Adrenocorticotropin stimulation tests in patients with hypothalamic-pituitary disease: low dose, standard high dose and 8-h infusion tests

Objectives Low doses of ACTH [1-24] (0.1, 0.5 and 1.0 mug per 1.73 m(2)) ma y provide a more physiological level of adrenal stimulation than the standa rd 250 mug test, but not all studies have concluded that the 1.0 fig is a m ore sensitive screening test for central hypoadrenalism. Eight-hour infusio ns of high dose ACTH [1-24] have also been suggested as a means of assessin g the adrenals' capacity for sustained cortisol secretion. In this study, w e compared the diagnostic accuracy of three low dose ACTH tests (LDTs) and the 8-h infusion with the standard 250 jig test (HDT) and the insulin hypog lycaemia test (IHT) in patients with hypothalamic-pituitary disease. Subjects and design Three groups of subjects were studied. A healthy contro l group (group 1, n=9) and 33 patients with known hypothalamic or pituitary disease who were divided into group 2 (n=12, underwent IHT) and group 3 (n =21, IHT contraindicated). Six different tests were performed: a standard I HT (0.15 U/kg soluble insulin); a 60-minute 250 mug HDT; three different LD Ts using 0.1 mug, 0.5 mug and 1.0 mug (all per 1.73 m(2)); and an 8-h infus ion test (250 mug ACTH [1-24] at a constant rate over 8 h). Results Nine out of the 12 patients in group 2 failed the IHT. Three out of 12 patients from group 2 who clearly passed the IHT, also passed all the A CTH [1-24] stimulation tests. Seven of the 9 patients who failed the lHT, f ailed by a clear margin (peak cortisol <85% of the lowest normal). Two of t he 7 also failed all the ACTH [1-24] tests. Five of the 7 patients had disc ordant results, four passed the 0.1 LDT, one (out of four) passed the 0.5 L DT, none (out of three) passed the 1.0 LDT, two passed the HDT and three pa ssed the 8-h test. Two patients were regarded as borderline fails in the IH T. Both passed the ACTH [1-24] tests, although one was a borderline pass in the 8-h test. Only five out of the 21 patients in group 3 showed discordan ce between the HDT and the LDTs, One patient passed the HDT and failed the 0.1 LDT, four patients failed the HDT but passed some of the different LDTS . Conclusions We conclude that in the diagnosis of central hypoadrenalism, AC TH [1-24] stimulation tests may give misleading results compared to the IHT . The use of low bolus doses of ACTH [1 -24] (1.0, 0.5 or 0.1 <mu>g) or a h igh dose prolonged infusion does not greatly improve the sensitivity of ACT H [1-24] testing. Dynamic tests that provide a central stimulus remain pref erable in the assessment of patients with suspected ACTH deficiency.