Publications by authors named "Rasa Verkauskiene"

44 Publications

Kinetics of C-peptide during mixed meal test and its value for treatment optimization in monogenic diabetes patients.

Diabetes Res Clin Pract 2021 Aug 1;178:108938. Epub 2021 Jul 1.

Pediatric Endocrine and Diabetes Unit, Department of Pediatrics, Gynecology and Obstetrics, University Hospitals of Geneva, 1211 Geneva, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.

Aim: The mixed meal tolerance test (MMTT) is a gold standard for evaluating beta-cell function. There is limited data on MMTT in monogenic diabetes (MD). Therefore, we aimed to analyze plasma C-peptide (CP) kinetics during MMTT in young MODY and neonatal diabetes patients as a biomarker for beta-cell function.

Methods: We included 41 patients with MD diagnosis (22 GCK, 8 HNF1A, 3 HNF4A, 4 KCNJ11, 2 ABCC8, 1 INS, 1 KLF11). Standardized 3-hour MMTT with glycemia and plasma CP measurements were performed for all individuals. Pancreatic beta-cell response was assessed by the area under the curve CP (AUC), the baseline CP (CP) and the peak CP (CP). Threshold points of CP, CP, CP and CP were determined from analysis of ROC curves.

Results: GCK diabetes patients had significantly higher AUC, CP and CP compared to HNF4A and KCNJ11 patients. In HNF4A, KCNJ11 and ABCC8 patients with all CP levels < 200 pmol/L, the treatment change attempt to sulfonylurea agent was unsuccessful. The ROC analysis showed that CP baseline threshold equal or higher to 133.5 pmol/L could be used to predict successful switch to oral agents.

Conclusion: A pretreatment challenge with MMTT might be used to guide the optimal treatment after molecular diagnosis of MD.
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http://dx.doi.org/10.1016/j.diabres.2021.108938DOI Listing
August 2021

Prevalence of Metabolic Syndrome and Impaired Glucose Metabolism among 10- to 17-Year-Old Overweight and Obese Lithuanian Children and Adolescents.

Obes Facts 2021 5;14(3):271-282. Epub 2021 May 5.

Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Background: Overweight (Ow) and obesity among adults and children increases the risk of metabolic consequences. Metabolic syndrome (MS) and impaired glucose metabolism are well-known risk factors for cardiovascular diseases and type 2 diabetes. The aim of this study was to evaluate the prevalence of MS and impaired glucose metabolism among Ow and obese (Ob) children and adolescents (aged 10-17 years) in Lithuania, and to evaluate the associations between insulin resistance (IR) indices and anthropometric parameters as well as metabolic disturbances.

Methods: The study population consisted of 344 OwOb children and adolescents of all pubertal stages. Oral glucose tolerance tests (OGTTs), IR and β cell function indices, lipid profile, and anthropometric parameters of all subjects were analyzed. MS was defined according to the International Diabetes Federation consensus guidelines.

Results: MS was found in 21.3% of the OwOb children and adolescents, and 12.1% had impaired glucose metabolism (6.9% with impaired fasting glucose, 4.5% with impaired glucose tolerance, and 0.6% with type 2 diabetes). IR was directly related to body mass index and waist circumference, waist-to-height and waist-to-hip ratios, and sum of skin-fold thicknesses. Children with MS were more insulin-resistant, had higher odds ratio for prediabetes and had a more disturbed lipid profile than subjects without MS. Moreover, total cholesterol and low-density lipoprotein cholesterol levels were significantly lower in the more mature OwOb adolescents.

Conclusion: MS and lipid profile disturbances are common in OwOb children and adolescents. MS is directly associated with IR. Therefore, OwOb children and adolescents should be carefully followed up for metabolic abnormalities during late childhood as these can persist into adulthood.
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http://dx.doi.org/10.1159/000514720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255643PMC
May 2021

Papillary Thyroid Carcinoma Tissue miR-146b, -21, -221, -222, -181b Expression in Relation with Clinicopathological Features.

Diagnostics (Basel) 2021 Mar 2;11(3). Epub 2021 Mar 2.

Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania.

We analyzed miR-146b, miR-21, miR-221, miR-21, and miR-181b in formalin fixed paraffin-embedded papillary thyroid carcinoma (PTC) tissue samples of 312 individuals and evaluated their expression relationship with clinicopathological parameters. A higher expression of miR-21 was related to unifocal lesions ( < 0.011) and autoimmune thyroiditis (0.007). miR-221, miR-222 expression was higher in the PTC tissue samples with extrathyroidal extension ( = 0.049, 0.003, respectively). In a group of PTC patients with pT1a and pT1b sized tumors, the expression of miR-146b, miR-21, miR-221, and miR-222 in PTC tissue samples was lower than in patients with pT2, pT3, and pT4 ( = 0.032; 0.0044; 0.003; 0.001; 0.001, respectively). Patients with lymph node metastases had higher expression of miR-21, -221, -222, and -181b ( < 0.05). A high expression of miR-146b, miR-21, miR-221 panel was associated with decreased overall survival (OS) (Log rank = 0.019). Univariate analysis revealed that presence of metastatic lymph nodes and high expression of miR-146b, miR-21, and miR-221 panels were associated with increased hazard of shorter OS. After multivariate analysis, only sex (male) and age (≥55 years) emerged as independent prognostic factors associated with shorter OS (HR 0.28 (95% CI 0.09-0.86) and HR 0.05 (95% CI 0.01-0.22), respectively). In conclusion, 5 analyzed miRs expression have significant relations to clinicopathologic parameters so further investigations of these molecules are expedient while searching for prognostic PTC biomarkers.
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http://dx.doi.org/10.3390/diagnostics11030418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001862PMC
March 2021

ESE audit on management of Adult Growth Hormone Deficiency in clinical practice.

Eur J Endocrinol 2020 Dec 1. Epub 2020 Dec 1.

T Kocjan, Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre, Ljubljana, Slovenia.

Guidelines recommend adults with pituitary disease in whom GH therapy is contemplated, to be tested for GH deficiency (AGHD); however, clinical practice is not uniform.

Aims: 1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; 2) To evaluate educational status of healthcare professionals about AGHD.

Design: On-line survey in endocrine centres throughout Europe.

Patients And Methods: Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017-2018.

Results: Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital mid-line malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine, 45%; insulin-tolerance, 42%, glucagon, 6%; GHRH alone and clonidine tests, 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved.

Conclusion: Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimize care of adults with GHD.
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http://dx.doi.org/10.1530/EJE-20-1180DOI Listing
December 2020

Association between symptoms of depression, diabetes complications and vascular risk factors in four European cohorts of individuals with type 1 diabetes - InterDiane Consortium.

Diabetes Res Clin Pract 2020 Dec 13;170:108495. Epub 2020 Oct 13.

Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Abdominal Center, Nephrology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Finland. Electronic address:

Aims: To investigate the association between depressive symptomatology and health markers in type 1 diabetes.

Methods: Four countries from the InterDiane Consortium had adopted the Finnish Diabetic Nephropathy Study protocol, including the Beck Depression Inventory (BDI). Associations between depression symptomatology, diabetes complications (diabetic nephropathy, proliferative retinopathy, major adverse cardiovascular events [MACE]) and vascular risk factors (metabolic syndrome, body mass index, glycaemic control) were investigated.

Results: In a sample of 1046 participants (Croatia n = 99; Finland n = 314; Latvia n = 315; Lithuania n = 318), 13.4% displayed symptoms of depression (BDI score ≥ 16) with no statistically significant difference in the prevalence of depression among the cohorts. The highest rates of diabetic nephropathy (37.1%) and proliferative retinopathy (36.3%) were observed in Lithuania. The rates of MACE and metabolic syndrome were highest in Finland. In joint analyses, individuals exhibiting depression symptomatology had higher HbA (79 vs. 72 mmol/mol, p < 0.001) and higher triglyceride concentration (1.67 vs. 1.28 mmol/l, p < 0.001), than those without. In the multivariable model, BDI score was positively associated with the presence of diabetic nephropathy, proliferative retinopathy, MACE, and metabolic syndrome and its triglyceride component. Moreover, BDI score was positively associated with the number of metabolic syndrome components, triglyceride concentration, and HbA.

Conclusions: Comorbid depression should be considered a relevant factor explaining metabolic problems and vascular outcomes. Causality cannot be inferred from this cross-sectional study.
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http://dx.doi.org/10.1016/j.diabres.2020.108495DOI Listing
December 2020

Plasma-Derived miRNA-222 as a Candidate Marker for Papillary Thyroid Cancer.

Int J Mol Sci 2020 Sep 3;21(17). Epub 2020 Sep 3.

Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania.

We analyzed five miRNA molecules (miR-221; miR-222; miR-146b; miR-21; miR-181b) in the plasma of patients with papillary thyroid cancer (PTC), nodular goiter (NG) and healthy controls (HC) and evaluated their diagnostic value for differentiation of PTC from NG and HC. Preoperative PTC plasma miRNA expression ( = 49) was compared with plasma miRNA in the HC group ( = 57) and patients with NG ( = 23). It was demonstrated that miR-221; miR-222; miR-146b; miR-21 and miR-181b were overexpressed in preoperative PTC plasma samples compared to HC ( < 0.0001; < 0.0001; < 0.0001; < 0.0001; < 0.002; respectively). The upregulation in tumor tissue of these miRNAs was consistent with The Cancer Genome Atlas Thyroid Carcinoma dataset. A significant decrease in miR-21; miR-221; miR-146b and miR-181b expression was observed in the plasma of PTC patients after total thyroidectomy ( = 0.004; = 0.001; = 0.03; = 0.036; respectively). The levels of miR-222 were significantly higher in the preoperative PTC compared to the NG group ( = 0.004). ROC curve (receiver operating characteristic curve) analysis revealed miR-222 as a potential marker in distinguishing PTC from NG (AUC 0.711; = 0.004). In conclusion; circulating miR-222 profiles might be useful in discriminating PTC from NG.
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http://dx.doi.org/10.3390/ijms21176445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503340PMC
September 2020

Association of MicroRNA Expression and BRAF Mutation with Recurrence of Thyroid Cancer.

Biomolecules 2020 04 17;10(4). Epub 2020 Apr 17.

Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, LT-50161 Eiveniu str. 2, Kaunas, Lithuania.

Many miRNAs and cancer-related mutations have been proposed as promising molecular markers of papillary thyroid carcinoma (PTC). However, there are limited data on the correlation between miRNA expression, BRAF mutation, and PTC recurrence. Therefore, to evaluate the potential of BRAF mutation and five selected miRNAs (-146b, -222, -21, -221, -181b) in predicting PTC recurrence, these molecular markers were analyzed in 400 formalin-fixed, paraffin-embedded PTC tissue specimens. The expression levels of miRNAs were measured using qRT-PCR. It was demonstrated that expression levels of all analyzed miRNAs are significantly higher in recurrent PTC than in non-recurrent PTC ( < 0.05). Moreover, higher expression levels of miR-146b, miR-222, miR-21, and miR-221 were associated with other clinicopathologic features of PTC, such as tumor size and lymph node metastases at initial surgery ( < 0.05). No significant differences in the frequency of BRAF mutation in recurrent PTC and non-recurrent PTC were determined. Our results suggest that miRNA expression profile differs in PTC that is prone to recurrence when compared to PTC that does not reoccur after the initial surgery while BRAF mutation frequency does not reflect the PTC recurrence status. However, the prognostic value of the analyzed miRNAs is rather limited in individual cases as the pattern of miRNA expression is highly overlapping between recurrent and non-recurrent PTC.
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http://dx.doi.org/10.3390/biom10040625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226510PMC
April 2020

Systematic Genetic Study of Youth With Diabetes in a Single Country Reveals the Prevalence of Diabetes Subtypes, Novel Candidate Genes, and Response to Precision Therapy.

Diabetes 2020 05 21;69(5):1065-1071. Epub 2020 Feb 21.

Pediatric Endocrine and Diabetes Unit, Department of Pediatrics, Gynecology and Obstetrics, University Hospitals of Geneva, Geneva, Switzerland

Identifying gene variants causing monogenic diabetes (MD) increases understanding of disease etiology and allows for implementation of precision therapy to improve metabolic control and quality of life. Here, we aimed to assess the prevalence of MD in youth with diabetes in Lithuania, uncover potential diabetes-related gene variants, and prospectively introduce precision treatment. First, we assessed all pediatric and most young-adult patients with diabetes in Lithuania ( = 1,209) for diabetes-related autoimmune antibodies. We then screened all antibody-negative patients ( = 153) using targeted high-throughput sequencing of >300 potential candidate genes. In this group, 40.7% had MD, with the highest percentage (100%) in infants (diagnosis at ages 0-12 months), followed by those diagnosed at ages >1-18 years (40.3%) and >18-25 years (22.2%). The overall prevalence of MD in youth with diabetes in Lithuania was 3.5% (1.9% for diabetes, 0.7% for , 0.2% for and , 0.3% for , and 0.1% for ). Furthermore, we identified likely pathogenic variants in 11 additional genes. Microvascular complications were present in 26% of those with MD. Prospective treatment change was successful in >50% of eligible candidates, with C-peptide >252 pmol/L emerging as the best prognostic factor.
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http://dx.doi.org/10.2337/db19-0974DOI Listing
May 2020

Sex Hormones, Gonad Size, and Metabolic Profile in Adolescent Girls Born Small for Gestational Age with Catch-up Growth.

J Pediatr Adolesc Gynecol 2020 Apr 7;33(2):125-132. Epub 2019 Nov 7.

Department of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania; Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Study Objective: To characterize and compare sex hormone concentrations, and uterine and ovarian volumes in adolescent girls born small for gestational age (SGA) who had experienced catch-up growth and girls born at a size appropriate for gestational age (AGA), and to investigate the association between these parameters and glucose metabolism, perinatal factors, and early growth.

Design: A prospective, longitudinal, observational study from birth until adolescence.

Setting: Mean age at final assessment was 12.7 ± 0.1 years.

Participants: We followed 55 girls (20 SGA, 35 AGA).

Interventions And Main Outcome Measures: Sex hormone concentrations (gonadotropins, estradiol, testosterone, and sex hormone binding globulin) were analyzed, and the oral glucose tolerance test conducted. Uterine and ovarian sizes were assessed using pelvic ultrasound.

Results: Uterine and ovarian volumes were smaller in SGA-born compared with AGA-born girls (P = .013 and P = .039, respectively). SGA girls had lower sex hormone binding globulin levels (P = .039) and higher testosterone levels (P = .003), free androgen index (P < .001), and glycemia 2 hours post glucose load (P = .005) compared with AGA-born girls. Birth weight and early infancy height velocity explained 37.4% of variation in ovarian volume (P = .004), and body mass index at birth, increase in peripheral skinfold thickness during second year of life, and early childhood height velocity explained 43.2% of variation in testosterone levels in adolescence (P = .006).

Conclusion: SGA-born girls who experienced catch-up growth remain at risk of biochemical hyperandrogenism in adolescence, and have reduced uterine and ovarian volumes, which might influence future reproductive function. Ovarian size and androgen levels in adolescence might be influenced by early growth and subcutaneous fat deposition.
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http://dx.doi.org/10.1016/j.jpag.2019.11.001DOI Listing
April 2020

Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen.

J Am Soc Nephrol 2019 10 19;30(10):2000-2016. Epub 2019 Sep 19.

Department of Biostatistics and.

Background: Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown.

Methods: To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function.

Results: Our GWAS meta-analysis included association results for up to 19,406 individuals of European descent with type 1 diabetes. We identified 16 genome-wide significant risk loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain ( gene, which encodes a major structural component of the glomerular basement membrane (GBM). Mutations in are implicated in heritable nephropathies, including the progressive inherited nephropathy Alport syndrome. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of diabetic kidney disease, including albuminuria and ESKD, and demonstrated a significant association with GBM width; protective allele carriers had thinner GBM before any signs of kidney disease, and its effect was dependent on glycemia. Three other loci are in or near genes with known or suggestive involvement in this condition ( or renal biology ( and ).

Conclusions: The 16 diabetic kidney disease-associated loci may provide novel insights into the pathogenesis of this condition and help identify potential biologic targets for prevention and treatment.
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http://dx.doi.org/10.1681/ASN.2019030218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779358PMC
October 2019

Relationship between Echocardiographic and Magnetic Resonance-Derived Measurements of the Thoracic Aorta in Turner Syndrome Patients.

Int J Endocrinol 2019 20;2019:9258726. Epub 2019 Aug 20.

Lithuanian University of Health Sciences, Department of Endocrinology, Medical Academy, Kaunas, Lithuania.

Introduction: Turner syndrome (TS) is assigned to the rare diseases group. Morbidity and mortality of TS patients are high, particularly due to the cardiovascular disorders, so monitoring for cardiovascular complications must be ensured. The data demonstrate a strong correlation between 2-dimensional echocardiographic (2Decho) evaluation and magnetic resonance imaging (MRI); still, according to recent guidelines, MRI remains a gold standard. In this study, we aimed to compare aortic dimensions on MRI and 2Decho in TS patients.

Methods: 50 TS patients (≥18 years) were enrolled into the cross-sectional study. 2Decho and MRI were performed. The measurements of the aorta were assessed in five standard positions on 2Decho and in 9 standard positions on MRI; ASI (aortic size index) of the ascending aorta was calculated since reduced adult height is observed in TS patients.

Results: ASI on echocardiography strongly correlated with ASI on MRI in all positions of the ascending aorta, but significantly larger medians of ASI were found on 2Decho in all positions of the ascending aorta and arch when compared with MRI measurements. Still, the prevalence of aortic sinus dilation was significantly and more frequently (52% vs. 38%, < 0.001) observed on MRI when compared with 2Decho.

Conclusion: The relation of aortic size was significant in all positions when comparing the MRI and 2Decho methods; still, the dilatation of the sinus of aorta was more frequently found on MRI compared with echocardiography.
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http://dx.doi.org/10.1155/2019/9258726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721444PMC
August 2019

Factors Affecting Cardiovascular Risk in Children, Adolescents, and Young Adults with Type 1 Diabetes.

J Diabetes Res 2019 16;2019:9134280. Epub 2019 May 16.

Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Cardiovascular risk and obesity are becoming major health issues among individuals with type 1 diabetes (T1D). The aim of this study was to evaluate cardiovascular risk factors and obesity in youth with T1D in Lithuania. . 883 patients under 25 years of age with T1D for at least 6 months were investigated. Anthropometric parameters, blood pressure, and microvascular complications were evaluated, and the lipid profile and HbA1c were determined for all patients. . Study subjects' mean HbA1c was 8.5 ± 2%; 19.5% were overweight and 3.6% obese. Hypertension and dyslipidemia were diagnosed in 29.8% and 62.6% of participants, respectively. HbA1c concentration was directly related to levels of total cholesterol ( = 0.274, < 0.001), LDL ( = 0.271, < 0.001), and triglycerides ( = 0.407, < 0.001) and inversely associated with levels of HDL ( = 0.117, = 0.001). Prevalence of dyslipidemia increased with duration of diabetes ( < 0.05). Hypertension was more prevalent in overweight and obese compared to normal-weight patients (40.6 and 65.6 vs. 25.6%, respectively, < 0.001). Frequency of microvascular complications was higher among patients with dyslipidemia (27.2 vs. 18.8%, = 0.005) and among those with hypertension (25.9 vs. 23.2%, < 0.001). . The frequency of cardiovascular risk factors is high in youth with T1D and associated with diabetes duration, obesity, and metabolic control.
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http://dx.doi.org/10.1155/2019/9134280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541948PMC
February 2020

Adrenal Function in Adolescence is Related to Intrauterine and Postnatal Growth.

Medicina (Kaunas) 2019 May 20;55(5). Epub 2019 May 20.

Department of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania.

Intrauterine growth restriction is thought to be implicated in long-term programming of hypothalamic-pituitary-adrenal axis activity. We investigated adrenal function in adolescents born small for gestational age (SGA) in relation to their postnatal growth and cardiovascular parameters. Anthropometric parameters, blood pressure, heart rate, dehydroepiandrosterone sulfate (DHEAS), and cortisol levels were assessed in 102 adolescents aged 11-14 years followed from birth (47 SGA and 55 born appropriate for gestational age (AGA)). Mean DHEAS levels were higher in SGA adolescents with catch-up growth (SGA), compared with AGA. Second-year height velocity and body mass index (BMI) gain during preschool years were positively related to DHEAS levels. Morning cortisol levels and systolic and diastolic blood pressure were higher in SGA adolescents without catch-up growth (SGA) compared with AGA. Second-year BMI gain was inversely, and 2-12 years increase in subscapular skinfold thickness was directly associated with cortisol levels. Size at birth and postnatal growth explained 47.8% and 38.2% of variation in DHEAS and cortisol levels, respectively. Adrenal function in adolescence is affected by prenatal and postnatal growth: small size at birth with postnatal catch-up growth is related to higher DHEAS secretion, whereas increased cortisol levels and blood pressure are higher in short SGA adolescents.
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http://dx.doi.org/10.3390/medicina55050167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571974PMC
May 2019

The main predictors of the enlargement of ascending aorta in Turner syndrome: a cross-sectional contrast-enhanced magnetic resonance angiography study.

Minerva Endocrinol 2019 Jun 1;44(2):185-191. Epub 2018 Oct 1.

Department of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Background: The aim of this study was to identify the main predictors of the enlargement of ascending aorta and to assess the possible relation between reduced bone mineral density and a diameter of ascending aorta in the specific Turner syndrome (TS) population.

Methods: Fifty adult females diagnosed with TS have been enrolled into the cross-sectional study. Dimensions of ascending aorta have been measured in four positions using thoracic magnetic resonance imaging, Aortic Size Index (ASI) has been calculated. BMD has been assessed on dual-energy-X ray absorptiometry (DXA) in 1-4 lumbar vertebrae and neck of the femur. According to Z Score on DXA two groups have been formed: a group of patients with normal BMD and a group with reduced BMD. Metabolic parameters and the measurements of ascending aorta have been compared between the two groups.

Results: Extremely high rate of the dilatation of the root of aorta (up to 50%) was identified in this study. The larger ASI has been found in patients with reduced BMD, negative relation between BMD and ASI has been identified, although after the adjustment for SHRT this correlation remained insignificant. In the multivariate analysis, the main factors affecting ASI were age, body surface area and bicuspid aortic valve.

Conclusions: The main factors associated with the enlargement of ascending aorta in Turner syndrome were age, body surface area and bicuspid aortic valve, the relation between diameter of ascending aorta and bone mineral density was not identified.
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http://dx.doi.org/10.23736/S0391-1977.18.02818-3DOI Listing
June 2019

The impact of FSH receptor polymorphism on time-to-pregnancy: a cross-sectional single-centre study.

BMC Pregnancy Childbirth 2018 Jun 28;18(1):272. Epub 2018 Jun 28.

Center of Reproductive Medicine and Andrology, University of Münster, 48149Münster, Münster, Germany.

Background: Single nucleotide polymorphism of the follicle-stimulating hormone (FSH) receptor (FSHR) is an important marker of ovarian function. However, its role in female fecundity remains debatable. The aim of the study to assess the relationship of FSHR polymorphism of Serine/Serine, Asparagine/Asparagine and Asparagine/Serine variants directly against the time-to-pregnancy (TTP) in women.

Methods: Data were collected from 291 consecutive selected post-partum Caucasians using this criterion: ethnicity, age between 21 and 34-year-old new mothers and, 0-3 days after delivery of newborns in the Klaipeda University Hospital, Lithuania. Questionnaires on factors associated with conception were given to patients, and blood samples were collected for genomic DNA extractions as well as for analysis of follicle-stimulating hormone receptor gene polymorphism. Odds ratios (OR) and 95% confidence intervals (CI) for time-to-pregnancy were estimated by multivariate logistic regression. Women with unplanned pregnancies and those who received assisted reproductive technologies were not included in the study.

Results: After adjustment for other possible factors, increased risk for time-to-pregnancy of 12 or more months was associated with: Serine/Serine polymorphism variant (OR = 1.38, 95% CI 1.56-2.71, p = 0.007), age of 30 or more years (OR = 1.95, 95% CI 1.25-2.71, p = 0.015), gynaecological diseases in the past (OR = 2.21, 95% CI 1.12-5.74, p = 0.027), prior contraception use (OR = 1.87, 95% CI 1.14-3.64, p = 0.016), and fertility problems in the past (OR = 1.57, 95% CI 1.16-4.76, p = 0.019).

Conclusion: The results suggest a possible relationship of FSH receptor gene Serine/Serine variant for the lower possibility of conception during the first 12 months of planned conception.
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http://dx.doi.org/10.1186/s12884-018-1910-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025715PMC
June 2018

Paediatric Endocrinology Subspecialty - The European Map, 55 Years Later.

Horm Res Paediatr 2018;89(1):71-72. Epub 2017 Nov 7.

Institute of Endocrinology, Kaunas, Lithuania.

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http://dx.doi.org/10.1159/000481505DOI Listing
October 2018

Thirty-Five Years of Thyroid Cancer Experience in a Paediatric Population: Incidence Trends in Lithuania between 1980 and 2014.

Eur Thyroid J 2017 Feb 9;6(1):40-46. Epub 2016 Nov 9.

Clinic of Endocrinology, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Background: Thyroid cancer (TC) is a rare condition in children. It may be associated with radiation, iodine deficiency or familial inheritance.

Aims: The objectives of this study were to analyse the prevalence and incidence trends over 3 decades and clinical features of TC in the paediatric population in Lithuania.

Methods: We reviewed all TC cases diagnosed in children aged less than 18 years during the period 1980-2014 using medical records from 3 main hospitals in Lithuania where such TC cases are managed.

Results: During the 35-year period (1980-2014) there were 57 cases (45 females) of TC in children in Lithuania. The mean age at the time of diagnosis was 14.51 ± 0.52 years. The crude incidence rate of TC ranged from 0 to 0.93 cases per 100,000 children per year and the mean annual increase was 5.26% (p < 0.001). Papillary carcinoma was the most common histological type (73.7%). No association was found between the incidence of TC and the reported areas of radioactive contamination after the Chernobyl accident. In total, 8.8% of patients had secondary TC after initial radiotherapy of a primary oncologic disease.

Conclusion: The incidence of TC in the Lithuanian paediatric population between 1980 and 2014 ranged from 0 to 0.93 cases per 100,000 children per year and there was a 5.26% annual increase (p < 0.001), most probably related to the increased use of ultrasound testing.
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http://dx.doi.org/10.1159/000450921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465728PMC
February 2017

Factors Associated with the Prevalence of Thyroid Nodules and Goiter in Middle-Aged Euthyroid Subjects.

Int J Endocrinol 2017 5;2017:8401518. Epub 2017 Mar 5.

Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.

The aim of the present study was to determine associations of thyroid hormone levels and different metabolic parameters and anthropometric measurements with volume of nodular and nonnodular thyroid as well as with prevalence of goiter and thyroid nodules in middle-aged euthyroid subjects. . The study consisted of 317 euthyroid subjects aged 48-49 from the Kaunas Cardiovascular Risk Cohort study. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and antithyroid peroxidase antibody (ATPO) levels, as well as anthropometric and metabolic parameters and smoking information, were evaluated. . In subjects with and without thyroid nodules, thyroid volume correlated with components of metabolic syndrome, body mass index (BMI), smoking, and TSH levels. In the nonnodular thyroid group, thyroid volume was also positively related to serum insulin and HOMA-IR, whereas a negative correlation between thyroid volume and leptin was identified in the nodular thyroid group. The goiter was identified in 12.3% of subjects. Female gender, thyroid nodules, smoking, BMI, and levels of TSH were independent predictors for goiter. Thyroid nodules were found in 31.2% of participants. Female gender, higher TSH levels, and thyroid volume were independent risk factors for thyroid nodules. . Female gender, thyroid nodules, smoking, BMI, and TSH levels were identified as potential predictors of goiter. Female gender, TSH levels, and thyroid volume predicted the presence of thyroid nodules.
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http://dx.doi.org/10.1155/2017/8401518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357546PMC
March 2017

Can coefficient of variation of time-domain analysis be valuable for detecting cardiovascular autonomic neuropathy in young patients with type 1 diabetes: a case control study.

BMC Cardiovasc Disord 2017 01 19;17(1):34. Epub 2017 Jan 19.

Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, LT-44307, Kaunas, Lithuania.

Background: Cardiovascular autonomic neuropathy (CAN) increases morbidity and mortality in diabetes through association with a high risk of cardiac arrhythmias and sudden death, possibly related to silent myocardial ischemia. During the sub-clinical stage, CAN can be detected through reduction in heart rate variability (HRV). The aim of our study was to estimate if the time and frequency-domain analysis can be valuable for detecting CAN in young patients with type 1 diabetes mellitus (T1DM).

Methods: For this case control study of evaluation of cardiovascular autonomic function the 15-25 years age group of patients with duration of T1DM more than 9 years (n = 208, 89 males and 119 females) were selected. 67 patients with confirmed CAN were assigned to the "case group" and 141 patients without CAN served as a control group, the duration of T1DM was similar (15.07 ± 4.89 years vs.13.66 ± 4.02 years; p = 0.06) in both groups. Cardiovascular autonomic reflex tests and time and frequency domains analysis of HRV were performed for all subjects.

Results: Time domain measures were significantly lower in CAN group compared with control (p < 0.05). R-R max / R-R min ratio and coefficient of variation (CV) were the lowest during deep breathing among T1DM patients with CAN. Receivers operating characteristic (ROC) curves were constructed to compare the accuracies of the parameters of time-domain analysis for diagnosing CAN. We estimated a more reliable cut-off value of parameters of time-domain. The CV values in supine position <1.65, reflected sensitivity 94.3%, specificity 91.5%. The CV values during deep breathing <1.45 reflected sensitivity 97.3%, specificity 96.2%. The CV values in standing position <1.50 reflected sensitivity 96.2%, specificity 93.0%. The most valuable CV was during deep breathing (AUC 0.899). The results of frequency-domain (spectral analysis) analysis showed significant decrease in LF power and LFPA, HF Power and HFPA, total power among subjects with CAN than compared with subjects without CAN (p < 0.05).

Conclusions: Time and frequency domain analysis of HRV permits a more accurate evaluation of cardiovascular autonomic function, providing more information about sympathetic and parasympathetic activity. The coefficient of variation (time-domain analysis) especially during deep breathing could be valuable for detecting CAN.
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http://dx.doi.org/10.1186/s12872-016-0467-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244586PMC
January 2017

The course of diabetes in children, adolescents and young adults: does the autoimmunity status matter?

BMC Endocr Disord 2016 Nov 15;16(1):61. Epub 2016 Nov 15.

Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Eiveniu 2, LT-50161, Kaunas, Lithuania.

Background: Initial classification of diabetes of young may require revision to improve diagnostic accuracy of different forms of diabetes. The aim of our study was to examine markers of beta-cell autoimmunity in a cohort of young (0-25 years) patients with type 1 diabetes and compare the presentation and course of the disease according to the presence of pancreatic antibodies.

Methods: Cross-sectional population-based study was performed covering 100% of pediatric (n = 860) and 70% of 18-25 years old adult patients (n = 349) with type 1 diabetes in Lithuania.

Results: No antibodies (GAD65, IA-2, IAA and ICA) were found in 87 (7.5%) cases. Familial history of diabetes was more frequent in those with antibodies-negative diabetes (24.1 vs. 9.4%, p < 0.001). Gestational age, birth weight and age at diagnosis was similar in both groups. Ketosis at presentation was more frequent in patients with autoimmune diabetes (88.1 vs. 73.5%, p < 0.05). HbA1c at the moment of investigation was 8.6 (3) vs. 8.7 (2.2)% in antibodies-negative and antibodies-positive diabetes groups, respectively, p > 0.05. In the whole cohort, neuropathy was found in 8.8% and nephropathy - in 8.1% of cases, not depending on autoimmunity status. Adjusted for age at onset, disease duration and HbA1c, retinopathy was more frequent in antibodies-negative subjects (13.8 vs. 7.8%, p < 0.05).

Conclusion: Antibodies-negative pediatric and young adult patients with type 1 diabetes in this study had higher incidence of family history of diabetes, higher frequency of retinopathy, less frequent ketosis at presentation, but similar age at onset, HbA1c, incidence of nephropathy and neuropathy compared to antibodies-positive patients.
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http://dx.doi.org/10.1186/s12902-016-0145-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109672PMC
November 2016

A description of clinician reported diagnosis of type 2 diabetes and other non-type 1 diabetes included in a large international multicentered pediatric diabetes registry (SWEET).

Pediatr Diabetes 2016 10;17 Suppl 23:24-31

Children's University Hospital Children's Endocrinology Centre, Riga Stradins University, Riga, Latvia.

Background: Although type 1 diabetes (T1D) remains the most frequent form of diabetes in individuals aged less than 20 years at onset, other forms of diabetes are being increasingly recognized.

Objectives: To describe the population of children with other forms of diabetes (non-type 1) included in the multinational SWEET (Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) database for children with diabetes.

Methods: Cases entered in the SWEET database are identified by their physician as T1D, type 2 diabetes (T2D) and other types of diabetes according to the ISPAD classification. Etiologic subgroups are provided for other types of diabetes. Descriptive analyses were tabulated for age at onset, gender, daily insulin doses, and hemoglobin A1c (A1C) for each type and subtype of diabetes and when possible, values were compared.

Results: Of the 27 104 patients included in this report, 95.5% have T1D, 1.3% T2D, and 3.2% other forms of diabetes. The two most frequent etiologies for other forms of diabetes were maturity onset diabetes of the young (MODY) (n = 351) and cystic fibrosis-related diabetes (CFRD) (n = 193). The cause was unknown or unreported in 10% of other forms of diabetes. Compared with T1D, children with T2D and CFRD were diagnosed at an older age, took less insulin and had lower A1C (all P < .0001).

Conclusion: In centers included in SWEET, forms of diabetes other than type 1 remain rare and at times difficult to characterize. Sharing clinical information and outcome between SWEET centers on those rare forms of diabetes has the potential to improve management and outcome.
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http://dx.doi.org/10.1111/pedi.12426DOI Listing
October 2016

Diabetes distress in males and females with type 1 diabetes in adolescence and emerging adulthood.

J Diabetes Complications 2016 Nov - Dec;30(8):1500-1505. Epub 2016 Aug 20.

Institute of Endocrinology, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Background: Age and gender are important factors in the adjustment and psychological well-being of patients with chronic physical illness.

Aim: To explore the gender and age differences in diabetes distress between adolescents and emerging adults with type 1 diabetes (T1D).

Subjects And Methods: Diabetes distress was compared in 255 adolescents and 283 emerging adults with T1D using Problem Areas in Diabetes scale.

Results: High diabetes distress level was found in 22.8% of participants. Lack of confidence in self-care (6.0 vs 3.0, p=0.002), negative emotional consequences (10.0 vs 6.0, p=0.004), and overall score (18.75 vs 11.25, p=0.002) were higher in adult than in adolescent males, when adjusted for age at T1D onset. Negative emotional consequences (13.0 vs 10.0, p=0.005) and overall score (25.0 vs 20.0, p=0.016) were higher in adult compared to adolescent females, when adjusted for age at T1D onset. Lack of confidence in self-care (6.0 vs 3.0, p=0.002), negative emotional consequences (10.0 vs 6.0, p=0.015), and overall score (20.0 vs 11.2, p=0.005) were higher in adolescent females compared to males, when adjusted for age at T1D onset. Negative emotional consequences score was higher in adult females compared to males (13.0 vs 10.0, p=0.029), when adjusted for age at T1D onset. In conclusion, our findings show that patients with T1D have greater burden of diabetes distress in emerging adulthood than in adolescence and add to evidence suggesting the importance of addressing diabetes distress in clinical care and the necessity of wider picture beyond the physical manifestation of diabetes to be taken into consideration.
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http://dx.doi.org/10.1016/j.jdiacomp.2016.08.013DOI Listing
March 2018

The effect of a drospirenone-containing combined oral contraceptive on female sexual function: a prospective randomised study.

Eur J Contracept Reprod Health Care 2016 Oct 18;21(5):395-400. Epub 2016 Aug 18.

d Department of Obstetrics and Gynaecology , University Hospital Basel , Basel , Switzerland.

Objectives: The study investigated the effects on female sexual function of a progestogen-containing combined oral contraceptives (COCs) with an antiandrogenic profile taken in a continuous regimen.

Methods: In this prospective randomised single-institution study, 80 healthy women with a monogamous partner and an active sexual life were randomised into two groups for a period of 3 months. Women in the exposed group (n = 40) took a COCs containing 30 μg ethinylestradiol (EE) and 3 mg drospirenone (DRSP) in a 21/7 regimen. Women in the control group (n = 40) used either a barrier contraceptive method (BCM) or a natural family planning method (NFPM). Participants were asked to complete a set of validated questionnaires to assess sociodemographic variables and measure Female Sexual Function Index (FSFI).

Results: The total FSFI score (p < 0.0001), as well as the desire (p = 0.04) and arousal (p = 0.03) scores, were significantly lower in the COCs group after 3 months of hormonal contraceptive use compared with baseline. Women using BCM or NFPM showed an improvement in total FSFI score (p = 0.02). Hormonal contraception with DRSP increased the likelihood of worse sexual function in the desire (odds ratio [OR] 2.47; 95% confidence interval [CI] 1.22, 4.98; p = 0.01) and arousal domains (OR 2.85; 95%CI 1.34, 5.93; p = 0.005) and in total FSFI score (OR 2.01; 95%CI 1.45, 2.79; p < 0.001). The results remained statistically significant even after adjustment for smoking status.

Conclusions: The study found evidence that women taking a combined EE/DRSP COCs for 3 months may have a worsening of sexual function as measured by FSFI.
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http://dx.doi.org/10.1080/13625187.2016.1217324DOI Listing
October 2016

Predictive Factors of Development of Graves' Ophthalmopathy for Patients with Juvenile Graves' Disease.

Int J Endocrinol 2016 16;2016:8129497. Epub 2016 Jun 16.

Eye Clinic, Medical Academy, Lithuanian University of Health Sciences, A. Mickevičiaus 9, LT-44307 Kaunas, Lithuania.

Background. Due to low incidence of Graves' ophthalmopathy (GO) among children, the manifestation is poorly analyzed, posing a risk to late identification of insidious disease. Purposes. To identify predictive factors that may influence the development of GO in pediatric and young patients with Graves' disease (GD). Methods. A cross-sectional study of patients newly diagnosed with pediatric or juvenile GD during 2002-2012 was conducted at the Hospital of Lithuanian University of Health Sciences. Ocular evaluation was based on European Group on Graves' Orbitopathy survey. The ocular manifestations were analyzed in relation to demographic, environmental, and clinical factors. Results. In total, 130 patients with juvenile GD were included; 29.2% had GO. Median age at GD onset was 17 yrs (IQR 4-29). Main symptoms of GO were eyelids retraction (73.7%), proptosis (65.8%), injection of conjunctiva (42.1%), and eyeball motility disturbance (21.1%). Major significant and independent risk factors for GO development were high initial concentration of FT4 (OR = 5.963), TTHAb (OR = 6.358), stress (OR = 6.030), and smoking (OR = 7.098). Conclusion. The major factors that could influence GO development were smoking, stress, and increased levels of initial TRAb, FT4. Slight proptosis, retraction of eyelids, and conjunctive injection were found as predominant ophthalmological symptoms in juvenile GO.
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http://dx.doi.org/10.1155/2016/8129497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928005PMC
July 2016

The current management of Turner Syndrome.

Minerva Endocrinol 2016 Mar;41(1):105-21

Lithuanian University of Health sciences, Kaunas, Lithuania -

Turner Syndrome (TS) is a rare disease, with the incidence of 1 of 2500 life born females. Characteristic features are: growth retardation, gonadal dysgenesis and impairment, congenital and acquired cardiovascular disorders. New management possibilities in Turner Syndrome are coming along with the new scientific evidence on the pathogenesis of TS developmental, metabolic, cardiovascular and reproductive issues. Attitude to the growth retardation treatment and hormone replacement therapy is changing. The effectiveness of additional androgen doses for growth improvement and low estrogen doses in the early childhood for better puberty induction and metabolic outcomes has been demonstrated recently. There are some new concerns about pregnancy induced progression of cardiovascular pathology in TS. Inadequate follow-up despite strict and clear guidelines of TS patients is still an issue in the health care system in many countries. This rare disorder requires multidiscipline approach of experienced professionals. The aim of this review is to overview recent studies evaluating TS, to focus on the possibilities to avoid crucial outcomes of this disorder and to improve management and follow-up.
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March 2016

Prevalence of overweight/obesity in relation to dietary habits and lifestyle among 7-17 years old children and adolescents in Lithuania.

BMC Public Health 2015 Oct 1;15:1001. Epub 2015 Oct 1.

Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Eiveniu str. 2, LT-50009, Kaunas, Lithuania.

Background: Until recently increasing prevalence of overweight and obesity among pediatric population in Europe and worldwide contributes to major well-known risks for metabolic consequences in later life. The aim of this study was to determine the prevalence of overweight/obesity among children and adolescents in Lithuania and assess its association with energy balance related behaviors as well as familial demographic and socioeconomic factors.

Methods: Cross-sectional study included 3990 7-17 years old schoolchildren from 40 schools of Kaunas region, Lithuania. Study participants underwent anthropometric measurements. Body mass index (BMI) was evaluated according to International Obesity Task Force (IOTF) criteria for children and adolescents. Children and adolescents and their parents filled in the questionnaires on parental sociodemographic characteristics, dietary habits, TV watching time, and family socioeconomic status.

Results: The prevalence of underweight, overweight, and obesity among boys and girls was 6.9 and 11.7 % (P < 0.05), 12.6 and 12.6 % (P > 0.05), and 4.9 and 3.4 % (P < 0.05), respectively. Obesity was significantly more prevalent in the 7-9 years old group (6.7 and 4.8 % in boys and girls, respectively, P < 0.05). Lower meals frequency and breakfast skipping were directly associated with overweight/obesity (P < 0.05); however, physical inactivity was not associated with higher BMI. Children's overweight/obesity was directly associated with lower paternal education and unemployment (OR 1.30, P = 0.013 and OR 1.56, P = 0.003, respectively).

Conclusions: The prevalence of overweight and obesity among 7-17 years old Lithuanian children and adolescents was more prevalent in younger age, still being one of the lowest across the European countries. Meals frequency, breakfast skipping, paternal education and unemployment as well as a family history of arterial hypertension were found to be associated with children's and adolescents' overweight/obesity.
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http://dx.doi.org/10.1186/s12889-015-2340-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590263PMC
October 2015

Genesis of two most prevalent PROP1 gene variants causing combined pituitary hormone deficiency in 21 populations.

Eur J Hum Genet 2016 Mar 10;24(3):415-20. Epub 2015 Jun 10.

Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic.

Two variants (c.[301_302delAG];[301_302delAG] and c.[150delA];[150delA]) in the PROP1 gene are the most common genetic causes of recessively inherited combined pituitary hormones deficiency (CPHD). Our objective was to analyze in detail the origin of the two most prevalent variants. In the multicentric study were included 237 patients with CPHD and their 15 relatives carrying c.[301_302delAG];[301_302delAG] or c.[150delA];[150delA] or c.[301_302delAG];[ 150delA]. They originated from 21 different countries worldwide. We genotyped 21 single-nucleotide variant markers flanking the 9.6-Mb region around the PROP1 gene that are not in mutual linkage disequilibrium in the general populations--a finding of a common haplotype would be indicative of ancestral origin of the variant. Haplotypes were reconstructed by Phase and Haploview software, and the variant age was estimated using an allelic association method. We demonstrated the ancestral origin of both variants--c.[301_302delAG] was carried on 0.2 Mb-long haplotype in a majority of European patients arising ~101 generations ago (confidence interval 90.1-116.4). Patients from the Iberian Peninsula displayed a different haplotype, which was estimated to have emerged 23.3 (20.1-29.1) generations ago. Subsequently, the data indicated that both the haplotypes were transmitted to Latin American patients ~13.8 (12.2-17.0) and 16.4 (14.4-20.1) generations ago, respectively. The c.[150delA] variant that was carried on a haplotype spanning about 0.3 Mb was estimated to appear 43.7 (38.4-52.7) generations ago. We present strong evidence that the most frequent variants in the PROP1 gene are not a consequence of variant hot spots as previously assumed, but are founder variants.
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http://dx.doi.org/10.1038/ejhg.2015.126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755373PMC
March 2016

Thiamine responsive megaloblastic anemia syndrome: a novel homozygous SLC19A2 gene mutation identified.

Am J Med Genet A 2015 Jul 23;167(7):1605-9. Epub 2015 Feb 23.

Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.

Thiamine responsive megaloblastic anemia syndrome (TRMAS) is a rare autosomal recessive disorder especially in countries where consanguinity is uncommon. Three main features are characteristic of the disease - megaloblastic anemia, early onset deafness, and non-type I diabetes. TRMAS is a Mendelian disorder; a gene SLC19A2 coding high affinity thiamine transporter mediating vitamin B1 uptake through cell membrane has been identified. We present the first patient with TRMAS in Lithuania - a 3-year-old boy born to a non-consanguineous family with a novel homozygous SLC19A2 gene mutation. The patient had insulin dependent diabetes (onset 11 months), respiratory illness (onset 11 months), bilateral profound hearing loss (onset at 7 months, verified at 20 months), refractory anemia (onset 2 years), and decreased vision acuity and photophobia (onset 2.5 years). The psychomotor abilities developed according to age. Phenotypic evaluation did not reveal any dysmorphic features. The clinical diagnosis of TRMAS was suspected and daily supplementation with thiamine 100 mg was started. The condition of the patient markedly improved several days after the initiation of treatment. The results of SLC19A2 gene molecular testing confirmed the clinical diagnosis - novel homozygous c.[205G>T], p.[(Val69Phe)] mutation changing conserved amino acid residue or even interfering the mRNA splicing. Clinical heterogeneity, diverse dynamics, and wide spectrum of symptoms are aggravating factors in the diagnosis. The possibility of treatment demands early recognition of disorder to facilitate the improvement of the patient's condition.
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http://dx.doi.org/10.1002/ajmg.a.37015DOI Listing
July 2015

Early development of endocrine and metabolic consequences after treatment of central nervous system tumors in children.

Medicina (Kaunas) 2014 4;50(5):275-80. Epub 2014 Nov 4.

Department of Children Diseases, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Background And Objective: Survival after childhood cancer has dramatically improved during last few decades, implying the need for evaluation and correction of late consequences of the disease and its treatment. The aim of this study was to characterize endocrine and metabolic late effects after treatment of brain tumors in children.

Materials And Methods: Late complications were analyzed in 51 children treated for brain tumors at the Hospital of Lithuanian University of Health Sciences during 2000-2011. Data on late endocrine and metabolic effects were collected from medical records. Most frequently patients suffered from low-grade glioma (n=17, 33.3%) and medulloblastoma (n=13, 25.5%). The majority (n=42, 82.4%) of the patients underwent surgery; 29 (56.9%) received radiotherapy (RT); 26 (51.0%), chemotherapy; and 17 (33.4%), combined treatment.

Results: The median follow-up was 21 months (range 0.25-10.6 years). Most common endocrine consequence was low serum insulin-like growth factor (IGF-I) levels (58.3%), found on average in 30.7 months after cancer treatment. Short stature was observed in 34.6% (mean time to development, 47.7 months), and hypothyroidism in 40.7% of patients (mean time to development, 63.6 months). Low bone mineral density was found in 50.0% of the cases after 44.5 months and overweight in 30.0% after 49.9 months of follow-up.

Conclusions: Survivors of brain tumors suffer from numerous endocrine and metabolic consequences, majority of them developing within the first 5 years after brain tumor therapy. An active follow-up aiming for early diagnosis and therapy is essential for improvement of quality of life in these patients.
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http://dx.doi.org/10.1016/j.medici.2014.10.006DOI Listing
September 2016
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