsequent testing. This implies that there is realistic potential for reversibility of secondary AI in these patients. We ( 17) and others ( 10) have previously described the use of a morning cortisol to assess adrenal reserve, but to date, there have been very little attempts to use the SST to inform a strategy for repeating testing that in addition might serve as a guide as to the likelihood of restoration of HPA axis function. The short Synacthen (corticotropin) test (SST) at the conventional dose of 250 μg has been validated against the “gold standard” insulin tolerance test (ITT) to be a reliable tool in the investigation of patients with suspected AI ( 13–16). In contrast to the ITT, it is a simple test to perform, is well tolerated with very few adverse effects, and is relatively low cost. We, and others, have described the utility of a morning cortisol level to predict SST outcome as a strategy to rationalize the use of dynamic testing ( 11, 17); however, the results from the SST have the potential to be far more informative. It is well established that the 30-minute cortisol level is used as the criterion to define adequate or inadequate adrenal cortisol reserve, and is the standard by which decisions are made to instigate (or terminate) glucocorticoid replacement. This result provides a readout as to how the adrenal gland is functioning on that day and whether this is adequate or not. The test results are reliant upon the ability of the adrenal gland to respond to a pharmacological stimulus of synthetic ACTH, and although this may be reflected by the 30-minute cortisol, we speculate that the incremental response (delta cortisol: 30-minute minus 0-minute) might provide a predictive indicator for future adrenal gland recovery of function. 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

The reliance on the 30-minute serum cortisol value stems from studies done with ITT and how it relates to serum cortisol levels attainted 30 minutes after an adrenocorticotrophic hormone (ACTH) injection. [5] However, Dorin et al showed that ACTH concentration remains well above the threshold for maximal cortisol secretion for up to 2 hours following cortisol sampling, after IV SST. He showed that serum cortisol continues to rise and peaks 60 minutes after the ACTH injection in normal healthy adults. This provides a rationale for measuring 60-minute serum cortisol rather than just up to 30 minutes in patients who undergo SST. [6] Alia et al studied the profile of serum cortisol in 10 healthy volunteers after the low and standard doses SST with at least 1 week between each test; they observed that cortisol continues to rise, reaching a peak after 30 minutes irrespective of the ACTH dose. [7] Longui et al drew a similar conclusion when they examined 64 healthy adults with a standard dose SST and determined that peak serum cortisol was attained, 60 minutes after the injection. [8] The short Synacthen test is a test of adrenal insufficiency which can be used as a screening procedure in the non-critically ill patient. The test is based on the measurement of serum cortisol before and after an injection of synthetic ACTH (also known as tetracosactrin). We conducted the survey according to the ethical principles and policies of the Clinical Research Department at the King Faisal Specialist Hospital & Research Centre, which, together with the Saudi Medical Council, approved the study. 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.

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We invited endocrinologists and internists, including those in other associated sub-specialties registered with the Saudi Medical Council. We extended the invitation to consultants, associate consultants, assistant consultants, registrars, and endocrinology training fellows. Failure to meet the above criteria indicates probable Addison's disease or very marked adrenal atrophy secondary to prolonged absence of ACTH stimulation. Further tests are required to differentiate between the two. Tukey Kramer analysis for pairwise group comparisons of cortisol change from time 0 to 30 minutes. 5 Discussion