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

Selene S Mak, Laura M Nally, Juanita Montoya et al.

BackgroundNumerous barriers to moderate to vigorous physical activity exist for youths with type 1 diabetes (T1D). The virtual exercise games for youth with T1D (ExerT1D) intervention implement synchronous support of moderate to vigorous physical activity including T1D peers and role models. ObjectiveThis study aims to understand the acceptability of this intervention to participants. MethodsWe conducted postprogram, semistructured, televideo interviews with participating youths to elicit perspectives on the acceptability of the intervention and experience with the program. Two coders independently reviewed and analyzed each transcript using a coding scheme developed inductively by senior researchers. Discrepancies were resolved by team discussion, and multiple codes were grouped together to produce 4 main thematic areas. ResultsAll 15 participants provided interviews (aged 14-19 years; 2 nonbinary, 6 females; median hemoglobin A1c level of 7.8% (IQR 7.4%-11.2%), 5 with a hemoglobin A1c level of ≥10%). Qualitative data revealed four themes: (1) motivation to engage in physical activity (PA)—improving their physical capabilities and stabilizing glucose levels were cited as motivation for PA and challenges of living with T1D were cited as PA barriers; (2) experience with and motivation to manage diabetes while engaging in PA—participants provided details of accommodating the inherent uncertainty or limitations of PA with diabetes and sometimes preparing for PA involved psychological and motivational adjustments while some relayed feelings of avoidance; (3) peer support encouraged engagement with the intervention—participants appreciated the peer aspects of components of ExerT1D and participants’ reflections of the facilitated group experience highlight many benefits of a small-group virtual program; and (4) improvements in PA and diabetes self-management efficacy—all participants credited the program with improving or at least raising awareness of T1D management skills. ConclusionsOur virtual PA intervention using an active video game and discussion component provided adolescents with T1D the confidence and peer support to engage in PA, improved awareness of diabetes-specific tasks to prepare for exercise, and improved understanding of the effect of PA on glucose levels. Engaging youths with a virtual video game intervention is a viable approach to overcome barriers to PA for adolescents with T1D. Trial RegistrationClinicalTrials.gov NCT05163912; https://clinicaltrials.gov/ct2/show/NCT05163912

Estela Lorza-Gil, Estela Lorza-Gil, Estela Lorza-Gil et al.

Min Zhang, Ye Bai, Yutong Wang et al.

BackgroundGeneral obesity is a well-established risk factor for gallstone disease (GSD), but whether central obesity contributes additional independent risk remains controversial. We aimed to comprehensively clarify the effect of body fat distribution on GSD.MethodsWe first investigated the observational association of central adiposity, characterized by waist-to-hip ratio (WHR), with GSD risk using data from UK Biobank (N=472,050). We then explored the genetic relationship using summary statistics from the largest genome-wide association study of GSD (ncase=43,639, ncontrol=506,798) as well as WHR, with and without adjusting for body mass index (BMI) (WHR: n=697,734; WHRadjBMI: n=694,649).ResultsObservational analysis demonstrated an increased risk of GSD with one unit increase in WHR (HR=1.18, 95%CI=1.14-1.21). A positive WHR-GSD genetic correlation (rg =0.41, P=1.42×10-52) was observed, driven by yet independent of BMI (WHRadjBMI: rg =0.19, P=6.89×10-16). Cross-trait meta-analysis identified four novel pleiotropic loci underlying WHR and GSD with biological mechanisms outside of BMI. Mendelian randomization confirmed a robust WHR-GSD causal relationship (OR=1.50, 95%CI=1.35-1.65) which attenuated yet remained significant after adjusting for BMI (OR=1.17, 95%CI=1.09-1.26). Furthermore, observational analysis confirmed a positive association between general obesity and GSD, corroborated by a shared genetic basis (rg =0.40, P=2.16×10-43), multiple novel pleiotropic loci (N=11) and a causal relationship (OR=1.67, 95%CI=1.56-1.78).ConclusionBoth observational and genetic analyses consistently provide evidence on an association of central obesity with an increased risk of GSD, independent of general obesity. Our work highlights the need of considering both general and central obesity in the clinical management of GSD.

Paris Kantaras, Niki Mourouti, Theodora Mouratidou et al.

In total, 3274 adults (65.2% females) from six European countries were included in this cross-sectional analysis using data from the baseline assessment of the Feel4Diabetes study. Anthropometric, sociodemographic, dietary and behavioral data were assessed, and the existence of metabolic syndrome (MetS) was recorded. Beverage consumption patterns (BCPs) were derived via principal component analysis. Three BCPs were derived explaining 39.5% of the total variation. BCP1 was labeled as “Alcoholic beverage pattern”, which loaded heavily on high consumption of beer/cider, wine and other spirits; BCP2 was labeled as “High in sugars beverage pattern” that was mainly characterized by high consumption of soft drinks with sugar, juice containing sugar and low consumption of water; and BCP3 was labeled as “Healthy beverage pattern” that was mainly characterized by high consumption of water, tea, fruit juice freshly squeezed or prepacked without sugar and low consumption of soft drinks without sugar. After adjusting for various confounders, BCP2 was positively associated with elevated triglycerides (<i>p</i> = 0.001), elevated blood pressure (<i>p</i> = 0.001) elevated fasting glucose (<i>p</i> = 0.008) and the existence of MetS (<i>p</i> = 0.006), while BCP1 was inversely associated with reduced HDL-C (<i>p</i> = 0.005) and BCP3 was inversely associated with elevated blood pressure (<i>p</i> = 0.047). The establishment of policy actions as well as public health nutritional education can contribute to the promotion of a healthy beverage consumption.

Grace Aprilia Helena, Shoen Kume

Diabetes is an epidemic caused by a multitude of factors. Despite the studies attempting to unravel its mechanism, there is still more to discover about glucose–insulin dynamics. In a recent issue of the Journal of Clinical Investigation, Cheruiyot et al. uncovered a translational regulatory circuit during β‐cell glucose toxicity that inherently affects the translational makeup and protein expression in functioning β‐cells.Journal of Clinical Investigation, Cheruiyot et al. uncovered a translational regulatory circuit during β‐cell glucose toxicity that inherently affects the translational makeup and protein expression in functioning β‐cells. Their multiomics approach might provide a deeper understanding of high glucose and translational regulation of genes involved in β‐cell insulin impairment caused by prolonged high‐glucose exposure.

M. G. Pavlova, O. Golounina, T. Morgunova et al.

Autoimmune polyglandular syndrome type 1 (APS-1) is an extremely rare monogenic autosomal recessive disease characterized by development of multiple organ failure with predominant endocrine glands involvement. The challenges of patient management are related to low adherence to the lifelong multicomponent therapy, high risk of complications, including pneumonia, adrenal insufficiency decompensation, necrotic colitis and other acute infectious and inflammatory diseases. Due to the rarity of this disorder, clinicians lack sufficient experience with management of such patients, which could lead to delayed medical care and patient death. Patient A., 28 years old, was followed up for 10 years in the Endocrinology clinic with the diagnosis of “Autoimmune polyglandular syndrome type 1. Mucocutaneous candidiasis. Primary hypoparathyroidism. Primary chronic adrenal insufficiency. Primary hypothyroidism. Chronic gastroduodenitis. Chronic colitis. Autoimmune alopecia.” The onset of the disease with chronic mucocutaneous candidiasis at the age below 1 year had defined the severe course of the disease, including a wide range of consequently occurring autoimmune diseases associated with recurrent episodes of decompensation of hypoparathyroidism and adrenal insufficiency, as well as the development of acute necrotic colitis at the age of 26. As an adult, the patient admitted that he had previously been insufficiently responsible and attentive to his disease and regular medication intake, with resulting episodes of adrenal insufficiency decompensation and occurrence of the symptoms related to serum calcium fluctuations. Due to abnormalities of cellular and humoral immunity, APS-1 patients are at an extremely high risk for a critical course of COVID-associated pneumonia. In 2020, the patient contracted the coronavirus infection complicated by bilateral pneumonia, followed by respiratory failure, bacterial sepsis and acute renal failure. Despite the timely hospitalization, administration of the state-of-the-art antibacterials and antifungals and all the necessary resuscitation measures, it was not possible to save his life. This clinical observation demonstrates the difficulties of therapeutic management of APS-1 patients with an early disease manifestation, who, due to severe genetically determined impaired immunity, are at high risk of death from an intercurrent infection. The combination of several chronic comorbidities and the need to take a large number of replacement treatments require an individual therapeutic approach, as well as psychological and social adaptation of the patients, starting from their childhood and throughout the whole life, taking into account the frequent psychological problems could lead to low treatment adherence. The timely diagnostics of the disease, understanding of pathophysiology and specifics of its course could contribute to increased qualityadjusted life years of APS-1 patients.

Danang Dwi Cahyadi, Tomoko Warita, Nanami Irie et al.

ABSTRACTNormalization is a crucial step in gene expression analysis to avoid misinterpretation. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression of 10 candidate housekeeping genes in non-differentiated (ND) and differentiated (DI) 3T3-L1 cells on days 5 and 10. We used geNorm, NormFinder, BestKeeper, RefFinder, and the ∆Ct method to evaluate expression stability. The findings revealed that (1) the expression levels of the reference genes changed over time, even in non-differentiating cells, and (2) peptidylprolyl isomerase A (Ppia) and TATA box-binding protein (Tbp) were stable reference genes for 10 days in both undifferentiated and differentiated 3T3-L1 cells. Notably, the expression of known reference genes in non-differentiating cells was altered throughout the experiment.

Kewei Wang, Kewei Wang, Rong Zhang et al.

Background and aimsWnt/β-catenin signaling plays an important role in regulating hepatic metabolism. This study is to explore the molecular mechanisms underlying the potential crosstalk between Wnt/β-catenin and mTOR signaling in hepatic steatosis.MethodsTransgenic mice (overexpress Wnt1 in hepatocytes, Wnt+) mice and wild-type littermates were given high fat diet (HFD) for 12 weeks to induce hepatic steatosis. Mouse hepatocytes cells (AML12) and those transfected to cause constitutive β-catenin stabilization (S33Y) were treated with oleic acid for lipid accumulation.ResultsWnt+ mice developed more hepatic steatosis in response to HFD. Immunoblot shows a significant increase in the expression of fatty acid synthesis-related genes (SREBP-1 and its downstream targets ACC, AceCS1, and FASN) and a decrease in fatty acid oxidation gene (MCAD) in Wnt+ mice livers under HFD. Wnt+ mice also revealed increased Akt signaling and its downstream target gene mTOR in response to HFD. In vitro, increased lipid accumulation was detected in S33Y cells in response to oleic acid compared to AML12 cells reinforcing the in vivo findings. mTOR inhibition by rapamycin led to a down-regulation of fatty acid synthesis in S33Y cells. In addition, β-catenin has a physical interaction with mTOR as verified by co-immunoprecipitation in hepatocytes.ConclusionsTaken together, our results demonstrate that β-catenin stabilization through Wnt signaling serves a central role in lipid metabolism in the steatotic liver through up-regulation of fatty acid synthesis via Akt/mTOR signaling. These findings suggest hepatic Wnt signaling may represent a therapeutic strategy in hepatic steatosis.

Francesca Mancuso, Iva Arato, Catia Bellucci et al.

IntroductionAmong substances released into the environment by anthropogenic activities, the heavy metal cadmium (Cd) is known to induce severe testicular injury causing male subfertility/infertility. Zinc (Zn) is another heavy metal that, unlike Cd, is physiologically present in the testis, being essential for spermatogenesis. We aimed to examine the possibility that 50 µM ZnCl2 could counteract the toxic effects induced by Cd in an in vitro model of porcine prepubertal Sertoli cells (SCs) exposed to both subtoxic (5 μM) and toxic (10 μM) concentrations of CdCl2 for 48 h.Materials and MethodsApoptosis, cell cycle, and cell functionality were assessed. The gene expression of Nrf2 and its downstream antioxidant enzymes, ERK1/2, and AKT kinase signaling pathways were evaluated.Materials and ResultsWe found that Zn, in co-treatment with subtoxic and toxic Cd concentration, increased the number of metabolically active SCs compared to Cd exposure alone but restored SC functionality only in co-treatment with subtoxic Cd concentration with respect to subtoxic Cd alone. Exposure of Cd disrupted cell cycle in SCs, and Zn co-treatment was not able to counteract this effect. Cd alone induced SC death through apoptosis and necrosis in a dose-dependent manner, and co-treatment with Zn increased the pro-apoptotic effect of Cd. Subtoxic and toxic Cd exposures activated the Nrf2 signaling pathway by increasing gene expression of Nrf2 and its downstream genes (SOD, HO-1, and GSHPx). Zn co-treatment with subtoxic Cd attenuated upregulation on the Nrf2 system, while with toxic Cd, the effect was more erratic. Studying ERK1/2 and AKT pathways as a target, we found that the phosphorylation ratio of p-ERK1/2 and p-AKT was upregulated by both subtoxic and toxic Cd exposure alone and in co-treatment with Zn.DiscussionOur results suggest that Zn could counteract Cd effects by increasing the number of metabolically active SCs, fully or partially restoring their functionality by modulating Nrf2, ERK1/2, and AKT pathways. Our SC model could be useful to study the effects of early Cd exposure on immature testis, evaluating the possible protective effects of Zn.

A. V. Hajrieva, N. Tarbaeva, N. Volevodz et al.

The study of the genetic aspects of endocrine diseases is based on the aspiration to develop the methods of early diagnosis, treatment and observation of patients. Von Hippel-Lindau syndrome is genetically determined disease characterized by damage of various organs and systems. The article presents a clinical case of treatment of a patient with retinal detachment who was first admitted to the surgical department of the Federal State Budgetary Institution «NMIC of Endocrinology» of the Ministry of Health of Russia with complaints of dry mouth, general weakness. Further examination, revealed pathological changes in the adrenal glands, kidneys, brain, pancreas, spleen, spinal cord. The presented clinical case demonstrates the need for a multidisciplinary approach to the management of patients with von Hippel-Lindau syndrome.

C. Hong, Y. Jeong, H. Kim et al.

Xinmi Liu, Hua Lou, Junwei Zhang et al.

ObjectiveTo investigate the clinical outcomes of Day 7 (D7) frozen-thawed embryo transfer (FET) and to provide a reference value for clinical work.MethodsThis was a retrospective cohort study. Patients undergoing FET cycles in the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University between December 2015 and January 2021 were included. According to the developmental stage of the embryos at transfer, the embryos were divided into three groups: Day (D) 5, D6 and D7 blastocysts. Group D7 was compared with Groups D5 and D6. Simultaneously, the preimplantation genetic testing (PGT) and non-PGT cycles in Group D7 were analyzed and compared. The main outcomes were the clinical pregnancy, live birth and miscarriage rates. The secondary outcomes were the implantation and euploidy rates.ResultsIn total, 5945, 4094 and 137 FET cycles were included in the D5, D6 and D7 groups, respectively. The clinical pregnancy rate was significantly lower in Group D7 than in Groups D5 (13.9% vs 62.9%, P &lt;0.001) and D6 (13.9% vs 51.4%, P &lt;0.001). Additionally, the live birth rate was significantly lower in Group D7 than in Groups D5 (7.3% vs 50.7%, P &lt;0.001) and D6 (7.3% vs 40.5%, P &lt;0.001). However, the miscarriage rate was significantly higher in Group D7 than in Groups D5 (47.4% vs 18.2%, P =0.001) and D6 (47.4% vs 20.6%, P =0.004). The clinical pregnancy and live birth rates for D7 blastocysts were significantly higher in the PGT group than in the non-PGT group (41.7% vs 13.9%, P=0.012; 33.3% vs 7.3%, P =0.003).ConclusionsD7 blastocyst transfer can yield a live birth rate that is lower than that for D5 and D6 blastocysts but has value for transfer. PGT for D7 blastocysts may reduce the number of ineffective transfers and improve the outcome of D7 blastocyst transfer, which can be performed according to a patient’s situation.

Sanna Laurila, Sanna Laurila, Sanna Laurila et al.

Secretin is the first hormone that has been discovered, inaugurating the era and the field of endocrinology. Despite the initial focus, the interest in its actions faded away over the decades. However, there is mounting evidence regarding the pleiotropic beneficial effects of secretin on whole-body homeostasis. In this review, we discuss the evidence from preclinical and clinical studies based on which secretin may have a role in the treatment of obesity.

Nobuya Inagaki

Joana Lima Ferreira, Francisco Simões de Carvalho, Ana Paula Marques et al.

Autoimmune polyglandular syndrome type 1 (APS-1) is a very rare autoimmune entity, accounting for about 400 cases reported worldwide. It is characterized by the presence of at least two of three cardinal components: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism and Addison’s disease. It typically manifests in childhood with CMC and years later with hypoparathyroidism. A 50-year-old man was referred to the Endocrinology outpatient clinic due to irregular follow-up of primary hypoparathyroidism diagnosed at age 7. Previous analysis reported frequent fluctuations of calcium and phosphate levels and persistent hypercalciuria. He presented several comorbidities, including bilateral cataracts, other ocular disorders, transient alopecia and chronic gastritis. Due to weight loss, fatigue, gastrointestinal complaints and the findings at objective examination, Addison’s disease and CMC were investigated and confirmed. Antifungal therapy and hormonal replacement were started with evident clinical improvement. Regarding hypoparathyroidism, calcium-phosphate product decreased and other extraskeletal calcifications were diagnosed, such as nephrolithiasis and in basal ganglia. Further evaluation by genetic analysis revealed homozygosity for a frameshift mutation considered to be a pathogenic variant. It was reported only in two Asian siblings in compound heterozygosity. This case highlights the broad phenotypic spectrum of APS-1 and the significative intra-familial phenotype variability. A complete clinical history taking and high index of suspicion allowed the diagnosis of this rare entity. This case clarifies the need for regular long-term follow-up. In the specific case of hypoparathyroidism and Addison’s disease in combination, the management of APS-1 can be complex.

Chieh-Liang Huang, Chieh-Liang Huang, Yao-Chang Chiang et al.

Methadone maintenance treatment (MMT) remains the cornerstone for the management of opiate abuse. However, MMT can be associated with complex factors, including complications during the tolerance phase, the inability of some patients to maintain treatment effects during the tapering or abstinence phases, and the development of methadone dependence. Previous studies have revealed a sex disparity in MMT efficacy, showing that women undergoing MMT experiencing an increase in psychological symptoms compared with men and suggesting a link between disparate responses and the effects of estrogen signaling on methadone metabolism. More specifically, estradiol levels are positively associated with MMT dosing, and the expression of a single-nucleotide polymorphism (SNP) associated with estrogen receptor (ER) regulation is also associated with MMT dosing. In addition to performing mechanistic dissections of estrogen signaling in the presence of methadone, past studies have also proposed the targeting of estrogen signaling during MMT. The present report provides an overview of the relevant literature regarding sex effects, including differences in sex hormones and their potential impacts on MMT regimens. Moreover, this article provides a pharmacological perspective on the targeting of estrogen signals through the use of selective ER modulators (SERMs) during MMT. Preliminary preclinical experiments were also performed to evaluate the potential effects of targeting estrogen signaling with tamoxifen on methadone metabolism.

Eiichi Araki, Atsushi Goto, Tatsuya Kondo et al.

Moritsugu Kimura, Masao Toyoda, Nobumichi Saito et al.

Objective. Podocytes have highly differentiated functions and are extremely difficult to grow; thus, damage of podocytes is associated with glomerular dysfunction. Desquamated podocytes can be detected in urine of patients with severe renal impairment. Unlike the rapidly progressive glomerular damage in glomerulonephritis, only a few desquamated podocytes are usually detected in diabetic nephropathy (DN). It is not clear whether the low podocyte count in DN is due to limitation of the conventional method or true pathological feature. The aim of this study was to compare the conventional method with a newly modified method in detecting podocytes in morning urine samples of patients with DN. Materials and Methods. The study subjects were patients with type 2 diabetes. Urine samples from these patients were analyzed by the conventional method (Cytospin®) and the modified method (SurePath™). We determined the rate of detection of urinary podocytes and the number of detected cells. Results. The detection rate and podocyte count were significantly higher by the modified method than by the conventional method. The differences in the detection rates and numbers of podocytes were not significant between patients with normoalbuminuria and those with macroalbuminuria. However, they were significant in patients with microalbuminuria. The number of podocytes in the urine correlated significantly with the albumin-to-creatinine ratio, but not with the estimated glomerular filtration rate. Conclusions. The true number of urinary podocytes, as measured by the modified SurePath™-based method, in patients with DN is much higher than that estimated by the conventional method.

Joaquín Abello, Fernando Silva

Fragmento En las células de los islotes de Langerhans pueden originarse tumores benignos, presumiblemente malignos y malignos. Cualquiera de éstos puede ser una de las causas orgánicas de hipoglicemia. El síndrome hipoglicémico asociado a tumores de las células de los islotes de Langerhans es debido a una liberación excesiva de insulina por el tejido tumoral. Nichols (1) reportó por primera vez un adenoma pancreático, hallazgo de necropsia. Howard y colaboradores (2) presentan en 1950 una revisión exhaustiva de 398 casos de tumores de los islotes pancreáticos. Reportaron 313 (78%) adenomas benignos y 48 (12%) sospechosos de malignidad, pero por no haber producido metástasis se catalogaron como benignos. Del total de tumores benignos, 361, 200 fueron intervenidos por combinarse con hiperinsulinismo y resultaron así, funcionantes. Treinta y siete de estos tumores (9%) probaron su malignidad y de éstos, veintidós fueron funcionantes. 

J. Newell-Price, Alia Munir, M. Debono

Endocrinology is the study of hormones (and their glands of origin), their receptors, the intracellular signalling pathways they invoke, and their associated diseases. The clinical specialty of endocrinology focuses specifically on the endocrine organs, that is, the organs whose primary function is hormone secretion, including the hypothalamus, the pituitary, the thyroid, the parathyroid, the adrenal glands, the pancreas, and the reproductive organs.