In secondary adrenal insufficiency (SAI), the Synacthen test can give a false negative result. If disease is strongly suspected, an insulin hypoglycaemia test or Metyrapone (Metopirone) test should be carried out. Insulin test could be hazardous for patients with adrenal insufficiency (due to high risk of severe hypoglycaemia), so in our clinic we use overnight single-dose Metyrapone test. Although this test is easy to perform, measurement of 11-deoxycortisol concentration is not a standard procedure in most laboratories. Since the essence of Metyrapone test in secondary adrenal insufficiency is to evaluate the corticotropin reserve of hypophysis, the assessment of ACTH increment would be the ideal single measurement to state the diagnosis. However, recommendations in different guidelines are inconsistent about interpretation of ACTH results in this test. Proposed cut-off values for post-metyrapone ACTH response vary from >75 (Endocrine testing protocols in Endotext) to >200 pg/ml (Summary of Product Characteristic). The aim of the study was evaluation of ACTH response to single-dose Metyrapone administered at midnight and comparison of ACTH and 11deoxycortisol concentrations achieved during the test. In 110 persons (101 women and 9 men) referred to our clinic with suspicion of secondary adrenal insufficiency, the overnight single-dose Metyrapone test was done. On the basis of low post-metyrapone 11deoxycortisol concentration (<7 μg/dl) the diagnosis was confirmed in 38 patients (6 men and 32 women). The post-metyrapone ACTH values were 2-327 pg/ml (120.7±94.3) in patients with confirmed SAI and 110645 pg/ml (270.6±156.7) in healthy subjects. There was no correlation between post-metyrapone ACTH and 11deoxycortisol levels in neither group (r=0.36 and 0.16 respectively). Using the lower ACTH cut-off value (75 pg/ml) 20 patients with SAI would be missed. Using the higher ACTH cut-off value (200 pg/ml) the diagnosis would still be false-negative in seven patients. Even though it seems logical that single ACTH measurement should be sufficient to establish the proper diagnosis of SAI, our results don ot support this hypothesis. Therefore, the concurrent assessment of 11deoxycortisol concentration is necessary. Moreover, proposed cut-off values for this test should be revised.
18 - 21 May 2019
European Society of Endocrinology