Hasil untuk "Diseases of the endocrine glands. Clinical endocrinology"

Khaled M. Elhusseiny, Farha G. Deceus, Lynn D. Cornell et al.

ObjectiveTo quantitatively examine immune cell markers and spatial distribution in human diabetic kidney disease (DKD) to enhance understanding of the inflammatory landscape contributing to injury. Maladaptive inflammation is an underrecognized contributor to DKD pathogenesis and progression and remains undertreated.Patients and methodsNanoString GeoMx™ Digital Spatial Profiling technology targeted antibodies labeled with unique oligonucleotide barcode in kidney biopsy [DKD (n=5), tubulointerstitial nephritis (TIN; n=4), and normal (n=2)] with regions of interest selection of compartments (glomeruli, tubules, interstitium). Inflammation-related proteins were analyzed with differential expression through linear mixed modeling.ResultsCompared to normal tissue, inflammatory cell surface protein markers were increased in DKD tubules and interstitium. Markers of T cells (CD4, CD44), macrophages (CD68; proinflammatory), and antigen-presenting cells (APCs; CD40 and CD11c) were increased across all DKD compartments (vs. normal). Macrophage (CD163; prorepair) marker was increased in DKD tubules and interstitium (vs. normal). Fewer differences were observed in glomeruli for normal vs. DKD or TIN vs. DKD groups. CD66b+ (granulocytes) cell marker was higher in DKD (vs. TIN). As expected, TIN had higher levels of T cell and macrophage markers in tubules and interstitium (vs. DKD). Interestingly, CD34, a hematopoietic stem cell and endothelial cell marker, was lower in DKD tubules and interstitium (vs. normal) but higher in DKD (vs. TIN).ConclusionNanoString GeoMx DSP technology may fulfil a role in enhancing the understanding the inflammatory landscape engaged in DKD pathogenesis as well as measuring response to therapy. Moreover, additional investigations of CD34 progenitor cell depletion in DKD may be warranted.

Guangzhong Jiao, Jinhao Xing, Zhaoli Du et al.

Oocyte maturation arrest (OMA) may occur at different stages, including the germinal vesicle (GV), metaphase I (MI), and metaphase II (MII). A total maturation arrest of human oocytes is rarely observed during in vitro fertilization (IVF). We have identified a case of infertile female for whom all oocytes fail to mature and are arrested at MI. Whole-exome sequencing revealed a compound heterozygous mutant (c.533C > A: p.Val458Ala; c.1373T > C: p.Ala178Glu) in cell division cycle 20 (CDC20). Through rigorous validation using Sanger sequencing technology, both of her parents have been confirmed as genetic carriers of these specific mutations. Based on the three-dimensional (3D) structures of the CDC20 protein used to assess the effect of the mutant, the mutant causes a change in hydrogen bond in the protein structure, which may affect the stability of the mutant protein. Previous studies have firmly established CDC20 as a pivotal member of the cell cycle regulation family, playing an indispensable role in the transition from metaphase to anaphase during cell division. Our findings not only broaden the current understanding of CDC20 gene mutations but also profoundly illuminate how these mutations serve as potential genetic mechanisms underlying the arrest of oocyte maturation.

Yujun He, Xiaoyi Wang, Lu Li et al.

ABSTRACT Background Diabetic kidney disease (DKD) is a prevalent and severe complication of diabetes that significantly impacts global health and quality of life. Most DKD is attributable to type 2 diabetes; therefore, chronic type 2 DKD warrants further examination. Objective To deliver targeted assistance in alleviating the worldwide, regional, and national burden of chronic type 2 DKD, we executed a survey assessing the prevalence of chronic type 2 DKD utilizing the Global Burden of Disease, Injury, and Risk Factors (GBD) database. Methods We examined the temporal trends of chronic type 2 DKD prevalence over the past 30 years using the 2021 GBD database, analyzed the trends by population, epidemiological change, and aging, and quantified cross‐country health inequalities. Additionally, we forecasted the trend during the subsequent two decades. Results In 2021, there were over 107 million cases of chronic type 2 DKD globally, reflecting an 85.11% rise from 58 million cases in 1990. The age‐standardized rate (ASR) declined with an estimated annual percentage change of 0.17% per annum. Epidemiological change and population expansion are the primary factors influencing the alterations. The contributions of epidemiological change, population, and aging vary with alterations in the sociodemographic index (SDI). Significant health inequalities were observed across 204 countries and territories, with the slope index of inequality increasing over time. The forecast for the worldwide burden of chronic type 2 DKD from 2020 to 2040 suggests a significant rise in case numbers, while the alterations in ASR remain largely stable. Conclusions These findings indicate the significant disease burden of chronic type 2 DKD, necessitating more targeted and effective interventions for its prevention and management.

Jiao Zhao, Qi Lu, Xianfeng Zhang

IntroductionThe effects of vitamin B12 metabolism on musculoskeletal health and the exact mechanism have not been fully determined. Our study aimed to assess the association of vitamin B12 and its biomarkers with musculoskeletal health in middle-aged and older adults.MethodsThe data from the National Health and Nutrition Examination Survey 2001–2002 were used to investigate the effects of serum vitamin B12 and its biomarkers (homocysteine and methylmalonic acid) on skeletal muscle health. Bone mineral density (BMD), lean mass, gait speed and knee extensor strength were used as indicators for musculoskeletal health.ResultsSerum vitamin B12 level was positively correlated with the total and appendicular lean mass (β = 584.83, P = 0.044; β = 291.65, P = 0.043) in older adults over 65 years of age. In the full population, plasma homocysteine was associated with total lean mass, appendicular lean mass, gait speed, and knee extensor strength (all P < 0.05). Among older adults over 65 years of age, homocysteine level was significantly negatively correlated with gait speed and knee extensor strength (β = -12.75, P = 0.019; β = -0.06, P <0.001). Plasma methylmalonic acid was negatively associated with total BMD and femur BMD in the full population (β = -0.01, P = 0.018; β = -0.01, P = 0.004). In older adults, methylmalonic acid significantly affected total BMD, femur BMD and knee extensor strength (β = -0.01, P = 0.048; β = -0.01, P = 0.025; β = -7.53, P = 0.015).ConclusionsVitamin B12 and its biomarkers are closely related to BMD, body composition, muscle strength and physical function in middle-aged and older adults. Vitamin B12 may be an important indicator of musculoskeletal health in the elderly.

Evelyn Frias Toral , Diana Cardenas

Editorial 

Peipei Zhou, Peipei Zhou, Ying Tan et al.

ObjectiveClinical trials have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2i) are closely associated with hepatic fibrosis and steatosis by FibroScan. This paper aimed at evaluating the effects of SGLT2i on hepatic fibrosis and steatosis, which are presented as liver stiffness measurement (LSM) and controlled attenuation parameter (CAP).MethodsPubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure Database, China Science and Technology Journal Database, and Wanfang Database were searched for randomized clinical trials from database establishment to 30 November 2022 with no language restrictions. The risk of bias was evaluated by Collaboration Handbook. Software Stata 17 and Review Manager (version 5.3) were used for meta-analysis.ResultsA total of eight articles including 686 patients were included. Compared with the control group, our results showed that SGLT2i could lower levels of LSM [MD = −0.82, 95%CI (−1.38, −0.25), p = 0.005] and CAP [MD = −12.80, 95%CI (−20.57, −5.03), p = 0.001]. Further subgroup analyses indicated that SGLT2i presented more advantages on longer treatment duration and more serious steatosis in decreasing LSM. For CAP, SGLT2i exhibited a clear advantage in subgroup analyses of longer treatment duration, younger people, dapagliflozin, worse fibrosis, and steatosis.ConclusionSGLT2i could reduce LSM and CAP in contrast to other antihyperglycemic drugs. However, the included studies are not definitive, and well-designed, more multi-centered, blinded randomized clinical trials are warranted to definitively establish reliable evidence.

Roosa Perämäki, Mika Gissler, Meri-Maija Ollila et al.

Aims: Women with a history of gestational diabetes (GDM) have an increased risk of developing type 2 diabetes (T2DM). We studied the risk for T2DM in women with and without GDM in relation to body mass index (BMI) and examined whether insulin treatment for GDM associates with the risk of developing T2DM. In addition, we investigated whether the risk of developing T2DM after GDM had changed in 15 years. Methods: We used data by linking four registers; Medical Birth Register, Hospital Discharge Register and Primary Care Register run by THL Finnish Institute for Health and Welfare, and Medical Reimbursement Statistics run by the Social Insurance Institution of Finland (Kela). Registry data were collected from 2005 to 2020. The follow-up started from woman's delivery in 2006-2020 and ended to the diagnosis of T2DM or December 2020. Cox proportional hazard modelling was used to estimate the effect of GDM exposure to T2DM. To assess whether the risk of developing T2DM after GDM had changed in 15 years, we compared the HR between years 2006-2008 and 2018-2020. Results: In total, 462 401 women were included in the study: 96 353 (21%) women had previous GDM. There were 5370 (1.2%) women who developed T2DM after childbirth during the follow-up. Among women with prior GDM, 3995 (4.1%) developed T2DM, while 1375 (0.4%) women without prior GDM developed T2DM during follow-up. The mean follow-up was 6.86 years (SD 4.21) for women with GDM and 9.07 years (SD 4.35) for women without GDM. The hazard ratio (HR) for developing T2DM after GDM was 18.49 (95% CI 17.39-19.67). The incidence of T2DM in women with a history of GDM began to rise almost steadily from the first year of follow-up. As BMI increased, T2DM incidence increased in both women with and without prior GDM but more in women with prior GDM. Insulin treatment had an independent association with increased risk of T2DM (HR 3.81, 95% CI 3.57-4.07). We did not observe any difference in HR between years 2006-2008 and 2018-2020. Conclusions: The relative risk for T2DM was 11-fold for women with previous GDM compared to women without previous GDM. A higher BMI and insulin treatment increased the risk of future diabetes. All measures to prevent the conversion of GDM to T2DM should be taken especially among women with overweight or obesity.

Jing Luo, Jing Luo, Yao Wang et al.

Thermogenic adipocytes possess a promising approach to combat obesity with its capability promoting energy metabolism. We previously discovered that deletion of GPR30 (GPRKO), a presumably membrane-associated estrogen receptor, protected female mice from developing obesity, glucose intolerance, and insulin resistance when challenged with a high-fat diet (HFD). In vivo, the metabolic phenotype of wild type (WT) and GPRKO female mice were measured weekly. Acute cold tolerance test was performed. Ex vivo, mitochondrial respiration of brown adipose tissue (BAT) was analyzed from diet-induced obese female mice of both genotypes. In vitro, stromal vascular fractions (SVF) were isolated for beige adipocyte differentiation to investigate the role of GPR30 in thermogenic adipocyte. Deletion of GPR30 protects female mice from hypothermia and the mitochondria in BAT are highly energetic in GPRKO animals while the WT mitochondria remain in a relatively quiescent stage. Consistently, GPR30 deficiency enhances beige adipocyte differentiation in white adipose tissue (WAT) and activates the thermogenic browning of subcutaneous WAT due to up-regulation of UCP-1, which thereby protects female mice from HFD-induced obesity. GPR30 is a negative regulator of thermogenesis, which at least partially contributes to the reduced adiposity in the GPRKO female mice. Our findings provide insight into the mechanism by which GPR30 regulates fat metabolism and adiposity in female mice exposed to excess calories, which may be instrumental in the development of new therapeutic strategies for obesity.

Kyuho Kim, Henry N. Ginsberg, Sung Hee Choi

Seung Eun Lee, Su-Kyung Park, Ye-Seul Park et al.

Background : The increasing prevalence of type 2 diabetes mellitus (T2DM) has led to a significant health burden. Technological advancements have highlighted the benefits of digital therapeutics for chronic diseases. In this study, we aimed to investigate the effects of a mobile application on weight reduction in patients with T2DM. Methods : A total of 48 patients with T2DM was included in this single-center, randomized, controlled trial. In addition to conventional treatment, participants in the intervention group used a mobile application-based self-management system for diet, exercise, and medication adherence. The primary outcome of this study was weight change after 3 months of intervention, and secondary outcomes were metabolic parameters. Results : After 12 weeks, no significant differences in body weight change were observed between the intervention and control groups (P=0.229). However, a significant difference was found in waist circumference (WC) between the two groups, wherein the control group showed an increase in WC (from 95.00±8.89 cm to 95.76±9.72 cm), while the intervention group showed a reduction (from 91.93±6.25 cm to 90.75±6.01 cm) with a significant time by group interaction (P=0.016). Additionally, participants with good compliance exhibited a more evident reduction in WC (P=0.037). However, no significant differences were found in other metabolic parameters between the two groups. Conclusion : Lifestyle modification using short-term mobile applications effectively reduced WC, especially in patients with good adherence to the application. However, weight reduction was not achieved.

Mohamed Abd-ElGawad, Mohamed Abdelmonem, Ahmed Eissa Ahmed et al.

Abstract Background The main purpose is to investigate the effect of LiCO3 as an add-on therapy with radioactive iodine in increasing the cure and decreasing the T4 level compared to radioactive iodine alone. The primary outcome is the cure rate as defined by the number of hyperthyroid patients who became euthyroid or hypothyroid. The secondary outcome is the T4 level. Methods Four databases were searched (PubMed, Scopus, Web of Science, and Cochrane central library). The inclusion criteria were randomized and non-randomized clinical trials of hyperthyroidism patients receiving LiCO3 with radioiodine compared with hyperthyroidism patients receiving radioactive iodine alone. Included studies were appraised with the risk of bias version 2 tool, according to the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. Results Nine studies were eligible for inclusion in the study, six randomized control trials and three non-randomized control trials. There were 477 patients in the intervention group and 451 patients in the control group. The cure rate was not significantly different between the two groups, while it was significantly increased with 5000 to 6500 mg optimized cumulative dose of LiCO3 compared with the control group, P = 0.0001. The T4 level showed no significant difference between the two groups, P = 0.13. Conclusions LiCO3 adjunct to radioactive iodine did not show significant differences compared with radioactive iodine alone in terms of cure rate or decreasing T4 level. However, the dose of 5000 to 6000 mg of LiCO3 may increase the cure rate.

Nakhoul Nakhoul, Tina Thawko, Evgeny Farber et al.

Background. Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes and is the leading cause of end-stage renal disease (ESRD) and replacement therapy worldwide. Vitamin D levels in DN patients are very low due to the decrease in the synthesis and activity of 1-α hydroxylase in the proximal tubule cells and decrease in the vitamin D receptor abundance. To date, few studies have shown the antioxidant effects of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] on hyperglycemia-induced renal injury. The selective activator of the vitamin D receptor, paricalcitol, reduces proteinuria and slows the progression of kidney injury. The precise mechanism through which vitamin D affects diabetic status and provides kidney protection remains to be determined. Methods. Diabetes mellitus (DM) was induced in 94 8-week-old DBA/2J mice by intraperitoneal injection of streptozotocin (STZ). DM mice were randomly divided into receiving vehicle or treatment with paricalcitol, the active vitamin D analog, 1 week after DM induction or paricalcitol treatment 3 weeks after DM induction. An additional control group of healthy wild-type mice was not treated. Urine albumin, blood urea nitrogen, and creatinine levels were measured before and at the end of the paricalcitol treatment. Periodic acid-Schiff, immunohistochemistry staining, and western blot of the renal tissues of vitamin D receptor, villin, nephrin, and podocin expressions, were analyzed. Results. Paricalcitol treatment restored villin, nephrin, and podocin protein levels that were downregulated upon DM induction, and reduced fibronectin protein level. Vitamin D receptor activation by paricalcitol may reduce proteinuria of DN in mice and alleviate high-glucose-induced injury of kidney podocytes by regulating the key molecules such nephrin-podocin. Conclusions. Paricalcitol treatment was associated with improved structural changes in type 1 diabetic mice including upregulation of vitamin D receptor expression, and decreased fibrosis markers such as fibronectin. These effects may contribute to the consistent benefit of vitamin D analog to slow the deterioration in glomerular function and reduce the risk of ESRD in patients with type 1 and 2 diabetes mellitus. Our results suggest that additional use of paricalcitol may be beneficial in treating patients with diabetes under standard therapeutic strategies.

Sriram Gubbi, Pavel Hamet, Pavel Hamet et al.

Di Feng, Bei Shi, Fangfang Bi et al.

Background: Recent reports have highlighted the role of monosaccharide biosynthesis in the pathogenesis of polycystic ovary syndrome (PCOS), suggesting that these processes may serve as a biomarker in PCOS. Mannose is the main monosaccharide for protein glycosylation in mammals; however, the correlation between mannose and PCOS remains largely unknown.Materials and Methods: A total of 132 Chinese Han women were recruited at Shengjing Hospital of China Medical University. Mannose levels were measured in serum samples collected from 71 patients with PCOS (29 lean, 42 obese) and 61 control subjects (28 lean, 33 obese). Receiver operating characteristics (ROC) curves were prepared to compare the diagnostic performance of mannose and hormonal parameters, individually or in combination. Multivariate logistic regression analysis was used to assess whether serum mannose levels were associated with PCOS after adjusting for other co-variables.Results: We showed that serum mannose levels were significantly increased in PCOS patients compared with control subjects regardless of obese status, and hyperandrogenic PCOS patients had higher serum mannose levels than normo-androgenic PCOS and control subjects. In addition, serum mannose levels were significantly correlated with serum androgen levels. Mannose had an area under the curve (AUC) of 73% at a cutoff value of 225.79 ng/mL with a sensitivity of 66.2% and specificity of 73.8% for predicting PCOS. There were no differences between mannose, total testosterone, free testosterone, or dehydroepiandrosterone sulfate in the reliability of predicting PCOS using the method outlined by Hanley and McNeil. Combining mannose and total testosterone resulted in a higher AUC of 83.3%, and had moderate sensitivity (78.9%) and specificity (77%) for predicting PCOS. The positive and negative predictive values were 80% and 75.8%, respectively. Multivariate logistic regression revealed that higher serum mannose levels were strongly associated with an increased risk of PCOS (P = 0.016; odds ratio, 5.623; 95% confidence interval, 1.371–23.070).Conclusion: Taken together, substantially elevated serum mannose levels are significantly associated with PCOS, highlighting the importance of further research into the role of mannose in the pathogenesis of PCOS.

Gábor Máté, Lori R. Bernstein, Lori R. Bernstein et al.

Approximately, 10–15% of women of reproductive age are affected by endometriosis, which often leads to infertility. Endometriosis often has an inherited component, and several causative predisposing factors are hypothesized to underlie the pathogenesis of endometriosis. One working hypothesis is the theory of retrograde menstruation. According to the theory of retrograde menstruation, components of refluxed blood, including apoptotic endometrial tissue, desquamated menstrual cells, lysed erythrocytes, and released iron, induce inflammation in the peritoneal cavity. This in turn activates macrophage release of reactive oxygen species (ROS), leading to oxidative stress via the respiratory burst. Refluxed blood promotes the Fenton reaction, terminating in the production of hydroxyl radical, the most potently destructive ROS. In this article, we review the papers that demonstrate decreased quantity and quality of oocytes and embryos retrieved from IVF/ICSI patients with endometriosis. We discuss literature data demonstrating that ROS are generated in endometriotic tissues that have physical proximity to gametes and embryos, and demonstrating adverse impacts on oocyte, sperm and embryo microtubule apparatus, chromosomes, and DNA. Data that addresses the notions that endometriosis causes oocyte and fetal aneuploidy and that these events are mediated by ROS species are also discussed. Literature data are also discussed that employ use of anti-oxidant molecules to evaluate the importance of ROS-mediated oxidative damage in the pathogenesis of endometriosis. Studies are discussed that have employed anti-oxidants compounds as therapeutics to improve oocyte and embryo quality in infertile subjects, and improve fertility in patients with endometriosis.

Xianbin Zhang, Jiaxin Song, Peng Liu et al.

Abstract Background The present study aims to improve the M-stage classification of pancreatic neuroendocrine neoplasms (pNENs). Methods Two thousand six hundred sixty six pNENs were extracted from the Surveillance, Epidemiology, and End Results database to explore the metastatic patterns of pNENs. Metastatic patterns were categorized as single, two, or multiple (three or more) distant organ metastasis. The mean overall survival and hazard rate of different metastatic patterns were calculated by Kaplan-Meier and Cox proportional hazards models, respectively. The discriminatory capability of the modified M-stage classification was evaluated by Harrell’s concordance index. Results The overall survival time significantly decreased with an increasing number of metastatic organs. In addition, pNENs with only liver metastasis had better prognosis when compared to other metastatic patterns. Thus, we modified the M-stage classification (mM-stage) as follows: mM0-stage, tumor without metastasis; mM1-stage, tumor only metastasized to liver; mM2-stage, tumor metastasized to other single distant organ (lung, bone, or brain) or two distant organs; mM3-stage, tumor metastasized to three or more distant organs. Harrell’s concordance index showed that the modified M-stage classification had superior discriminatory capability than both the American Joint Committee on Cancer (AJCC) and the European Neuroendocrine Tumor Society (ENETS) M-stage classifications. Conclusions The modified M-stage classification is superior to both AJCC and ENETS M-stage classifications in the prognosis of pNENs. In the future, individualized treatment and follow-up programs should be explored for patients with distinct metastatic patterns.

Manish Bathla, Manpreet Singh

Xin Zhang, Huanxin Meng, Li Xu et al.

Vitamin D-binding protein (DBP) is the main transport protein of vitamin D and plays an important role in the immune system and host defenses. The purpose of this study was to measure DBP levels in plasma and gingival crevicular fluid (GCF) of patients with generalized aggressive periodontitis (GAgP), in comparison to healthy controls, with the goal of elucidating the relationship between DBP and GAgP. Fifty-nine GAgP patients and 58 healthy controls were recruited for the study; clinical parameters of probing depths (PD), bleeding index, and attachment loss (AL) were recorded. DBP levels were measured by enzyme-linked immunosorbent assay. From the results, GAgP patients had higher plasma DBP concentrations (P<0.001) but lower GCF DBP concentrations (P<0.001) than healthy controls. In GAgP group, after controlling the potential confounders of age, gender, smoking status, and BMI index, GCF DBP concentrations correlated negatively with PD (P<0.001) and AL (P=0.009). Within the limits of the study, we concluded that decreased GCF DBP level and increased plasma DBP level are associated with periodontitis.

G.P. Mykhalchyshyn, P.M. Bodnar, N.M. Kobyliak

We examined 72 patients with type 2 diabetes mellitus (DM) and nonalcoholic fatty liver disease (NAFLD). According to course of therapy all patients were divided into two groups. Patients of the main group (n = 45) received oral hypoglycemic agents and multiprobiotic symbiter within 30 days. To assess the functional state of the liver we studied protein, pigment, enzyme and lipid metabolism. All patients underwent ultrasound examination, including shear wave elastography. The efficacy of using multiprobiotic symbiter acidophilic concentrated in patients with DM type 2 and NAFLD has been proved. With increasing transaminases, hepatoprotective effect is a decrease of their levels in the blood, inflammatory and necrotic changes in the liver parenchyma. In patients with normal transaminases, hypolipidemic and antisteatogenic effects of multiprobiotic are present.

Gafni Amiram, Thabane Lehana, Sawka Anna M et al.

<p>Abstract</p> <p>Background</p> <p>Biochemical testing for pheochromocytoma by measurement of fractionated plasma metanephrines is limited by false positive rates of up to 18% in people without known genetic predisposition to the disease. The plasma normetanephrine fraction is responsible for most false positives and plasma normetanephrine increases with age. The objective of this study was to determine if we could improve the specificity of fractionated plasma measurements, by statistically adjusting for age.</p> <p>Methods</p> <p>An age-adjusted metanephrine score was derived using logistic regression from 343 subjects (including 33 people with pheochromocytoma) who underwent fractionated plasma metanephrine measurements as part of investigations for suspected pheochromocytoma at Mayo Clinic Rochester (derivation set). The performance of the age-adjusted score was validated in a dataset of 158 subjects (including patients 23 with pheochromocytoma) that underwent measurements of fractionated plasma metanephrines at Mayo Clinic the following year (validation dataset). None of the participants in the validation dataset had known genetic predisposition to pheochromocytoma.</p> <p>Results</p> <p>The sensitivity of the age-adjusted metanephrine score was the same as that of traditional interpretation of fractionated plasma metanephrine measurements, yielding a sensitivity of 100% (23/23, 95% confidence interval [CI] 85.7%, 100%). However, the false positive rate with traditional interpretation of fractionated plasma metanephrine measurements was 16.3% (22/135, 95% CI, 11.0%, 23.4%) and that of the age-adjusted score was significantly lower at 3.0% (4/135, 95% CI, 1.2%, 7.4%) (p < 0.001 using McNemar's test).</p> <p>Conclusion</p> <p>An adjustment for age in the interpretation of results of fractionated plasma metanephrines may significantly decrease false positives when using this test to exclude sporadic pheochromocytoma. Such improvements in false positive rate may result in savings of expenditures related to confirmatory imaging.</p>