METABOLIC ACTIONS AND FATE OF INTRAVENOUSLY ADMINISTERED ADRENOCORTICOTROPIC* HORMONE IN MAN†§

Abstract

Large single doses of pituitary ACTH were admd. to 2 healthy young adults by slow intraven. infusion. No change in blood pressure occurred in either subject. The only untoward reaction was a mild chill and fever experienced by one of the subjects. The tropin disappeared rapidly from the plasma, reaching control levels 2 hrs. after the infusion was terminated. Negligible quantities of ACTH appeared in the urine. Fasting blood sugar was not influenced by ACTH. However, glycosuria and a diabetic type of blood sugar response followed the ingestion of a meal 6 hrs. after the start of the infusion. Urinary N and uric acid were elevated. A marked decrease in the number of circulating lymphocytes and eosinophils occurred concomitantly with an increase in the number of circulating neutrophils. The electro-phoretic distribution of serum proteins was unchanged. The titers of antistreptolysin O, isoagglutinins, typhoid H and O and diphtheria antibodies were uninfluenced. Certain serum pep-tidases underwent small but inconsistent increases. There was an elevation in the pH of the blood of one subject which appeared to be related to the chill and fever. There was no change in either the pH or CO2 of the plasma of the other subject. Plasma Na and chloride concns. remained unchanged, but plasma K declined significantly in both subjects at a time when the other metabolic effects were maximal. There was an early increase in the urinary excretion of K followed by return to a normal or slightly subnormal K excretion from the 6th to the 24th hr. One subject showed a slight retention of Na and chloride during the first 6 hrs.; the other subject, in whom an inhibition of a water diuresis occurred, showed sodiumphoresis and chloruresis during this same period. There was a marked retention of Na and chloride in both subjects from the 6th to the 24th hr. The quantity of 17-ketosteroids and of neutral-lipid reducing substances in the urine was markedly elevated. The peak rate of excretion of these substances occurred at about 3 hrs. after ACTH admn. and their level in the urine returned to normal by the 12th hr. The sequence of metabolic and other events was such that the secretory activity of the adrenal cortex appeared to reach a maximum by the 3d hr. after ACTH admn. and to return to pretreatment activity by the 6th hr. Most of the alterations in metabolic constituents reached a maximal deviation from pretreatment levels at the 6th hr.; the values returned to normal by the 12th hr. The significance of the observed results for pituitary-adrenal function is discussed.