[The effects of o,p'-DDD on human adrenal steroid synthesis].
In the present study, the effects of o,p'-DDD on plasma levels of pregnenolone, 17 alpha-hydroxypregnenolone, progesterone, 17 alpha-hydroxyprogesterone, 11-deoxycorticosterone, deoxycortisol, corticosterone, cortisol, androstenedione and testosterone were studied in 6 patients with adrenal carcinoma (3 with Cushing's syndrome, 2 with adrenogenital syndrome, one without clinical manifestation) and 6 with Cushing's disease. Plasma levels of these steroids were decreased in all of the patients with adrenal carcinoma. The decrement of progesterone and 17 alpha-hydroxyprogesterone was greater than that of pregnenolone and 17 alpha-hydroxypregnenolone. These results indicate that o,p'-DDD inhibits both cholesterol cleavage enzyme and 3 beta-hydroxysteroid dehydrogenase coupled with delta 5 to 4 isomerase system. Plasma levels of pregnenolone and 17 alpha-hydroxypregnenolone showed a twofold increase on the 7th day after consecutive administrations of o,p'-DDD in patients with Cushing's disease. Plasma levels of cortisol were decreased to normal one month after continuous o,p'-DDD treatment. Urinary 17-OHCS and 17-KS have been decreased out of proportion to the decrease in plasma cortisol in the first week of o,p'-DDD treatment. Such a disparity suggests that o,p'-DDD might affect the extra-adrenal metabolism of cortisol. However, no evidence was found for the inhibition of hepatic C17-20lyase and glucuronyl transferase. Regression of pulmonary metastases was observed in one case with Cushing's syndrome due to adrenal carcinoma, suggesting that o,p'-DDD causes necrosis of the metastatic adrenal carcinoma. A remission of the disease was obtained in one patient with Cushing's disease after 6 months of continuous o,p'-DDD treatment. The usefulness of o,p'-DDD for the treatment of adrenal carcinoma with metastases and Cushing's disease was confirmed.
D006907:17-alpha-Hydroxypregnenolone / Q000097:blood; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis / Q000097:blood*; D000306:Adrenal Cortex Neoplasms / Q000097:blood* / Q000188:drug therapy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D002675:Child, Preschool; D003480:Cushing Syndrome / Q000097:blood* / Q000188:drug therapy; D003900:Desoxycorticosterone / Q000097:blood; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006908:Hydroxyprogesterones / Q000097:blood; D008297:Male; D008875:Middle Aged; D008939:Mitotane / Q000494:pharmacology* / Q000627:therapeutic use; D011284:Pregnenolone / Q000097:blood
D000305:Adrenal Cortex Hormones; D006908:Hydroxyprogesterones; D006907:17-alpha-Hydroxypregnenolone; D003900:Desoxycorticosterone; D011284:Pregnenolone; D008939:Mitotane; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone