11-deoxycortisol, other hormones and pituitary function characteristics in the diagnosis of adrenal insufficiency in the overnight oral metyrapone test

Summary The oral metyrapone test is utilized to assess pituitary adrenal axis function. We asked whether 17-hydroxyprogesterone, androstenedione or corticotropin are similarly as useful as 11-deoxycortisol to detect adrenal insufficiency. Of the SHIP-PAGE study participants, 190 patients underwent an oral metyrapone test. The diagnosis of adrenal insufficiency included information from the clinical course, concentrations of adrenal steroids and ACTH before or after metyrapone as well as results of other pituitary function tests. Of the 190 patients, 67 had adrenal insufficiency and 123 had not. ROC analysis showed the highest sensitivity (83 %), specificity (>90 %) and area under the curve of 0.9 for 11-deoxycortisol at a cut-off of 197 nmol/l. Surges in 11-deoxycortisol were related to those of 17-hydroxyprogesterone, androstenedione, and corticotropin that displayed lower sensitivities, specificities and areas under the curve with cut-off values of 5.55 nmol/l, 8.11 nmol/l and 89.60 pg/ml, respectively. Presence of gonadal dysfunction had a high sensitivity of 61 % and prolactin deficiency a high specificity (96 %) for prediction of adrenal insufficiency as had a combined dysfunction of the gonadal, growth hormone, and thyroid axes (97 %). In conclusion, 11-deoxycortisol is an already established parameter with a good performance in the oral metyrapone test which was not outperformed by 17-hydroxyprogesterone, androstenedione, or corticotropin. However, there maybe a substantial bias to this result. Therefore, determination of pituitary-end-organ axes functions is likewise helpful to provide probability information in the assessment of adrenal insufficiency which remains a diagnosis based on clinical information and endocrine function tests. Significance statement The oral metyrapone test is very useful for the characterization of adrenal function. If available, analysis of 11-deoxycortisol is better than measurements of other adrenal steroid hormones or corticotropin. However, there may be a bias from previous studies on the metyrapone test. Therefore, analysis of corticotropin, androstenedione, and 17-hydroxyprogesterone concentrations at baseline and the day after metyrapone administration are also very helpul for evaluation of adrenal function when the results from other pituitary function tests are included in the diagnostic process.