Novel therapeutic directions in Cushings
Pituitary-dependent Cushings is a rare disease of unknown aetiology that is prone to relapse and damaging to quality of life even in remission. About one half of all patients subjected to primary pituitary surgery are not cured in the long term even in the best hands, and as the routine use of adjuvant radiotherapy has become an increasingly unattractive proposition to clinicians striving to spare their patients future complications, pharmacotherapeutic alternatives that are safer and as effective in the long term as the steroid synthesis inhibitors would be most welcome.
Given variable patterns of hormone secretion such as cyclical hypercortisolaemia and the distinct trophic characteristics of different subgroups of corticotroph adenomas, pituitary-dependent Cushings might well be considered as a cluster of closely related conditions rather than a single entity. Even though in these circumstances it might be unfair to expect single agents to work across the board, the therapeutic foreshore is strewn with the wreckage of reserpine, valproate, trilostane and other neuromodulators.
New, high-affinity, broad-spectrum somatostatin receptor agonists and PPAR-gamma receptor ligands are some of the glimmering lights on the horizon, but will agents directed against these rather unexpected receptor targets fare any better?
How much might we harm our patients by delaying the application of more established therapies whilst we try and find out?
At the time of writing the answer to all of these questions, is, as usual, ‘we dont know’.