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

Marissa Cantu, Prianka Kandhal

Alejandro Román-González, Ines Califano, Marcio Concepción-Zavaleta et al.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor accounting for less than 5% of all thyroid cancers. An estimated 25% of cases are familial secondary to a germline mutation on the rearranged during transfection proto-oncogene ( RET ); this gene can be present as a somatic mutation in approximately 40%–60% of sporadic MTC tumors. There is an existing genotype-phenotype correlation in the clinical behavior of MTC, with the RET M918T variant associated with aggressive disease. The current systemic treatment profile for progressive metastatic MTC involves antiangiogenics multikinase inhibitors (MKI), specifically cabozantinib and vandetanib, and high-specific RET inhibitor therapy. Decisions on the timing of systemic therapy initiation in this population should involve multidisciplinary care and individualization on a case-by-case scenario; a comprehensive evaluation of performance status, tumor burden, progression rate, medical comorbidities, possible medication interactions, and goals of care must be considered in a patient-centered approach. This review summarizes the evidence on the safety, efficacy, and limitations of systemic therapies for MTC; the aim is to empower clinicians with the knowledge to optimally manage patients with advanced, progressive, or metastatic MTC.

Hossein Yarmohammadi, Masood Soltanipur, Mahdi Rezaei et al.

ABSTRACT Background This study aimed to compare the gut microbiome (GM) composition, serum inflammatory markers and faecal short‐chain fatty acids among individuals with type 1 and type 2 diabetes mellitus (DM) and healthy controls. Methods This case–control study examined 49 subjects with type 2 DM, 21 with type 1 DM and 40 healthy controls. Blood and faecal samples were collected. Serum inflammatory markers, including CRP, IL‐1β, IL‐6, TNF‐α and IFN‐γ, were measured using enzyme‐linked immunosorbent assays (ELISA). Bacterial populations were quantified using RT‐qPCR and NGS. Faecal metabolites were analysed using gas chromatography. Results Simpson's alpha diversity was higher among types 1 and 2 DM than in the control. The frequency of the bacterial genera Gemmiger, Dorea, Collinsella, Escherichia/Shigella, Dialister, Coprococcus, Achromobacter, Intestinimonas and Allisonella in type 2 DM was higher than in the control, and the frequency of the genera Romboutsia and Clostridium was decreased in type 2 DM. The frequency of the Prevotella, Bacteroides and Faecalibacterium genera in type 1 DM was lower than in the other groups. Acetate, propionate and butyrate levels were significantly higher in type 2 DM patients compared to the other groups. Participants with diabetes had significantly higher hs‐CRP, IL1‐β, TNF, IL‐6 and IFG levels compared to the controls. Compared to healthy controls, both T1DM and T2DM patients showed a significant increase in the abundance of the Lactobacillus genus (p = 0.01) and a decrease in Faecalibacterium (p = 0.02). Additionally, serum levels of IL‐6 and TNF‐α were significantly elevated in T2DM patients (p = 0.003 and p = 0.005, respectively). Faecal levels of butyrate were significantly reduced in both diabetic groups compared to the controls (p = 0.004). Conclusion By determining the GM alterations in patients with diabetes, interventional strategies could be designed to modulate the GM composition as an adjunctive therapy in diabetes.

Javad Anjom-Shoae, Christine Feinle-Bisset, Michael Horowitz et al.

It is well established that high-protein diets (i.e. ~25–30% of energy intake from protein) provide benefits for achieving weight loss, and subsequent weight maintenance, in individuals with obesity, and improve glycemic control in type 2 diabetes (T2D). These effects may be attributable to the superior satiating property of protein, at least in part, through stimulation of both gastrointestinal (GI) mechanisms by protein, involving GI hormone release and slowing of gastric emptying, as well as post-absorptive mechanisms facilitated by circulating amino acids. In contrast, there is evidence that the beneficial effects of greater protein intake on body weight and glycemia may only be sustained for 6–12 months. While both suboptimal dietary compliance and metabolic adaptation, as well as substantial limitations in the design of longer-term studies are all likely to contribute to this contradiction, the source of dietary protein (i.e. animal vs. plant) has received inappropriately little attention. This issue has been highlighted by outcomes of recent epidemiological studies indicating that long-term consumption of animal-based protein may have adverse effects in relation to the development of obesity and T2D, while plant-based protein showed either protective or neutral effects. This review examines information relating to the effects of dietary protein on appetite, energy intake and postprandial glycemia, and the relevant GI functions, as reported in acute, intermediate- and long-term studies in humans. We also evaluate knowledge relating to the relevance of the dietary protein source, specifically animal or plant, to the prevention, and management, of obesity and T2D.

Uk-Su Choi, Yul-Wan Sung, Seiji Ogawa

IntroductionIn clinical research on pituitary disorders, pituitary gland (PG) segmentation plays a pivotal role, which impacts the diagnosis and treatment of conditions such as endocrine dysfunctions and visual impairments. Manual segmentation, which is the traditional method, is tedious and susceptible to inter-observer differences. Thus, this study introduces an automated solution, utilizing deep learning, for PG segmentation from magnetic resonance imaging (MRI).MethodsA total of 153 university students were enrolled, and their MRI images were used to build a training dataset and ground truth data through manual segmentation of the PGs. A model was trained employing data augmentation and a three-dimensional U-Net architecture with a five-fold cross-validation. A predefined field of view was applied to highlight the PG region to optimize memory usage. The model’s performance was tested on an independent dataset. The model’s performance was tested on an independent dataset for evaluating accuracy, precision, recall, and an F1 score.Results and discussionThe model achieved a training accuracy, precision, recall, and an F1 score of 92.7%, 0.87, 0.91, and 0.89, respectively. Moreover, the study explored the relationship between PG morphology and age using the model. The results indicated a significant association between PG volume and midsagittal area with age. These findings suggest that a precise volumetric PG analysis through an automated segmentation can greatly enhance diagnostic accuracy and surveillance of pituitary disorders.

Fanny Luterbacher, Jean-Louis Blouin, Valerie M. Schwitzgebel

Abstract Background New-onset diabetes in youth encompasses type 1 diabetes, type 2 diabetes, monogenic diabetes, and rarer subtypes like Type B insulin resistance syndrome and ketosis-prone atypical diabetes in African populations. Some cases defy classification, posing management challenges. Here, we present a case of a unique, reversible diabetes subtype. Case presentation We describe an adolescent African girl recently diagnosed with systemic lupus erythematosus. At age 15, she presented with ketoacidosis, HbA1c of 108.7 mmol/mol (12.1%), and positive anti-insulin antibodies. Initially diagnosed with type 1 diabetes, insulin was prescribed. Due to the presence of obesity and signs of insulin resistance, we added metformin. Concurrently, she received treatment for lupus with hydroxychloroquine, mycophenolate mofetil, and prednisone. After discharge, she stopped insulin due to cultural beliefs. Five months later, her glycemia and HbA1c normalized (37 mmol/mol or 5.5%) without insulin, despite corticosteroid therapy and weight gain. Autoantibodies normalized, and lupus activity decreased. Genetic testing for monogenic diabetes was negative, and the type 1 genetic risk score was exceptionally low. Conclusions We present a complex, reversible diabetes subtype. Features suggest an autoimmune origin, possibly influenced by overlapping HLA risk haplotypes with lupus. Lupus treatment or immunomodulation may have impacted diabetes remission. Ancestry-tailored genetic risk scores are currently designed to improve diagnostic accuracy.

Fabian Lurquin, Sophie Gohy, Michel P. Hermans et al.

Aims: Combined CFTR modulator therapies have dramatically altered pulmonary outcomes in patients with cystic fibrosis (CF). Their impact on glucose metabolism requires further investigations. This study aims to evaluate insulin requirements after initiation of combined CFTR modulator therapy in patients with CF-related diabetes (CFRD) and HOMA indices changes in CF patients without diabetes. Methods: We retrospectively analyzed: 1) the effects of tezacaftor + ivacaftor and elexacaftor + tezacaftor + ivacaftor on FEV1, weight, BMI, HbA1c, and daily insulin dose, in 17 CFRD patients and 2) the impact of tezacaftor + ivacaftor on HOMA indices in 15 CF patients without diabetes. Results: Age was 37±12y in the CFRD group (70% men), 88% of whom were homozygous for F508del mutation. Diabetes duration was 15±10y. Median duration of combined CFTR modulator therapy was 16 months (IQR: 4) Thirteen patients received tezacaftor + ivacaftor, of whom 9 were switched to elexacaftor + tezacaftor + ivacaftor. Four patients received elexacaftor + tezacaftor + ivacaftor up front. A decrease in insulin needs was noticed in 88% of patients (0.85±0.3 vs 0.71±0.3U/kg/day; p = 0001). Total daily insulin dose decreased from 50±16 to 44±20U/day (p = 0.017). BMI improved (20.9 (IQR: 1.90) vs 22.1 kg/m2 (IQR: 3.70); p = 0.014). HbA1c went from 7.3±1.1 to 7.7±1.6% (p = 0.072). Median age was 22y (IQR: 11) in the CF group without diabetes (67% men), 93% of whom were homozygous for F508del mutation. Duration of combined CFTR modulator therapy was 10±5 months. HOMA-B changes were not significant (129.2 (IQR: 84.8) vs 103.5% (IQR: 66.3) nor were HOMA-S changes (from 94±64 to 95±49%). HOMA-BxS decreased from 112±45 to 104±29% (NS). BMI rose from 21.9±3 to 23.1±3.5 kg/m2 (p = 0.047). HbA1c was unchanged (5.0±0.5%). FEV1 improved in both groups (+11% and + 7% of predicted value; p < 0.001; p = 0.013). Conclusion: Combined CFTR modulator therapies are correlated with a decrease in insulin doses and positive effects on BMI and FEV1. HOMA indices did not change on tezacaftor + ivacaftor among CF patients without diabetes.

Yerai Vado, Arrate Pereda, Africa Manero-Azua et al.

ObjectiveiPPSD2 (which includes PHP1A and PPHP/POH) is a rare inherited autosomal dominant endocrine disorder caused by inactivating GNAS pathogenic variants. A high percentage of de novo cases has been suggested. In rare cases, parental mosaicism has been described, but its real frequency is unknown.DesignA retrospective study including a series of 95 genetically confirmed iPPSD2 probands.MethodsThe frequency of de novo cases was evaluated and the distribution of the type of variants was compared according to the type of inheritance. The putative involved allele was determined by reverse transcriptase PCR (RT-PCR) or allele specific oligonucleotide RT-PCR (ASO-RT-PCR). The possibility of GNAS mosaicism was studied by next-generation sequencing (NGS) on the corresponding parental DNA.ResultsIn 41 patients the variant was of de novo origin and in 24 the origin could not be established. In both cases 66.67% of variants generated a truncated or absent protein whereas the rest of the variants were missense or in-frame deletion/duplication. Parental origin was studied in 45 of those patients and determined in 35. Curiously, the percentage of de novo variants at the paternal allele was higher than when paternally inherited (31.1% vs 6.67%). NGS detected mosaicism in three independent families: one from paternal DNA (allelic ratio 10%) and two from maternal DNA (allelic ratio 10% and 2%).ConclusionDe novo pathogenic variants are frequent in iPPSD2 (around 45%). Parental mosaicism is infrequent (8.11%) but should be analyzed with NGS, taking into account its importance in genetic counselling.

Giovanna Muscogiuri, Luigi Barrea, Evelyn Frias-Toral et al.

Youngsook Kim, Ji Hye Huh, Minyoung Lee et al.

AimsGlucagon‐like peptide 1 (GLP-1) receptor agonists have demonstrated strong glycemic control. However, few studies have investigated the effects of switching from insulin to GLP-1 receptor agonists. We aimed to investigate, using real-world data, whether switching to dulaglutide improves glycemic control in patients with type 2 diabetes mellitus (T2D) inadequately controlled with conventional insulin treatment.Materials and methodsWe retrospectively evaluated 138 patients with T2D who were switched from insulin to dulaglutide therapy. We excluded 20 patients who dropped out during the follow-up period. The participants were divided into two groups according to whether they resumed insulin treatment at 6 months after switching to a GLP-1 receptor agonist (group I) or not (group II). A multiple logistic regression analysis was performed to evaluate the parameters associated with the risk of resuming insulin after replacement with dulaglutide.ResultsOf 118 patients initiated on the GLP-1 receptor agonist, 62 (53%) resumed insulin treatment (group I), and 53 (47%) continued with GLP-1 receptor agonists or switched to oral anti-hypoglycemic agents (group II). Older age, a higher insulin dose, and lower postprandial glucose levels while switching to the GLP-1 receptor agonist were associated with failure to switch to the GLP-1 receptor agonist from insulin.ConclusionsA considerable proportion of patients with T2D inadequately controlled with insulin treatment successfully switched to the GLP-1 receptor agonist. Younger age, a lower dose of insulin, and a higher baseline postprandial glucose level may be significant predictors of successful switching from insulin to GLP-1 receptor agonist therapy.

Huan-Xin Liu, Yan-Yan Ren, Cui-Qiao Meng et al.

BackgroundThe association between free triiodothyronine/free thyroxine (FT3/FT4) and non-alcoholic fatty liver disease (NAFLD) in euthyroid subjects is unclear. In addition, few studies have explored whether VAI mediates the association between FT3/FT4 ratio and NAFLD in the euthyroid population. We aimed to analyze the mediating effect of VAI on the FT3/FT4 ratio and NAFLD risk in the euthyroid population.MethodsThis cross-sectional study included 7 946 annual health examinees from the Health Examination Center, Hebei General Hospital, from January to December 2020. The basic information and biochemical parameters, as well as calculated FT3/FT4 ratio and VAI were collected. NAFLD was diagnosed according to abdominal ultrasonography. The fibrosis score for NAFLD positive subjects (NFS) was calculated to reflect the extent of liver fibrosis. The risk of NAFLD was analyzed by quartiles of FT3/FT4 ratio (Q1-Q4 quartiles) and VAI (V1-V4 quartiles), respectively. Pearson correlation analysis was performed to investigate the correlation between FT3/FT4 ratio and VAI. Multivariate logistic regression analysis was applied to analyze the effect of FT3/FT4 ratio and VAI on NAFLD and NFS status. Bootstrap was conducted to explore whether VAI mediated the association between FT3/FT4 ratio and NAFLD.ResultsOf the 7 946 participants, 2 810 (35.36%) had NAFLD and 5 136 (64.64%) did not. Pearson correlation analysis indicated that FT3/FT4 ratio was positively associated with VAI (P&lt;0.05). Multivariate logistic regression analysis indicated that compared to the Q1 group, the risk of NAFLD significantly increased in Q3 group [OR=1.255, 95%CI (1.011, 1.559)] and Q4 group [OR=1.553, 95%CI (1.252, 1.926)](P&lt;0.05). Compared to the V1 group, the risk of NAFLD notably increased in V2 group [OR=1.584, 95%CI (1.205, 2.083)], V3 group [OR=2.386, 95%CI (1.778, 3.202)] and V4 group [OR=4.104, 95%CI (2.835, 5.939)] (P&lt;0.01). There was no relevance between FT3/FT4 ratio, VAI and NFS status. Mediating effect analysis showed that FT3/FT4 ratio significantly directly influenced NAFLD prevalence [β=3.7029, 95%CI (2.9583, 4.4474)], and VAI partly mediated the indirect effect of the FT3/FT4 ratio on NAFLD prevalence [β=2.7649, 95%CI (2.2347, 3.3466)], and the mediating effect accounted for 42.75% of the total effects.ConclusionBoth FT3/FT4 ratio and VAI were predictors of NAFLD, and VAI partly mediated the indirect effect of the FT3/FT4 ratio on NAFLD prevalence in the euthyroid population.

Aysegul Bestel, Burak Elmas, Osman Samet Günkaya et al.

Objective PCOS (polycystic ovary syndrome) is one of the most common endocrinological disorders and it is the threshold of many systemic disorders. There are many studies in the literature on the mechanisms that cause increased oxidation in PCOS. Sestrin protein is known to regulate the oxidation. In this study, it is aimed to examine the changes in the level of sestrin protein in women with PCOS.Methods A total of 60 women participated the study, 30 of whom were diagnosed with PCOS according to the Rotterdam criteria. Also, 30 women were included in the study as the control group. Demographic information, biochemical analysis results, and sestrin levels of the patients in each group were compared.Results The median sestrin level was 6.2 ± 0.8 in the PCOS group and 3.38 ± 0.4 in the control group (p < 0.001). As a result of the evaluation made with ROC analysis, it is observed that serum sestrin levels may be meaningful in the diagnosis of polycystic ovary syndrome. The area under the curve (AUC) value for the 4.69 level was 99.4% (p < 0.001, 95% CI: 96.7% vs. 100%, sensitivity: 100%, specificity: 96.7%).Conclusions Sestrin protein is associated with oxidative stress. Sestrin protein can be used as an indicator of increased oxidative stress in PCOS.

Wieland Kiess, Gabriele Haeusler

Mengge Yang, Mengge Yang, Lusi Xu et al.

AimsTo investigate the clinical features and mitochondrial mutations for maternally inherited diabetes and deafness.MethodsPubMed, Embase, Medline, Web of Science, the China National Knowledge Infrastructure, and Wanfang were searched with the following search terms: “Maternally inherited diabetes and deafness” OR “MIDD” OR “Mitochondrial diabetes”. The mutations and clinical features were analyzed. Correlation between the heteroplasmy levels of the m.3243A&gt;G mutation in the peripheral blood and age at the onset of diabetes was conducted by Spearman test. The significance level was set as p &lt; 0.05. Statistical analysis was performed using the Statistical Package for the Social Sciences version 26 for Windows.ResultsTotally 161 patients with 21 different mitochondrial mutations were enrolled. The most common mutation was the m.3243A&gt;G mutation in 136 cases. Of 142 patients, 120 (84.51%) had family histories of diabetes or hearing loss. Hearing loss presented in 85.71% of the patients with mitochondrial mutations. Central nervous system diseases were found in 29.19%, myopathy in 22.98%, oculopathy in 23.60%, cardiac disease in 23.60%, and nephropathy in 13.66% of the patients. Forty-two of 101 (41.58%) patients were underweight. A significant negative correlation was found between the heteroplasmy levels of the m.3243A&gt;G mutation in the peripheral blood and age at the onset of diabetes.ConclusionsThe young onset of diabetes with low or normal BMI, maternal inheritance, and presence of impairments of multiple systems should prompt a genetic testing in order to differentiate MIDD from other types of diabetes earlier.

Gerardo Weisstaub

Symposium 18: Psychosocial factors, diabetes, current epidemics and pandemics Psychosocial factors in childhood obesity: its impact on morbidity and mortality Childhood obesity is a pandemic that continues to grow almost all over the world. This type of malnutrition has a great impact on the health of children and adolescents and, in general, healthcare teams in charge of treatment and prevention mainly focus on the biological complications (such as arterial hypertension, diabetes). However, many publications show higher morbidity in the mental health area during childhood (low self-esteem, depression and bullying at school). To be able to understand the genesis of this pathology, it is important to consider the development of the eating behavior from the beginning of the complementary feeding, which is an aspect healthcare professionals don’t usually put the focus on. Although we understand “eating behavior” as a complex construct to evaluate, there are some instruments that allow us to measure it, such as the Child Eating Behavior Questionnaire (CEBQ).

P. Sunsundegui, V. Santesteban-Moriones, M. F. Landecho

Ai Ishiguro, Yasuhisa Munakata, Koumei Shirasuna et al.

Abstract Purpose Improvement of in vitro oocyte growth by addition of granulosa cells derived from differential developmental stages of follicles. Methods Granulosa cells (GCs) collected from either early antral follicles (EAFs) or antral follicles (AFs) were added to oocyte‐granulosa cell complexes (OGCs) derived from EAFs, and the in vitro growth of the oocytes was evaluated. Results Granulosa cells were incorporated into OGCs to form new OGCs within 2 days of culture. After 14 days of culture, the number of GCs surrounding oocytes was similar among the three OGCs conditions (unmanipulated “natural OGCs,” “EAF‐GCs add OGCs,” and “AF‐GCs add OGCs”), whereas the survival rate of the GCs and diameter of oocytes grown in vitro were the greatest for “AF‐GCs added OGCs.” After parthenogenetic activation, developmental rate till the blastocyst stage tended to be higher for “AF‐GCs add OGCs” compared with other groups. Addition of AF‐GCs significantly increased a hypoxic marker (pimonidazole staining) and increased the lipid content in oocytes grown in vitro compared with unmanipulated OGCs. Conclusion Addition of GCs derived from more advanced stages of follicles to the OGCs changes the metabolism of oocytes and is beneficial for in vitro growth of oocytes derived from EAFs.

Andrey N. Molchanov, Valery V. Romachkin, Irina A. Urvantseva

Aim. Conduct a comparative analysis of the patient's quality of life in the long-term period after surgical correction of aortic valve stenosis after undergoing transcatheter aortic valve replacement with the results of patients undergoing aortic valve replacement with a seamless biological prosthesis under artificial blood circulation. Materials and methods. A comprehensive examination and dynamic observation in the middle and late postoperative period for 251 patients of the older age group with aortic stenosis was performed. The average age of patients at the time of treatment was 67.62±9.94 years. Group 1 included 128 patients who underwent transcatheter aortic valve replacement. In turn, Group 1 is divided into two subgroups. Subgroup A consisted of 56 patients, due to the severity of the underlying disease, concomitant pathology EuroSCORE II more than 20% and STS SCORE more than 10%. Subgroup B consisted of 72 patients with a risk of outcome of EuroSCORE II surgical intervention less than 20% and STS SCORE less than 10%. Group 2 patients (n=123) were comparable to subgroup B by the severity of the underlying disease EuroSCORE II less than 20% and STS SCORE less than 10%. All patients in group II underwent aortic valve replacement under artificial circulation.To assess the quality of life, the SF-36 questionnaire was used 12, 24, 36, 48 and 60 months after surgery. Results. The greatest increase in the total total score in the postoperative period was noted in subgroup A - 3 times (p=0.000001), and in subgroups B and group 2 was 2.66 times (p=0.0000011). By the end of the observation period, the highest total score was recorded in subgroup B, in subgroup A it was lower by 3% (p=0.95), in group 2 - by 2.4% (p=0.97). A correlation is established between the average degree between the total score, reflecting the quality of life of patients after aortic valve replacement, and the rate of ejection fraction (R=0.23, p=0.034), and the left ventricular myocardium mass (R=-0.25, p=0.028) and shock volume (R=0.29, p=0.021) according to echocardiography. Conclusions. Thus, despite a number of difficulties that were observed after surgical correction of aortic stenosis in patients of the older age group, including the presence of concomitant somatic pathology, marked cardiac changes according to echocardiography, the analysis of quality of life indicators demonstrates the positive effect of surgical treatment with a significant improvement in quality of life.