Rate of Adrenal Cortisol Production in Response to Maximal Stimulation with ACTH

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Abstract
The rate of cortisol production during maximal stimulation with ACTH can be determined with radioisotopes, but a practical non-isotopic technique would be of 4 value. Previous methods based on plasma 17-hydroxycorticosteroid (17-OHCS) determinations have been difficult to interpret because their results were influenced by the rate of cortisol disposal, the degree of protein binding and the volume of distribution of cortisol in addition to its rate of production. To overcome these problems, patients were studied won separate occasions with cortisol and ACTH infusions. The cortisol infusions were given at the rate normal subjects produced cortisol in response to maximal stimulation with ACTH. At the onset of the cortisol infusion and again during the last hour of the infusion, when equilibration has been approximated, blood specimens were obtained for plasma 17-OHCS determinations. Dexamethasone was given to suppress endogenous ACTH secretion. During the infusion of cortisol, when dexamethasone is effective in suppressing adrenal secretion of cortisol, its only source is the infusion pump. The ACTH was given on another day as a 6-hr infusion of 25 IU to induce maximal stimulation of adrenal cortisol production, and again blood specimens were obtained at the onset and end of the infusion. Since the, ACTH and the cortisol infusions were given under the same conditions, abnormalities in the disposal, binding or distribution of cortisol should modify the plasma concentration similarly when the production rate attained with ACTH stimulation and the rate of infusion of cortisol are the same. Consequently, if the subject attains the same plasma 17-OHCS concentration after 6 hr of the ACTH infusion as he did during the cortisol infusion, it can be presumed that his adrenal capacity to secrete cortisol is normal. To illustrate the validity of this method, the infusions were performed on normal subjects and patients with abnormalities of cortisol production, disposal or binding. Administration of 1 mg of dexamethasone at 11:00 pm resulted in low 8:00 am plasma 17-OHCS concentrations in normal subjects and in patients with cirrhosis or adrenal insufficiency, but not in critically ill patients or patients taking estrogens or patients with Cushing's syndrome. Normal subjects produced cortisol at a rate of 110 μg/kg each hr in response to maximal stimulation with ACTH, while patients with adrenal insufficiency and some patients with cirrhosis produced less, and patients with Cushing's syndrome produced more.

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