In the present study, the effects of o,
p'-DDD on plasma levels of pregnenolone, 17α-hydroxypregnenolone, progesterone, 17α-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 diesease.
Plasma levels of these steroids were decreased in all of the patients with adrenal carcinoma. The decrement of progesterone and 17α-hydroxyprogesterone was greater than that of pregnenolone and 17α-hydroxypregnenolone. These results indicate that o,
p'-DDD inhibits both cholesterol cleavage enzyme and 3β-hydroxysteroid dehydrogenase coupled with delta 5 to 4 isomerase system.
Plasma levels of pregnenolone and 17α-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 C
17-20lyase 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.
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