Further Studies with the Salt Tolerance Test in Normal Individuals and in Patients with Adrenal Cortical Hyperfunction.

In a previous paper (1) we reported on the utilization of intravenously injected salt before and after the injection of desoxycorticosterone acetate in normal individuals and in patients with Cushing's syndrome. It was pointed out that the injection of this steroid in normal individuals resulted in a decrease in the urinary excretion of sodium and chloride ions as compared to the control values. This is the expected and orthodox effect. On the other hand, the injection of this compound in patients with Cushing's syndrome under the circumstances of our test resulted in an increase in the urinary excretion of sodium and chloride. Since the publication of the original paper several reports have appeared describing a similar phenomenon occurring under a variety of conditions. Reifenstein (2) has noted a paradoxical salt loss in patients with Cushing's syndrome treated with testosterone. Kriss and Futcher (3) have observed that in two of three patients with Cushing's syndrome, the rate of urinary excretion of sodium, chloride, and water following the rapid intravenous administration of 400 c.c. of 5% saline exceeded that observed in similarly treated control subjects. In the patients with Cushing's syndrome the increased excretion of the ions and water was accompanied by a reduction in renal tubular reabsorption of these substances, as compared to the controls. In addition, these authors report the instances of two obese females with arterial hypertension in whom the salt tolerance test, employing our technique, was positive at the time of menstruation and negative in the same patients during the intermenstrual period. They suggest that during the menstrual cycle there is a temporary preponderance of adrenocortical influence. In one patient with Cushing's syndrome the salt tolerance test resulted in a normal salt retaining response, despite the fact that the patient exhibited salt diuresis during the clearance study performed five days previously. More recently, Forsham and his coworkers (4) confirmed the paradoxical salt loss following the injection of desoxycorticosterone acetate in patients with Cushing's syndrome. They suggested that the mechanism of this phenomenon was perhaps dependent upon a competitive renal inhibition of desoxycorticosterone as against some other non-salt retaining adrenal cortical fractions. The mechanism of this paradoxical effect is obscure. We have speculated that it is at least theoretically possible that in some patients with adrenal cortical hyperfunction excessive amounts of saltretaining fractions, manufactured by the increased activity of the adrenal cortex or injected from an exogenous source, are converted into substances lacking salt-retaining effects. The basic structural similarity between those adrenal cortical steroids exercising a salt retaining effect and those lacking it would suggest that the conversion of one into another is perhaps chemically feasible.