LONG-TERM TREATMENT OF HYPOTHALAMIC-PITUI TARY CUSHINGS-SYNDROME WITHMITOTANE (O,P'-DDD)

Background and objective: Drug treatment of hypothalamic-pituitary Gus hing's syndrome is indicated if standard surgical intervention is not possible or has failed, The question arises whether, after unsatisfact ory treatment with Various adreno-static drugs, mitotane (o,p'-DDD), u sed against adrenal cortical cancer, is efficacious and free of signif icant side effects when used long-term. Patients and methods: The resu lts of long-term administration of mitotane to six patients, including one pregnant woman, were analysed retrospectively. After a moderate i nitial dosage of 3.0 g daily a maintenance dose of minimally 0.5 g per week was given or the treatment temporarily interrupted. The concentr ation of urinary free cortisol served as the main criterion of efficac iousness, together with the clinical course. The plasma concentrations of cortisol, aldosterone and ACTH were also determined, as well as ro utine clinicochemical parameters. Results: Cortisol excretion became n ormal in all patients between the 2nd and 10th treatment month, fallin g from 919 +/- 621.3 nmol daily in the six months before treatment to 162 +/- 93.0 nmol daily in the third six-month treatment period (mean +/- Standard deviation). Normal cortisol excretion and regression of s ymptoms was noted, dose-dependent, as long as the 12th year after star t: of treatment. Adrenocortical insufficiency occurred in one patient and at timer required hormone substitution, followed by lasting remiss ion without: special treatment. Significant side effects were not obse rved other than a reversible increase in gamma-glutamyl transpeptidase . Conclusion: Mitotane proved to be an efficacious drug which in excep tional cases can be used without significant side effects in low dosag e for the long-term treatment of hypothalamic-pituitary Gushing diseas e.