Corticotropin response to combined administration of human corticotropin-releasing hormone and small-dose arginine vasopressin in normal subjects

Abstract

Arginine vasopressin (AVP) is known to potentiate corticotropin (ACTH) secretion by human corticotropin-releasing hormone (hCRH), and a combined administration of hCRH and AVP appears useful as a pituitary ACTH reserve test. This study was designed to evaluate the appropriate dose of AVP and its route of administration for better estimation of pituitary ACTH reserve in humans, when used in combination with a conventional hCRH stimulation test. First, intravenous (IV) doses of hCRH (100 μg) and AVP (0, 0.1, and 0.3 U) were administered simultaneously in six normal subjects. Second, IV hCRH was administered with intramuscular (IM) AVP (0, 1.0, 3.0, and 5.0 U) in 10 normal subjects. Blood samples for measurement of plasma ACTH were obtained at 0, 15, 30, 45, 60, 90, and 120 minutes after the hCRH with and without AVP administration. The order of AVP doses was randomly chosen in each subject. The peak plasma ACTH level was 65.0 ± 16.0 pg/mL (30 minutes) with hCRH alone and 139.5 ± 35.6 pg/mL (15 minutes) with hCRH plus 0.3 U IV AVP in six normal subjects. Similarly, the peak plasma ACTH level was 43.5 ± 5.6 pg/mL (30 minutes) with hCRH alone and 116.0 ± 19.6 (15 minutes) and 96.6 ± 24.0 pg/mL (15 minutes) with hCRH plus 3.0 and 5.0 U IM AVP in 10 normal subjects, respectively. The hCRH-induced ACTH responses (Δ ACTH) with both IV and IM AVP were significantly ( P < .05) greater than the respective control values with hCRH alone. The responses (Δ ACTH) were comparable between the two phases of 3.0 and 5.0 U IM AVP. Two subjects complained of facial flushing with 5.0 U IM AVP, whereas the tests with hCRH plus 3.0 U IV AVP and 3.0 U IM AVP were well tolerated in all subjects. The results suggest that the simultaneous administration of hCRH (100 μg) with IV AVP (0.3 U) or with IM AVP (3.0 U) is useful and safe method for evaluating the pituitary ACTH reserve in humans. The clinical significance of the test in pituitary-adrenal disorders remains to be seen in future studies.