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

Smita Gawandi, Harshlata Khati, Gaurav Malhotra et al.

Abstract Background Inherited Thyroxine-binding globulin (TBG) deficiency is a rare X-linked disorder caused by mutations in the SERPINA7 gene. This study aimed to investigate the underlying molecular defect in a hypothyroid patient undergoing levothyroxine (L-T4) therapy who exhibited persistent discordant thyroid function test (TFT) results and to characterise the structural and functional consequences of the mutation identified. Methods Thyroid function tests (TFT) were estimated by immunoassays. Genomic DNA from the proband, her family members, and control subjects was PCR-amplified for SERPINA7 exons using specific primers, followed by Sanger sequencing. Allele-specific PCR was employed to validate the mutation site. Further, Whole-exome sequencing was performed as an orthogonal validation to reconfirm the genomic location and exclude additional variants. In silico tools were used to model the mutant protein’s secondary and tertiary structures to assess potential structural alterations. Results A complex indel mutation in SERPINA7, annotated as NM_000354.6:c.1117_1118delinsCAG, resulting in NP_000345.2:p.Ser353Glnfs*5, was detected in exon 4 (mature protein numbering). This mutation, referred to as TBG-CD-Ind (GenBank accession no. PV670074), was previously documented in another unrelated family and resulted in a frameshift that introduces a premature stop codon at position 357. Consequently, the translation process was prematurely terminated, leading to the production of a truncated TBG protein. Structural modelling of the mutant TBG predicted significant alterations in its secondary and tertiary structures, providing mechanistic insights into the mutation-induced conformational changes. Superimposition of native and mutant TBG structures indicated gross conformational collapse, indicating likely misfolding, degradation, and secretion failure of the mutant protein. Conclusion In silico structural analysis indicated that TBG-CD-Ind belongs to the list of convoluted mutations reported in the SERPINA7 gene so far. Recurrent identification of the TBG-CD-Ind mutation in unrelated Indian families, together with its absence from global population databases, indicates potential founder effect-driven enrichment and warrants further population-based studies. Its coexistence with hypothyroidism complicated therapeutic decision-making. Awareness of this rare condition is essential to avoid misinterpretation of TFT, inappropriate dose escalation, and suboptimal management, supporting the inclusion of TBG assessment in routine thyroid evaluation.

Merve Korkmaz Yilmaz, Huseyin Sehit Burhan, Sebnem Burhan et al.

BackgroundCushing’s disease (CD) is characterized by chronic hypercortisolism and is associated with persistent metabolic, psychological, and neurocognitive disturbances. While metabolic consequences are well described, the impact of disease activity and remission on eating behavior remains insufficiently explored.ObjectiveThis study aimed to compare multidimensional eating behavior patterns among patients with active Cushing’s disease, patients in biochemical remission, and healthy controls, and to examine their associations with cortisol biomarkers.MethodsIn this cross-sectional study, 74 participants were enrolled, including patients with active CD (n = 21), patients in remission (n = 32), and age-, sex-, and BMI-matched healthy controls (n = 21). Eating behavior was assessed using validated questionnaires: the Night Eating Questionnaire (NEQ), Emotional Appetite Questionnaire (EMAQ), Three-Factor Eating Questionnaire–Revised 18 (TFEQ-R18), Mindful Eating Questionnaire (MEQ), and Dutch Eating Behavior Questionnaire (DEBQ). Group differences were analyzed using Kruskal–Wallis tests followed by Dunn’s post-hoc comparisons with Bonferroni correction. Associations between eating behavior scores and cortisol parameters were evaluated using Spearman correlation analysis.ResultsActive Cushing’s disease was associated with higher night eating (NEQ; p < 0.001) and greater emotional and situational eating compared with remission and healthy controls (EMAQ total; p < 0.001). Positive emotion and situation subscales were higher in active disease (both p = 0.008), whereas negative total scores differed significantly only between active disease and healthy controls (p = 0.014). Mindful eating was reduced in both patient groups versus controls (MEQ total; p < 0.001), with active disease showing higher disinhibition (p = 0.002), greater interference (p < 0.001), and lower conscious nutrition (p = 0.016). Remission patients demonstrated partial but incomplete behavioral recovery. Late-night salivary cortisol correlated with MEQ interference (r = 0.5, p = 0.01), and cortisol levels after the 1-mg DST correlated with DEBQ emotional eating (r = 0.5, p = 0.01).ConclusionCushing’s disease is associated with marked alterations in eating behavior, particularly during active disease, including increased night eating, emotional susceptibility, and reduced mindful regulation. Although partial improvement occurs after remission, residual behavioral disturbances persist. These findings underscore the importance of integrating behavioral assessment into the long-term management of Cushing’s disease.

Xingquan Zhao, Qian Zhang, Shengyun Chen et al.

Introduction The effects of different glucose metabolic states and diabetes-controlled status on asymptomatic carotid atherosclerosis has not been well investigated. Herein, we aimed to investigate the association of different diabetes status with asymptomatic carotid plaques and carotid intima–media thickness (CIMT).Research design and methods 4752 participants aged over 40 years, free of stroke or myocardial infarction, from the China National Stroke Screen Survey programme were enrolled. Carotid plaque and CIMT were assessed using duplex ultrasonography. Logistic regression analysis was used to assess the relationship between diabetes status and the presence of asymptomatic carotid plaques or abnormal CIMT.Results A total of 1977 (41.6%) subjects had carotid plaques and 804 (16.9%) had abnormal CIMT. In multivariate analyses, compared with normoglycemia, individuals with pre-diabetes showed significantly higher odds of asymptomatic carotid plaques (OR 1.22, 95% CI 1.03 to 1.45) and patients with diabetes also had higher odds (OR 1.66, 95% CI 1.41 to 1.92). Diabetes (OR 1.79, 95% CI 1.50 to 2.14) was associated with vulnerable plaques, while pre-diabetes was not (OR 1.17, 95% CI 0.96 to 1.43). Poorly controlled diabetes (HbA1c ≥7.5%) had higher odds of carotid plaques (OR 1.93, 95% CI 1.53 to 2.44), especially of vulnerable plaques (OR 2.03, 95% CI 1.55 to 2.67). No significant association was found between diabetes and abnormal CIMT.Conclusions Pre-diabetes and diabetes, especially poorly controlled diabetes, were associated with increased odds of asymptomatic carotid plaques. Implementing the most effective strategies to achieve optimal glycemic control is crucial for the prevention and management of atherosclerosis.

Elżbieta Moszczyńska, Marta Baszyńska-Wilk, Aleksandra Tutka et al.

Mo Awchi, Mo Awchi, Kapil Dev Singh et al.

PurposeThis feasibility study aimed to investigate the use of exhaled breath analysis to capture and quantify relative changes of metabolites during resolution of acute diabetic ketoacidosis under insulin and rehydration therapy.MethodsBreath analysis was conducted on 30 patients of which 5 with DKA. They inflated Nalophan bags, and their metabolic content was subsequently interrogated by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS).ResultsSESI-HRMS analysis showed that acetone, pyruvate, and acetoacetate, which are well known to be altered in DKA, were readily detectable in breath of participants with DKA. In addition, a total of 665 mass spectral features were found to significantly correlate with base excess and prompt metabolic trajectories toward an in-control state as they progress toward homeostasis.ConclusionThis study provides proof-of-principle for using exhaled breath analysis in a real ICU setting for DKA monitoring. This non-invasive new technology provides new insights and a more comprehensive overview of the effect of insulin and rehydration during DKA treatment.

Camila Lemos Marques, Mileni Vanti Beretta, Raquel Eccel Prates et al.

ABSTRACT Objectives: Body composition changes are associated with adverse effects such as increased insulin resistance (IR) in individuals with diabetes mellitus. This study aims to evaluate the association between different body adiposity markers and IR in adults with type 1 diabetes (T1D). Subjects and methods: The cross-sectional study included outpatient adults with T1D from a university public hospital in southern Brazil. The body adiposity markers studied were waist circumference (WC), waist-height ratio (WHtR), body mass index (BMI), conicity index (CI), lipid accumulation product (LAP) and body adiposity index (BAI). IR was calculated using an Estimated Glucose Disposal Rate (EGDR) equation (analyzed in tertiles), considering an inverse relation between EGDR and IR. Poisson regression models were used to estimate the odds ratio (OR) and 95% CIs of association of adiposity markers with IR. Results: A total of 128 patients were enrolled (51% women), with a median EGDR of 7.2 (4.4-8.7) mg.kg−1.min−1. EGDR was negatively correlated with WC (r = −0.36, p < 0.01), WHtR (r = −0.39, p < 0.01), CI (r = −0.44, p < 0.01), LAP (r = −0.41, p < 0.01) and BMI (r = −0.24, p < 0.01). After regression analyses, WC (OR = 2.07; CIs: 1.12-3.337; p = 0.003), WHtR (OR = 2.77; CIs: 1.59-4.79; p < 0.001), CI (OR = 2.59; CIs: 1.43-4.66; p = 0.002), LAP (OR = 2.27; CIs: 1.25-4.11; p = 0.007) and BMI (OR = 1.78; CIs: 1.09-2.91; p = 0.019) remained associated with IR. Conclusions: The authors suggest using the studied adiposity markers as a routine since they were shown to be suitable parameters in association with IR.

Ruth Naomi, Rusydatul Nabila Mahmad Rusli, Fezah Othman et al.

Maternal obesity is the key predictor for childhood obesity and neurodevelopmental delay in the offspring. Medicinal plants are considered to be the safe and best option, and at the same time, probiotic consumption during pregnancy provides beneficial effects for both the mother and the child. Current research has shown that Elateriospermum tapos (E. tapos) yoghurt is safe to consume and consists of many bioactive compounds that can exert an anti-obesity effect. Thus, this study has been designed to study the role of E. tapos yoghurt in mitigating maternal obesity. In this study, a total of 48 female Sprague Dawley (SD) rats were assigned to six groups, with eight rats per group, and obesity was induced over 16 weeks with a high-fat diet (HFD) pellet. On the 17th week, the rats were allowed to mate and pregnancy was confirmed through vaginal smear. The obese induced group was further divided into negative and positive control groups, followed by E. tapos yoghurt treatment groups with three different concentrations (5, 50, and 500 mg/kg). The changes in body weight, calorie intake, lipid profile, liver profile, renal profile, and histopathological analysis were measured on postnatal day (PND) 21. The results show that the group with the highest concentration of E. tapos yoghurt (HYT500) supplementation shows gradual reduction in body weight and calorie intake on PND 21 and modulates the lipid level, liver, and renal enzymes to a normal level similar to the normal group. In histological analysis, HYT500 reverses the damage caused by HFD in liver and colon, and reverses the adipocytes’ hypertrophy in retroperitoneal white adipose tissue and visceral fat. In conclusion, supplementation of E. tapos yoghurt during the gestational period up to weaning is effective in the gradual weight loss of maternal obese dams from the 500-mg/kg-supplemented group in this study.

Tianyu Zhou, Yilin Zhou, Dongdong Ge et al.

ObjectiveEleutheroside E (EE) is an anti-inflammatory natural compound derived from the edible medicinal herb Acanthopanax senticosus. This study aims to investigate the underlying mechanism of the anti-osteoporosis action of EE through network pharmacology, molecular docking and gut microbiota.Materials and methodsNetwork pharmacology was used to explore the potential core targets and main pathways mediated by EE in osteoporosis (OP) treatment. Molecular docking was exploited to investigate the interactions between the active anti-OP compounds in EE and the potential downstream targets. Following the multi-approach bioinformatics analysis, ovariectomy (OVX) model was also established to investigate the in vivo anti-OP effects of EE.ResultsThe top 10 core targets in PPI network were TP53, AKT1, JUN, CTNNB1, STAT3, HIF1A, EP300, CREB1, IL1B and ESR1. Molecular docking results that the binding energy of target proteins and the active compounds was approximately between −5.0 and −7.0 kcal/mol, which EE has the lowest docking binding energy with HIF1A. Enrichment analysis of GO and KEGG pathways of target proteins indicated that EE treatment could potentially alter numerous biological processes and cellular pathways. In vivo experiments demonstrated the protective effect of EE treatment against accelerated bone loss, where reduced serum levels of TRAP, CTX, TNF-α, LPS, and IL-6 and increased bone volume and serum levels of P1NP were observed in EE-treated mice. In addition, changes in gut microbiota were spotted by 16S rRNA gene sequencing, showing that EE treatment increased the relative abundance of Lactobacillus and decreased the relative abundance of Clostridiaceae.ConclusionIn summary, these findings suggested that the characteristics of multi-target and multi-pathway of EE against OP. In vivo, EE prevents the onset of OP by regulating gut microbiota and inflammatory response and is therefore a potential OP drug.

Jianhan Fu, Guoqiang Li, Ruixiang Luo et al.

BackgroundEmerging evidence suggests an important role for pyroptosis in tumorigenesis and recurrence, but it remains to be elucidated in prostate cancer (PCa). Considering the low accuracy of common clinical predictors of PCa recurrence, we aimed to develop a novel pyroptosis-related signature to predict the prognosis of PCa patients based on integrative analyses of bulk and single-cell RNA sequencing (RNA-seq) profiling.MethodsThe RNA-seq data of PCa patients was downloaded from several online databases. PCa patients were stratified into two Classes by unsupervised clustering. A novel signature was constructed by Cox and the Least Absolute Shrinkage and Selection Operator (LASSO) regression. The Kaplan-Meier curve was employed to evaluate the prognostic value of this signature and the single sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to analysis tumor-infiltrating immune cells. At single-cell level, we also classified the malignant cells into two Classes and constructed cell developmental trajectories and cell-cell interaction networks. Furthermore, RT-qPCR and immunofluorescence were used to validate the expression of core pyroptosis-related genes.ResultsTwelve prognostic pyroptosis-related genes were identified and used to classify PCa patients into two prognostic Classes. We constructed a signature that identified PCa patients with different risks of recurrence and the risk score was proven to be an independent predictor of the recurrence free survival (RFS). Patients in the high-risk group had a significantly lower RFS (P&lt;0.001). The expression of various immune cells differed between the two Classes. At the single-cell level, we classified the malignant cells into two Classes and described the heterogeneity. In addition, we observed that malignant cells may shift from Class1 to Class2 and thus have a worse prognosis.ConclusionWe have constructed a robust pyroptosis-related signature to predict the RFS of PCa patients and described the heterogeneity of prostate cancer cells in terms of pyroptosis.

Yanni Sun, Yanni Sun, Bo Zhu et al.

ObjectiveTo explore the effect of maternal body mass index (BMI) on steroid hormone profiles in women with gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT).MethodsWe enrolled 79 women with NGT and 80 women with GDM who had a gestational age of 24–28 weeks. The participants were grouped according to their BMI. We quantified 11 steroid hormones profiles by liquid chromatography-tandem mass spectrometry and calculated the product-to-precursor ratios in the steroidogenic pathway.ResultsWomen with GDM and BMI&lt;25kg/m2 showed higher concentrations of dehydroepiandrosterone (DHEA) (p&lt;0.001), testosterone (T) (p=0.020), estrone (E1) (p=0.010) and estradiol (E2) (p=0.040) and lower Matsuda index and HOMA-β than women with NGT and BMI&lt;25kg/m2. In women with GDM, concentrations of E1 (p=0.006) and E2 (p=0.009) declined, accompanied by reduced E2/T (p=0.008) and E1/androstenedione (A4) (p=0.010) in the BMI&gt;25 kg/m2 group, when compared to that in the BMI&lt;25 kg/m2 group. The values of E2/T and E1/A4 were used to evaluate the cytochrome P450 aromatase enzyme activity in the steroidogenic pathway. Both aromatase activities negatively correlated with the maternal BMI and positively correlated with the Matsuda index in women with GDM.ConclusionsNGT women and GDM women with normal weight presented with different steroid hormone profiles. Steroidogenic pathway profiling of sex hormones synthesis showed a significant increase in the production of DHEA, T, E1, and E2 in GDM women with normal weight. Additionally, the alteration of steroid hormone metabolism was related to maternal BMI in women with GDM, and GDM women with overweight showed reduced estrogen production and decreased insulin sensitivity compared with GDM women with normal weight.

S. Y. Rybakov

Chronic insufficiency of the cortical substance of the adrenal glands or hypocorticism until recently belonged to rare forms of endocrine pathology. This included a few cases of Addison’s disease of tuberculous etiology, a relatively small number of patients after bilateral adrenalectomy for Cushing’s disease, removal of bilateral, sometimes unilateral, hormonally active tumors of the cortex and medulla of the adrenal glands. Bilateral adrenalectomy is also practiced for some types of hormone‑dependent tumors of the mammary glands, ovaries, prostate, and malignant hypertension. The evolution of ideas about the pathophysiology of adrenal glands contributed to a significant expansion and increase in the number of patients suffering from hypocorticism. A decrease in the incidence of tuberculosis contributed to a decrease in the number of patients with classic Addison’s disease. However, an increasing number of patients with hypocorticism of autoimmune, genetically determined and other genesis are currently being discovered. The improvement of diagnostic methods contributes to the increase in the number of operations for adrenal glands tumors and, accordingly, the number of cases of post‑adrenalectomy hypocorticism. Operations on the pituitary gland for various types of tumors, the number of which is steadily increasing, also contribute to the increase in the number of cases of hypothyroidism. In the mid‑70s of the XX century. a new direction in the treatment of various forms of endocrine insufficiency by the method of transplanting cultures of cells and tissues of endocrine glands took shape. Disorders of the endocrine glands seem to be particularly suitable for the transplantation method of treatment, since it is expected that living and functionally active donor endocrine tissue, transplanted into a patient with endocrine insufficiency, will secrete hormones and provide the body’s physiological needs and clinical compensation of the insufficiency. Similar experimental studies have been conducted since the beginning of the 20th century. The methods of obtaining cultures of cells and tissues of various endocrine organs were developed in detail, the issue of their viability, morphological and hormonal characteristics, and the possibility of compensation of certain forms of endocrine insufficiency were studied.&#x0D;

He Tai, He Tai, Xiao-lin Jiang et al.

To assess the variations in pulmonary function and vascular endothelial function in their early stages (without related complications). A total of 162 type 2 diabetes mellitus (T2DM) patients without diabetes complications and 55 healthy people were selected, comprising the T2DM group and the control group, respectively, to evaluate changes in vascular endothelial function and lung function and determine the correlation between them. In this study, the T2DM group exhibited significantly lower pulmonary function than that of the control group (P &lt; 0.05). The T2DM group also showed significantly lower flow-mediated dilation (FMD) and nitric oxide (NO) (P &lt; 0.05) than those of the control group. Pulmonary functional indexes correlated positively with FMD and NO (P &lt; 0.05) and correlated negatively with endothelin-1 (ET-1) (P &lt; 0.05). FMD and NO correlated negatively with diabetes duration/HbA1c (P &lt; 0.05), whereas ET-1 correlated positively with glycosylated hemoglobinA1c (HbA1c)/diabetes duration (P &lt; 0.05). Pulmonary functional indexes negatively correlated with HbA1c/diabetes duration (P &lt; 0.05). Multiple linear regression was used to analyze the relationship between vascular endothelial function indexes (FMD, ET-1, and NO) and pulmonary functional indexes. The results indicated that each vascular endothelial function index (FMD, ET-1, and NO) was significantly correlated with the pulmonary functional index (P &lt; 0.05). The patients with T2DM presented changes in the subclinical vascular endothelial and pulmonary function. They also had impaired vascular endothelial functions, which were characterized by reduced vascular endothelial function relative to those of healthy people. Regulating glycemia may improve vascular endothelial and pulmonary functions. Moreover, microvascular lesions in preclinical stages, vascular endothelial function indexes (FMD, ET-1, and NO) were valid predictors of alterations in pulmonary function in T2DM patients without related complications.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03575988.

Merve İşeri Nepesov, Eylem Kıral, Gürkan Bozan et al.

Brain abscess formation is extremely rare in patients with osteopetrosis. Herein, we report a case of viridans streptococci brain abscess in an immunocompromised child diagnosed with osteopetrosis. The patient presented with a sudden change in mental status and convulsions. Radiological evaluation revealed a temporal lobe brain abscess, and intravenous antibiotherapy was started immediately. The patient underwent abscess drainage, and laboratory investigation of pus material revealed viridans streptococci.

Katarzyna Wyskida, Grzegorz Franik, Piotr Choręza et al.

Objective. The aim of the study was to assess PTX3 levels in PCOS and non-PCOS women in relation to nutritional status and circulating markers of inflammation. Methods. The study enrolled 99 stable body mass PCOS women (17 normal weight, 21 overweight, and 61 obese) and 61 non-PCOS women (24 normal weight, 19 overweight, and 18 obese). Body composition was assessed by bioimpedance, and plasma levels of pentraxin 3 (PTX3), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein 1 (MCP-1) were measured. Homeostatic model assessment of insulin resistance (HOMA-IR) was made. Results. Plasma PTX3, TNF-α, and IL-6 levels and HOMA-IR were higher in PCOS than in non-PCOS group p<0.001. There were positive correlations between log10 (PTX3) and log10 (BMI), waist circumference and fat percentage, as well as log10 (HOMA-IR) and free androgen index but negative between log10 (estradiol) levels in PCOS. While in the non-PCOS group, the correlations between log10 (PTX3) and log10 (BMI), waist circumference and fat percentage, as well as log10 (HOMA-IR) were negative. The positive correlations between PTX3 and MPC-1 and log10 (IL-6) were shown in the PCOS group only. In multivariate regression analyses, variability in PTX3 levels in the PCOS group was proportional to log10 (BMI), waist circumference, and fat percentage, but inversely proportional to log10 (estradiol) levels. While in the non-PCOS group, PTX3 levels were inversely proportional to all anthropometric parameters. Conclusions. Our results show that the decrease in PTX3 levels observed in obese is distorted in PCOS by microinflammation, and possibly, dysfunction of stroma adipose tissue and liver steatosis is reflected by enhanced insulin resistance.

Lucia Pacifico, Francesco Massimo Perla, Luciana Tromba et al.

Background: Emerging evidence suggests that structural adventitial modifications and perivascular adipose tissue (PAT) may have a role in early atherogenesis. In a cohort of children and adolescents, we explored (1) the association of carotid extra-media thickness (cEMT), an ultrasound measure whose main determinants are arterial adventitia and PAT, with obesity and its cardiometabolic complications; and (2) the interplay between cEMT and endothelial function.Methods: The study participants included 286 youths (age, 6–16 years; 154 boys, and 132 girls). Anthropometric and laboratory parameters, liver ultrasound, vascular structure measures [cEMT and carotid intima-media thickness (cIMT)], endothelial function [brachial artery flow-mediated dilation (FMD)] were obtained in all subjects. Non-alcoholic fatty liver disease (NAFLD) was diagnosed in the presence of hepatic fat on ultrasonography, in the absence of other causes of liver disease. Diagnosis of metabolic syndrome (MetS) was established on the basis of three or more of the following cardiovascular disease (CVD) risk variables: abdominal obesity, high triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure (BP), and impaired fasting glucose.Results: cEMT demonstrated significant associations with body-mass index (BMI) and waist circumference (WC), BP, insulin resistance, NAFLD, and inflammation. No association was found between cEMT and lipid values, and between cEMT and MetS. A stepwise multivariate linear regression analysis indicated that WC (β coefficient, 0.35; P &lt; 0.0001) was the only determinant of cEMT, independently of other major cardiometabolic risk factors. Further adjustment for cIMT did not significantly alter this association. FMD was correlated to age, Tanner stage, total and abdominal obesity, BP, NAFLD, and cEMT. The association between FMD and cEMT was independent of age, sex, Tanner stage, WC, and BMI (β coefficient, −0.14; P = 0.027). After controlling for CVD risk factors and basal brachial artery diameter, cEMT remained associated with FMD (β coefficient, −0.11; P = 0.049).Conclusions: In youths, cEMT is associated with abdominal fat, a well-established body fat depot with important implications for cardiovascular diseases. Furthermore, cEMT is related to FMD, suggesting that arterial adventitia and PAT may be involved in the early changes in endothelial function.

Joy Yaplito‐Lee, Gautham Pai, Winita Hardikar et al.

Abstract Lathosterolosis is a rare autosomal recessive disorder of cholesterol biosynthesis. It is caused by defects in the SC5D (sterol C5‐desaturase) gene which encodes for the 3‐beta‐hydroxysteroid‐delta‐5‐desaturase (also called sterol‐C5‐desaturase or lathosterol dehydrogenase). Only six cases have been described in the literature, but it is possible that a number of patients with milder forms of the condition might have been missed. Lathosterolosis manifests as microcephaly, bilateral cataracts, dysmorphism, limb anomalies, and developmental delay/intellectual disability. Liver involvement is variable and can range from normal liver function tests to portal fibrosis and cirrhosis. Diagnosis is made by demonstration of specific mutations in the SC5D gene and by plasma sterol analysis to confirm elevated lathosterol levels. In this report, we describe a girl with transaminitis in association with developmental delay/intellectual disability, facial dysmorphism, limb anomalies, and bilateral cataracts. Fibroscan showed severe liver fibrosis. Plasma sterol analysis and exome sequencing confirmed the diagnosis of lathosterolosis. Simvastatin treatment resulted in lowering of plasma lathosterol levels, improvement in transaminitis, and liver fibrosis grade, suggesting that children with this condition should be actively treated in order to prevent progression of liver disease.

Ruiyang Pu, Dian Shi, Ting Gan et al.

Objective: Some studies have shown that metformin can reduce body weight. However, metformin has not been officially approved as a medicine for weight loss because its effect on different populations remains inconsistent. This meta-analysis aimed to summarize the weight loss effect of metformin quantitatively. Method: The randomized controlled and high-quality case-control trials of metformin monotherapy in obesity treatment were eligible. Baseline body mass index (BMI) was chosen as a self-control to compare the changes in BMI of different populations before and after treatment. All changes were calculated as differences between the final and initial BMI values (with negative values indicating a decrease). Results were presented as weighted mean difference (WMD) with a 95% confidence interval (CI 95%). Subgroup analysis was performed based on baseline BMI, age, daily dose, and duration of medication. Results: A total of 21 trials ( n  = 1004) were included, and the meta-analysis of metformin treatment in different populations showed that metformin has a modest reduction in the BMI of included participants (WMD −0.98; 95% CI, −1.25 to −0.72), and the reduction of BMI was most significant in the simple obesity population (WMD −1.31; 95% CI, −2.07 to −0.54). The subgroup analysis showed that metformin treatment significantly reduced BMI in obesity patients with a BMI >35kg/m 2 (WMD −1.12; 95% CI, −1.84 to −0.39) compared with before treatment. BMI in the high dose group decreased by 1.01 units (WMD−1.01; 95% CI, −1.29 to −0.73) and BMI did not continue to decrease significantly after treatment of more than 6 months. Conclusion: Patients treated with metformin experienced about a one-unit reduction in BMI at the end of treatment. But whether this decreased value produced enough weight loss (5% of baseline body weight) to qualify as a “weight loss drug” as current guidelines require, requires larger specific randomized control trials.

Graham P. Leese

Abstract The new NICE guidelines on thyroid disease and its management do not recommend the routine use of liothyronine, but do not completely rule it out either. Guidelines from the British and European Thyroid Associations are open to a “trial of liothyronine” on an individual basis. Some patients do not feel well on L-thyroxine despite a serum TSH in the reference range. Key issues to consider in such patients include establishing whether the patient had established hypothyroidism initially, and whether the L-thyroxine has been titrated carefully enough, possibly using small increments, to achieve a careful balance between symptoms and serum TSH concentrations. Patients should also be considered for other causes of the symptoms which may be wide-ranging. Meta-analyses of several, but small, randomised control trials show no advantage, or disadvantage of liothyronine over L-thyroxine. However, detailed sub-analysis identifies some tantalising results eg on preferential weight loss, patient preference, and possibly genetic markers. Although linked with plausible theoretical explanations, these results may be over-interpreted. The key questions are whether a short-term trial treatment is worthwhile and safe, and whether in the future sub-groups of patients can be identified who may benefit from liothyronine. These questions remain divisive but require additional focussed research. It could be argued that inflated costs of liothyronine in some countries have either distracted from or helped focus on the science. Costs need to be addressed. However better biomarkers of tissue level thyroid action, and a better understanding of the impact of genetic polymorphisms will help to make progress when choosing if there is a place for liothyronine in the future. (words: 262)

Sonia Sifuentes-Franco, Diego Enrique Padilla-Tejeda, Sandra Carrillo-Ibarra et al.

Diabetic nephropathy (DN) is the second most frequent and prevalent complication of diabetes mellitus (DM). The increase in the production of oxidative stress (OS) is induced by the persistent hyperglycemic state capable of producing oxidative damage to the macromolecules (lipids, carbohydrates, proteins, and nucleic acids). OS favors the production of oxidative damage to the histones of the double-chain DNA and affects expression of the DNA repairer enzyme which leads to cell death from apoptosis. The chronic hyperglycemic state unchains an increase in advanced glycation end-products (AGE) that interact through the cellular receptors to favor activation of the transcription factor NF-κB and the protein kinase C (PKC) system, leading to the appearance of inflammation, growth, and augmentation of synthesis of the extracellular matrix (ECM) in DN. The reactive oxygen species (ROS) play an important role in the pathogenesis of diabetic complications because the production of ROS increases during the persistent hyperglycemia. The primary source of the excessive production of ROS is the mitochondria with the capacity to exceed production of endogenous antioxidants. Due to the fact that the mechanisms involved in the development of DN have not been fully clarified, there are different approaches to specific therapeutic targets or adjuvant management alternatives in the control of glycemia in DN.

V.A. Maslianko

The objective — to establish the incidence of diabetic nephropathy (DN) depending on duration of type 1 diabetes mellitus (DM), and also the content of cystatin С as a marker of early kidney damage. Materials and methods. Twenty eight patients with type 1 DM were enrolled in prospective study (11 men and 17 women aged 34.8 ± 7.2 years). Clinical and functional examination included the standard evaluation of renal function, and also the study of serum level of cystatin С. Results. In 17 out of 28 patients, the indexes of glomerular filtration rate calculated using the formulas of CKD-ЕРIcreat and CKD-ЕРIcys, indicated the different stages of chronic kidneys disease. Conclusions. Determination of cystatin C level and calculation of glomerular filtration rate using this index allows diagnosing the preclinical stages of kidney dysfunction in patients with type 1 DM in the normal creatinine level in the blood and without decline in glomerular filtration rate calculated using creatinine value. According to a retrospective study, the incidence and severity of DN in patients with type 1 DM increases with disease duration of more than 10 years.