Effect of Plasma Osmolality on Pituitary-Adrenal Responses to Corticotropin-Releasing Hormone and Atrial Natriuretic Peptide Changes in Central Diabetes Insipidus*

The objective of the present study was to examine the effect of changes in plasma osmolality (pOsm) on the responses of the pituitary-adrenal axis to CRH and atrial natriuretic peptide (ANP) release in patients with central diabetes insipidus (DI). Eight normal subjects and six DI patients were subjected to human CRH (hCRH) (1 μg/kg) stimulation alone or associated with isotonic volume loading (0.9% NaCl, 12 mL·kg·60 min) or an osmotic stimulus (5% NaCl, 0.06 mL·kg/min·120 min). The DI group showed significantly increased pOsm and undetectable or low plasma arginine vasopressin (AVP) during all tests. In the control group, pOsm and plasma AVP increased only during the osmotic stimulus. The DI group presented lower plasma ANP levels than controls during osmotic stimulus and isotonic volume loading. The lower ANP secretion in DI patients corroborates the importance of neurohypophyseal hormones in ANP regulation. Basal plasma ACTH and cortisol levels did not differ between controls and DI. The latter group presented a higher ACTH response than controls during stimulation with hCRH alone [area under the curve (AUC) 1138 ± 99 vs. 709 ± 62 pmol·L/min] and hCRH/5% NaCl (AUC 1602 ± 209 vs. 1158 ± 187 pmol·L·min). The DI cortisol AUC were higher than controls during stimulation with hCRH alone (65,471 ± 6,070 vs. 48,062 ± 3,476 nmol·L·min) and hCRH/5% NaCl (89,005 ± 10,043 vs. 62,105 ± 5,600 nmol·L·min). The highest ACTH and cortisol responses to hCRH in both groups were obtained with hCRH/5% NaCl. There was a significant correlation between mean pOsm and ACTH response to hCRH (r = 0.62). The increased responses to hCRH with increasing pOsm were present in control subjects and in patients with DI. However, at any given level of pOsm, there was no difference in ACTH response between controls and DI. These data indicate that the acute increases in pOsm augmented the ACTH and cortisol responses to hCRH that involve other factors besides magnocellular AVP.