Resistant prolactinomas.

Best Pract Res Clin Endocrinol Metab 2026 Mar; 40(2):102100.BP

Prolactinomas as the most common type of functional pituitary adenoma and most will respond to dopamine agonist (DA) therapy with normalization of prolactin levels, restoration of gonadal function and/or reduction in tumor volume. A minority of prolactinomas are refractory to conventional doses of DA and present a clinical challenge. Characteristics associated with DA resistance include male sex, certain radiologic features (large size, cavernous sinus invasion, other characteristics), histopathologic evidence of high cell proliferation, and in a small number of cases, inherited pathologic germline variants of genes associated with pituitary tumors, such as MEN1 and AIP. Clinical management often requires a multimodal approach including titration of DA to higher than usual doses, surgical resection or debulking, and targeted radiotherapy. Robust evidence is lacking for non-approved adjunct therapies, such as aromatase inhibitors and estrogen receptor modulators, although the somatostatin receptor ligand pasireotide may have potential in select patients.