Low-dose short synacthen test with salivary cortisol in patients with suspected central adrenal insufficiency

Context: the low-dose short synacthen test (LDSST) is recommended for patients with suspected central adrenal insufficiency (AI) if their basal serum cortisol (F) levels are not indicative of an intact hypothalamic-pituitary-adrenal (HPA) axis. Objective: to evaluate diagnostic threshold for salivary F before and 30 minutes after administering 1 μg of synacthen, performed before 09:30 h. Design: a cross-sectional study from 2014 to 2020. Setting: a tertiary referral university hospital. Patients: 174 patients with suspected AI: 37 with central AI and 137 adrenal sufficient (AS). Main outcome measure: the diagnostic accuracy (sensitivity [SE], specificity [SP]) of serum and salivary F levels, measured respectively by chemiluminescence immunoassay and liquid chromatography-tandem mass spectrometry. Results: low basal serum or salivary F levels could predict AI. For the LDSST, the best ROC-calculated threshold for serum F to differentiate AI from AS was 427 nmol/L (SE 79%, SP 89%), serum F >500 nmol/L reached SP 100%. A salivary F peak >12.1 nmol/L after administering synacthen reached SE 95% and SP 84% for diagnosing central AI, indicating a conclusive reduction in the likelihood of AI. This ROC-calculated threshold for salivary F was similar to the 2.5th percentile of patients with a normal HPA axis, so it was considered sufficient to exclude AI. Considering AS those patients with salivary F >12.1 nmol/L after LDSST we could avoid unnecessary glucocorticoid treatment: 99/150 subjects (66%) had an inadequate serum F peak after synacthen, but salivary F was >12.1 nmol/L in 79 cases, who could therefore be considered AS. Conclusions: Salivary F levels >12.1 nmol/L after synacthen administration can indicate an intact HPA axis in patients with an incomplete serum F response, avoiding the need to start glucocorticoid replacement treatment.