Glucocorticoid resistance.

Changes in glucocorticoid (GC) receptor sensitivity can be categorized in three different types. First, generalized GC resistance syndrome is a hereditary disease. Patients present with signs and symptoms of increased androgen and/or mineralocorticoid action, combined with biochemical hypercortisolism, but lack of cushingoid features. Second, at a tissue level, transient changes in GC sensitivity are present during disease. Transient changes in GC sensitivity of leukocytes during infectious diseases like sepsis have been found, but also acquired forms or GC resistance occur, in particular in some types of neoplasms, major depression, AIDS, and several autoimmune diseases. Third, at the level of the general population, the diversity in GC sensitivity has a wide interindividual variation which in part can be explained by genetic variation of the GC receptor gene. Several single nucleotide polymorphisms of the gene have been associated with changes in GC sensitivity and its clinical phenotype. In this chapter, four genetic variants are described of which two (rs6198 and rs6189/6190) are associated with a relative GC resistance and two (rs1695 and rs41423247) are associated with a relative GC hypersensitivity.