scholarly journals MON-323 IGF-I Variability and Its Association with Demographic and Clinical Characteristics in Patients with Acromegaly Treated with Injectable Somatostatin Receptor Ligands (SRLS); Results from an International Prospective Phase III Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Susan Leanne Samson ◽  
Lisa B Nachtigall ◽  
Maria Fleseriu ◽  
Ehud Ur ◽  
William Henry Ludlam ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Phase Iii ◽  
Receptor Ligands ◽  
Percent Change ◽  
Period 2 ◽  
Somatostatin Receptor Ligands ◽  
Igf I ◽  
Phase Iii Study ◽  
The Mean

Abstract Background: In clinical practice, most patients responding to injectable somatostatin receptor ligands exhibit IGF-I variability around the upper limit of normal (ULN) during long-term follow up. These fluctuations are thought to result from various factors such as assay variability, nutrition, comorbid conditions, concomitant medications and other unknown factors. The magnitude of this variability, and the factors affecting it, is not well understood in patients with acromegaly treated with injectable SRLs. Methods: IGF-I levels of patients responding to and stably treated with injectable SRLs were measured over time in the CHIASMA OPTIMAL phase III study. Two time periods were assessed - Period 1, three assessments during screening phase before randomization to octreotide capsules (N=56), and Period 2 - multiple assessments up to week 36, in patients rescued with SRL injections for at least 12 weeks (N=21). The time from the last injection to each of the 3 assessments in period 1 [Screening visits 1 and 2 (SV1 & SV2), and Baseline (BL)], was on average 6.8 ± 10.7 (SD), 15.8 ± 2.7, and 29.0 ± 1.8 days respectively. Correlation with various demographics and Baseline characteristics, including age, gender, weight, BMI and residual tumor size to IGF-I variability was assessed. Percent change for each individual patient from Minimal to Maximal IGF-I values within each period was computed and the overall population mean was calculated (lowest value was used as the denominator and all other values were expression as a positive % above this value). Results: The overall mean within-patient percent change of IGF-I levels during Period 1 was 20.48 ± 15.56 (range: 0.6-81). Mean IGF-I levels for SV1, SV2 and BL were 0.78 ± 0.18, 0.79 ± 0.18, and 0.85 ± 0.22 x ULN respectively. The overall increase in mean IGF-I levels from SV1 to BL (longest time interval) was statistically significant (p=0.0002; paired T-test). Analysis of IGF-I levels in patients during Period 2, revealed that the overall mean within-patient percent change of IGF-I levels was 15.27 ± 12.20 (range: 0-41.5). The mean duration of follow up during this period, after patients were already treated for ≥12 weeks with injectable SRL, was 1.72 (± 1.29) months. The variability observed in Period 2 was similar to that observed in the entire sample evaluated in Period 1. No significant differences were found in the mean IGF-I percent change between any demographic or baseline characteristic subgroup examined. Conclusion: IGF-I levels fluctuate in patients with acromegaly who are responsive to injectable SRLs. These fluctuations are wide and can be up to 81% higher than the lowest (most controlled) value, with an average increase of approximately 20%. Significant IGF-I increases were observed at the end of the long acting SRL injection interval. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

scholarly journals Biliary adverse events in acromegaly during somatostatin receptor ligands: predictors of onset and response to ursodeoxycholic acid treatment

Pituitary ◽  
2020 ◽  
Author(s):  
N. Prencipe ◽  
C. Bona ◽  
D. Cuboni ◽  
M. Parasiliti-Caprino ◽  
A. M. Berton ◽  
...  
Keyword(s):  
Adverse Events ◽  
Ursodeoxycholic Acid ◽  
Somatostatin Receptor ◽  
Stone Disease ◽  
Receptor Ligands ◽  
First Line ◽  
Metabolic Markers ◽  
Somatostatin Receptor Ligands ◽  
Igf I

Abstract Purpose Somatostatin receptor ligands (SRL) are the first-line medical treatment for acromegaly. Gallbladder alterations are one of most important SRL side effect, but according to some authors growth hormone hypersecretion itself is a risk factor for gallstones. This single center, longitudinal retrospective study evaluated the incidence and the predictors of biliary adverse events (BAE) in acromegaly during SRL therapy and their response to ursodeoxycholic acid (UDCA). Methods 91 acromegaly patients with indication to SRL were enrolled. Evaluations of acromegaly activity (GH, IGF-I, IGF-I/ULN) and metabolic profile were collected before starting treatment, yearly during follow-up and at BAE onset. In patients developing BAE we searched for predictors of UDCA effectiveness. Results 61.5% of patients developed BAE (58.9% cholelithiasis; 41.1% only sludge). IGF-I and IGF-I/ULN proved to be positive predictor of BAE, which occur about 5 years after SRL starting. None of metabolic markers proved to be associated with BAE. Only five patients (5.5%) underwent cholecystectomy for symptomatic cholelithiasis. 71% of patients started UDCA treatment, achieving regression of BAE in 60% of cases (88% in patients developing only sludge and 30% in patients affected by cholelithiasis, p < 0.001). BMI and obesity were negative predictors of UDCA efficacy. In 50% of the subjects BAE resolved after 36 months of therapy with a lower rate if cholelithiasis was present. Conclusion Biliary stone disease is a frequent SRL adverse event, although it is often symptomless. Ultrasound follow-up mainly in the first 5 years of therapy, early UDCA starting and proper lifestyle represent a valid strategy in their detection and management.

MRI follow‐up of patients with acromegaly treated after surgery with first‐generation somatostatin receptor ligands

2021 ◽  
Author(s):  
Naia Grandgeorge ◽  
Giovanni Barchetti ◽  
Solange Grunenwald ◽  
Fabrice Bonneville ◽  
Philippe Caron
Keyword(s):  
First Generation ◽  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands

scholarly journals MON-303 Giant Growth Hormone Secreting Pituitary Adenomas: A Single Institution Case Series

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Bahadir Koylu ◽  
Suleyman Nahit Sendur ◽  
Seda Hanife Oguz ◽  
Selcuk Dagdelen ◽  
Tomris A Erbas
Keyword(s):  
Growth Hormone ◽  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Postoperative Radiotherapy ◽  
Somatostatin Receptor ◽  
Case Series ◽  
Tumor Diameter ◽  
Somatostatin Receptor Ligands ◽  
The Mean

Abstract The prevalence of growth hormone (GH)-secreting pituitary adenoma is around 11-13% of all pituitary adenomas. Giant GH-secreting pituitary adenomas (≥ 4 cm) are rare tumors, and its prevalence of among acromegalic patients is &lt;5%. This is a retrospective cohort study including patients with giant GH-secreting pituitary adenomas. The study population consisted of 10 patients (5 M/5 F). The mean age at diagnosis was 33.0±12.9 yrs (11-55 yrs). The mean delay between first symptom onset and diagnosis was 2.9 years. The most frequent symptoms were acral enlargement and facial changes (80%), followed by headache (70%) and visual deterioration (50%). One patient had epilepsy. Amenorrhea was presented in three females but obvious galactorrhea in two. The mean adenoma diameter was 42.6±4.7 mm (40-51 mm) at diagnosis. The vast majority of adenomas presented suprasellar extension (100%) or cavernous sinus invasion (80%). Cystic adenomas accounted for 50%. At presentation, mean GH and IGF-1 levels were 40.0±21.4 ng/mL (14.8-51.0) and 2.62±1.09 x ULN (1.08-3.96), respectively. Six patients presented with PRL cosecretion. At diagnosis maximal tumor diameter was not correlated with GH or IGF-1 levels. All patients underwent pituitary surgery as first-line treatment. Three cases were treated with an endoscopic approach and four cases with a microscopic approach. Transcranial approach was also employed in three cases. Postoperative mean GH and IGF-1 levels were 14.9±16.1 ng/mL (0.6-51.0) and 2.25.±0.82 x ULN (1.48-3.74), respectively. After first surgery, only one patient had more than 50% reduction in IGF-1 levels. Five patients (50%) underwent repeat surgery on two to three procedures because remission was not achieved. Postoperative somatostatin receptor ligands (SRLs) were used by all patients. Six patients were treated with dopamine agonist in combination with SRL. Six patients (60%) received postoperative radiotherapy. The mean follow-up period was 12.6±5.3 yrs (4-21 yrs). The mean GH and IGF-1 levels were 1.47±1.54 ng/mL (0.08-5.25) and 0.73±0.44 x ULN (0.08-1.56), respectively at the last visit. Residual adenoma was present at the last MRI in eight patients (mean diameter 9.0±3.6 mm). Panhypopituitarism rose from 10% at baseline to 30% at the last visit. During follow-up, one patient diagnosed breast cancer, while another diagnosed thyroid papillary cancer. Giant GH-secreting pituitary adenomas can have a clinically aggressive behavior with mass effect. Moreover, treatment in patients with giant GH-secreting pituitary adenoma is complex and multimodal therapy is necessary.

Machine Learning-based Prediction Model for Treatment of Acromegaly With First-generation Somatostatin Receptor Ligands

2021 ◽  
Author(s):  
Luiz Eduardo Wildemberg ◽  
Aline Helen da Silva Camacho ◽  
Renan Lyra Miranda ◽  
Paula C L Elias ◽  
Nina R de Castro Musolino ◽  
...  
Keyword(s):  
Machine Learning ◽  
Support Vector Machine ◽  
Prediction Model ◽  
Predictive Value ◽  
First Generation ◽  
Somatostatin Receptor ◽  
Support Vector ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Igf I

Abstract Context Artificial intelligence (AI), in particular machine learning (ML), may be used to deeply analyze biomarkers of response to first-generation somatostatin receptor ligands (fg-SRLs) in the treatment of acromegaly. Objective To develop a prediction model of therapeutic response of acromegaly to fg-SRL. Methods Patients with acromegaly not cured by primary surgical treatment and who had adjuvant therapy with fg-SRL for at least 6 months after surgery were included. Patients were considered controlled if they presented growth hormone (GH) &lt;1.0 ng/mL and normal age-adjusted insulin-like growth factor (IGF)-I levels. Six AI models were evaluated: logistic regression, k-nearest neighbor classifier, support vector machine, gradient-boosted classifier, random forest, and multilayer perceptron. The features included in the analysis were age at diagnosis, sex, GH, and IGF-I levels at diagnosis and at pretreatment, somatostatin receptor subtype 2 and 5 (SST2 and SST5) protein expression and cytokeratin granulation pattern (GP). Results A total of 153 patients were analyzed. Controlled patients were older (P = .002), had lower GH at diagnosis (P = .01), had lower pretreatment GH and IGF-I (P &lt; .001), and more frequently harbored tumors that were densely granulated (P = .014) or highly expressed SST2 (P &lt; .001). The model that performed best was the support vector machine with the features SST2, SST5, GP, sex, age, and pretreatment GH and IGF-I levels. It had an accuracy of 86.3%, positive predictive value of 83.3% and negative predictive value of 87.5%. Conclusion We developed a ML-based prediction model with high accuracy that has the potential to improve medical management of acromegaly, optimize biochemical control, decrease long-term morbidities and mortality, and reduce health services costs.

scholarly journals A Phase 3 Large International Noninferiority Trial (MPOWERED): Assessing Maintenance of Response to Oral Octreotide Capsules in Comparison to Injectable Somatostatin Receptor Ligands

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A517-A517
Author(s):  
Maria Fleseriu ◽  
Alexander V Dreval ◽  
Yulia Pokramovich ◽  
Irina Bondar ◽  
Elena Isaeva ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Safety Data ◽  
Biochemical Response ◽  
Receptor Ligands ◽  
Phase 3 ◽  
Landmark Analysis ◽  
End Point ◽  
Noninferiority Trial ◽  
Somatostatin Receptor Ligands ◽  
Igf I

Abstract Background: MPOWERED, a large phase 3 trial, assessed maintenance of response to oral octreotide capsules (OOC; MYCAPSSA®) compared to injectable somatostatin receptor ligands (iSRLs) in patients with acromegaly who responded to OOC and iSRLs (octreotide or lanreotide). OOC were recently approved in the US for patients with acromegaly who responded to and tolerated iSRLs. Methods: Eligibility criteria included age 18-75 years at screening, acromegaly diagnosis, disease evidence, biochemical control (insulin-like growth factor I [IGF-I] &lt;1.3 × upper limit of normal [ULN] and mean integrated growth hormone [GH] &lt;2.5 ng/mL) at screening, and ≥6 months’ iSRL treatment. Effective OOC dose was determined in a 26-week Run-in phase. Eligible patients (IGF-I &lt;1.3 × ULN and mean integrated GH &lt;2.5 ng/mL, week 24) were randomized to a 36-week controlled treatment phase (RCT), receiving OOC or iSRLs starting at week 26. The primary end point was a noninferiority assessment of proportion of patients biochemically controlled in the RCT (IGF-I &lt;1.3 × ULN using time-weighted average). Other end points included nonresponse imputation of the primary end point, landmark analysis using proportion of responders based on average of last 2 IGF-I values at end of RCT, and change from baseline RCT (week 26) IGF-I and GH levels. Results: Of 146 enrolled patients, 92 entered the RCT (OOC, n=55; iSRLs, n=37). Both arms were well balanced for age, sex, and acromegaly duration. OOC demonstrated noninferiority to iSRLs in maintaining biochemical response, with 91% (CI, 80%-97%) of OOC and 100% (CI, 91%-100%) of iSRL groups maintaining control during the RCT. Of those responding at end of Run-in, 96% of patients on OOC maintained response during RCT. Using nonresponse imputation, 89% of OOC and 95% of iSRL groups were biochemically controlled in RCT. Landmark analysis of those respnding at end of Run-in showed that 94% of patients in each group maintained response at RCT end. In both groups, IGF-I levels were stable in the RCT, average IGF-I at baseline and RCT end being 0.9 × ULN (OOC) and 0.8 × ULN (iSRL). Mean change in GH from RCT start to RCT end was -0.03 ng/mL (OOC) and +0.29 ng/mL (iSRL). Safety data were mostly similar between groups; the OOC group did not experience injection site reactions. Conclusion: In this noninferiority trial in patients with acromegaly, OOC demonstrated maintenance of biochemical response compared to iSRLs. Results support the efficacy of OOC as a possible iSRL alternative.

scholarly journals MON-LB55 Biochemical Control of Most Patients Reverting to Injectable Long-Acting Somatostatin Receptor Ligands Is Achieved After One Dose: Results From the Phase 3, Randomized, Double Blind, Placebo-Controlled Optimal Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Maria Fleseriu ◽  
Susan Leanne Samson ◽  
Lisa B Nachtigall ◽  
Artak Labadzhyan ◽  
Atanaska Elenkova ◽  
...  
Keyword(s):  
Rescue Therapy ◽  
Somatostatin Receptor ◽  
Clinical Signs ◽  
Placebo Treatment ◽  
Receptor Ligands ◽  
Biochemical Control ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Somatostatin Receptor Ligands ◽  
Igf I

Abstract Background: Injectable somatostatin receptor ligands (SRLs) are currently the most widely used medical therapy for acromegaly worldwide. Oral octreotide capsules (OOC) have been formulated as a potential therapy for this disorder and the safety and efficacy were evaluated in the CHIASMA OPTIMAL pivotal study (Samson et al. ENDO 2020). As reported, mean IGF-I levels of the OOC treatment group were maintained within normal range at the end of treatment in all patients. However, some patients may not respond to OOC treatment (25% of OOC group and 68% of placebo groups required rescue, P=0.003). This analysis describes the degree and rapidity with which patients achieve biochemical control (IGF-I ≤1.0 x ULN) when reverted to their prior injectable SRL treatment. Methods: Patients with confirmed acromegaly and receiving a stable dose of injectable SRL (≥3 months) were randomized to OOC (40mg/day; N=28) or placebo (N=28) for 36 weeks. Patients were dose titrated to 60 or 80mg of OOC (or placebo) through week 24 at investigator discretion based on increased IGF-I levels and/or worsening acromegaly signs/symptoms. Patients could be rescued via reversion to prior injectable SRL therapy if they met the predefined withdrawal criteria (i.e., IGF-I ≥1.3 x upper limit of normal [ULN] for 2 consecutive visits on the highest dose, and exacerbation of clinical signs/symptoms) or discontinued treatment early for any other reason. In the study, 7 patients in the OOC group and 19 in the placebo group required rescue. The change in IGF-I from Baseline was compared to the end of the Double-blind Placebo Controlled period. Results: In patients rescued up to week 32 and in whom there were at least 4 weeks of follow up, baseline IGF-I levels (mean of Screening Visit 2 and Baseline) were 0.80 and 0.87 x ULN in the OOC and placebo groups, respectively. In patients receiving rescue therapy, the end of study IGF-I levels (mean of week 34 and 36) were 0.80 and 0.89 x ULN in the OOC and placebo groups, respectively, virtually unchanged. The median time to return to normal baseline IGF-I values following loss of response was 4.0 weeks after discontinuing OOC and 4.0 weeks after discontinuing placebo treatment. Therefore, most patients who required rescue following a short trial of therapy with OOC returned to their baseline values following a single SRL injection. Conclusion: Most treatment failures in the CHIASMA OPTIMAL trial (on either OOC or placebo) rescued with injectable SRL re-established their baseline response levels after a single injectable SRL administration (at pre-study dose). Based on this data, patients may potentially be treated with OOC and for those not responding, either not biochemically controlled or who have adverse effects, they may be able to return to injectable SRLs with immediate IGF-I control after one SRL injection.

COMPARATIVE EFFICACY OF MEDICAL TREATMENT FOR ACROMEGALY: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS OF INTEGRATED RANDOMIZED TRIALS AND OBSERVATIONAL STUDIES

2020 ◽  
Vol 26 (4) ◽  
pp. 454-462 ◽  
Author(s):  
Nidan Qiao ◽  
Min He ◽  
Ming Shen ◽  
Qilin Zhang ◽  
Zhaoyun Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Observational Studies ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Somatostatin Receptor ◽  
Credible Interval ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
The Mean ◽  
Long Acting

Objective: Comprehensive evidence comparing different medications for acromegaly is scarce. The aim of this study was to perform a network meta-analysis based on evidence from both randomized trials and observational studies of medical treatments for acromegaly. Methods: Electronic databases were searched for both observational studies and randomized trials that enrolled acromegaly patients treated with medications of interest. Simulated trials were generated by a machine learning algorithm and then synthesized with Bayesian random-effects network meta-analyses. The main outcome was the rate of insulin-like growth factor 1 (IGF-1) control after medical treatment. Results: We included 90 studies (100 arms, 4,523 patients) before matching. After matching, 28 simulated trials were generated. Balance of matched arms was checked by spatial distance and correlation matrix. Cotreatment with somatostatin receptor ligands and pegvisomant was the most effective treatment compared with other treatments. In unselected patients, pegvisomant was better than octreotide long-acting release (logOR, 0.85; 95% credible interval [CrI], 0.05 to 1.65) or lanreotide (logOR, 1.09, 95% CrI, 0.05 to 2.14), and the mean absolute IGF-1 control rate ranged from 40 to 60%. In partially responsive patients, cotreatment with somatostatin receptor ligands and pegvisomant was similar to pegvisomant monotherapy, ranking as the most two effective treatments, and the mean absolute IGF-1 control rate was over 60%. Conclusion: Our analysis suggested that the combination of data from observational studies and randomized trials in network meta-analysis was feasible. The findings of this network meta-analysis provided robust evidence supporting the current guidelines in treatment strategy for acromegaly. Abbreviations: CrI = credible interval; DA = dopamine agonist; GH = growth hormone; IGF-1 = insulin-like growth factor 1; ITT = intention-to-treat; LAN = lanreotide; LAN-ATG = lanreotide autogel; OCT = octreotide; OCT-LAR = octreotide long acting repeatable; OR = odds ratio; PEG = pegvisomant; PP = per-protocol; SRL = somatostatin receptor ligand

scholarly journals MON-LB50 Poor Response to Pre-Surgical Treatment With Somatostatin Receptor Ligands Is Associated With Diabetes Mellitus in Patients With Acromegaly

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Stefano Frara ◽  
Marco Losa ◽  
Erika Pedone ◽  
Eugenia Resmini ◽  
Francesco Tecilazich ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Surgical Treatment ◽  
Somatostatin Receptor ◽  
Fasting Blood Glucose ◽  
Receptor Ligands ◽  
Time Of Surgery ◽  
Percent Change ◽  
Somatostatin Receptor Ligands ◽  
Pre Treatment

Abstract Introduction: somatostatin receptor ligands (SRL) represent the first-line medical therapy in acromegaly patients who were not cured by surgery and in those where surgical remission is unlikely. It is well known that SRL may negatively act on insulin secretion, with consequent hyperglycemia and diabetes mellitus (DM). Purpose: To evaluate whether the degree of response to surgical pre-treatment with SRL predicts alterations in blood glucose levels.Patients and Methods: We retrospectively studied 181 patients attending the Unit of Neurosurgery of our Hospital prior to transsphenoidal surgery. All patients had a biochemical and radiological diagnosis of acromegaly (nadir GH during OGTT &gt;0.4 ng/mL; IGF-I above age-standardized UNL and pituitary adenoma at MRI scans); diagnosis of DM and impaired fasting glucose (IFG) was performed on fasting blood glucose (FBG) according to the American Diabetes Association guidelines; all parameters of the pituitary axes were determined. The response to SRL treatment was determined as percent change of GH levels. Data are presented as mean±SD; Continuous data normally distributed were analyzed using a two-tailed Student’s t-test to compare two groups, and one-way ANOVA to compare several groups, followed by the Bonferroni post-hoc procedure for pairwise comparison of groups after the null hypothesis was rejected (p&lt;0.05); categorical data were analyzed by chi-squared test.Results: 97 (54%) patients with acromegaly underwent pre-surgical treatment with SRL; we found no difference in age (53±11 vs. 51±12 years; p=NS) and sex (M/F: 51/46 vs. 43/41; p=NS) between SRL treated and non-treated patients. We found no difference in FBG between SRL treated vs. non-treated patients. In contrast, we found increased proportions of IFG and DM patients in SRL treated when compared to non-treated patients (euglycemic: 45%, IFG: 42%, DM: 13% vs. euglycemic: 70%, IFG: 22%, DM: 8%, respectively; p=0.006). In addition, SRL treatment increased the odds ratio of IFG and DM (OR 4.7; 95%CI 2.1-10.3). When considering the degree of response to SRL pre-surgical treatment, we found that poor responders displayed at the time of surgery glycemias diagnostic of DM; whereas, good responders displayed glycemias in the range of IFG (percent change in GH levels 50±35% vs 79±22%, respectively; p&lt;0.05).Conclusions: Our findings show that the proportion of patients with acromegaly undergoing surgery with glycemic levels diagnostic of DM, is modest. Interestingly, pre-treatment with SRL represents an independent risk factor for high glucose levels. Moreover, among patients on SRL pre-treatment, the ones that respond poorly are the ones that at the time of surgery display glycemias diagnostic of DM. Our findings suggest that SRL pre-treatment may predispose to worsened glucose metabolism but selectively affecting those patients in whom biochemical control is not reached.

scholarly journals MON-311 Glucose Metabolism in Acromegaly Patients Resistant to First Generation Somatostatin Receptor Ligands Treated with Pegvisomant And/Or Pasireotide Lar

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sabrina Chiloiro ◽  
Antonella Giampietro ◽  
Antonio Bianchi ◽  
Felicia Visconti ◽  
Anna Maria Formenti ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
First Generation ◽  
Systemic Disease ◽  
Somatostatin Receptor ◽  
High Growth ◽  
Study Entry ◽  
Close Monitoring ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Igf I

Abstract Introduction: Acromegaly (Acro) is a systemic disease characterized by high growth hormone (GH) and insulin like growth factor-I (IGF-I), insulin resistance, glucose intolerance (IGT) and higher diabetes mellitus (DM) risk in 15% - 38% of patients (pts). Moreover, different medical therapies of Acro are reported to have variable effects on glucose metabolism. An association between blood glucose (BG) and serum IGF-I levels in patients with DM and Acro has been suggested, while IGF-I levels and hemoglobin A1c (HbA1c) correlation is still controversial because of the multifactorial influence.Study aim: to investigate glucose metabolism in pts with Acro resistant to 1st gen somatostatin receptor ligands (SRLs) treated with Pegvisomant (Peg) or Pasireotide LAR (Pasi). Patients and Methods: Retrospective, international, multicenter study; consecutive pts enrolled according to following inclusion criteria for at least 6 consecutive months: (1) resistant to 1st gen SRLs, (2) treated with Pasi or Peg for active Acro. Patients with concomitant treatments with known action on glucose metabolism were excluded, with the exception of glucocorticoid replacement for central hypoadrenalism. Results: 72 pts with active Acro, mean age at study entry 37 ±15 yrs, 47 females (65.3%). 28 (38.9%) pts were treated with Pasi and 44 pts with Peg (61.1%). Peg was monotherapy in 18 pts (40.9%) and in combo with first generation SRLs for 26 pts (59.1%). The number of pts with IGT and DM2 was superimposable between the 2 groups (Pasi and Peg). In Pasi group, 19 pts had Acro control (67.9%); glucose metabolism worsened in 16 pts (57.1%). Worsening of glucose metabolism occurred most frequently in pts with persistently active Acro (62.5%) and in pts with higher BG and HbA1c values at study start. Similarly, HbA1c was higher in pts with active Acro, although HbA1c worsened during Pasi treatment both in euglycemic and IGT at study entry, regardless of Acro control. In Peg group, 31 pts reached Acro control (73%); glucose metabolism worsened in 12 (27.3%) but improved in 5 pts (11.4%). All pts who experienced glucose metabolism improvement had controlled Acro, regardless of the use of a combo with first generation SRL. Among the 13 pts with active Acro after Peg, BG worsened in 5 cases (38.4%). Moreover, we found that pts with worsening BG control had higher HbA1c (p=0.03) and required higher Peg doses (mean ±SD 25 ±10 mg/day; p=0.04). Patients with higher HbA1c had higher IGF-I, both at study entry and at study end and were treated with higher Peg dose (mean 25 mg/day). Conclusion: Impaired glucose metabolism was more frequent after Pasireotide treatment and in patients of both Pasireotide and Pegvisomant groups with altered pre-treatment glucose and persistently active disease. Therefore, in such acromegaly patients close monitoring of glucose status is recommended during treatment.

scholarly journals Pegvisomant and not somatostatin receptor ligands (SRLs) is first-line medical therapy for acromegaly

2020 ◽  
Vol 182 (6) ◽  
pp. D17-D29 ◽  
Author(s):  
Aart J van der Lely ◽  
Emmanuelle Kuhn ◽  
Ammar Muhammad ◽  
Eva C Coopmans ◽  
Sebastian J Neggers ◽  
...  
Keyword(s):  
Medical Treatment ◽  
Medical Therapy ◽  
Remission Rate ◽  
Somatostatin Receptor ◽  
Line Treatment ◽  
Receptor Ligands ◽  
First Line ◽  
Somatostatin Receptor Ligands ◽  
Igf I ◽  
First Line Treatment

Current guidelines recommend the use of long-acting somatostatin receptor ligands (SRLs) first when surgery fails to correct GH/IGF-I hypersecretion in patients with acromegaly. In this issue of the journal, a pro- and contra debate will outline which arguments are in favour and which are against positioning pegvisomant (PEGV), a GH receptor antagonist, as the first-line treatment modality of acromegaly. The task of the pros was to promote a paradigm shift towards repositioning PEGV as first-line treatment as PEGV is safe and more effective than the first- and second-generation of SRLs. SRLs, when prescribed together with PEGV can still reduce tumour size when necessary, while they decrease the necessary dose of PEGV by around 50% in the average patient. They conclude that PEGV must move up towards the first-line treatment. For the cons, SRLs remain the first-line medical treatment. Indeed, even if, in recent studies, the remission rate is lower than initially claimed, SRLs are still effective not only for normalizing GH/IGF-I levels in half of the patients but also for inducing tumour shrinkage, improving comorbidities and headaches and reversing excess mortality. They are more convenient for use with their monthly administration and have a remarkable safety profile as demonstrated by the very prolonged experience acquired by more than 30 years of use. Finally, the cost-effectiveness of first-generation SRLs is better than that of PEGV. For all these reasons, cons consider that SRLs remain the best first medical treatment in patients requiring medical therapy.

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