gms | German Medical Science

Surgery is the treatment of choice in Cushing`s and Nelson's disease. Although not always successful in terminating the ACTH-hypersecretion disease, an effective long-term medical treatment is still missing in persistent cases. It has been recently demonstrated that the nuclear receptor peroxisome proliferator-activated receptor γ (PPAR-γ) is abundantly expressed in pituitary adenomas. First in vitro data on the inhibiting effect of the PPAR-γ ligand rosiglitazone on hormone hypersecretion in a pituitary cell line and adenoma cell culture experiments (mainly ACTH-secreting AtT20 cell line) have indicated a possible functional significance. With regard to human pituitary adenomas, however, little is known about a possible therapeutic effect of Rosiglitazone treatment in vitro and in vivo.

Seven patients with persistent ACTH-hypersecretion (3 Nelson tumors, 4 persistent Cushing's disease) were treated with Rosiglitazone in a dosage established in the therapy of diabetes mellitus (4 mg and 16 mg/day). In vitro tests were performed in explant cultures (MEM with Hank's salts) from eight different human ACTH-secreting pituitary adenomas with 80 µmol Rosiglitazone over a time period of 14 days.

There was neither statistical significant in vivo nor in vitro effect of rosiglitazone on serum ACTH and/or Cortisol levels. In only one out of eight explant cultures, an inhibiting effect of Rosiglitazone on ACTH-secretion was detected. Additionally we have only seen a mild clinical effect in 1 of the 7 patients at best. In a female patient with persistent Cushing's disease, diabetes mellitus improved under medical therapy (propably because of the known insulin-sensitizing effect of rosiglitazone).

In contrast to the promising first laboratory data on pituitary cell line experiments published two years ago, our human pituitary adenoma explant culture experiments as well as the clinical experiences support the disappointing data on medical treatment of ACTH-hypersecretion with rosiglitazone published since then. The few numbers of publications so far all indicate a much lower clinical significance than assumed initially.