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Secretory failure of the adrenal glands has continued to be implicated as a factor in the pathogenesis of peripheral circulatory collapse due to infection since the original reports of Waterhouse (1) and of Friderichsen (2). This association of adrenal function and circulatory failure has been cited in recent reviews (3)(4)(5). However, a deficit of adrenal secretory products or their urinary metabolites in peripheral collapse due to infection has not been reported. Investigations in our laboratory have shown that shock produced in dogs by endotoxins of gram-negative bacteria was accompanied by an elevation of the concentration of cortisol in the plasma, and the output of cortisol in adrenal venous blood rose abruptly immediately after the injection of endotoxin (6).This report is concerned with the assessment of adrenal cortical function in human patients having peripheral circulatory failure due to severe infections. Studies with a 21-hemisuccinate ester of cortisol, which is rapidly hydrolyzed to free cortisol in %vio, were undertaken in order to delineate the metabolism of cortisol, the principal adrenal secretory product in man (7). METHODSThe subjects in this study included 9 healthy adults and 22 patients with severe infections complicated by circulatory collapse. Fifteen of these patients had demonstrable bacteremia at the time the studies were carried out.All of the patients were hypotensive with systolic blood pressures under 90 mm. of Hg. A summary of the clinical data on these patients is recorded in Table I.Blood samples for the determination of cortisol concentrations in the plasma were analyzed by a modification of the method of Silber and Porter (8) as described by Peterson, Karrer and Guerra (9). This method is specific for steroids with the 17,21-dihydroxy-20-keto configuration including cortisol, cortisone, Compound S and their dihydro-and tetrahydro-derivatives. Of these, only cortisol exists in the plasma in significant concentrations; therefore, the method may be regarded as highly specific for cortisol.Adrenal stimulation was carried out in eight normal subjects and in six patients with shock due to infection by an intravenous infusion of 25 U.S.P. units of corticotropin (Upjohn, Sterile Corticotropin Injection) dissolved in 500 ml. of 5 per cent dextrose in water, which was given over a period of four hours. Specimens of 15 ml. of heparinized blood were secured initially and at the conclusion of the infusion of corticotropin. The erythrocytes were separated from the plasma within 30 minutes. The samples were frozen and plasma cortisol levels were determined within 72 hours.In order to determine the rate of disappearance of exogenous cortisol, an intravenous injection of 100 mg. of cortisol sodium succinate dissolved in 2 ml. of distilled water (Upjohn, Hydrocortisone Sodium Succinate) was given to each of 9 normal subjects and to 20 patients with shock. Samples of blood were obtained immediately preceding the injection of cortisol sodium succinate and at 30, 90, 150, 210 and 270 minutes t...

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