Glucose metabolism outcomes in acromegaly patients on treatment with pasireotide-LAR or pasireotide-LAR plus Pegvisomant.

INTRODUCTION: Disorders of glucose metabolism are a serious acromegaly comorbidity and may be differently impacted by medical treatments of acromegaly. In this retrospective longitudinal multicenter study, we investigated the outcome of glucose metabolism and its predictors in patients treated with Pasireotide LAR (PAS-LAR) alone or in combination with Pegvisomant (PAS-LAR + Peg-V). SUBJECTS AND METHODS: Acromegaly patients treated continously with PAS-LAR or PAS-LAR + Peg-V for at least 6 months. RESULTS: Forty patients (25 females, 15 males) were enrolled. At last visit, 27/40 patients (67.5%) reached biochemical control of acromegaly. Overall, glucose metabolism improved in 3 (all in PAS-LAR + Peg-V; 7.5%), worsened in 26 (65%) and remained unchanged in 11 patients (27.5%). Glucose metabolism worsened in 25 patients (73.5%) treated with PAS-LAR and in a single patient (16.7%) treated with PAS-LAR + Peg-V (p < 0.001). Among patients treated with Pas-LAR alone, GH at baseline was higher in those with worsening of glucose metabolism (p = 0.04) as compared to those with stable glucose status. A significantly higher reduction of HbA1c was observed in patients treated with PAS-LAR + Peg-V, as compared with those treated with PAS-LAR alone (p = 0.005). CONCLUSIONS: Our data confirmed that glucose metabolism in patients treated with PAS-LAR is often worsened, and may be predicted by entity of baseline GH hypersecretion and by the dose of PAS-LAR. Moreover, our data, although limited by small numbers, may suggest that the combination treatment PAS-LAR + Peg-V can improve glucose homeostasis in selected patients.

The Role of Growth Hormone Receptor Isoforms and Their Effects in Bone Metabolism and Skeletal Fragility.

Acromegaly and Growth Hormone Deficiency (GHD) are associated with skeletal fragility and with an increased prevalence of Vertebral Fractures (VFs). In the most recent years, several authors tried to investigate surrogate markers that may predict the risk of bone fragility in these endocrine disorders. The aim of this review is to evaluate the role of GH receptor polymorphisms in skeletal fragility in patients affected by GHD and acromegaly. In fact, until now, two different isoforms of the GH Receptor (GHR) were described, that differ for the presence or the absence of transcription of the exon 3 of the GHR gene. Both the isoforms produce a functioning receptor, but the exon 3-deleted isoforms (d3-GHR) has a higher sensitivity to endogenous and recombinant GH as compared to the full-length isoform (fl-GHR).

Proteomics of Pancreatic Neuroendocrine Tumors: A Systematic Review.

Pancreatic neuroendocrine tumors (PanNETs) are rare tumors having usually an indolent behavior, but sometimes with unpredictable aggressiveness. PanNETs are more often non-functioning (NF), unable to produce functioning hormones, while 10-30% present as functioning (F) - PanNETs, such as insulinomas , gastrinomas , and other rare tumors. Diagnostic and prognostic markers, but also new therapeutic targets, are still lacking. Proteomics techniques represent therefore promising approaches for the future management of PanNETs. We conducted a systematic review to summarize the state of the art of proteomics in PanNETs. A total of 9 studies were included, focusing both on NF- and F-PanNETs. Indeed, proteomics is useful for the diagnosis, the prognosis and the detection of therapeutic targets. However, further studies are required. It is also warranted to standardize the analysis methods and the collection techniques, in order to validate proteins with a relevance in the personalized approach to PanNETs management.