[New medical treatments in Cushing disease]

The standard treatment of Cushing disease is surgery. Radiotherapy and steroïdogenesis inhibitors are second-line treatments. The new multi-ligand somatostatin analogs, such as SOM230, having a much higher affinity with several receptors of somatostatin (SSTR1,3, and 5) than octreotid (mostly a SSTR2 receptor) have been synthetized. Some studies have shown that SSTR5 is predominantly expressed in corticotroph pituitary adenomas and that SOM230 has more efficacy than octreotid in the treatment of Cushing disease. It has been suggested that the thiazolinidinediones, PPAR-gamma agonists, might also be useful in the treatment of this disease, but studies are still limited and give conflicting results. In a recent study conducted on dogs, Castillo et al have shown that the retinoïds give encouraging results and might open a new pathway in the treatment of Cushing disease. But further studies, especially on humans, are necessary before conclusions can be reached. Labeur and his team have contributed a study on the use of gamma-interferon on murine pituitary cells and on human and murine corticotroph pituitary adenoma cells, and they have evidenced a 20 to 60% decrease in the production of ACTH in 5 cases out of 7 in the tumoral cells treated--versus the non-treated ones. Eventually, Pivonello and his team have confirmed the D2 dopaminergic receptor expression in corticotroph pituitary cells, mainly in the intermediary zone. Thus they have suggested that the dopaminergic agonists--such as cabergoline-could be used in corticotroph pituitary adenomas derivated from the intermediary zone.