Glucose metabolism outcomes after pituitary surgery in patients with acromegaly.

AIM: To investigate the impact of pituitary surgery on glucose metabolism and to identify predictors of remission of diabetes after pituitary surgery in patients with acromegaly. METHODS: A national multicenter retrospective study of patients with acromegaly undergoing transsphenoidal surgery for the first time at 33 tertiary Spanish hospitals (ACRO-SPAIN study) was performed. Surgical remission of acromegaly was evaluated according to the 2000 and 2010 criteria. RESULTS: A total of 604 acromegaly patients were included in the study with a total median follow up of 91 months (interquartile range [IQR] 45-163). At the acromegaly diagnosis, 23.8% of the patients had diabetes mellitus (DM) with a median glycated hemoglobin (HbA1c) of 6.9% (IQR 6.4-7.9) [51.9 mmol/mol (IQR 46.4-62.8)]. In the multivariate analysis, older age (odds ratio [OR] 1.02, 95% CI 1.00-1.05), dyslipidemia (OR 5.25, 95% CI 2.81 to 9.79), arthropathy (OR 1.39, 95% CI 2.82 to 9.79), and higher IGF-I levels (OR 1.30, 95% CI 1.05 to 1.60) were associated with a greater prevalence of DM. At the last follow-up visit after surgery, 21.1% of the DM patients (56.7% of them with surgical remission of acromegaly) experienced diabetes remission. The cure rate of DM was more common in older patients (hazard ratio [HR] 1.77, 95% CI 1.31 to 2.43), when surgical cure was achieved (HR 2.10, 95% CI 1.01 to 4.37) and when anterior pituitary function was not affected after surgery (HR 3.38, 95% CI 1.17 to 9.75). CONCLUSION: Glucose metabolism improved in patients with acromegaly after surgery and 21% of the diabetic patients experienced diabetes remission; being more frequent in patients of older age, and those who experienced surgical cure and those with preserved anterior pituitary function after surgery.

A Two-Faced Gut Microbiome: Butyrogenic and Proinflammatory Bacteria Predominate in the Intestinal Milieu of People Living with HIV from Western Mexico.

HIV infection results in marked alterations in the gut microbiota (GM), such as the loss of microbial diversity and different taxonomic and metabolic profiles. Despite antiretroviral therapy (ART) partially ablating gastrointestinal alterations, the taxonomic profile after successful new ART has shown wide variations. Our objective was to determine the GM composition and functions in people living with HIV (PLWHIV) under ART in comparison to seronegative controls (SC). Fecal samples from 21 subjects (treated with integrase strand-transfer inhibitors, INSTIs) and 18 SC were included. We employed 16S rRNA amplicon sequencing, coupled with PICRUSt2 and fecal short-chain fatty acid (SCFA) quantification by gas chromatography. The INSTI group showed a decreased α-diversity (p < 0.001) compared to the SC group, at the expense of increased amounts of Pseudomonadota (Proteobacteria), Segatella copri, Lactobacillus, and Gram-negative bacteria. Concurrently, we observed an enrichment in Megasphaera and Butyricicoccus, both SCFA-producing bacteria, and significant elevations in fecal butyrate in this group (p < 0.001). Interestingly, gut dysbiosis in PLWHIV was characterized by a proinflammatory environment orchestrated by Pseudomonadota and elevated levels of butyrate associated with bacterial metabolic pathways, as well as the evident presence of butyrogenic bacteria. The role of this unique GM in PLWHIV should be evaluated, as well as the use of butyrate-based supplements and ART regimens that contain succinate, such as tenofovir disoproxil succinate. This mixed profile is described for the first time in PLWHIV from Mexico.

Gut microbiota from Mexican patients with metabolic syndrome and HIV infection: An inflammatory profile.

AIM: A remarkable increase in metabolic syndrome (MetS) has occurred in HIV-infected subjects. Gut dysbiosis is involved in the pathogenesis of metabolic disorders. Therefore, the aim is to explore the profile of the gut microbiota in Mexican population with HIV infection and MetS. METHODS AND RESULTS: In all, 30 HIV-infected patients with MetS were compared to a group of 30 patients without MetS, treated with integrase inhibitors and undetectable viral load were included in the study. Stool samples were analysed by 16S rRNA next-generation sequencing. High-sensitivity C-reactive protein >3 mg L-1 and higher scores in cardiometabolic indices were associated with MetS. The group with MetS was characterized by a decrease in α-diversity, higher abundance of Enterobacteriaceae and Prevotella, as well as a dramatic decrease in bacteria producing short-chain fatty acids. Prevotella negatively correlated with Akkermansia, Lactobacillus and Anaerostipes. Interestingly, the group without MetS presented higher abundance of Faecalibacterium, Ruminococcus, Anaerofilum, Oscillospira and Anaerostipes. Functional pathways related to energy metabolism and inflammation were increased in the group with MetS. CONCLUSIONS: HIV-infected patients with MetS present a strong inflammatory microbiota profile; therefore, future strategies to balance intestinal dysbiosis should be implemented.

Design and Development of an IoT Smart Meter with Load Control for Home Energy Management Systems.

Electricity consumption is rising due to population growth, climate change, urbanization, and the increasing use of electronic devices. The trend of the Internet of Things has contributed to the creation of devices that promote the thrift and efficient use of electrical energy. Currently, most projects relating to this issue focus solely on monitoring energy consumption without providing relevant parameters or switching on/off electronic devices. Therefore, this paper presents in detail the design, construction, and validation of a smart meter with load control aimed at being part of a home energy management system. With its own electronic design, the proposal differs from others in many aspects. For example, it was developed using a simple IoT architecture with in-built WiFi technology to enable direct connection to the internet, while at the same time being big enough to be part of standardized electrical enclosures. Unlike other smart meters with load control, this one not only provides the amount of energy consumption, but rms current and voltage, active, reactive, and apparent power, reactive energy, and power factor-parameters that could be useful for future studies. In addition, this work presents evidence based on experimentation that the prototype in all its readings achieves an absolute percentage error of less than 1%. A real-life application of the device was also demonstrated in this document by measuring different appliances and switching them on/off manually and automatically using a web-deployed application.

From Propargylic Alcohols to Substituted Thiochromenes: gem-Disubstituent Effect in Intramolecular Alkyne Iodo/hydroarylation.

This work describes the 6-endo-dig cyclization of S-aryl propargyl sulfides to afford 2H-thiochromenes. The substitution at the propargylic position plays a crucial role in allowing intramolecular silver-catalyzed alkyne hydroarylation and N-iodosuccinimide-promoted iodoarylation. Additionally, a PTSA-catalyzed thiolation reaction of propargylic alcohols was developed to synthesize the required tertiary S-aryl propargyl ethers. The applicability of merging these two methods is demonstrated by synthesizing the retinoic acid receptor antagonist AGN194310.

Earthquake-related stressors associated with suicidality, depression, anxiety and post-traumatic stress in adolescents from Muisne after the earthquake 2016 in Ecuador.

BACKGROUND: The Ecuadorian earthquake in April 16th was the second strongest and deadliest in 2016 worldwide, with approximately one million people affected. In this paper, we analyzed the psychological impact and the relationship between mental health events and various earthquake-related stressors related to the earthquake, 9 months after the event. METHODS: We conducted an analytical cross-sectional study, applying an anonymous survey to 316 adolescents (13-19 years old) from Muisne, Ecuador. Suicidal tendency, depression, anxiety and post-traumatic stress (PTSD) were evaluated via the Child PTSD Symptom Scale (CPSS), Spence Children's Anxiety Scale, Okasha Suicidality Scale, and the Center for Epidemiologic Studies Depression Scale (CES-D) and the adapted seven-questions earthquake-related stressors survey. RESULTS: We found a high prevalence of suicidal ideations and behavior, posttraumatic stress, depression and anxiety compared to international studies. Even though adolescents currently living in shelters had higher levels of anxiety, their suicidal tendency was significantly lower than those living in their own or their relatives' home. Finally, the earthquake-related stressors were not associated with suicidality and mental health events, with the exception of economic damage suffered by the family. CONCLUSIONS: High levels of depression, post-traumatic stress and anxiety among high-school students were found, especially among those who have suffered serious economic damage. The economic impact in their families and high unemployment rates among their parents seems to be related to lack of hope and favorable perspectives for their future, situation that might lead to lead to emotional disturbances and psychological disorders. Although prolonged homelessness experience in shelters may be a stressful occurrence, might also be related with spiritual growth among adolescents, and may work as a protective factor against suicidal ideations and attempts.

Cytomegalovirus and disseminated histoplasmosis-related hemophagocytic lymphohistiocytosis syndrome in an HIV-patient late presenter with IRIS: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis syndrome (HLS) is an immune-mediated life-threatening disease considered as a medical emergency, with a potentially fatal multisystem inflammatory outcome. We present a patient that developed HLS and was able to be diagnosed efficiently with the help of an academic research institute of immunology. CASE PRESENTATION: A 21 years old male Mexican with human immunodeficiency virus (HIV), late presenter; who developed cytomegalovirus (CMV) infection and a disseminated histoplasmosis-related HLS, as part of an immune reconstitution inflammatory syndrome (IRIS). The patient required a long course of corticotherapy, intravenous immunoglobulin and massive transfusions (more than 10 units in 24 h, and a total of 83 units), besides amphotericin-B and ganciclovir treatment. An academic research institute of immunology aided in the accurate diagnosis of HLS with the implementation of tests not available within the hospital, thus improving the care provided to the patient. The patient recovered, was discharged, and continue to improve. CONCLUSION: The objective of this report is to highlight the importance of having multidisciplinary support, including basic medical sciences groups providing specific tests that are sometimes very difficult to get, which provides a benefit to patients in the well-aimed diagnosis as part of applied translational medicine.

Influence of knot complexity on glass-formation in low molecular mass ring polymer melts.

We perform molecular dynamics simulations on a coarse-grained polymer melt to study the dynamics of glass-formation in ring polymer melts of variable knot complexity. After generating melts of non-concatenated polymeric rings having a range of minimum crossing number values, mc, we compute the coherent intermediate scattering function, the segmental α-relaxation time, fragility, and the glass transition temperature as a function of mc. Variation of knot complexity is found to have a pronounced effect on the dynamics of polymer melts since both molecular rigidity and packing are altered, primary physical factors governing glass-formation in polymeric materials.

The interfacial zone in thin polymer films and around nanoparticles in polymer nanocomposites.

We perform coarse-grained simulations of model unentangled polymer materials to quantify the range over which interfaces alter the structure and dynamics in the vicinity of the interface. We study the interfacial zone around nanoparticles (NPs) in model polymer-NP composites with variable NP diameter, as well as the interfacial zone at the solid substrate and free surface of thin supported polymer films. These interfaces alter both the segmental packing and mobility in an interfacial zone. Variable NP size allows us to gain insight into the effect of boundary curvature, where the film is the limit of zero curvature. We find that the scale for perturbations of the density is relatively small and decreases on cooling for all cases. In other words, the interfaces become more sharply defined on cooling, as naively expected. In contrast, the interfacial mobility scale ξ for both NPs and supported films increases on cooling and is on the order of a few nanometers, regardless of the polymer-interfacial interaction strength. Additionally, the dynamical interfacial scale of the film substrate is consistent with a limiting value for polymer-NP composites as the NP size grows. These findings are based on a simple quantitative model to describe the distance dependence of relaxation that should be applicable to many interfacial polymer materials.

Communication: A comparison between the solution properties of knotted ring and star polymers.

We computationally investigate the good solvent solution properties of knotted ring and star polymers by combining molecular dynamics (MD) simulation and path-integral calculations. We consider knotted rings having a minimal crossing number m c in the range, 0 ≤ m c ≤ 9, and star polymers having a range of f star arms, 2 ≤ f ≤ 20, attached to a common core monomer particle. After generating configurational ensembles of these polymers by MD, we use the path-integration program ZENO to calculate basic configurational properties, i.e., radius of gyration, hydrodynamic radius, intrinsic viscosity, as well as fluctuations in these properties. Our simulations indicate that the configurational properties of knotted rings and star polymers in solution show a similar decrease with increasing m c and f. Moreover, fluctuations in these properties also decrease with increasing topological complexity. Our findings should be helpful in polymer characterization and more generally for understanding the role of polymer topology in polymer material properties.

Phosphatidylethanolamine Induces an Antifibrotic Phenotype in Normal Human Lung Fibroblasts and Ameliorates Bleomycin-Induced Lung Fibrosis in Mice.

Lung surfactant is a complex mixture of phospholipids and specific proteins but its role in the pathogenesis of interstitial lung diseases is not established. Herein, we analyzed the effects of three representative phospholipid components, that is, dipalmitoilphosphatidylcoline (DPPC), phosphatidylglycerol (PG) and phosphatidylethanolamine (PE), on collagen expression, apoptosis and Ca2+ signaling in normal human lung fibroblasts (NHLF) and probed their effect in an experimental model of lung fibrosis. Collagen expression was measured with RT-PCR, apoptosis was measured by using either the APOPercentage assay kit (Biocolor Ltd., Northern Ireland, UK) or the Caspase-Glo 3/7 assay (Promega, Madison, WI, USA) and Ca2+ signaling by conventional epifluorescence imaging. The effect in vivo was tested in bleomycin-induced lung fibrosis in mice. DPPC and PG did not affect collagen expression, which was downregulated by PE. Furthermore, PE promoted apoptosis and induced a dose-dependent Ca2+ signal. PE-induced Ca2+ signal and apoptosis were both blocked by phospholipase C, endoplasmic reticulum pump and store-operated Ca2+ entry inhibition. PE-induced decrease in collagen expression was attenuated by blocking phospholipase C. Finally, surfactant enriched with PE and PE itself attenuated bleomycin-induced lung fibrosis and decreased the soluble collagen concentration in mice lungs. This study demonstrates that PE strongly contributes to the surfactant-induced inhibition of collagen expression in NHLF through a Ca2+ signal and that early administration of Beractant enriched with PE diminishes lung fibrosis in vivo.

Molecular rigidity and enthalpy-entropy compensation in DNA melting.

Enthalpy-entropy compensation (EEC) is observed in diverse molecular binding processes of importance to living systems and manufacturing applications, but this widely occurring phenomenon is not sufficiently understood from a molecular physics standpoint. To gain insight into this fundamental problem, we focus on the melting of double-stranded DNA (dsDNA) since measurements exhibiting EEC are extensive for nucleic acid complexes and existing coarse-grained models of DNA allow us to explore the influence of changes in molecular parameters on the energetic parameters by using molecular dynamics simulations. Previous experimental and computational studies have indicated a correlation between EEC and changes in molecular rigidity in certain binding-unbinding processes, and, correspondingly, we estimate measures of DNA molecular rigidity under a wide range of conditions, along with resultant changes in the enthalpy and entropy of binding. In particular, we consider variations in dsDNA rigidity that arise from changes of intrinsic molecular rigidity such as varying the associative interaction strength between the DNA bases, the length of the DNA chains, and the bending stiffness of the individual DNA chains. We also consider extrinsic changes of molecular rigidity arising from the addition of polymer additives and geometrical confinement of DNA between parallel plates. All our computations confirm EEC and indicate that this phenomenon is indeed highly correlated with changes in molecular rigidity. However, two distinct patterns relating to how DNA rigidity influences the entropy of association emerge from our analysis. Increasing the intrinsic DNA rigidity increases the entropy of binding, but increases in molecular rigidity from external constraints decreases the entropy of binding. EEC arises in numerous synthetic and biological binding processes and we suggest that changes in molecular rigidity might provide a common origin of this ubiquitous phenomenon in the mutual binding and unbinding of complex molecules.

Universal interrelation between measures of particle and polymer size.

The characterization of many objects involves the determination of a basic set of particle size measures derived mainly from scattering and transport property measurements. For polymers, these basic properties include the radius of gyration Rg, hydrodynamic radius Rh, intrinsic viscosity [η], and sedimentation coefficient S, and for conductive particles, the electric polarizability tensor αE and self-capacity C. It is often found that hydrodynamic measurements of size deviate from each other and from geometric estimates of particle size when the particle or polymer shape is complex, a phenomenon that greatly complicates both nanoparticle and polymer characterizations. The present work explores a general quantitative relation between αE, C, and Rg for nanoparticles and polymers of general shape and the corresponding properties η, Rh, and Rg using a hydrodynamic-electrostatic property interrelation.

Confronting the complexity of CNT materials.

The morphology of commercially available carbon nanotube materials is often much more complex than the term "carbon nanotube" (CNT) would imply. Commercial CNT materials are typically composed of roughly spherical CNT domains having a highly ramified internal structure and a size on the order of microns. Clearly, such structures cannot reasonably be modeled as "rods". To address this problem, we first perform molecular dynamics simulations (MD) to generate structures similar to those measured experimentally, based on the presumptions that CNT domains are composed of worm-like cylinders having observed persistence lengths and that these CNTs are confined to spherical domains having the observed average domain size. This simple model generates structures remarkably similar to those observed experimentally. We then consider numerical path-integral computations to calculate the self-capacitance C and intrinsic conductivity [σ]∞ of these CNT rich domains. This information is then incorporated in a generalized effective medium theory to estimate the conductivity of bulk composite materials composed of these complex-shaped "particles". We term these CNT structures "tumbleweeds", given their evident morphological similarity to this naturally occurring growth form. Based on this model, we find that the conductivity percolation threshold of the tumbleweeds can be quite low, despite their quasi-spherical average shape. We also examine the structure factor S(q) of the CNT-rich domains as function of the number N of CNTs within them, to aid in the structural characterization of CNT nanocomposites. The structure factor S(q) of our model tumbleweed is found to resemble that of hyperbranched, star and dendrimer polymers, and also domain structures observed in polyelectrolytes. Commercial CNT materials at high loading should then have physical features in common with suspension of "soft" colloidal particles by virtue of their deformability and roughly spherical shape.

Dimensional reduction of duplex DNA under confinement to nanofluidic slits.

There has been much interest in the dimensional properties of double-stranded DNA (dsDNA) confined to nanoscale environments as a problem of fundamental importance in both biological and technological fields. This has led to a series of measurements by fluorescence microscopy of single dsDNA molecules under confinement to nanofluidic slits. Despite the efforts expended on such experiments and the corresponding theory and simulations of confined polymers, a consistent description of changes of the radius of gyration of dsDNA under strong confinement has not yet emerged. Here, we perform molecular dynamics (MD) simulations to identify relevant factors that might account for this inconsistency. Our simulations indicate a significant amplification of excluded volume interactions under confinement at the nanoscale due to the reduction of the effective dimensionality of the system. Thus, any factor influencing the excluded volume interaction of dsDNA, such as ionic strength, solution chemistry, and even fluorescent labels, can greatly influence the dsDNA size under strong confinement. These factors, which are normally less important in bulk solutions of dsDNA at moderate ionic strengths because of the relative weakness of the excluded volume interaction, must therefore be under tight control to achieve reproducible measurements of dsDNA under conditions of dimensional reduction. By simulating semi-flexible polymers over a range of parameter values relevant to the experimental systems and exploiting past theoretical treatments of the dimensional variation of swelling exponents and prefactors, we have developed a novel predictive relationship for the in-plane radius of gyration of long semi-flexible polymers under slit-like confinement. Importantly, these analytic expressions allow us to estimate the properties of dsDNA for the experimentally and biologically relevant range of contour lengths that is not currently accessible by state-of-the-art MD simulations.

A study of the impact of the 21-gene breast cancer assay on the use of adjuvant chemotherapy in women with breast cancer in a Mexican public hospital.

BACKGROUND: The majority of breast cancer patients in Mexico are treated through the public health system and >80% receive adjuvant chemotherapy. The aim of this prospective study was to characterize the impact of the Oncotype DX assay on adjuvant therapy decision making and the confidence in those decisions amongst public sector physicians in Mexico. METHODS: Ninety-eight consecutive patients with ER+, HER2-, stage I-IIIa, N0/N1-3 node-positive breast cancer from the Instituto Nacional de Cancerología were eligible for the study. The primary endpoint was the overall change in treatment recommendations after receiving the assay results. RESULTS: Of 96 patients, 48% received a chemohormonal therapy recommendation prior to testing. Following receipt of results, treatment decisions changed for 31/96 (32%) patients, including 17/62 (27%) node-negative patients and 14/34 (41%) node-positive patients. The proportion of patients with a chemotherapy-based recommendation decreased from 48% pre- to 34% post-assay (P=0.024). 92% of physicians agreed that they were more confident in their treatment recommendation after ordering the assay. CONCLUSIONS: These results suggest that use of the 21-gene assay in the Mexican public health system has a meaningful impact on adjuvant treatment recommendations that may reduce the overall use of chemotherapy.

Intrinsic conductivity of carbon nanotubes and graphene sheets having a realistic geometry.

The addition of carbon nanotubes (CNTs) and graphene sheets (GSs) into polymeric materials can greatly enhance the conductivity and alter the electromagnetic response of the resulting nanocomposite material. The extent of these property modifications strongly depends on the structural parameters describing the CNTs and GSs, such as their shape and size, as well as their degree of particle dispersion within the polymeric matrix. To model these property modifications in the dilute particle regime, we determine the leading transport virial coefficients describing the conductivity of CNT and GS composites using a combination of molecular dynamics, path-integral, and finite-element calculations. This approach allows for the treatment of the general situation in which the ratio between the conductivity of the nanoparticles and the polymer matrix is arbitrary so that insulating, semi-conductive, and conductive particles can be treated within a unified framework. We first generate ensembles of CNTs and GSs in the form of self-avoiding worm-like cylinders and perfectly flat and random sheet polymeric structures by using molecular dynamics simulation to model the geometrical shapes of these complex-shaped carbonaceous nanoparticles. We then use path-integral and finite element methods to calculate the electric and magnetic polarizability tensors (αE, αM) of the CNT and GS nanoparticles. These properties determine the conductivity virial coefficient σ in the conductive and insulating particle limits, which are required to estimate σ in the general case in which the conductivity contrast Δ between the nanoparticle and the polymer matrix is arbitrary. Finally, we propose approximate relationships for αE and αM that should be useful in materials design and characterization applications.

High-speed, high-purity separation of gold nanoparticle-DNA origami constructs using centrifugation.

DNA origami is a powerful platform for assembling gold nanoparticle constructs, an important class of nanostructure with numerous applications. Such constructs are assembled by the association of complementary DNA oligomers. These association reactions have yields of <100%, requiring the development of methods to purify the desired product. We study the performance of centrifugation as a separation approach by combining optical and hydrodynamic measurements and computations. We demonstrate that bench-top microcentrifugation is a simple and efficient method of separating the reaction products, readily achieving purities of >90%. The gold nanoparticles play a number of critical roles in our system, functioning not only as integral components of the purified products, but also as hydrodynamic separators and optical indicators of the reaction products during the purification process. We find that separation resolution is ultimately limited by the polydispersity in the mass of the gold nanoparticles and by structural distortions of DNA origami induced by the gold nanoparticles. Our study establishes a methodology for determining the design rules for nanomanufacturing DNA origami-nanoparticle constructs.

Differences between GH and PRL co-secreting and GH-secreting pituitary adenomas. A series of 604 cases.

PURPOSE: To evaluate differences in clinical presentation and in surgical outcomes between growth hormone-secreting pituitary adenomas (GH-PAs) and GH and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). METHODS: Multicenter retrospective study of 604 patients with acromegaly submitted to pituitary surgery. Patients were classified into two groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal and IHC for GH and PRL was positive or PRL levels were >100ng/and PRL IHC was not available (n=130) and b) GH-PAs who did not meet the previously mentioned criteria (n=474). RESULTS: GH&PRL-PAs represented 21.5% (n=130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P<0.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs. 77.4%, P=0.001) and tended to be more invasive (33.6% vs. 24.7%, P=0.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (OR 2.8, 95% CI 1.83-4.38). IGF-1 upper limit of normality (ULN) levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [IQR 1.73-3.29] vs. 2.7 [IQR 1.91-3.67], P=0.023). There were no differences in the immediate (41.1% vs 43.3%, P=0.659) or long-term post-surgical acromegaly biochemical cure rate (53.5% vs. 53.1%, P=0.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs. 2.4%, P=0.011) in GH&PRL-PAs patients. CONCLUSIONS: GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.