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. 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. Of the 965 patients identified from pharmacy, medical, and laboratory records, 849 were included. Mean baseline, 30-, and 60-minute cortisol levels after ACTH injection were 394 ± 286.58, 722 ± 327.11, and 827 ± 369.30 nmol/L, respectively. Overall, 715 (84%) and 134 (16%) patients had normal and abnormal responses, respectively. Primary and secondary adrenal insufficiency was diagnosed in 10% and 35%, respectively, while ACTH levels were not measured in 55% of the patients. Overall, 9.49% (n = 72) of the patients had a suboptimal response at 30 minutes, but reached the threshold value of 550 nmol/L at 60 minutes. This particular subgroup's mean change (240 nmol/L) in cortisol level from baseline to 30-minute was higher than that observed in patients with abnormal response at both time-points (mean change, 152 nmol/L). No patient with 30-minute optimal responses had 60-minute suboptimal responses. The baseline serum cortisol threshold of ≥226 nmol/L had 80% sensitivity, 71% specificity, and 93% positive predictive value for detecting a normal SST ( P -value < .0001). Relying on a 60-minute cortisol level can identify all normal and abnormal responses, while relying on 30-minute cortisol level alone may produce false-positives. Additionally, a baseline cortisol level of ≥226 nmol/L is a reliable threshold for determining adequate adrenal function, particularly with a low pretest hypoadrenalism probability.
Purpose of reviewThe pivotal phase III trials demonstrating efficacy and safety of direct oral anticoagulants (DOACs) in the treatment of venous thromboembolism (VTE) or nonvalvular atrial fibrillation (NVAF) excluded patients with important and common comorbidities, including obesity, advanced chronic kidney disease, cirrhosis, cancer and antiphospholipid antibody syndrome. Despite the lack of large prospective randomized control trials in these patient populations, the use of DOACs has led to a wealth of efficacy and safety data within these groups. Recent findingsRetrospective studies, meta-analyses, national databases and pharmacokinetic data have shed light on the efficacy and safety of DOACs in these patient populations. Although DOACs should be avoided in those with high-risk triple positive antiphospholipid antibody syndrome, advanced cirrhosis, advanced kidney disease and intact gastrointestinal cancers, and used with caution in genitourinary cancers, their use extends beyond the inclusion criteria of the initial randomized control trials. SummaryDOACs have revolutionized anticoagulant management and have become the cornerstone for VTE treatment and stroke prevention in NVAF. The decision to use DOACs must be individualized. Patient preference, underlying comorbidities and informed consent must always be considered when selecting the most appropriate anticoagulant.
Background SST is done to assess adrenal gland function by measuring basal serum cortisol followed by injecting 250 μg of Synacthen (ACTH) & measuring cortisol at 30 & 60 minutes. Design All patients over 14 years (adulthood age in the region) who had undergone a SST from January 2010 to December 2017 were included. Patients who underwent pituitary surgery in preceding 2 months, on exogenous steroids, opioids & oral contraceptives were excluded. Stimulated cortisol of 550 nmol/L or more achieved at 30, 60 minutes or both was classified as a normal response. Results 965 patients were identified from pharmacy, medical & laboratory records. 116 patients were excluded and 849 were included in the analysis. Mean age was 50.5 ± 20.45 years. Mean weight was 67 ± 21 Kg. 54% patients were female. Mean basal, 30 and 60 minutes cortisol values after ACTH injection were 394 ± 286.58 nmol/L, 722 ± 327.11 nmol/L, 827 ± 369.30 nmol/L respectively. 715 patients (84 %) had a normal response and 134 patients (16 %) had suboptimal response. Primary and secondary adrenal insufficiency was diagnosed in 10% and 35% respectively. No ACTH value was available in 55% of the patients. Suboptimal response was observed at 30 minutes in 9.49% (n=72) of the patients: all crossed 550 nmol/L threshold at 60 minutes. Mean change of cortisol level from baseline to 30 minutes was 240 nmol/L in this particular sub group which was higher than the mean change of 152 nmol/L observed in patients who failed the test overall up to 60 minutes. No patient with optimal response at 30 minutes had suboptimal response at 60 min. Morning basal cortisol threshold of 226 nmol/L or over had 80% sensitivity, 71 % specificity & 93% positive predictive value to detect a normal SST (P-value <.0001). Conclusion 60 minute cortisol correctly identified all normal and abnormal results. Relying only on 30 min value resulted in significant false positive results. Morning basal cortisol over 226 nmol/L should be considered reliable threshold for adequate adrenal function particularly when clinicians have low pretest probability for hypoadrenalism.
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