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The role of ACTH in various clinical disorders has been difficult to ascertain because the available assay methods have lacked the sensitivity necessary for valid quantitation of the hormone in the plasma of normal subjects (1-4). Even the method of Lipscomb and Nelson (5), the most sensitive practical bioassay procedure now available, usually requires the injection of at least 0.05 mUof ACTHper rat, if responses are to be elicited that will be statistically significant without the use of a prohibitive number of animals. It is usually impractical to inject more than 5 ml of crude human plasma into a single rat. Therefore, in order to be accurately measurable by this procedure, the concentration of ACTH in the plasma must be at least 0.05 mUper 5 ml, or 1 mUper 100 ml. Numerous studies indicate that normal plasma levels of ACTHare well below this concentration. Byr the adrenal ascorbic acid depletion assay method, Sydnor, Sayers, Brown, and Tyler (1) were unable to detect ACTH in plasma of normal subjects, even after attempting to extract the hormone with oxvcellulose in preparation for the bioassay. These workers concluded that blood ACTH concentrations of normal human subjects were less than 0.5 mUper 100 ml. Using a similar procedure, Fujita (3) estimated the normal level of ACTHto be about 1 mUper L, i.e., 0.1 mUper 100 ml. Cooper and Nelson (6) were able to detect ACTH in the plasma of only 3 of 10 patients before surgery, by a method that they

the journal of clinical investigation/the journal of clinical investigation

CORRELATION OF PLASMA ACTH CONCENTRATION WITH ADRENOCORTICAL RESPONSE IN NORMAL HUMAN SUBJECTS, SURGICAL PATIENTS, AND PATIENTS WITH CUSHING'S DISEASE*