Urine output in the SIADH

INTRODUCTION

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a disorder in which water excretion is partially impaired because of the inability to shut off the secretion of ADH [1]. In severe cases, the urine output does not exceed one liter per day, despite a water intake well above this level. The ensuing water retention will then lead to the development of hyponatremia.

The degree to which water excretion is impaired is primarily determined by the level of ADH secretion [1]. There are, however, two other important determinants of the urine output in this disorder: the rate of solute excretion; and partial escape from the effect of ADH.

SOLUTE EXCRETION

In normal subjects, the urine output primarily reflects water intake. Changes in water intake lead to alterations in the plasma osmolality that are sensed by the osmoreceptors in the hypothalamus that regulate both ADH release and thirst. As an example, an increase in water intake sequentially lowers the plasma osmolality, decreases ADH secretion, and reduces collecting tubule permeability to water; the net effect is the rapid excretion of the excess water in a dilute urine.

There is, however, no direct way to respond to changes in water intake in the SIADH, where ADH release is relatively fixed. Suppose that a patient has moderately severe SIADH with a urine osmolality that cannot be reduced below 750 mosmol/kg (normal minimum urine osmolality is 40 to 100 mosmol/kg). In this setting, the excretion of solutes (primarily sodium and potassium salts and urea) is the major determinant of the urine output. If solute excretion is in the normal range at 750 mosmol/kg, then the maximum daily urine output will be only one liter (750 ÷ 750 = 1).

One way to increase water excretion in this disorder is to put the patient on a high salt and protein intake. If, for example, solute excretion rose to 1200 mosmol/day, the urine output would increase to 1.6 L/day; the increase in water excretion would then tend to raise the plasma sodium concentration toward normal. (Similar considerations concerning the role of solute intake apply when ADH effect is relatively fixed at a low level in central or nephrogenic diabetes insipidus; (see "Urine output in diabetes insipidus".