Mechanisms of Impaired Water Excretion in Adrenal and Pituitary Insufficiency. I. The Role of Altered Glomerular Filtration Rate and Solute Excretion12

Abstract

The inability to excrete an oral or parenteral load of water in a normal manner is a characteristic of the adrenalectomized or hypophysectomized animal and of the patient with adrenal or pituitary insufficiency ( 1-9). This defect persists in the presence of a normal salt balance, extracellular volume, and an adequate supply of salt-retaining hormone, desoxycorticosterone acetate (DCA) or aldosterone (4,7,8,10,11), but it can usually be corrected by the administration of hydrocortisone-like steroids (3,4,7,9).The basic mechanisms responsible for impaired water tolerance in these diseases have not been adequately clarified, nor have the processes by which hydrocortisone causes a normal water diuresis to occur.Gaunt, Birnie and Eversole (8) and others (7, 12) have suggested that a homeostatic "balance" exists between the antidiuretic hormone (ADH) of the neurohypophysis and the 11, 17 hydroxylated steroids of the adrenal cortex. They suggest that in the absence of these steroids, a relative or absolute excess of ADH exists, preventing a normal water diuresis. To prove this hypothesis, a sustained level of secretion of ADH should be demonstrated after the adrenal or anterior pituitary deficient animal has been water loaded, a procedure which ordinarily inhibits ADH secretion. To date, no such sustained activity has been observed using a generally acceptable and specific assay technique (6,13,14). Furthermore, the patient with adrenal or pituitary insufficiency normally inactivates and is not hypersensitive to exogenous antidiuretic hormone (Pitressin®) (6). Recent studies have stressed the importance of nonhormonal factors in determining the characteristics of water diuresis in normal subjects. The rate of glomerular filtration and solute excretion, and the distribution of the reabsorbed solutes between the proximal and distal tubules can profoundly alter the diuretic response to water in the absence of circulating ADH (15-21). Reduced glomerular filtration and renal blood flow are usually present in subjects with pituitary and adrenal insufficiency. In the latter, and occasionally in the former group, tubular reabsorption of sodium is impaired. Welt (22) postulated that the impaired water diuresis of these states is related primarily to alterations in the nonhormonal factors rather than to any disturbance in the secretion, metabolism, or action of ADH. If this theory is correct, it should be possible, while these subjects are under the influence of a sustained water load, to improve considerably their response to water loading by techniques which increase glomerular filtration rate and alter the distribution of solute (sodium) reabsorption between the proximal and distal tubule.This approach formed the basis of the present study. Aminophyllin was used to increase glomerular filtration acutely and alter the tubular reabsorption of solute. Its effect was compared in the same subject with the subsequent administration of hydrocortisone. The results indicate that the marked improvement in the execretion of water which...

On the Renal Site and Mode of Action of Glucocorticoid in Cirrhosis*

“…Goldsmith and associates have postulated such a defect in saltrestricted dogs (12). It does not appear likely, however, that glucocorticoids act by increasing collecting duct permeability, since other studies have shown that in the hydrated state, glucocorticoids produce more free water excretion, suggesting that these agents render the tubule less permeable to water (3,7,14).…”

Importance of sodium intake and mineralocorticoid hormone in the impaired water excretion in adrenal insufficiency

“…There is considerable evidence that adrenal insufficiency is associated with an impaired ability to attain a normal water diuresis (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). The mechanisms involved in this impairment of water excretion have not been clearly elucidated, however, two possible mechanisms have been proposed.…”

“…The mechanisms involved in this impairment of water excretion have not been clearly elucidated, however, two possible mechanisms have been proposed. One (3)(4)(5)(6)(7)(8) is that, although the release of antidiuretic hormone (ADH)' from the hypothalamus in adrenal insufficiency is normally suppressed during water loading, the water impermeability of the distal nephron is incomplete in the absence of glucocorticoid hormone. In contrast, other authors (9)(10)(11) have suggested that the release of ADH is not suppressed normally during water loading in the presence of adrenal insufficiency and increased circulating levels of ADH account for the inability to excrete water normally.…”

Gestational Changes in Renal Responsiveness to Cortisol in the Ovine Fetus

“…As the kidney matures it becomes capable of increasing distal tubular sodium reabsorption to compensate for any increased distal tubular fluid delivery. (Pediatr Res 26: [6][7][8][9][10]1989) Abbreviations FRN,, fractional reabsorption of sodium FR,,i, fractional reabsorption of lithium uN,,v, uKV, UclV, Uc.V, renal excretion rate of sodium/ potassium/chloride/calcium may be responsible for neonatal hyponatremia. However, subsequent investigations have shown that a characteristic of this defect is decreased proximal tubule reabsorption of sodium (2) implying that renal insensitivity to aldosterone may be only partially responsible.…”