Potentiation of the classic ovine corticotrophin releasing hormone stimulation test by the combined administration of small doses of lysine vasopressin

Abstract

To assess the corticotrophic response to ovine corticotrophin releasing hormone (CRH) with the lowest dose of lysine vasopressin able to induce both the greatest stimulation and the lowest degree of side-effects. Fourteen healthy young adult males. Increasing intravenous doses (either 0, 0.03, 0.1, 0.3, or 1 IU) of lysine vasopressin, infused over 20 minutes, combined with a bolus of 100 micrograms ovine CRH. Radioimmunoassay of plasma ACTH, lipotrophin hormones and cortisol levels. (1) Responses to stimulation tests were evaluated as the area under the curves of plasma levels versus sample times, from 0 to 120 minutes after injection or start of perfusion (six subjects). The lowest dose of lysine vasopressin that induced an additional stimulation in the CRH-stimulated ACTH response was 0.3 IU. The combination of 1 IU lysine vasopressin with CRH doubled values of the area under the curve for the ACTH. Lysine vasopressin alone (0.3 and 1 IU) failed to stimulate ACTH responses. (2) The combined test (100 micrograms CRH and 1 IU lysine vasopressin) was carried out on eight additional control subjects. From a mean basal level of 23 +/- 5.6 (SEM), plasma ACTH peaked to 104.5 +/- 8 ng/l (23.0 +/- 1.8 pmol/l) as early as 20-30 minutes after the start of injection. When repeated after a two-week interval, the combined test induced identical stimulation in a given subject. Results of lipotrophin hormone determinations roughly paralleled those of ACTH. However the effects on cortisol levels were less clear. Subjects injected with CRH experienced slight facial flush. Following the 1 IU lysine vasopressin dosage, side-effects were reduced to skin pallor. No changes in heart-rate or blood-pressure were observed. Under these conditions, the combination of 100 micrograms CRH with 1 IU lysine vasopressin constitutes a powerful test for direct assessment of the pituitary reserve and therefore can be employed as a routine investigational tool.