Recent years have seen major advances in our understanding of the causes of adrenal and pituitary Cushings syndrome. Careful molecular analyses have yielded new information about the underlying cellular mechanisms leading to the excess secretion of ACTH from the pituitary or cortisol from the adrenal. Unpicking these mechanisms has allowed proposals for new clinical trials of medical treatments for Cushings disease. Intriguingly, inherited germ line mutations appear to account for some uncommon forms of bilateral adrenal disease, and this has implications for family screening of potentially affected relatives.
Diagnostic strategies are evolving and the most recent data suggest that salivary cortisone rather than salivary cortisol best reflects serum cortisol, and it is being assessed in states of cortisol excess. It is likely to be a sensitive and accurate means for diagnosis and monitoring.
A large-scale global clinical trial has demonstrated the efficacy of monthly pasireotide for Cushings disease, a treatment which is already approved as an s.c formulation by NHSE for the treatment of Cushings disease under certain constraints. Another global trial is now fully recruited assessing olidrostat, a new steroidogenesis inhibitor. Other novel approaches include assessment of levo-ketoconazole, antisense to the glucocorticoid receptor and antibodies designed to prevent the action of ACTH.
Careful quality of life assessments and disease-specific questionnaires have allowed demonstration of the devastating impact that Cushings can have, even after remission of active disease.
Together, these are exciting times for Cushings research, which should translate into better care for patient for patients within the next few years.