Comparison of Adrenocorticotropin (ACTH) Stimulation Tests and Insulin Hypoglycemia in Normal Humans: Low Dose, Standard High Dose, and 8-Hour ACTH-(1–24) Infusion Tests1

• Published in: The journal of clinical endocrinology and metabolism 1999-10, Vol.84 (10), p.3648-3655
• Main Authors: Nye, Elisabeth J., Grice, Jeffrey E., Hockings, Gregory I., Strakosch, Christopher R., Crosbie, Georgina V., Walters, Margaret M., Jackson, Richard V.
• Format: Article
• Language: English
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.84.10.6062

The efficacy of the standard high dose ACTH stimulation test (HDT), using a pharmacological 250-μg dose of synthetic ACTH-(1–24), in the diagnosis of central hypoadrenalism is controversial. The insulin hypoglycemia test is widely regarded as the gold standard dynamic stimulation test of the hypothalamo-pituitary-adrenal (HPA) axis that provides the most reliable assessment of HPA axis integrity and reserve. Alternatively, a prolonged infusion of ACTH causes a continuing rise in plasma cortisol levels that may predict the adrenals’ capacity to respond to severe ongoing stress. In nine normal subjects, we compared plasma ACTH and cortisol levels produced by three iv bolus low doses of ACTH-(1–24) (0.1, 0.5, and 1.0μ g/1.73 m2; LDTs) with those stimulated by hypoglycemia (0.15 U/kg insulin) and with the cortisol response to a standard 250-μg dose of ACTH-(1–24). The normal cortisol response to an 8-h ACTH-(1–24) infusion (250 μg at a constant rate over 8 h) was determined using three modern cortisol assays: a high pressure liquid chromatography method (HPLC), a fluorescence polarization immunoassay (FPIA), and a standard RIA. In the LDTs, stepwise increases in mean peak plasma ACTH were observed (12.4 ± 2.0, 48.2 ± 7.2, 120.2 ± 15.5 pmol/L for the 0.1-, 0.5-, and 1.0-μg LDTs, respectively; P values all