Diagnostic utility of morning serum cortisol in predicting short synacthen test outcomes in outpatients with suspected adrenal insufficiency

BACKGROUND: Adrenal insufficiency (AI) often presents with non-specific symptoms such as fatigue, posing a diagnostic challenge in outpatient settings. While the 250 µg short Synacthen test (SST) remains the gold standard for assessing adrenal function, it may be resource-intensive and inconvenient. Morning serum cortisol (MSC) offers a potential alternative for initial screening, but its predictive value for SST outcomes in community-referred patients remains uncertain. OBJECTIVE: To evaluate the correlation between MSC and SST outcomes in outpatients presenting with non-specific symptoms suggestive of AI, and to identify MSC thresholds predictive of normal SST. METHODS: This retrospective cross-sectional study analyzed 228 SSTs performed between 2006 and 2021 on adult outpatients without known endocrine disease. MSC was measured prior to 250 µg intravenous Synacthen administration, with cortisol levels re-assessed 30 min post-injection (Cort30). Pearson correlation and Receiver Operating Characteristic (ROC) curve analysis were used to assess associations and identify optimal MSC cutoffs for predicting normal SST, defined as Cort30 ≥ 18 µg/dL (500 nmol/L). RESULTS: The mean MSC and Cort30 values were 9.4 ± 3.9 (259 ± 108 nmol/L) and 20.8 ± 7 µg/dL (574 ± 193 nmol/L), respectively. Applying ROC analysis, MSC threshold of 8.7 µg/dL (240 nmol/L) yielded the optimal performance, providing 83.2% sensitivity, 49.5% specificity, 69% PPV, 68.9% NPV, and 68.9% accuracy. Among patients with MSC ≥ 8.7 µg/dL (240 nmol/L), 83.2% had normal SST. MSC values of 3 µg/dL (83 nmol/L) and 15.5 µg/dL (428 nmol/L) demonstrated 100% sensitivity and 100% specificity for predicting normal SST, respectively. CONCLUSION: In patients referred from the community with non-specific symptoms, MSC measurement may provide a useful adjunct for evaluating adrenal function, especially when MSC results are at the extremes. CLINICAL TRIAL NUMBER: 0133-21-BNZ.