Increased Plasma Arginine Vasopressin in Clinical Adrenocortical Insufficiency and Its Inhibition By Glucosteroids*

Abstract

Summary. Trichloroacetic acid extracts of plasma were fractionated on a CG-50 resin column and the 50% acetic acid eluents chromatographed on silicic acid-impregnated glass paper in butanol-acetic acid-water. The specific arginine vasopressin (AVP) zone was eluted and assayed for antidiuretic activity in the diuretic rat. Thioglycolate inactivation was used to confirm AVP activity. Recovery of as little as 4 FLU AVP per ml plasma ranged between 80 and 90%. In normal subjects after an overnight fast, plasma AVP ranged between 2.5 and 10.0 ,U per ml. AVP secretion was inhibited by hemodilution and stimulated with nicotine and hypertonic saline. Plasma AVP was absent in patients with diabetes insipidus even after neurohypophyseal stimulation. Plasma AVP was abnormally elevated during mild dehydration and remained above the normal range despite hemodilution in patients with untreated adrenocortical insufficiency demonstrating a delayed water diuresis. Glucosteroid therapy lowered plasma AVP to normal in dehydrated patients. A normal diuretic response to hydration was accompanied by a fall in plasma AVP to zero in steroid-treated patients. These findings suggest that hypersecretion of AVP may play an important role in the abnormal water metabolism of adrenocortical insufficiency and that the glucosteroids promote normal water diuresis by inhibiting the secretion of AVP from the neurohypophysis. IntroductionIncreased or sustained antidiuretic hormone (ADH) secretion has long been implicated in the abnormal water metabolism of primary and secondary adrenocortical insufficiency. The gluco-

Hyponatraemia

“…The authors concluded that cortisol de®ciency may have a permissive effect on vasopressin release; certainly glucocorticoids suppress vasopressin release (Raff, 1993;Erkut et al, 1998) and raised plasma vasopressin levels have been reported in other studies where hyponatraemia was associated with ACTH de®ciency in the absence of hypotension (Mora et al, 1995). Glucocorticoid replacement lowered plasma vasopressin concentrations and normalized the plasma sodium in Oelkers' study and in other reports (Ahmed et al, 1967). Cortisol de®ciency per se therefore seems suf®cient to stimulate vasopressin secretion, though in a commentary on Oelkers' study, Robertson (1989) did stress that subtle volume contraction may have been overlooked as a stimulus to vasopressin secretion.…”

“…The effects of thiazide diuretics are prolonged, and hyponatraemia may re¯ect drug treatment which has been discontinued up to a month before diagnosis. In Addison's disease, a 5±10% reduction in blood volume is suf®cient to stimulate baroregulated secretion of vasopressin (Ahmed et al, 1967;Robertson, 1977;Boykin et al, 1979), with reduction in water excretion. However, studies in the rat have shown that vasopressin antagonists cannot entirely reverse the hyponatraemia associated with adrenal insuf®ciency, indicating that impaired water excretion is not totally due to increased action of vasopressin (Ishikawa et al, 1985).…”

Close association of severe hyponatremia with exaggerated release of arginine vasopressin in elderly subjects with secondary adrenal insufficiency

“…There are several factors that could be involved in the mechanisms for hyponatremia: enhanced secretion of AVP, attenuated renal handling of Na, decreased intake of Na, change in water intake, and others. Enhanced secretion of AVP is closely involved in the mechanism for impaired water excretion and hyponatremia in hypopituitarism, particularly hypofunction of the pituitary and adrenocortical axis (3,9,10). In experimental models of glucocorticoid deficiency non-suppressible release of AVP is found despite hypo-osmolality, which should suppress AVP release to undetectable levels (5 -7).…”

“…There has been an important debate since the 1950s regarding the mechanisms for hyponatremia in adrenal insufficiency, that is, whether water retention or renal deficit of sodium (Na) is more prominent in producing hyponatremia (2 -6). Studies performed in isolated glucocorticoid deficiency showed that impaired water excretion occurred in the patients with hypopituitarism and in experimental models of glucocorticoid deficiency (3,(5)(6)(7)(8)(9)(10). Non-suppressible release of arginine vasopressin (AVP) was found despite hypo-osmolality which should suppress AVP release to undetectable levels (3,6,7,11).…”

“…Studies performed in isolated glucocorticoid deficiency showed that impaired water excretion occurred in the patients with hypopituitarism and in experimental models of glucocorticoid deficiency (3,(5)(6)(7)(8)(9)(10). Non-suppressible release of arginine vasopressin (AVP) was found despite hypo-osmolality which should suppress AVP release to undetectable levels (3,6,7,11). In addition, the expression of aquaporin-2 (AQP-2) water channel mRNA and protein in kidney was upregulated in glucocorticoid-deficient rats (12).…”