Objective: To discover the value of low-dose (LDAT) and standard-dose ACTH tests (SDAT) as compared with the metyrapone test in the diagnosis of secondary adrenal insufficiency. Patients and Methods: LDAT (0.5 mug/m(2)), SDAT (250 mug/m2) and overnight metyrapone (30 mg/kg) tests were carried out in 29 patients with suspected adrenal insufficiency. LDAT and SDAT were also performed in 36 control subjects. Results: 18 of 29 patients were grouped in the adrenal-sufficient (AS) group and 11 of 29 patients in the adrenal-deficient (AD) group according to the metyrapone test results. The control group had significantly higher cortisol responses than the AS and AD groups during LDAT. The control group had similar cortisol responses to the AS group but higher cortisol responses than the AD group during SDAT. The AS group was divided into 2 subgroups: AS patients with multiple pituitary hormone deficiencies (AS-multiple) and AS patients with idiopathic growth hormone deficiencies (AS-isolated). The AS-multiple group had statistically lower cortisol responses than the control group during LDAT. Receiver-operating characteristics analysis revealed that the cortisol cutoff value in LDAT was 19.8 mug/dl (100% sensitivity, 89% specificity) and 30.4 mug/dl in SDAT (82% sensitivity, 78% specificity). Conclusion: LDAT is capable of identifying patients with adrenal insufficiency more effectively than SDAT. The cortisol cutoff value in LDAT was calculated as 19.8 mug/dl with 100% sensitivity. AS patients with multiple pituitary hormone deficiencies had lower cortisol responses to LDAT than the control group implying that these patients might have a lower cortisol secretory capacity than healthy subjects. Copyright (C) 2003 S. Karger AG, Basel.