Explore the vast range of titles available.

Purpose This analysis evaluates the 2-year effectiveness and safety of lanreotide depot/autogel (LAN), as well as treatment convenience and acromegaly symptom relief, from the Somatuline ® Depot for Acromegaly (SODA) registry, a post-marketing, open-label, observational, multicenter, United States registry study. Methods Patients with acromegaly treated with LAN were eligible for enrollment. Demographics, LAN dose, extended dosing interval (EDI) (interval of injections ≥42 days), insulin-like growth factor 1 (IGF-1), growth hormone (GH), glycated hemoglobin, adverse events (AEs), injection convenience, and symptom data were collected. Results As of September 29, 2014, 241 patients were enrolled in SODA. IGF-1 levels below age- and gender-adjusted upper normal limit (ULN) were achieved in 71.2% at month (M) 12 and 74.4% at M24; GH ≤2.5 µg/L in 83.3% at M12 and 80.0% at M24; GH <1.0 µg/L in 61.7% at M12 and 61.4% at M24. Both IGF-1 < ULN and GH ≤2.5 µg/L were achieved in 65.0% at M12 and 54.8% at M24; both IGF-1 < ULN and GH < 1.0 µg/L were achieved in 51.7 and 42.9% at M12 and M24, respectively. EDI regimen was 5.0% at baseline and 12.0% at M24. At M24, acromegaly symptoms appeared stable or improved. The most common AE was arthralgia (25.7%). Among 106 serious AEs reported by 42 patients, 10 were deemed related to therapy in 9 patients. At M24, 73.1% of patients rated LAN as convenient. Conclusions SODA indicates 2-year biochemical control with majority of patients achieving both IGF-1 < ULN and GH ≤2.5 µg/L. LAN was generally well tolerated with no new or unexpected safety signals reported during the observation period. clinicaltrials.gov Clinical Trial Identifier: NCT00686348

Nanoparticles are becoming an increasingly popular tool for biomedical imaging and drug delivery. While the prevalence of nanoparticle drug-delivery systems reported in the literature increases yearly, relatively little translation from the bench to the bedside has occurred. It is crucial for the scientific community to recognize this shortcoming and re-evaluate standard practices in the field, to increase clinical translatability. Currently, nanoparticle drug-delivery systems are designed to increase circulation, target disease states, enhance retention in diseased tissues, and provide targeted payload release. To manage these demands, the surface of the particle is often modified with a variety of chemical and biological moieties, including PEG, tumor targeting peptides, and environmentally responsive linkers. Regardless of the surface modifications, the nano–bio interface, which is mediated by opsonization and the protein corona, often remains problematic. While fabrication and assessment techniques for nanoparticles have seen continued advances, a thorough evaluation of the particle’s interaction with the immune system has lagged behind, seemingly taking a backseat to particle characterization. This review explores current limitations in the evaluation of surface-modified nanoparticle biocompatibility and in vivo model selection, suggesting a promising standardized pathway to clinical translation.

Dysregulated growth hormone (GH) hypersecretion is usually caused by a GH-secreting pituitary adenoma and leads to acromegaly - a disorder of disproportionate skeletal, tissue, and organ growth. High GH and IGF1 levels lead to comorbidities including arthritis, facial changes, prognathism, and glucose intolerance. If the condition is untreated, enhanced mortality due to cardiovascular, cerebrovascular, and pulmonary dysfunction is associated with a 30% decrease in life span. This Review discusses acromegaly pathogenesis and management options. The latter include surgery, radiation, and use of novel medications. Somatostatin receptor (SSTR) ligands inhibit GH release, control tumor growth, and attenuate peripheral GH action, while GH receptor antagonists block GH action and effectively lower IGF1 levels. Novel peptides, including SSTR ligands, exhibiting polyreceptor subtype affinities and chimeric dopaminergic-somatostatinergic properties are currently in clinical trials. Effective control of GH and IGF1 hypersecretion and ablation or stabilization of the pituitary tumor mass lead to improved comorbidities and lowering of mortality rates for this hormonal disorder.

Abstract Context Nonalcoholic fatty liver disease (NAFLD) is a metabolical disorder and can lead to liver fibrosis. Because it is commonly seen, several noninvasive scores (NS) have been validated to identify high-risk patients. Patients with NAFLD have been shown to have higher serum angiopoietin-like protein-8 (ANGPTL-8) levels. Objective The risk of NAFLD is known insufficiently in acromegaly. Moreover, the utility of the NS and the link between NAFLD and ANGPTL-8 in acromegaly is unknown. Methods Thirty-two patients with acromegaly (n = 15, active [AA] and n = 17, controlled acromegaly [CA]) and 19 healthy controls were included. Magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) was used to evaluate hepatic steatosis, and magnetic resonance elastography to evaluate liver stiffness measurement. ANGPTL-8 levels were measured with ELISA. Results Median liver MRI-PDFF and NAFLD prevalence in AA were lower than in CA (P = .026 and P < .001, respectively). Median magnetic resonance elastography-liver stiffness measurement were similar across groups. Of the NS, visceral adiposity index, fatty liver index, hepatic steatosis index, and triglyceride-glucose index (TyG) all showed positive correlation with the liver MRI-PDFF in the control group. However, only TyG significantly correlated with liver fat in the AA and CA groups. There was no correlation between traditional NAFLD risk factors (body mass index, waist circumference, C-reactive protein, homeostasis model assessment for insulin resistance, visceral adipose tissue) and liver MRI-PDFF in the AA and CA. Patients with acromegaly with NAFLD had lower GH, IGF-1, and ANGPTL-8 levels than in those without NAFLD (P = .025, P = .011, and P = .036, respectively). Conclusion Active acromegaly may protect from NAFLD because of high GH. In patients with acromegaly, NAFLD risk cannot be explained with classical risk factors; hence, additional risk factors must be identified. TyG is the best score to evaluate NAFLD risk. Lower ANGPTL-8 in patients with acromegaly and NAFLD implies this hormone may be raised because of insulin resistance rather than being a cause for NAFLD.

Acromegaly, caused by growth hormone-secreting pituitary tumors, often causes significant challenges in its management due to poor surgical outcomes and resistance to pharmacological treatment. The present study aims to explore the expression of Filamin A (FLNA), a cytoskeletal protein involved in somatostatin receptor signaling, and its clinical relevance in acromegaly. We conducted immunohistochemical (IHC) study on 34 GH-secreting pituitary tumors to evaluate FLNA expression intensity and its associations with somatostatin receptors (SSTR2, SSTR5), E-Cadherin, tumor characteristics obtained through imaging studies, and pharmacological treatment responses. Our findings revealed a 100% FLNA positivity rate, with moderate to strong FLNA expression correlating significantly with SSTR5 expression and the presence of suprasellar tumor extension, indicating a potential role in tumor invasiveness. Moreover, patients with macrodenomas presented significantly higher FLNA intensity compared to the ones with microadenomas. FLNA expression showed no significant association with SSTR2, E-Cadherin, surgical cure rate or first-generation somatostatin receptor ligand (fgSRL) responses. However, the series of patients treated with Pasireotide ( n  = 4) demonstrated a trend suggesting better biochemical control with higher FLNA expression. In conclusion, our results suggest that FLNA may be associated with tumor invasiveness in GH-secreting pituitary tumors. While data on Pasireotide-treated patients are exploratory, further studies are needed to assess FLNA’s potential as a treatment response marker in acromegaly.

Abstract Purpose The molecular pathogenesis of growth hormone-secreting pituitary adenomas is not fully understood. Cytogenetic alterations might serve as alternative driver events in GNAS mutation–negative somatotroph tumors. Experimental Design We performed cytogenetic profiling of pituitary adenomas obtained from 39 patients with acromegaly and four patients with sporadic gigantism by using array comparative genomic hybridization analysis. We explored intratumor DNA copy-number heterogeneity in two tumor samples by using DNA fluorescence in situ hybridization (FISH). Results Based on copy-number profiles, we found two groups of adenomas: a low–copy-number alteration (CNA) group (<12% of genomic disruption, 63% of tumors) and a high-CNA group (24% to 45% of genomic disruption, 37% of tumors). Arm-level CNAs were the most common abnormalities. GNAS mutation–positive adenomas belonged exclusively to the low-CNA group, whereas a subgroup of GNAS mutation–negative adenomas had a high degree of genomic disruption. We detected chromothripsis-related CNA profiles in two adenoma samples from an AIP mutation–positive patient with acromegaly and a patient with sporadic gigantism. RNA sequencing of these two samples identified 17 fusion transcripts, most of which resulted from chromothripsis-related chromosomal rearrangements. DNA FISH analysis of these samples demonstrated a subclonal architecture with up to six distinct cell populations in each tumor. Conclusion Somatotroph pituitary adenomas display substantial intertumor and intratumor DNA copy-number heterogeneity, as revealed by variable CNA profiles and complex subclonal architecture. The extensive cytogenetic burden in a subgroup of GNAS mutation–negative somatotroph adenomas points to an alternative tumorigenic pathway linked to genomic instability. Using cytogenetic profiling and DNA FISH analysis, we identified extensive intertumor and intratumor DNA copy-number heterogeneity reflecting a complex clonal architecture in somatotroph adenomas.

The nature of somatotroph adenomas has not been clearly revealed in studies. We consider that there are macroscopic differences in intraoperative tumor consistency in acromegaly patients. We aimed to determine whether there is a relationship between intraoperative tumor consistency and histopathological subtypes by planning a prospective study to determine whether these differences are significant. Between August 1997 and December 2021, 1118 patients with GH-secreting tumors underwent endoscopic endonasal surgery at our Pituitary Research Center. Between January 2022 and May 2023, pure GH-secreting adenomas operated via the endoscopic endonasal approach were sequentially categorized into three types(Type-1:Soft, Type-2:Mucinous/Adhesive, Type-3:Mix/Intermediate) according to the intraoperative tumor consistency. The final patient cohort consisted 218 cases. The ratio of densely granulated adenomas(DG-A) to sparsely granulated adenomas(SG-A) was as follows: Type-1, 89/11; Type-2, 5/95; Type-3, 13/5. Logistic regression revealed that Type-1 tumors were associated with a high remission rate( p  = 0.011), and Type-2 were associated with SG-A( p  < 0.001). Furthermore, no or weak staining for E-cadherin was associated with Type-2 tumors( p  < 0.001). Surgeon could predict the prognosis and histopathological subtype of the pure somatotroph adenoma by observing the intraoperative tumor consistency. This could facilitate better intraoperative planning of patient-specific surgical strategies to increase the remission rates.

ContextThe high risk of vertebral fractures (VFs) in acromegaly patients despite normal bone mineral density (BMD) is well known. The reasons for this paradoxical finding of skeleton fragility are poorly understood due to the limited data on bone histomorphometry in acromegaly.ObjectiveThis study aimed to analyze histomorphometric parameters including bone microarchitecture in acromegaly patients with VFs and normal BMD compared to normal subjects, and also to evaluate the differences between active and controlled acromegaly patients.Patients and methodsForty-seven acromegaly patients (17 active, 30 controlled), median (range) age 57 years (30–88) were evaluated for bone turnover, morphometric VFs and BMD by dual-energy X-ray absorptiometry at lumbar spine and hip; 12 patients with VFs and normal BMD underwent iliac crest bone biopsy; 12 biopsies were taken at the autopsy in healthy sex and age—matched control subjects.ResultsThe histomorphometric evaluation of acromegaly fractured patients was compared with that of normal controls and showed significantly reduced median (range) levels of bone volume/tissue volume (BV/TV: 15.37% (7.93–26.75) vs. 18.61% (11.75–27.31), p = 0.036), trabecular thickness (TbTh: 77.6 µm (61.7–88.3) vs. 82.7 µm (72.3–92.0) p = 0.045), with increased trabecular separation (TbSp: 536.4 µm (356.2–900.6) vs. 370.3 µm (377.1–546.3) p = 0.038) and increased cortical thickness (1268 μm (752–2521) vs. 1065 μm (851–1205) p = 0.025) and porosity (11.9% (10.2–13.3) vs. 4.8% (1.6–8.8) p = 0.0008). While active acromegaly patients showed histomophometric features of increased bone turnover, patients with controlled disease presented normal bone turnover with significantly lower osteoblastic activity, expressed as osteoblast number (p = 0.001), active osteoblasts and vigor (p = 0.014) in the presence of reduced osteocyte number (p = 0.008) compared to active disease.ConclusionsThe apparent paradox of bone fragility in acromegaly patients with a normal BMD can be explained by increased cortical thickness and porosity and reduced trabecular thickness with increased trabecular separation. These structural and microarchitectural abnormalities persist in the controlled phase of acromegaly despite bone turnover normalization. The main determinant of bone disease after hormonal control is severe osteoblastic dysfunction.

Purpose The existing data on colon lesions in acromegaly is notably heterogeneous. This study aimed to analyze the endoscopic and histopathological characteristics of colon polyps and other colonic lesions in acromegaly patients. Methods This case-control study included 192 acromegaly patients and 256 controls. Colon polyps were categorized based on their size and histopathological classification. Colon malignancies and other colonic lesions, such as anal fissures, hemorrhoids, and diverticulosis, were also documented. Results The prevalence of colon polyps was higher in the acromegaly group than in controls ( p  = 0.003), however, no differences were observed in the number, size, or histopathological subtypes of the polyps. Polyps in acromegaly patients were predominantly located in the distal colon and rectum. Multiple polyp locations and histopathological subtypes were more frequent in the control group ( p  = 0.042 and p  = 0.018). Rates of low-grade dysplasia, high-grade dysplasia, and malignancy were similar between groups. Anal fissures were more common in the acromegaly group, whereas diverticulosis was less frequent ( p  = 0.001 and p  < 0.001; respectively). Logistic regression analysis identified no significant clinical or laboratory predictors for colon polyps in acromegaly. Conclusion Patients with acromegaly exhibited a higher prevalence of colon polyps, predominantly located in the distal colon, which typically displayed a single histopathological subtype. No increased rates of colonic dysplasia, colon cancer, or other colonic lesions were observed in patients with acromegaly, except for an elevated prevalence of anal fissures.

Acromegaly is an insidious disease associated with severe somatic morbidity but data on socioeconomic status are scarce. To study the socioeconomic status in acromegaly in a population-based follow-up study. All incident cases of acromegaly (n = 576) during the period 1977-2010 were included. For every patient, 100 persons were sampled from the general population matched for date of birth and gender (comparison cohort). Cox regression and hazard ratios (HR), conditional logistic regression and linear regression with 95% confidence intervals (CI) were used. Retirement, social security benefit, annual income, cohabitation, separation, parenthood and educational level. The proportion of retired individuals was significantly higher in patients with acromegaly after the time of diagnosis (HR, 1.43; 95% CI, 1.26-1.62) and also during the 5-year pre-diagnostic period (HR, 1.15; 95% CI, 1.03-1.28). More individuals with acromegaly received social security benefit compared with the comparison cohort during the initial period after the time of diagnosis. Among patients who maintained a job, the annual income was similar to the comparison cohort. Compared with the background population, cohabitation was lower (HR, 0.69; 95% CI, 0.50-0.95) as was parenthood (HR, 0.56; 95% CI, 0.39-0.80), whereas neither educational level (HR, 0.61; 95% CI, 0.35-1.06) nor separation (HR, 1.13; 95% CI, 0.86-1.47) were different. Female gender and insufficient disease control were associated with a significantly worse socioeconomic status. 1) Socioeconomic status is impaired in patients with acromegaly even before a diagnosis of acromegaly. 2) Females and patients without disease remission have worse outcomes. 3) Early diagnosis and effective treatment of acromegaly could be important factors in mitigating the negative impact on socioeconomic factors.