CORTROSYN™ (cosyntropin) for Injection exhibits slight immunologic activity, does not contain animal protein and is therefore less risky to use than natural ACTH. Patients known to be sensitized to natural ACTH with markedly positive skin tests will, with few exceptions, react negatively when tested intradermally with CORTROSYN™. Most patients with a history of a previous hypersensitivity reaction to natural ACTH or a pre-existing allergic disease will tolerate CORTROSYN™. Despite this however, CORTROSYN™ is not completely devoid of immunologic activity and hypersensitivity reactions including rare anaphylaxis are possible. Therefore, the physician should be prepared, prior to injection, to treat any possible acute hypersensitivity reaction.
This failure to respond to metyrapone may be interpreted as evidence of impaired pituitary‑adrenal reserve. In view of the normal response to exogenous ACTH, the failure to respond to metyrapone is inferred to be related to a defect in the CNS‑pituitary mechanisms which normally regulate ACTH secretions. Presumably the ACTH secreting mechanisms of these individuals are already working at their maximal rates to meet everyday conditions and possess limited “reserve” capacities to secrete additional ACTH either in response to stress or to decreased cortisol levels occurring as a result of metyrapone administration.
The pharmacological effect of Metopirone (metyrapone) is to reduce cortisol and corticosterone production by inhibiting the 11-β-hydroxylation reaction in the adrenal cortex. Removal of the strong inhibitory feedback mechanism exerted by cortisol results in an increase in adrenocorticotropic hormone (ACTH) production by the pituitary. With continued blockade of the enzymatic steps leading to production of cortisol and corticosterone, there is a marked increase in adrenocortical secretion of their immediate precursors, 11-desoxycortisol and desoxycorticosterone, which are weak suppressors of ACTH release, and a corresponding elevation of these steroids in the plasma and of their metabolites in the urine. These metabolites are readily determined by measuring urinary 17-hydroxycorticosteroids (17-OHCS) or 17-ketogenic steroids (17-KGS).