A Bridge Too Far? Towards Medical Therapy for Clinically Nonfunctioning Pituitary Tumors

Clinically nonfunctioning pituitary tumors (CNFPTs) typically do not cause hormonal excess, progress insidiously, and are often large and invasive at presentation. Complete resection is frequently not attainable; radiotherapy (RT) may effectively limit growth but carries a significant risk of hypopituitarism. Medical therapy with dopamine D2 receptor agonists and/or somatostatin analogs has been explored in CNFPTs but have yielded inconsistent results, and there is an unmet need for novel efficacious and safe medical therapies. The authors used the PubMed database to identify and review articles published from January 1982 to July 2024, that discussed the medical treatment of CNFPTs. The most commonly studied medical therapies were somatostatin receptor ligands (SRLs) and dopamine D2 receptor agonists. Of 111 patients with CNFPTs treated with SRLs, 31 (28%) exhibited tumor shrinkage. Following dopamine agonist treatment in 355 patients, tumor shrinkage occurred in 113 (32%), tumor stabilization in 182 (51%), and tumor growth in 60 (17%). The efficacy of other less commonly employed therapies such as GnRH analogs, PRRT, and temozolomide was also reviewed. Efficacious and safe medical therapies evaluated in robust randomized placebo-controlled clinical trials are needed to improve the management of CNFPTs.