Validation of the 1 μg short synacthen test: an assessment of morning cortisol cut-off values and other predictors

Clinical practice shows that many low-dose short synacthen tests (LD-SSTs) for diagnosing adrenal insufficiency in an outpatient setting have a normal outcome and could be considered superfluous. The objective of this study is to provide a guideline to safely reduce the number of unnecessarily performed LD-SSTs.

Data of LD-SSTs performed in outpatients were collected. Optimal morning cortisol cut-off values were determined using ROC analysis. Subsequently the predictive value of several variables was tested using univariable and multivariable logistic regression analyses.

A morning cortisol lower cut-off value of 145 nmol/l (specificity 89.9%, positive predictive value 90.0%) and an upper cut-off value of 375 nmol/l (sensitivity 100.0%, negative predictive value 100.0%) were found. Chronic fatigue symptoms and symptoms of hypotension or orthostasis as the main reason for performing the test predict a normal outcome. The use of glucocorticosteroids predicts an abnormal outcome of the LD-SST. Oral, topical, nasal and inhaled glucocorticosteroids are each significant predictors when analysed specifically for predicting central adrenal insufficiency.

By using morning cortisol cut-off values of 145 nmol/l and 375 nmol/l instead of the conventional cut-off values, the number of LD-SSTs performed in an outpatient setting can be reduced by 12%, while maintaining high sensitivity and specificity. Furthermore, the outcome of the LD-SST can be predicted by additional variables such as the indication for performing the test and the use of glucocorticosteroids. Different routes of administration of glucocorticosteroids such as inhalation or topical use should be taken into account when central insufficiency is suspected.