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Endocrine Abstracts (2019) 63 S17.3 | DOI: 10.1530/endoabs.63.S17.3

ECE2019 Symposia Where do pituitary tumours come from? (3 abstracts)

‘From Lab to Clinic – Can we translate into effective therapeutics’

Peter Kamenický


France.


The first line treatment of somatotroph adenomas is pituitary surgery, that aims at removing the tumor, but which is frequently incomplete, as invasion into cavernous sinuses often limits the surgical resection. Multimodal medical treatment, which is burdensome, very expensive and has variable therapeutic efficacy, is currently required in more than 60% of the patients. New therapeutic approaches are therefore necessary for controlling hormone secretion, tumor development and (invasive) growth. Besides activating GNAS gene mutations, promoting tumor development in ~30% of cases, the molecular pathogenesis of somatotroph adenomas is rather poorly understood. We have recently described a distinct molecular subclass of GNAS mutation-negative somatotropinomas, clinically revealed by a paradoxical increase of GH to oral glucose load related to pituitary glucose-dependent insulinotropic polypeptide receptor (GIPR) expression. This ectopic GIPR expression occurred through hypomorphic transcriptional activation and is likely driven by GIPR gene micro-amplifications and/or DNA methylation abnormalities (Hage et al. 2018a). These findings provide useful molecular profiling that refines the somatotroph tumor classification. However, to what extent the ectopic GIPR is functionally involved tumor growth and GH hypersecretion? A hallmark of GIP-dependent Cushing syndrome is the low fasting plasma cortisol concentration that increases following GIP release after meals. In patients with acromegaly with ectopic GIPR in their somatotropinomas, fasting GH concentrations are not suppressed. The impact of prolonged fasting is difficult to address because of ethical issues. Recently, a specific naturally occurring GIP antagonist GIP (3–30) NH2 has been investigated in humans (Gasbjerg et al. 2018). Targeting the ectopic GIPR by this antagonist could be an interesting novel therapeutic strategy in some acromegalic patients. However, the important intra-tumor heterogeneity of pituitary adenomas with GIPR expressed only in some cell clones challenges the therapeutic efficacy of this approach.

Volume 63

21st European Congress of Endocrinology

Lyon, France
18 May 2019 - 21 May 2019

European Society of Endocrinology 

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