njection test, further studies are indicated to determine if it is primary or secondary. primary adrenal insufficiency (addison's disease) is the result of an intrinsic disease process, such as tuberculosis within the gland. the production of adrenocortical hormones is deficient despite high acth levels (feedback mechanism). secondary or relative insufficiency arises as the result of defective production of acth leading in turn to disuse atrophy of the adrenal cortex. it is commonly seen, for example, as result of corticosteroid therapy, sheehan's syndrome and pituitary tumors or ablation. the differentiation of both types is based on the premise that a primarily defective gland cannot be stimulated by acth whereas a secondarily defective gland is potentially functional and will respond to adequate stimulation with acth. patients selected for further study as the result of a subnormal cosyntropin for injection test should be given a 3 or 4 day course of treatment with repository corticotropin injection usp and then retested. suggested doses are 40 usp units twice daily for 4 days or 60 usp units twice daily for 3 days. under these conditions little or no increase in plasma cortisol levels will be seen in addison's disease whereas higher or even normal levels will be seen in cases with secondary adrenal insufficiency.

e of 0.125 mg will often suffice. a second blood sample is collected exactly 30 minutes later. both blood samples should be refrigerated until sent to the laboratory for determination of the plasma cortisol response by some appropriate method. if it is not possible to send them to the laboratory or perform the fluorimetric procedure within 12 hours, then the plasma should be separated and refrigerated or frozen according to need. two alternative methods of administration are intravenous injection and infusion. cosyntropin for injection can be injected intravenously in 2 to 5 ml of saline over a 2-minute period. when given as an intravenous infusion: cosyntropin for injection, 0.25 mg may be added to glucose or saline solutions and given at the rate of approximately 40 micrograms per hour over a 6-hour period. it should not be added to blood or plasma as it is apt to be inactivated by enzymes. adrenal response may be measured in the usual manner by determining urinary steroid excretion before and after treatment or by measuring plasma cortisol levels before and at the end of the infusion. the latter is preferable because the urinary steroid excretion does not always accurately reflect the adrenal or plasma cortisol response to acth. the usual normal response in most cases is an approximate doubling of the basal level, provided that the basal level does not exceed the normal range. patients receiving cortisone, hydrocortisone or spironolactone should omit their pre-test doses on the day selected for testing. patients taking inadvertent doses of cortisone or hydrocortisone on the test day and patients taking spironolactone or women taking drugs which contain estrogen may exhibit abnormally high basal plasma cortisol levels. a paradoxical response may be noted in the cortisone or hydrocortisone group as seen in a decrease in plasma cortisol values following a stimulating dose of cosyntropin for injection. in the spironolactone or estrogen group only a normal incremental response is to be expected. many patients with normal adrenal function, however, do not respond to the expected degree so that the following criteria have been established to denote a normal response: 1. the control plasma cortisol level should exceed 5 micrograms/100 ml. 2. the 30-minute level should show an increment of at least 7 micrograms/100 ml above the basal level. 3. the 30-minute level should exceed 18 micrograms/100 ml. comparable figures have been reported by greig and co-workers (2). plasma cortisol levels usually peak about 45 to 60 minutes after an injection of cosyntropin for injection and some prefer the 60-minute interval for testing for this reason. while it is true that the 60-minute values are usually higher than the 30-minute values, the difference may not be significant enough in most cases to outweigh the disadvantage of a longer testing period. if the 60-minute test period is used, the criterion for a normal response is an approximate doubling of the basal plasma cortisol value. in patients with a raised plasma bilirubin or in patients where the plasma contains free hemoglobin, falsely high fluorescence measurements will result. the test may be performed at any time during the day but because of the physiological diurnal variation of plasma cortisol the criteria listed by wood cannot apply. it has been shown that basal plasma cortisol levels and the post cosyntropin for injection increment exhibit diurnal changes. however, the 30-minute plasma cortisol level remains unchanged throughout the day so that only this single criterion should be used (3). parenteral drug products should be inspected visually for particulate matter and discoloration whenever solution and container permit. reconstituted cosyntropin for injection should not be retained.

lanotropic activity, increased growth hormone secretion and an adipokinetic effect. these are considered to be without physiological or clinical significance. animal, human and synthetic acth (1 to 39) which all contain 39 amino acids exhibit similar immunologic activity. this activity resides in the c-terminal portion of the molecule and the 22 to 39 amino acid residues exhibit the greatest degree of antigenicity. in contrast, synthetic polypeptides containing 1 to 19 or fewer amino acids have no detectable immunologic activity. those containing 1 to 26, 1 to 24 or 1 to 23 amino acids have very little immunologic although full biologic activity. this property of cosyntropin for injection assumes added importance in view of the known antigenicity of natural acth.