Assessment of Long-acting Synthetic Corticotrophin in Hypersensitive Asthmatics and Normal Subjects

Abstract

Summary: The synthetic polypeptide depot-tetracosactrin (Synacthen-Depot) was given to nine steroidtreated asthmatic patients hypersensitive to animal corticotrophin. Eight had a satisfactory increase in plasma and urinary 17-hydroxycorticosteroids (17-OHCS). The remaining patient had been shown previously to have adrenal suppression. None of the patients developed allergic reactions to depot-tetracosactrin, and seven have been receiving regular injections of the polypeptide twice weekly for the past eight months.In 13 normal subjects intramuscular injections of 1 mg. and 0.5 mg. of depot-tetracosactrin and 40 units of corticotrophin-gel were equally potent in raising the plasma 17-OHCS, but depot-tetracosactrin had a significandy longer action than corticotrophin-gel.

Potassium metabolism in patients with rheumatoid arthritis. Effects of treatment with depot tetracosactrin, spironolactone, and oral supplements of potassium chloride.

“…4. The plasma 11-OHCS 'profile' after a single intramuscular injection of 0 5 mg depot tetracosactrin was similar to that previously described (Nelson, Neill, Montgomery, MacKay, Sheridan, and Weaver, 1968;El Shaboury, 1968;Nuki and others, 1970). Plasma 1 1-OHCS levels rose significantly at 30 minutes, were maximal after 8 hours and still significantly raised after 24 but not after 48 hours.…”

“…Tetracosactrin in doses as small as 3 ,cg/h has been shown to elicit a maximal rise in plasma 1 1-OHCS (Landon, James, Cryer, Wynn, and Frankland, 1964). Injection of 0 5 mg depot tetracosactrin results in a maximal rise in 1 1-OHCS which is similar to that induced by 40 units of ACTH gel (Nelson and others, 1968;El Shaboury, 1968) but the adrenocortical stimulation is more prolonged. Maximal stimulation of cortisol and corticosterone can be obtained with a dose of 1250,ug, but the threshold for stimulation of aldosterone is much higher (Fraser, Brown, Chinn, Lever, and Robertson, 1969).…”

“…While it seems most likely that the fluid and electrolyte changes observed after a short course of depot tetracosactrin are induced by the relatively intense and prolonged stimulation of 11-OHCS which follows each injection (Besser, Butler, and Plumpton, 1967;Nelson and others, 1968;El Shaboury, 1968;Nuki and others, 1970) the possibility that significant aldosterone stimulation occurs after such an intermittent treatment regimen cannot be ruled out and warrants investigation. Long-term studies of potassium balance and whole body potassium, as well as of other elements of body composition, are in progress now to determine whether prolonged courses of treatment with tetracosactrin result in depletion of body potassium or these other elements in patients with RA.…”

Tetracosactrin for the management of asthmatic patients after long-term corticosteroids.

“…In another patient we had a similar, though less alarming, reaction to depot injections with swellings at the site of every previous depot injection. ' CONCLUSIONS Our studies have confirmed previous suggestions (Nelson et al, 1968;el-Shaboury, 1968;Galvao-Teles, Burke, and Russell Fraser, 1971;Westerhof et al, 1972) that the use of depot tetracosactrin injections, albeit for a prolonged time, is usually successful in reactivation of the adrenal glands and in providing more satisfactory control of asthma in those whose condition was severe enough to warrant long-term oral steroid administration. We failed to produce satisfactory adrenal response in only six out of 41 patients, even though initial testing had sometimes suggested complete adrenal suppression.…”

Prolonged Corticotrophic Action of a Synthetic Substituted 1-18 ACTH

“…However, this preparation may produce painful local reactions if given subcutaneously or sometimes intramuscularly (Besser et al, 1967;Nelson et al, 1968;Treadwell and Dennis, 1969), and this seems to be due to the contained zinc complexes. Occasionally generalized allergic reactions after tetracosactrin depot occur though in general it can be used in patients who are hypersensitive to animal ACTH (El-Shaboury, 1968;Jensen and Sneddon, 1969). …”