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Objective: Increasing referrals to Endocrinology with nonspecific symptoms of suspected adrenal insufficiency (AI) has increased use of the short-synacthen test (SST). Prevailing resource and safety concerns emphasise importance of patient selection criterion to optimise SST use. This study aimed to (1) document the adverse event profile of the SST (2) identify any pretest predictors of SST outcome., Design, Patients and Measurements: Retrospective data analysis of all patients referred for SST in Oxford from 2017 to 2021. Pretest clinical variables (age, sex, BMI, blood pressure and electrolytes), symptoms (fatigue, dizziness, weight loss) and pretest morning cortisol were included in the statistical model with the aim of identifying any variables that could predict SST outcome in Group 1 primary AI, Group 2 central AI and Group 3 glucocorticoid induced AI. Symptoms and signs during and post SST were also noted with the aim of describing adverse effects to synacthen across a large cohort., Results: A total 1480 SSTs (Males:38%, age 52 [39-66] years) were performed: 505 (34.1%) in Group 1, 838 (57%) in Group 2, and 137 (9.3%) in Group 3. Adverse-effects were recorded in 1.8% of tests, including one episode of anaphylaxis. Pretest morning-cortisol was the only predictor for an "SST pass" (whole cohort: B = 0.015, p < 0.001, Group 1: B = 0.018, p < .001; Group 2: B = 0.010, p < 0.012; Group 3: B = 0.018, p = <.001). A threshold of ≥343 nmol/l (receiver-operating characteristic [ROC] area under the curve [AUC] = 0.725, 95% confidence interval [CI] 0.675-0.775, p < 0.001) for the whole cohort, ≥300 nmol/L (ROC AUC = 0.763, 95% CI 0.675 to 0.850, p < 0.001) for Group 1, ≥340 nmol/L (ROC AUC = 0.688, 95% CI 0.615 to 0.761, p < 0.001) for Group2, and ≥376 nmol/L [baseline cortisol] (ROC AUC = 0.783, 95% CI 0.708 to 0.859, p < 0.001) for Group 3, predicted an 'SST pass' with 100% specificity., Conclusions: Adverse effects to synacthen are rare. Pretest morning cortisol is a reliable predictor for SST outcome and is a helpful tool to rationalise use of the SST. Predictive morning-cortisol thresholds vary according to the aetiology of AI., (© 2023 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Competing Interests: We declare no competing interests.

Background: Low-grade incomplete post-dexamethasone cortisol suppression in patients with adrenal incidentalomas - recently defined as possible autonomous cortisol secretion (pACS) - has been associated with increased cardiovascular events and mortality. However, prospective studies documenting cardiac abnormalities in these patients are lacking., Subjects and Methods: Between July 2016 and September 2017, 71 consecutive patients with adrenal lesions were prospectively screened for hypercortisolism by dexamethasone suppression test (NCT 02611258). Complete anthropometric, metabolic and hormonal parameters were recorded along with full cardiac ultrasound assessment and noninvasive measurement of arterial stiffness. All patients underwent chemical-shift magnetic resonance imaging to characterize the lesions. Cardiovascular outcomes were recorded in blind., Results: According to post-dexamethasone suppression cortisol values (post-DST), 34 patients had pACS and 37 non-functioning adenomas (NFA). The two groups were similar in sex, BMI, age distribution, cardiovascular risk factors and comorbidities. Left ventricular mass index (LVMI BSA ) was increased in pACS compared to NFA ( P  = 0.006) and mildly correlated to the post-DST cortisol level (rho = 0.347; P  = 0.004). The post-DST cortisol levels explained up to 13.7% of LVMI BSA variance ( P  = 0.002). Compared to NFA, patients with pACS had a higher prevalence of diastolic dysfunction (35.1% vs 82.6%; P  = 0.001) and worse arterial stiffness assessed by pulse wave velocity ( P  = 0.033)., Conclusions: In apparently asymptomatic patients, mild autonomous cortisol secretion can sustain early cardiac and vascular remodeling, independently of other risk factors. The morphological and functional cardiovascular changes observed in pACS underline the need for further studies to correctly define the long-term management of this relatively common condition., (© 2018 The authors.)

Context The adrenocorticotropin hormone stimulation test (AST) is used to diagnose adrenal insufficiency, and is often repeated in patients when monitoring recovery of the hypothalamo–pituitary–adrenal axis. Objective To develop and validate a prediction model that uses previous AST results with new baseline cortisol to predict the result of a new AST. Methods This was a retrospective, longitudinal cohort study in patients who had undergone at least 2 ASTs, using polynomial regression with backwards variable selection, at a Tertiary UK adult endocrinology center. Model was developed from 258 paired ASTs over 5 years in 175 adults (mean age 52.4 years, SD 16.4), then validated on data from 111 patients over 1 year (51.8, 17.5) from the same center, data collected after model development. Candidate prediction variables included previous test baseline adrenocorticotropin hormone (ACTH), previous test baseline and 30-minute cortisol, days between tests, and new baseline ACTH and cortisol used with calculated cortisol/ACTH ratios to assess 8 candidate predictors. The main outcome measure was a new test cortisol measured 30 minutes after Synacthen administration. Results Using 258 sequential ASTs from 175 patients for model development and 111 patient tests for model validation, previous baseline cortisol, previous 30-minute cortisol and new baseline cortisol were superior at predicting new 30-minute cortisol (R 2 = 0.71 [0.49-0.93], area under the curve [AUC] = 0.97 [0.94-1.0]) than new baseline cortisol alone (R 2 = 0.53 [0.22-0.84], AUC = 0.88 [0.81-0.95]). Conclusion Results of a previous AST can be objectively combined with new early-morning cortisol to predict the results of a new AST better than new early-morning cortisol alone. An online calculator is available at https://endocrinology.shinyapps.io/sheffield%5fsst%5fcalculator/ for external validation. [ABSTRACT FROM AUTHOR]