Corticotrophinomas are characterized by a relative resistance to the negative feedback action of cortisol on ACTH secretion. In this respect there is a similarity with the clinical syndrome of cortisol resistance (CR). As CR can be caused by genetic abnormalities in the glucocorticoid receptor (GR) gene, we investigated whether the insensitivity of corticotrophinomas to cortisol is also caused by the Novo Mutations in the GR gene. We found that somatic mutations of the GR gene are not a frequent cause of relative CR in these cells, but our observations indicate that loss of heterozygosity (LOH) at the GR gene locus is a relativity frequent phenomenon in pituitary adenomas of patients with Cushing's disease.