Miliarial-type gout in association with chronic use of glucocorticoids.

A 59-year-old male patient with long-standing tophaceous gout (more than 30 years) characterized by polyarticular involvement and recurrent disseminated tophi formation; his past medical history is relevant for poor adherence to urate-lowering medications, as well as persistent use of self-prescribed systemic glucocorticoids. Despite achieving therapeutic goals for serum uric acid levels, new tophi formation with an intradermal location in the form of "miliarial-type gout" was documented. Due to functional limitations, the patient underwent surgical resection of the olecranon bursa. This case illustrates a widespread and recurrent tophi formation associated with long-standing gout and regular and sustained glucocorticoid use, despite an adequate disease control based on serum urate levels and involving an intradermal location of tophi presenting as "miliarial-type" lesions. In addition, the coexistence of urate and cholesterol crystal deposition disease in olecranon gouty bursitis is presented. Finally, a sonographic extended field of view of lesions distributed along the patient's extremities is presented as a novel characterization of this condition.

The silent variants of pituitary tumors: demographic, radiological and molecular characteristics.

INTRODUCTION: Tumors of the anterior pituitary gland (PTs) are mostly benign tumors with a low prevalence, which has nevertheless increased with advances in brain radiology techniques. Nearly half of PTs are not associated with a clinical endocrine syndrome. These tumors have been indistinctly named non-functioning pituitary adenomas (NFPAs) or silent pituitary tumors (SPTs) and the mechanisms of silencing are not fully known. AIM: To study the frequency and characterize the silent variant of PTs in a large local series, and to assess their pituitary adenohypophyseal gene expression. METHODS: This observational, cross-sectional study was performed in a Pituitary Tumor Center of Excellence and involved 268 PTs. After identifying the different subtypes according to the immunohistochemical (IHC) expression of adenohypophyseal hormones, we studied their gene expression by RT-qPCR. RESULTS: We found that silent tumors were larger and more invasive, but not more proliferative than their functional counterparts. The RT-qPCR complements the IHC typification of PTs, reducing the proportion of null-cell subtype. Finally, some silent PT subtype variants showed lower specific adenohypophyseal hormone gene expression than their functional counterparts, which may contribute to the absence of endocrine manifestations. CONCLUSIONS: This paper highlights the importance of identifying the silent variant of the PTs subtypes. As expected, silent tumors were larger and more invasive than their functioning counterparts. However, there was no difference in the proliferation activity between them. Finally, the lower specific gene expression in the silent than in the functioning counterparts of some PTs subtypes gives insights into the silencing mechanisms of PTs.

Is Somatostatin Receptor and Dopamine Receptor profiling useful in the management of silent somatotroph tumors?

Silent somatotroph tumors (sSTs) are pituitary neuroendocrine tumors (PitNETs) which do not give rise to the clinical syndrome of acromegaly. Differently to their functioning counterparts, the adjuvant medical treatment with somatostatin analogues (SSAs) or dopamine receptors agonists (DAs) has been scarcely addressed in these tumors. As preliminary results of an ongoing research on silencing mechanisms involved in the pathogenesis of sSTs, we have characterized by qRT-PCR the expression of SSTRs and DRDs in a large series of 18 silent and 68 functioning STs. Although the expression of SSTR2 and SSTR5 was lower in sSTs than in functioning ones, we found a negative correlation between SSTR2 and the tumor size of the sSTs. Additionally, levels of expression of DRD2 were similar between the two subtypes suggesting a possible basis for the treatment of these tumors with SSAs and DAs.

Pheochromocytoma: A three-decade clinical experience in a multicenter study. / Feocromocitoma: experiencia clínica de tres décadas en un estudio multicéntrico.

OBJECTIVE: To analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). DESIGN AND METHODS: A multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. RESULTS: A total of 106 patients (61 [57.5%] women, mean age 52.3 ± 14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8 ± 14.2 years vs. 54.5 ± 13.9 years, p<.001). Familial PCCs were more frequently associated with MEN2A (n=8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3cm (3-6cm); 27.7% of the patients had tumors ≥6cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4cm [2.4-5.0cm] vs. 5.6cm [4.0-7.0cm], p<.001). Scintigraphy by 123I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). CONCLUSIONS: PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low.

Mating system and intrapopulational genetic diversity of Copernicia prunifera (Arecaceae): a native palm from Brazilian semiarid.

The aim of this study was to investigate the mating system and genetic diversity of the palm Copernicia prunifera using inter-simple sequence repeat markers. We found that the C. prunifera has multiple inflorescences with hermaphroditic flowers and pollen viability of 62%. Outcrossing rates at the population level (N = 267) produced a multilocus outcrossing rate (tm) of 0.878 and a single-locus outcrossing rate (ts) of 0.738, indicating that C. prunifera has a mixed mating system that is preferentially allogamous. The rate of mating among relatives (tm - ts) was low, indicating limited outcrossing between closely related individuals. The fixation index between seed trees (F) was negative (0.200), suggesting an absence of inbreeding, while the correlation of selfing (rs) was high (0.914). The values of the diversity indices among adults and progenies did not differ statistically (HE = 0.319 and I = 0.470; HE = 0.337 and I = 0.505, respectively). In testing for the presence of genetic bottlenecks using the infinite allele model and the stepwise mutation model, we observed a reduction in the effective population, as well as a deficit in heterozygosity (P < 0.0001). The results of this study inform management strategies for the conservation and genetic improvement of the C. prunifera palm.

Anthropization as a determinant factor in the genetic structure of Copernicia prunifera (Arecaceae).

This study uses ISSR molecular markers to characterize the demographic pattern, and spatial genetic structure (SGS) at different life stages of development (cohorts) in a natural population of Copernicia prunifera in the Rio Grande do Norte State, Brazil. All individuals were sampled and georeferenced in a 0.55-ha plot. The demographic analyses showed a clustered pattern in the first-distance classes and a random or segregated pattern at higher distance classes for all cohorts. Among the three studied life stages, juveniles showed the greatest value for Nei's genetic diversity index (HE = 0.369), while the lowest was found among reproductive adults (HE = 0.341). Greater genetic differentiation was found within life stages (98.61%) than among stages (1.39%). The total population (N = 161) showed positive and significant kinship in the first-distance class (12.3 m). The juveniles showed significant kinship up to 10.5 m. Non-reproductive adults had a positive kinship in the first-distance class (11.0 m) and a random distribution of genotypes in the remaining classes, while reproductive adults showed a random spatial distribution of genotypes. Tests for genetic bottleneck showed that the number of loci with excess observed heterozygosity was greater than expected. The SGS results reflected the restricted seed dispersion of the species, and the genetic bottleneck reflected the reduction of genotypes as a result of the anthropization of C. prunifera natural environments.

Potential risk of acute toxicity induced by AgI cloud seeding on soil and freshwater biota.

Silver iodide is one of the most common nucleating materials used in cloud seeding. Previous cloud seeding studies have concluded that AgI is not practically bioavailable in the environment but instead remains in soils and sediments such that the free Ag amounts are likely too low to induce a toxicological effect. However, none of these studies has considered the continued use of this practice on the same geographical areas and thus the potential cumulative effect of environmental AgI. The aim of this study is to assess the risk of acute toxicity caused by AgI exposure under laboratory conditions at the concentration expected in the environment after repeated treatments on selected soil and aquatic biota. To achieve the aims, the viability of soil bacteria Bacillus cereus and Pseudomonas stutzeri and the survival of the nematode Caenorhabditis elegans exposed to different silver iodide concentrations have been evaluated. Freshwater green algae Dictyosphaerium chlorelloides and cyanobacteria Microcystis aeruginosa were exposed to silver iodide in culture medium, and their cell viability and photosynthetic activity were evaluated. Additionally, BOD5 exertion and the Microtox® toxicity test were included in the battery of toxicological assays. Both tests exhibited a moderate AgI adverse effect at the highest concentration (12.5µM) tested. However, AgI concentrations below 2.5µM increased BOD5. Although no impact on the growth and survival endpoints in the soil worm C. elegans was recorded after AgI exposures, a moderate decrease in cell viability was found for both of the assessed soil bacterial strains at the studied concentrations. Comparison between the studied species showed that the cyanobacteria were more sensitive than green algae. Exposure to AgI at 0.43µM, the reference value used in monitoring environmental impact, induced a significant decrease in photosynthetic activity that is primarily associated with the respiration (80% inhibition) and, to a lesser extent, the net photosynthesis (40% inhibition) in both strains of phytoplankton and a moderate decrease in soil bacteria viability. These results suggest that AgI from cloud seeding may moderately affect biota living in both terrestrial and aquatic ecosystems if cloud seeding is repeatedly applied in a specific area and large amounts of seeding materials accumulate in the environment.

Increased relatedness among the neighboring plants from seedling to adult stages in carnaúba wax palm.

The objective of this study was to assess the spatial genetic structure (SGS) at different life stages (cohorts) in a remnant population (N = 101) of Copernicia prunifera in the semiarid region of northeastern Brazil. Using seven inter-simple sequence repeat molecular markers, we were able to analyze 93 loci with 100% polymorphism. Seedlings had the highest level of genetic diversity (HE = 0.411, HO = 0.599), followed by juveniles (HE = 0.394, HO = 0.579) and adults (HE = 0.267, HO = 0.427). Based on analysis of molecular variance, the majority of genetic variations were observed to occur within the life stages (93.42%) rather than between the life stages (6.58%). We found a recent reduction in the population size (bottleneck) based on the number of loci with heterozygosity excess for the two models used (infinite allele = 92 and stepwise = 91). All the life stages showed significant SGS, with positive and significant kinship values. Sp values were 0.040 for seedlings, 0.093 for juveniles, 0.156 for adults, and 0.053 for the total population. We found an increase in SGS from the seedling to adult stages, indicating that the plants were from related adult progenitors. Data from this study can be used in designing effective management and conservation strategies for the species.

Insertion of exogenous epitopes in the E3-19K of oncolytic adenoviruses to enhance TAP-independent presentation and immunogenicity.

Oncolytic adenoviruses can promote immune responses against tumors by expressing and/or displaying tumor-associated antigens. However, the strong immunodominance of viral antigens mask responses against tumor epitopes. In addition, defects in major histocompatibility complex class I antigen presentation pathway such as the downregulation of the transporter-associated with antigen processing (TAP) are frequently associated with immune evasion of tumor cells. To promote the immunogenicity of exogenous epitopes in the context of an oncolytic adenovirus, we have taken advantage of the ER localization of the viral protein E3-19K. We have inserted tumor-associated epitopes after the N-terminal signal sequence for membrane insertion of this protein and flanked them with linkers cleavable by the protease furin to facilitate their TAP-independent presentation. This strategy allowed an enhanced presentation of the exogenous epitopes in TAP-deficient tumor cells in vitro and the generation of higher specific immune responses in vivo that were able to significantly control tumor growth.

Genetic and non-genetic factors that increase the risk of non-syndromic cleft lip and/or palate development.

OBJECTIVES: We investigated the relationship between non-syndromic cleft lip/palate (NSCLP) and polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and RFC1, as well as the corresponding interactions with environmental factors. SUBJECTS AND METHODS: One hundred and forty NSCLP patients and their mothers, as well as 175 control individuals and their mothers, were recruited. Information regarding smoking and alcohol consumption was recorded. Blood samples were obtained in order to measure serum folate and cobalamin, as well as, plasma total homocysteine concentrations and to extract DNA. Polymorphisms in MTHFR(677C>T and 1298A>C), MTR(2756A>G), MTR(66A>G), and RFC1(80A>G) were analyzed by PCR-restriction fragment length polymorphism. RESULTS: Among the patients, 59.5% had cleft lip and palate, 22.0% had cleft palate, and 18.5% had cleft lip only. Maternal alcohol consumption and reduced folic acid concentrations in both children and mothers (P < 0.001 and P = 0.003, respectively) were risk factors for NSCLP. Patients and their mothers carrying the MTHFR 667T allele showed lower serum folate than CC (P = 0.011 and P = 0.030, respectively). Mothers who carried the MTHFR 1298C allele exhibited increased risk of having a child with NSCLP, after adjusting for alcohol consumption (OR: 1.75, 95% CI: 1.03-2.99, P = 0.038). CONCLUSIONS: Reduced folic acid levels, alcohol consumption, and the MTHFR 677T and 1298C alleles may have contributed to NSCLP development in this sample population from Rio Grande do Norte.

Influence of polyethylene-type microplastics on long-term exposure to heavy metals in freshwater phytoplankton.

The use of plastic materials has brought about significant social benefits but has also led to negative consequences, particularly their accumulation in aquatic environments. Studies have shown that small plastic particles, known as microplastics (MPs), can carry various harmful pollutants, such as heavy metals (HMs). Therefore, the aim of this research is to investigate the impact of polyethylene-type MPs on the long-term exposure of different HMs on freshwater microalgae Scenedesmus armatus and cyanobacteria Microcystis aeruginosa, in both isolated cultures and phytoplanktonic community conditions. Over a period of 28 days, the strains were subjected to concentrations of Ag+, Cu+2, and Cr+6 corresponding to their respective 72 h-EC10, with or without the presence of MPs. Throughout this period, the growth cell ratio, photosynthetic activity, and reactive oxygen species (ROS) were monitored. The findings indicated a substantial inhibitory impact on cell growth during the initial 7-14 days of exposure, followed by a reduction until reaching values like the controls after 28 days of exposure. There was a disturbance in photosynthetic activity during the first 72 h of exposure, which gradually returned to control levels, mainly significantly affected the respiration phase. Reactive oxygen species (ROS) activity was also affected during the initial 14 days of exposure. The presence or absence of MPs in the culture medium did not significantly alter the observed effects. However, interspecies competition created a more favorable environment for M. aeruginosa over the freshwater microalgae S. armatus. These findings suggest that the formation of MP-HMs complexes may have a limited impact on reducing the adverse effects of HMs in long-term exposures. However, because the impact depends on the specific HM involved, further studies are needed to gain a better understanding of the interaction between these pollutants.

Tissue distribution and expression dynamics of trefoil factor genes in the hydroid Hydractinia symbiolongicarpus.

Proteins of the trefoil factor family (TFF) participate in mucosal repair and are formed by single or tandemly repeated trefoil domains. TFFs have been extensively studied in mammals and amphibians, but they have not been functionally characterized in other animals. Here we report the identification of two genes expressed in the hydroid Hydractinia symbiolongicarpus, predicted to encode trefoil domain-containing peptides, one with four trefoil domains in tandem and the other one with a trefoil domain flanked by two ShKT domains. Differential expression analyses by qPCR after an immune challenge and an induced mechanical damage, reveal that the former gene (hysyTFF) had no significant changes in expression after the inductions. However, the latter (hysyTFF-like) was overexpressed after three hours post immune challenge and was downregulated after the first hour post epithelial damage. Immunoblot analyses using specific IgY antibodies revealed that hysyTFF is secreted as a high molecular weight complex. Finally, whole mount immunofluorescence assays showed that hysyTFF was predominantly expressed in the endoderm of stolons and polyps, and sparsely in the ectoderm of both polyps and larvae. Thus, the tissue distribution and expression dynamics of trefoil factor genes in H. symbiolongicarpus suggest that hysyTFF is part of an ancient mechanism of epithelial restitution, and the newly reported hysyTFF-like might act as an immune effector gene, perhaps encoding an antibacterial peptide.

Using single-species and algal communities to determine long-term adverse effects of silver nanoparticles on freshwater phytoplankton.

The physical and chemical properties of silver nanoparticles (AgNPs) have led to their increasing use in various fields such as medicine, food, and industry. Evidence has proven that AgNPs cause adverse effects in aquatic ecosystems, especially when the release of Ag is prolonged in time. Several studies have shown short-term adverse effects of AgNPs on freshwater phytoplankton, but few studies have analysed the impact of long-term exposures on these populations. Our studies were carried out to assess the effects of AgNPs on growth rate, photosynthesis activity, and reactive oxygen species (ROS) generation on the freshwater green algae Scenedesmus armatus and the cyanobacteria Microcystis aeruginosa, and additionally on microcystin (MC-LR) generation from these cyanobacteria. The tests were conducted both in single-species cultures and in phytoplanktonic communities exposed to 1 ngL-1 AgNPs for 28 days. The results showed that cell growth rate of both single-species cultures decreased significantly at the beginning and progressively reached control-like values at 28 days post-exposure. This effect was similar for the community-cultured cyanobacteria, but not for the green algae, which maintained a sustained decrease in growth rate. While gross photosynthesis (Pg) increased in both strains exposed in single cultures, dark respiration (R) and net photosynthesis (Pn) decreased in S. armatus and M. aeruginosa, respectively. These effects were mitigated when both strains were exposed under community culture conditions. Similarly, the ROS generation shown by both strains exposed in single-species cultures was mitigated when exposure occurred in community cultures. MC-LR production and release were significantly decreased in both single-species and community exposures. These results can supply helpful information to further investigate the potential risks of AgNPs and ultimately help policymakers make better-informed decisions about their utilization for environmental restoration.

MSX1 gene polymorphisms in non-syndromic cleft lip and/or palate.

OBJECTIVE: The aim of this study was to investigate the contribution of 6 polymorphic variants of the MSX1 gene in non-syndromic cleft lip and/or palate (NSCL/P). METHODS: Three hundred and fifty-eight individuals (158 NSCL/P cases and 200 controls) were genotyped by TaqMan allelic discrimination using predesigned SNP assays. Statistical analyses were conducted using the software spss 15.0 and the r statistical suite. Haplotype block structure and haplotype frequencies were determined using the Haploview. A P-value of 0.05 and confidence interval of 95% were used for all of statistical tests. RESULTS: The patients with non-syndromic cleft lip and/or palate were characterized by similar distribution of MSX1 genotypes and allele in comparison to subjects without oral clefts (P > 0.05). Two haplotype blocks were constructed with polymorphisms of MSX1 gene and haplotypes formed showed a similar frequency in patients with and without oral clefts. CONCLUSIONS: The present study provides no evidence that MSX1 polymorphisms (rs3775261, rs1042484, rs12532, rs6446693, rs4464513 and rs1907998) play a major role in NSCL/P.

Adverse effects of iron-based nanoparticles on freshwater phytoplankton Scenedesmus armatus and Microcystis aeruginosa strains.

Zero-valent nano-iron particles (nZVI) are increasingly present in freshwater aquatic environments due to their numerous applications in environmental remediation. However, despite the broad benefits associated with the use and development of nZVI nanoparticles, the potential risks of introducing them into the aquatic environment need to be considered. Special attention should be focused on primary producer organisms, the basal trophic level, whose impact affects the rest of the food web. Although there are numerous acute studies on the acute effects of these nanoparticles on photosynthetic primary producers, few studies focus on long-term exposures. The present study aimed at assessing the effects of nZVI on growth rate, photosynthesis activity, and reactive oxygen activity (ROS) on the freshwater green algae Scenedesmus armatus and the cyanobacteria Microcystis aeruginosa. Moreover, microcystin production was also evaluated. These parameters were assessed on both organisms singly exposed to 72 h-effective nZVI concentration for 10% maximal response for 28 days. The results showed that the cell growth rate of S. armatus was initially significantly altered and progressively reached control-like values at 28 days post-exposure, while M. aeruginosa did not show any significant difference concerning control values at any time. In both strains dark respiration (R) increased, unlike net photosynthesis (Pn), while gross photosynthesis (Pg) only slightly increased at 7 days of exposure and then became equal to control values at 28 days of exposure. The nZVI nanoparticles generated ROS progressively during the 28 days of exposure in both strains, although their formation was significantly higher on green algae than on cyanobacteria. These data can provide additional information to further investigate the potential risks of nZVI and ultimately help decision-makers make better informed decisions regarding the use of nZVI for environmental remediation.

End of life, death and dying in neonatal intensive care units in Latin America.

AIM: Most analyses of end of life decisions in Neonatal Intensive Care Units (NICUs) have come from Europe/English-speaking countries. Would decisions be different in Latin American NICUs? Therefore, we aim to evaluate the approach to dying infants/families in NICUs in Latin America. METHODS: Multinational descriptive study of all deaths in babies born at >22 weeks in eight NICUs in five Latin American countries. Deaths were categorized as: (i) no Cardiopulmonary Resuscitation (CPR) or life support offered; (ii) life support initiated but do not resuscitate (DNR) orders written or no CPR provided; (iii) full life support and CPR; and (iv) unclassifiable. RESULTS: There were 100 deaths, 81% in >27 weeks. Seventeen infants received no CPR/life support at birth, 10 died in DR and seven in NICU. There were 27 infants in group 2, 54 in group three and two in group 4. No baby had care withdrawn or care withdrawn/CPR withheld. Thirty-two infants had 'do not resuscitate' order. Decisions without parents' involvement in 15%, both parents present at death 24% and sedatives/narcotics documented 14%. CONCLUSIONS: Latin American NICUs differ from those in Northern Europe/English-speaking countries. More deaths are accompanied by full life support and CPR. DNR orders are rare. Withdrawal of life support is virtually non-existent. Latin American's doctors are more likely to make decisions without the objections of family about withholding life-sustaining treatment.

Autotrophic denitrification with sulphide in a sequencing batch reactor.

In this study a sequencing batch reactor was used to simultaneously remove both sulphide and nitrate via an autotrophic denitrification process. The sulphide loading rates were gradually increased from 200 mg S(2-) L(-1) d(-1)-450 mg S(2-) L(-1)d(-1)while the nitrogen loading rates were kept at 450 mg NO(3)(-)-N L(-1)d(-1). The obtained results demonstrated that it was possible to carry out autotrophic denitrification in a Sequencing Batch Reactor with removal efficiencies of sulphide and nitrogen of 100% and 67%, respectively. The efficiency of the process was influenced by the pH value in the reactor. The operation at pH values higher than 9.0 decreased the efficiency of sulphide oxidation into sulphate to 11.3%. The main bacteria populations present in the sludge belonged to Thiobacillus genus.

Short- and long-term effects of ammonium and nitrite on the Anammox process.

Autotrophic anaerobic ammonium oxidation (Anammox) is a biological process in which Planctomycete-type bacteria combine ammonium and nitrite to generate nitrogen gas. Both substrates can exert inhibitory effects on the process, causing the decrease of the specific activity of the biomass and the loss of the stable operation of reactors. The aim of the present work is to evaluate these effects in short- and long-term experiments. The short-term effects were carried out with two different types of Anammox biomass, biofilm on inorganic carriers and flocculent sludge. The effects of ammonium on both kinds of biomass were similar. A decrease of the Specific Anammox Activity (SAA) of 50% was observed at concentrations about 38 mg NH(3)-N·L(-1), while 100 mg NH(3)-N·L(-1) caused an inhibition of 80%. With regards to nitrite, the SAA was not affected at concentrations up to 6.6 µg HNO(2)-N·L(-1) but it suffered a decrease over 50% in the presence of 11 µg HNO(2)-N·L(-1) in the case of the biofilm. The flocculent biomass was much less resistant and its SAA sharply decreased up to 30% of its initial value in the presence of 4.4 µg HNO(2)-N·L(-1). The study of the long-term effects was carried out in lab-scale Sequencing Batch Reactors (SBR) inoculated with the biofilm biomass. Concentrations up to 20 mg NH(3)-N·L(-1) showed no effects on either reactor efficiency or biomass activity. However, when free ammonia concentrations reached values between 35 and 40 mg NH(3)-N·L(-1), the operation turned unstable and the efficiency was totally lost. Nitrous acid concentrations around 1.5 µg HNO(2)-N·L(-1) caused a loss of the efficiency of the treatment and a destabilization of the system. However, a total restoration of the SAA was observed after the stoichiometric feeding was applied to the SBR.

Pheochromocytoma: A three-decade clinical experience in a multicenter study.

OBJECTIVE: To analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). DESIGN AND METHODS: A multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. RESULTS: A total of 106 patients (61 [57.5%] women, mean age 52.3 ±â€¯14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8 ±â€¯14.2 years vs 54.5 ±â€¯13.9 years, p < .001). Familial PCCs were more frequently associated with MEN2A (n = 8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3 cm (3-6 cm); 27.7% of the patients had tumors ≥6 cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4 cm [2.4-5.0 cm] vs 5.6 cm [4.0-7.0 cm], p < .001). Scintigraphy by ¹²³I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). CONCLUSIONS: PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low.