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. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. We conducted the study following the guidelines outlined in the declaration of Helsinki. This study was approved by the Institutional Ethics Committee of King Faisal Specialist Hospital & Research Centre and a waiver for the need for informed consent was granted. 3.1 Local SST protocol and interpretation Our study has the following strengths including: a large sample size with generalizability in terms of age, sex, body habitus, and reflected daily clinical practice; it is the largest study on this subject to the best of our knowledge; and no previous studies have reported on this subject from our geographical area. Therefore, this research adds valuable information to the literature. Since different cortisol assays have different sensitivity and specificity, we used the same assay to perform all tests to ensure accuracy of the results.

Adrenal insufficiency (AI) is a life-threatening condition with an established increase in morbidity and mortality ( 1–3) that is characterized by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids ( 4). 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. 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. 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. 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.We conducted the study from mid-January 2021 to the end of February 2021. After the initial invitation, we sent three further reminders, each 1 week apart. We concluded the survey 6 weeks after the initial invitation, then proceeded with data analysis. We collaborated with the institutional biostatistics department in the design of the questionnaire survey and the data analysis. 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

Section 10(2) of the 2014 Act amends section 37 to reflect the fact that a short SST can be extended. The amendments ensure that where a tenancy is a short SST given on any of the antisocial behaviour grounds and the landlord has not served a notice of proceedings for recovery of possession of the tenancy on the tenant before the expiry of the “relevant period”, the tenancy becomes an SST with effect from the expiry of the “relevant period”. 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. The authors would like to thank the Clinical Pharmacist, Mohamed Ahmed for the support. Author contributions We used frequency measures and percentages to describe physicians' common practices and attitudes toward the test protocols. We used chi-square tests to analyze the associations between the indications of SST with physicians' specialties and grades.Two cortisol assays were used to analyze samples across the SST: Siemens ADVIA Centaur (Siemens Health Care Diagnostics, Frimley, United Kingdom) and the Roche Modular System (Roche, Mannheim, Germany). Of the 1912 SSTs that were included in the analysis, 1368 (from 559 patients) were analyzed on the Roche assay and 544 (from 217 patients) on the Siemens assay. The same assay was used for repeated testing on the same patient. Serum cortisol analyzed by Siemens ADVIA Centaur showed an interassay imprecision of 10.5% at 83 nmol/L, 6.0% at 524 nmol/L, and 7.0% at 904 nmol/L and by the Roche Modular System of <8% for levels between 76 and 925 nmol/L. An analysis directly comparing the results from the Roche and Siemens assays is presented within the Results section. SST protocol and interpretation As described above, two different cortisol assays were used in this cohort study. In the main cohort, the logistic regression model as well as the ROC analysis did not show significant differences between assays. However, to confirm these findings, an analysis was performed for each assay individually using the value of the 30-minute cortisol and the subsequent random morning cortisol. Surprisingly, a 30-minute cortisol of 350 nmol/L (12.7 μg/dL) and a random morning cortisol of 200 nmol/L (7.3 μg/dL) represented the 95% specificity in the ROC analysis for both the assays. In addition, the proportion of patients that subsequently went on to pass the SST at 1, 2, and 4 years was entirely comparable between assays (1 year: 55% vs 57%; year 2: 88% vs 89%; year 4: 98% vs 99%; Roche vs Siemens) ( Supplemental Table 2). Discussion 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. As our study was a retrospective analysis, we collected data on all protocols adopted by the clinicians. We defined a normal response as a stimulated cortisol value ≥550 nmol/L achieved at 30 or 60 minutes or at both time points. An abnormal response referred to a stimulated cortisol value <550 nmol/L. Primary adrenal insufficiency was defined when the patient had an inadequate response (ie, cortisol <550 nmol/L with corresponding elevated ACTH levels when ACTH results were available). Secondary adrenal insufficiency was defined by an inadequate response (ie, cortisol <550 nmol/L with corresponding low ACTH levels when ACTH results were available). 3.2 Statistical analysis In accordance with the STROBE guidelines, we performed a retrospective cross-sectional review of data of all patients who underwent SST from January 2010 to December 2017 at our institution. We used a cut off age of 14 years (considered adulthood in the region) and identified eligible patients using the hospital electronic clinical documentation, laboratory, and prescription records.

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.Preparations should be made in advance to combat any anaphylactic reaction that may occur after the injection of Synacthen.