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The Low Dose (1-µg) Adrenocorticotropin Stimulation Test in the Evaluation of Patients with Suspected Central Adrenal Insufficiency

Division of Endocrinology and Metabolism, Department of Internal Medicine, Emory University School of Medicine (L.M.T.), Atlanta, Georgia 30322; and the Division of Endocrinology and Diabetes, Department of Internal Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Address all correspondence and requests for reprints to: Leonard M. Thaler, M.D., Division of Endocrinology, 1639 Pierce Drive, Room 1301 WMRB, Atlanta, Georgia 30322. E-mail: lthaler{at}emory.edu

Currently, the most popular test for adrenal insufficiency is the conventional rapid ACTH stimulation test (250 µg ACTH). This method is quick and safe, but incorporates a dose of ACTH that is supraphysiological and capable of transiently stimulating the adrenal cortex in many patients with documented central adrenal insufficiency. In recent years, several investigators have published substantial evidence for a more sensitive ACTH stimulation test using a lower dose of ACTH (1 µg). Further analysis of these data, including the calculation of likelihood ratios, demonstrates that the 1-µg test performs significantly better than the 250-µg test compared to the gold standard, insulin tolerance test. We suggest that the 1-µg ACTH stimulation test replace the conventional 250-µg test when evaluating for central adrenal insufficiency. A cortisol level below 500 nmol/L after 30 min signifies impaired adrenocortical reserve. An insulin tolerance test should be performed if this low dose test results in a borderline value and the diagnosis is questioned. The 1-µg test should not be used if recent pituitary injury is suspected. Pharmaceutical companies should be encouraged to provide synthetic ACTH in 1-µg vials.

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