IN THE widely used method of Sayers et at. (1) for the assay of ACTH in rats, using the adrenal depletion of ascorbic acid as an index of adrenal cortical activation, the material is given intravenously. More reliable results are obtained by that route of administration than by intramuscular injection. Ingle (2) was the first to demonstrate the value of continuous subcutaneous administration of small quantities of ACTH in producing maximal hypertrophy of the adrenal cortices of rats. After two to three days the size of the gland increased to an extent never observed when the hormone was administered in separate injections. Sayers et al. (3) were the first to administer ACTH intravenously in man. Large doses, given over thirty minutes to 2 normal subjects, produced most of the known physiologic effects in spite of the rapid disappearance of ACTH from the blood stream following the end of the infusion. In clinical usage the intramuscular route of administration remained the method of choice until Gordon (4) demonstrated the usefulness of the intravenous route in man, using a continuous infusion extending over a period of days. Gordon's findings, which have been amply confirmed and extended, established the intravenous use of ACTH as a clinically effective and economical method of inducing adrenal cortical stimulation (5, 6, 7, 8).
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Renold et al. (1952) studied this question.