GEOFFREY HARRIS AWARD 2019: Translational research in pituitary tumours

STALLA, GÜNTER K; ARZT, EDUARDO; CIATO, DENIS; JUNG-SIEVERS, CAROLINE; THEODOROPOULOU, MARILY; DIMOPOULOU, CHRISTINA; PAEZ PEREDA, MARCELO; RENNER, ULRICH

EUROPEAN JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Año: 2019 vol. 182 p. 1 - 13

0804-4643

Although effective treatment regimens (surgical resection, drug treatment with dopamine agonists or somatostatinanalogues, radiotherapy) have been established for the therapy of most pituitary tumours, a considerableproportion of affected patients cannot completely cured due to i ncomplete resection or drug resistance. Moreover,even if hormone levels have been normalized, patients with horm one-secreting tumours still show persistentpathophysiological alterations in metabolic, cardiovascular or neuropsychiatric parameters and have an impairedquality of life. In this review reasons for the discrepancy bet ween biochemical cure and incomplete recovery fromtumour-associated comorbidities are discussed and the clinical management is delineated exemplarily for patientswith acromegaly and Cushing?s disease. In view of the developme nt of additional treatment concepts for the treatmentof pituitary adenomas we speculate about the relevance of RSUME as a potential target for the development of ananti-angiogenic therapy. Moreover, the role of BMP-4 which stim ulates prolactinoma development through the Smadsignalling cascade is described and its role as putative drug t arget for the treatment of prolactinomas is discussed.Regarding the well-known resistance of a part of somatotropinom as to somatostatin analogue treatment, recentlyidentified mechanisms responsible for the drug resistance are su mmarized and ways to overcome them in futuretreatment concepts are presented. Concerning novel therapeutic options for patients with Cushing?s disease theimpact of retinoic acid, which is currently tested in clinical studies, is shown, and the action and putative therapeuticimpact of silibinin to resolve glucocorticoid resistance in the se patients is critically discussed.