On the role of antidiuretic hormone in the inhibition of acute water diuresis in adrenal insufficiency and the effects of gluco- and mineralocorticoids in reversing the inhibition

Abstract

A B S T R A C T In order to determine whether or not antidiuretic hormone (ADH) is essential to the inhibition of an acute water diuresis in adrenal insufficiency, the response to oral water loads was tested in rats with hereditary hypothalamic diabetes insipidus (DI) which lack ADH. It was found that 60 min after water loads of 3 or 5% of body weight urine flow was significantly lower and urine osmolality significantly higher in adrenalectomized DI rats than in the same DI rats before removal of their adrenal glands.The efficacy of gluco-and mineralocorticoids in reversing the inhibition was then determined in the same adrenalectomized DI rats. Prednisolone alone, administered either acutely or chronically, restored the response in urine flow to that seen in the same rats before adrenalectomy, but failed to correct the defect in urinary dilution. Aldosterone when given alone tended to correct the diluting ability but not the response in urine flow. When these two adrenal cortical hormones were given simultaneously, both the urine flow and urine osmolality were nearly identical to what they had been in the same DI rats before adrenalectomy. These studies strongly suggest (a) that ADH is not essential to the inhibition of an acute water diuresis in adrenal insufficiency, although it may abet the inhibition in individuals without diabetes insipidus, which can elaborate ADH; and (b) that both gluco-and mineralocorticoids are required in adrenal insufficiency in order to fully restore the water diuresis as judged by the dual criteria of urine flow and urine osmolality. INTRODUCTIONThe mechanism by which an acute water diuresis is inhibited in adrenal insufficiency has been the subject of intensive investigation and debate. (For a list of references, see reference 1.) Although changes such as decreased extracellular fluid volume or decreased glomerular filtration rate (GFR) may contribute to the inhibition, it seems clear that these are not the only, or even the major, factors involved. The main current controversy centers about the role of the antidiuretic hormone (vasopressin or ADH). One view states that in adrenal insufficiency water diuresis is inhibited by sustained high blood concentrations of ADH because in the absence of adrenal corticoids, secretion of ADH from the posterior pituitary gland cannot be shut off (2). Proponents of the second view contend that ADH has little to do with the inhibited water diuresis, but rather, that the adrenal steroids alter the water permeability of the distal renal tubules and collecting ducts (3). Both views have been supported by results of bioassays, the first showing sustained, high concentration of ADH in the blood of patients with adrenal insufficiency even after an acute water load (2), the second showing undetectable blood levels of ADH under similar circumstances (3).

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

“…Also, similar results were obtained with hydrocortisone replacement in glucocorticoid-deficient rats and patients with hypopituitarism, i.e. hydrocortisone replacement normalizes AVP secretion, urinary excretion of AQP-2 and water diuresis (4,6,9,10,12,22). Therefore, non-suppressible secretion of AVP plays a crucial role in impaired water excretion in secondary adrenal insufficiency.…”

Aldosterone Decreases UT-A1 Urea Transporter Expression via the Mineralocorticoid Receptor

“…They concluded that aldosterone corrected the diluting ability of adrenalectomized rats (4). Downregulation of UT-A1 would tend to decrease the urea concentration in the inner medulla, thereby decreasing the ability to reabsorb water.…”

“…Adrenalectomy reduces urine-concentrating ability (1-3) but also inhibits acute water diuresis (4). Both glucocorticoids and mineralocorticoids must be administered to reverse the inhibition of acute water diuresis (4).…”

“…Both glucocorticoids and mineralocorticoids must be administered to reverse the inhibition of acute water diuresis (4). Valtin and colleagues (4) showed that giving aldosterone to adrenalectomized rats after an acute water load corrected their diluting ability, whereas prednisolone corrected urine flow. These findings suggest that both adrenal steroids are involved in the regulation of urinary concentration and dilution.…”

Hyponatraemia

“…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. Where hypotension accompanies hypopituitarism, baroregulation of vasopressin will assume greater importance in the development of hyponatraemia and in addition there is evidence to show that free water excretion is impaired in the presence of glucocorticoid de®ciency, even in the absence of circulating vasopressin (Green et al, 1970). SIADH, ®rst described by Bartter & Schwartz (1967), is a common complication of a wide range of clinical disorders and drug therapies, and is characterized by hyponatraemia secondary to increased total body water with decreased total body sodium.…”