Background: Transsphenoidal adenomectomy (TSS) of somatotroph pituitary neuroendocrine tumor (PitNET) is the first-line treatment of acromegaly. Pharmacological treatment is recommended if surgery is contraindicated or did not lead to disease remission. The choice of treatment best fitting each patient should be based on thorough investigation of patients' characteristics. The current analysis attempts to create a tool for personalized treatment planning.Aim: This study aimed to assess whether clinical, biochemical, imaging and pathological characteristics can predict surgical remission and response to firstgeneration somatostatin receptor ligands (SRLs) and pasireotide-LAR in acromegaly.Patients and methods: A retrospective study of 153 acromegaly patients, treated in the Department of Endocrinology in Bielanski Hospital in Warsaw, Poland was performed. Data on demographics, hormonal and imaging results, pathological evaluation, and treatment outcome was extracted from the Polish Acromegaly Registry collecting information from 11 endocrinology centers in Poland and analyzed.Results: Patients with surgical remission had lower GH and IGF-1 concentrations at diagnosis (median GH 5.5 µg/L [IQR: 3.1-16.0] vs. 19.9 µg/L [IQR: 9.8-42.4], p=<0.001 and mean IGF-1 3.1xULN ± SD=1.2 vs. 3.7xULN ± SD=1.2, p=0.007, respectively) and smaller tumors (median 12.5mm [IQR: 9-19] vs. 23mm [IQR: 18-30], p<0.001). These tumors were more often densely granulated (DG) (73.2% vs. 40.0%, p=0.001) with positive staining for alpha-Frontiers in Endocrinology frontiersin.org 01

Context Pasireotide-LAR, a second-generation somatostatin receptor ligand (SRL), is recommended for patients with acromegaly as second-line treatment. Its efficacy and safety were assessed in clinical trials; however, the real-world evidence is still scarce. Objective The aim of this study was to evaluate the impact of 1-year treatment with pasireotide-LAR on disease control and glucose metabolism in acromegaly patients resistant to first-generation SRLs. Design A single-center prospective study. Methods Twenty-eight patients with active acromegaly or acrogigantism on first-generation SRLs following ineffective pituitary surgery were switched to treatment with pasireotide-LAR 40 or 60 mg i.m. every 28 days. To assess the efficacy of the treatment GH and IGF-1 levels were measured every 3 months. Safety of treatment was carefully evaluated, especially its impact on glucose metabolism. Results Complete biochemical control (GH ≤ 1 ng/mL and IGF-1 ≤ 1 × ULN) was achieved in 26.9% of patients and partial + complete response (GH ≤ 2.5 ng/mL and IGF-1 ≤ 1.3 × ULN) in 50.0% of patients. Mean GH level decrease was the largest within first 6 months (P = 0.0001) and mean IGF-1 level decreased rapidly within the first 3 months (P < 0.0001) and they remained reduced during the study. Blood glucose and HbA1c levels increased significantly within 3 months (P = 0.0001) and stayed on stable level thereafter. Otherwise, the treatment was well tolerated and clinical improvement was noticed in majority of patients. Conclusions This real-life study confirmed good effectiveness of pasireotide-LAR in patients resistant to first-generation SRLs. Pasireotide-LAR was overall safe and well tolerated, however significant glucose metabolism worsening was noted.

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Introduction Permanent right ventricle pacing leads to left ventricle remodeling, its systolic dysfunction and symptomatic heart failure in the long run. Valsartan is well known for its preventive anti-remodeling function in the post infarction heart remodeling. Objectives To assess the effect of valsartan on left ventricle remodeling in patients with second and third degree atrioventricular block with first-time implantation of dual chamber pacemaker. Methods This was a randomized, double-blind, placebo controlled single center study. One hundred eligible patients were assigned in a 1:1:1 fashion to receive placebo, valsartan 80mg or 160mg once daily, respectively. Echocardiographic assessment of left ventricle geometry, its systolic and diastolic function was performed at baseline and at twelve months. One patient from placebo group suffered stroke. We present the baseline date for 100 enrolled patients and follow-up data for 88 patients who have completed the study. Data in valsartan arms are pooled in one group. Concentration of soluble ST2 was measured in duplicates with Aspect Reader (Critical Diagnostics). Results Results are presented in table. Data are presented as mean and standard deviation. Table 1 Placebo (n=28) Valsartan (n=60) ANOVA Baseline 12 mths Baseline 12 mths sST2, ng/mL 36.0±16.0 39.4±15.3 35.1±15.2 19.9±6.5 0.01 LVEF, % 60±8 55±9 60±8 58±8 0.01 LVEDD, mm 48±5 50±4 48±6 49±5 NS LVESD, mm 29±4 32±5 29±5 31±4 NS LVEDV, mL 79±12 84±13 80±12 81±13 NS LVESV, mL 32±5 38±7 31±5 34±6 0.01 E/A 0.94±0.12 0.92±0.13 0.94±0.15 0.95±0.15 NS DecT, ms 211±38 226±43 223±45 218±37 0.01 IVRT, ms 98±14 108±17 101±17 99±18 0.01 Conclusion Valsartan has protective effect of left ventricle remodeling and function. It may be useful in prevention of pacing induced heart failure. Decrease in soluble ST2 concentration may help explain the alternative mechanism for protective role of valsartan. (NCT01805804)

Introduction: First generation somatostatin analogs (SSAs) are the treatment of choice in persistent acromegaly after transsphenoidal surgery. However, they are effective in 25% to 45 % of patients and a second generation SSA - pasireotide LAR may be a more effective alternative. Aim Our aim was to evaluate the impact of 1-year treatment with pasireotide LAR on disease control and on glucose metabolism in patients with acromegaly after debulking surgery resistant to first-generation SSAs. Material and methods In this single-center prospective study 29 consecutive patients with resistant acromegaly were treated with pasireotide LAR. The initial drug dose was 40 mg i.m. every 28 days. If patient did not achieve biochemical control (GH &lt;2.5 ng/mL and IGF-1 ≤ULN for age and sex) at month 3, the dose was increased to 60 mg i.m. every 28 days. Assessment (GH, IGF-1, glucose, HbA1c) was performed at month 3, 6, 9 and 12. Results: In total, 22 patients (10 females, 12 males) completed a 1-year treatment. Mean age was 41.8±13.8 years. Twelve patients (54.5%) were ≤ 40 years old (including 6 (27.3%) patients of age ≤30 years). At baseline, mean IGF-1 level was 2.3 (SD 0.7) x ULN (age- and sex-specific) (583.9 ng/mL; SD 182.2) and mean GH concentration was 3.9 (SD 2.8) ng/mL. Both values decreased significantly after 1 year of treatment (P&lt;0.001). Pasireotide LAR dose was increased to 60 mg in 16 (72.7%) patients and decreased to 20 mg in one patient patient due to worsening of diabetes control. The magnitude of mean GH level decrease was the largest within first 6 months (mean change from baseline: -1.75 ng/mL, 95% CI: -2.64, -0.85, P=0.0006). Mean IGF-1 level decreased rapidly within the first 3 months (mean change from baseline: -153.20 ng/mL, 95% CI: -203.20, -103.19, P&lt;0.0001) and remained low during 12-month follow-up. GH level ≤ 1 ng/mL and ≤2.5 ng/mL was achieved by 7 (31.8%) and 17 (77.3%) patients, respectively. Six patients (27.3%) achieved normal IGF-1 level (IGF-1 ≤1 x ULN) (P=0.0275). IGF-1 ≤1.3 x ULN was observed in 11 (50.0%) of patients. Full biochemical control (GH ≤1 ng/mL and IGF-1 ≤1 x ULN) was achieved in 3 (13.6%) patients. Pasireotide LAR treatment resulted in significant increase of mean fasting glucose level: 119.2 (SD 17.3) vs. 107.5 (SD 13.9) mg/dL, P&lt;0.001. The largest change was observed in first 3 months, and it remained stable until month 12. HbA1c level also increased significantly during first 3 months and stayed on similar level during follow-up (mean for month 12: 6.3 (SD 0.6) vs. 5.9 (SD 0.5) % at baseline, P&lt;0.001). Conclusions: Pasireotide LAR is an effective treatment in most patients with persistent acromegaly after surgical debulking resistant to first generation SSAs. The largest increase of glycemia occurs during first 3 months of treatment and it remains stable afterwards.