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.

: Acromegaly and Growth Hormone (GHD) deficiency 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).

Background: Despite a profound improvement in the clinical outcome of young HL patients, in the elderly, 5-year survival is estimated at only 40% to 55%. This difference is attributed to the increased rate of comorbidity, treatment toxicity, dose reductions, and lack of standard treatment recommendations in this age group. Under representation of this age group in clinical studies and perhaps different disease biology in the elderly might also contribute to this difference.Methods: All consecutive patients (age ≥ 60), diagnosed with HL between 1998 to 2016 were retrospectively reviewed. Clinical data were recorded and statistical analysis, looking at survival predictors, was performed.Results: Ninety-five patients were identified. Median age at diagnosis was 71 (range, 60-89) years. Sixty-three (69%) patients had advanced disease, mean international prognostic score (IPS) was 3.5 ± 1.4.Forty-four (46%) patients had significant lung or heart disease at diagnosis. Fifty-nine (63%) patients received first line treatment with ABVD and 17 (18%) received BEACOPP-like therapy. Sixty-seven (82%) patients achieved complete remission, 6 (7%) achieved a partial response, 7 (9%) were primary refractory, and 9 (10%) died during induction. Fifteen (21%) patients experienced relapse. At 5 years progression free survival (PFS) and overall survival (OS) were 53.5% and 78% respectively. A significant heart/lung disease was associated with shorter PFS (median PFS 18.9 mo vs not reached at a median follow-up of 5 y, P = .04). Age,, disease status at presentation (early vs advanced, favorable vs unfavorable, and IPS), and treatment regimen had no a statistically significant impact on PFS (5-y PFS = 55% with ABVD vs 50% with BEACOPP-like, :50% with AVD and 33% with MOPP). Nevertheless, 5 year OS in patients receiving ABVD was significantly higher than reported with other therapies (82% with ABVD vs 58% with BEACOPP, P = .04).[ Figure].Restricted analysis, assessing factors that predict the outcome of ABVD treated patients only, found. A higher risk for relapse in patients with a reduced lymphocyte recovery at 12 months post therapy (average lymphocyte count 1250 vs 2057/ml, P < .01).Conclusions: Treatment outcome in our study was comparable or even superior to previously published cohorts. Traditional outcome measures for HL were not predictive according to our results. Nevertheless, cardio-respiratory disease was associated with shorter PFS, and the employment of a non-ABVD regimen was associated with shorter survival. A delayed lymphocyte recovery predicted a higher risk for relapse in ABVD treated patients.Larger studies, investigating prognostic factors and new therapies in elderly HL patients are warrented.

: 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.