Endocrine Abstracts (2006) 11 P599

Sensitivity and specificity of different provocative tests for the diagnosis of secondary hypoadrenalism in patients with hypothalamo-pituitary disorders

A Picu, R Giordano, L Bonelli, M Balbo, M Pellegrino, R Berardelli, G Corneli, V Gasco, E Ghigo & E Arvat


Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy.


Insulin tolerance test (ITT) is considered the golden standard test to evaluate HPA axis in suspected hypopituitarism. Low dose (1 μg) ACTH1–24 short stimulation test (LDSST) and metyrapone are often used when ITT is contraindicated. The diagnostic reliability of LDSST is, however, controversial, as even this dose has been considered supramaximal, while very low ACTH doses have been suggested more reliable to assess the adrenal sensitivity. Thus, in patients with hypothalamo-pituitary disorders, we compared the reliability of ITT (0.1 U/kg i.v., 28 patients), metyrapone (MET, 30 mg/kg p.o., 28 patients), very low (VLDSST, 0.06 μg ACTH1–24 i.v., 14 patients), low (LDSST, 1.0 μg ACTH1–24 i.v., 28 patients) or supra-maximal ACTH1–24 doses (HDSST, 250 μg ACTH1–24 i.v., 28 patients) on ACTH and/or cortisol (F) secretion. SROC curve analysis was applied with the ITT as reference test, considering a normal response as cortisol peak >180 μg/l.

The higher ROC AUC values were found for LDSST, HDSST and MET. Particularly, LDSST sensitivity approached 0.85 with a specificity of 0.80 for cut-off values of F >210 μg/L; either HDSST or MET sensitivity approached 0.8 with a specificity of 0.85 for cut-off values of F>220 μg/l and ACTH >100 pg/ml, respectively. A sensitivity of at least 0.8 for VLDSST was associated to a very low specificity.

In conclusion, this study shows that, if compared with ITT, testing with very low ACTH doses may be misleading if used as a screening test in patients suspected for corticotroph deficiency. On the other hand, both low and high ACTH doses as well as metyrapone stimulation tests are equally reliable for the diagnosis of secondary hypoadrenalism, when used with appropriated cut-off limit.