Medical therapy of pituitary adenomas

The physiologic experiments of the 1950s and 1960s that established the hypothalamic regulation of pituitary function led to the biochemical characterization of the various release and inhibiting hormones and their receptors over the next two decades and ultimately to the development of medical therapies for the various pituitary adenoma types. The paradigm of medical therapy is the extremely successful use of dopamine agonists (DA) for the treatment of prolactinomas, which built upon the basic knowledge that dopamine is the physiologic prolactin (PRL) inhibitor factor. The discovery of somatostatin and its receptors led to the development of somatostatin receptor ligands (SRLs) for the treatment of acromegaly and thyrotropin (TSH)-secreting adenomas, Knowledge of how growth hormone (GH) interacts with its receptor led to the development of pegvisomant, which blocks the binding of GH to its receptor. Early clinical observations of patients with acromegaly have led to the use of estrogens and selective estrogen receptor modulators to aid in its treatment. DAs and SRLs have only modest activity in Cushing's disease and most therapies involve enzymatic blockade of the various steps in cortisol synthesis, the two most recent being osilodrostat and levoketoconazole. Blockade of the cortisol receptor by mifepristone was found accidentally but then was established as a good treatment for Cushing's syndrome. The finding that clinically nonfunctioning adenomas had dopamine receptors led to the use of DA in these patients as well. Finally, an understanding of some of the abnormal molecular pathways underlying the rare aggressiveness of some adenomas and carcinomas has led to the use of temozolomide and now other chemotherapies and immunotherapies in such patients.