Advances in the Treatment of Prolactinomas

Abstract

Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future.

Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas

“…Criteria for the definition of resistance to dopaminergic agents as well as the standard CB dose thresholds required for the assessment of this status are not clearly established. 2 For the purpose of this genotype/ phenotype analysis, patients were defined as resistant when they failed to normalize PRL levels taking 43 mg/week CB. In agreement with previous studies, 2 resistance to CB was observed in about 10% of patients and was associated with a lack of tumor-size reduction.…”

“…The criteria for responsiveness to the therapy were the following: (1) normalization of PRL levels at CB dosage of p3 mg/week; (2) reduction of the tumor size more than 30% at CB dosage of p3 mg/week, an arbitrary cutoff in the range of the proposed cutoffs (20-80) used in literature. 2 Finally, as it is known that the size of the tumor is one of the major determinants of PRL levels, the study included a similar number of patients with either micro-or macro-PRLoma consecutively seen by the different centers. As CB dosages used in these patients were definitely lower than 2-5 mg/day, a dosage reported to be responsible for cardiac valvulopathy in subjects affected with Parkinson disease, periodical ultrasound heart examination was not carried out.…”

“…Resistance to CB, defined as failure to normalize PRL levels and/or to reduce tumor size, is reported in 10-15% of patients with PRL-omas. 2 Reduction of dopaminergic binding sites, decreased expression of DRD2 mRNA and a relative decrease in Gai expression have been described in resistant PRL-omas, as well as reduced levels of the short receptor isoform. [3][4][5] Finally, no mutations in the DRD2 gene have been so far described in PRL-omas resistant to medical treatment.…”

Hyperprolactinemia: Diagnosis and treatment principles

“…Значајна хиперплазија лактотропа настаје током последња два триместра трудноће и првих месеци лактације. Секреција ПРЛ је пулзатилна, са највећим секреторним пиковима током спавања (2). Максималан серумски ниво ПРЛ настаје између четири и шест часова, док полуживот циркулишућег ПРЛ износи око 50 минута.…”

“…Хиперпролактинемија је чест ендокрини поремећај, и постоји код око 15-20% жена са менструалним поремећајима, 43-87% жена са аменорејом и галакторејом и 30-40% инфертилних жена (2). Преваленца клинички апарентних пролактинома је од 6-10 до 50/100.000.…”