Verkauskienė, Rasa

Introduction: WAGR syndrome is a rare contiguous gene deletion disorder characterized by the classical tetrad: Wilms tumor, aniridia, genitourinary anomalies, and a spectrum of developmental delays. It is caused by a deletion on chromosome 11p13, typically involving critical genes such as WT1 and PAX6. Objectives: To present a rare clinical case of WAGR syndrome with multisystem involvement, including endocrine and metabolic abnormalities. Methods: A 4-year-old girl was referred to a pediatric endocrinologist due to rapid weight gain and metabolic disturbances. Her anthropometric measurements were: height 100.2 cm (10th–25th percentile), weight 19 kg (75th–90th percentile), and BMI 18.92 kg/m² (approaching the 97th percentile). Laboratory evaluation revealed fasting hyperglycemia (up to 5.84 mmol/L) with insulin resistance (HOMA-IR 3.63), and central hypothyroidism (low TSH and low FT4). Previous medical history: she was the first child in the family. Aniridia was diagnosed shortly after birth. At the age of 1.5 years, she was diagnosed with nephroblastoma (Wilms tumor) of the right kidney. Given the suspicion of a rare syndromic condition, the patient was referred for genetic evaluation. Results: Genetic testing identified a pathogenic heterozygous deletion >7 Mb on chromosome 11p13, encompassing multiple genes including PAX6, WT1, BDNF, FSHB, DCDC1, ELP4, RCN1, HIPK3, and CD44. Haploinsufficiency of WT1, PAX6, and BDNF is considered central to the patient’s phenotype, contributing to tumor predisposition, ocular abnormalities, and neurodevelopmental and metabolic features. Conclusions: This case highlights the critical role of genetic testing in patients with congenital anomalies and multisystem involvement. WAGR syndrome may also present with endocrine and metabolic disturbances, including obesity, insulin resistance, and hypothyroidism. Early diagnosis and coordinated multidisciplinary management are essential to optimize clinical outcomes.

Introduction: Physiological response and the role of the incretins are well-characterized in healthy individuals. However, there is limited data regarding the incretin-insulin axis in patients with monogenic diabetes (MD). Objectives: Evaluate the timing between GLP-1 and C-peptide peaks during a mixed meal tolerance test (MMTT). By comparing GCK, HNF1A, HNF4A patients vs. healthy controls, we aim to assess β-cell responsiveness and incretin sensitivity across different MD types. Methods: 17 subjects with GCK diabetes (median age 15.3 yrs (IQR 13.6 – 17.8 yrs); 6 - HNF1A, with a median age 20.0 yrs (IQR 15.2 – 23.8 yrs); and two - HNF4A diabetes, aged 24.5 and 25.9 yrs. Control group consisted of 19 subjects (median age 23.2 yrs (IQR 22.6 – 24.6 yrs). C-peptide and GLP-1 levels were measured at 9 time points during a standard MMTT. Area under the curve (AUC) was calculated using the trapezoidal method. An incretin responsiveness index was defined as AUCC-peptide divided AUCGLP-1. GLP-1 – to – C-peptide lag analysis: lag=Tmax (C-peptide) – Tmax (GLP-1). Mann–Whitney U test was used for group comparisons. Results: The incretin responsiveness index was significantly reduced across all MD subtypes. Compared to controls 78.6 [62.4– 96.8], the index was lower in GCK 32.1 [24.7–41.3], p< 0.00001; in HNF1A 27.4 [21.9–33.8, p=0.0004; and in HNF4A 1.08 [0.89–1.27, p=0.0002. GLP-1–to–C-peptide lag differed across groups. Controls demonstrated a median lag of 0 min. (IQR 0–45), while GCK showed marked variability with a wide range including negative values (median 0, IQR −60 to 30). In contrast, HNF1A and HNF4A exhibited a more consistent positive lag (median 30 min.), indicating delayed but preserved temporal coupling. Conclusions: The incretin responsiveness index demonstrated a stepwise impairment in incretin-mediated β-cell responsiveness: Controls->GCK->HNF1A->HNF4A, suggesting the failure of β-cells to respond appropriately in time.

Background

Physical activity (PA) is widely recommended to improve glycemic control in diabetes, whereas prolonged sedentary behavior is linked to adverse cardiometabolic risk. Regular daily activity is critical to healthy aging and reducing risk for falls, maintaining function, and reducing premature morbidity. Multiple national guidelines recommend a multimodal exercise as the single most beneficial intervention to improve health in older adults. Regular PA enhances β-cell function, insulin sensitivity, and vascular function, which leads to better diabetes and health management as well as disease risk reduction. This study aimed to analyze physical activity and sitting time assessed by the IPAQ short questionnaire (IPAQ-SF) and their associations with key demographic and clinical factors in adults with diabetes.

Methods

In this cross-sectional study of 137 adults with diabetes (type 1, n = 69, type 2, n = 68), physical activity was assessed using the IPAQ-SF, with total MET-min/week calculated according to standard scoring rules. Participants were classified into low (<600 MET-min/week), moderate (600-3000 MET-min/week), or high (>3000 MET-min/week.) PA level. Sitting time was grouped as <6 or ≥6 hours/day. PA and sitting metrics were compared across sex, BMI group, diabetes type, education level, HbA1c, complications status, and age. Data on patients’ clinical characteristics were collected from medical records.

Results

The median diabetes duration was 15 years, age—55 years. 57.7% of participants were women. By IPAQ classification, 10.9% of participants had low, 45.3% moderate, and 43.8% high PA level. A progressive decrease in BMI with increase in PA level was found (P < .05). In subgroup analyses, PA category did not differ significantly by sex (P = .70), diabetes type (P = .13), HbA1c level (P = .98), complication status (P = .67), or age group (P = .71). However, significant differences were apparent when analyzing social status: patients with higher education were more often in the moderate/high PA groups compared to patients with lower education (P < .05). 54.7% of participants reported sitting time <6h/day. Median sitting time was 300 (180-360) min/day with no differences by any subgroup.

Conclusions

In this cohort of people with diabetes, most patients achieved at least moderate IPAQ-defined activity levels. PA level varied significantly only by education level and BMI. Higher-educated individuals are more likely to engage in moderate or high levels of PA. Nearly half of patients reported prolonged sitting time. These findings highlight the need to promote greater PA and reduce sedentary behavior in diabetes care, especially targeting individuals with lower education.

Introduction

Autoimmune polyglandular syndrome (APS) is a rare group of immune-mediated disorders. APS type 2 is the most common subtype with a characteristic clinical triad, which includes adrenal insufficiency, autoimmune thyroiditis and diabetes mellitus (DM) type 1.

Case Presentation

A 37-year-old woman with Down syndrome (DS) and autoimmune thyroiditis treated with levothyroxine, was admitted to the emergency department with an 8-day history of progressive weakness, nausea, and dizziness. The patient's height 142 cm, weight 47 kg, BMI 23 kg/m2.,Initial laboratory evaluation revealed hyperkalemia 8.02 mmol/L (3.5-5.1) and hyponatremia 130 nmol/L (136-144). Patient was hospitalized to the intensive care unit. Patient developed persistent hypotension (79/50 mmHg) and ongoing hyperkalemia (6.1 mmol/L), hyponatremia (130 nmol/L) raising suspicion for adrenal crisis. Diagnostic evaluation confirmed adrenal insufficiency with markedly elevated ACTH level of 210.8 pmol/L (1.63-14.5) and low cortisol level of 101.18 nmol/L. Immediate treatment consisted of intravenous hydrocortisone 100 mg IV bolus. Hydrocortisone 200 mg /24 h was administered further using automatic syringe pump. After correcting the electrolyte imbalance, maintaining stable blood pressure, oral hydrocortisone was administered, gradually decreasing to a maintenance dose (30 mg/day). In the presence of a tendency to slight hypotension, with signs of aldosterone deficiency, elevated renin concentration of 134.9 ng/L (3.78-32.61), fludrocortisone was added resulting in systolic blood pressure increase toto 90-100 mmHg. Anti-GAD65, anti-IA2 antibodies were negative and glucose tolerance test was within normal range. At discharge, the patient's treatment consisted of hydrocortisone (15/10/5 mg), fludrocortisone 50 μg per day and levothyroxine 75 μg per day. A month later, laboratory tests revealed elevated renin level of 401 ng/L (3.78-32.61) and elevated TSH level of 14.78 mU/L (0.4-3.6), sodium 133 mmo/L (135-144), potassium 4.7 nmol/L (3.5-5.1), a tendency to a lower blood pressure was found. Fludrocortisone dose was increased to 75 μg per day and levothyroxine—to 100 μg per day, hydrocortisone dose was unchanged and follow up visit was planned in 2 months.

In conclusion, DS is associated with an increased risk of autoimmune diseases due to disruption of immune tolerance. This case highlights the challenges and risks of APS type 2 in patients with DS, indicating the need for screening and timely treatment of these serious endocrine conditions.

Diabetinė ketoacidozė (DKA) - ūmi ir gyvybei pavojinga būklė, kuri atsiranda dėl insulino stygiaus, kortizolio, augimo hormono, gliukagono, katecholaminų aktyvumo padidėjimo. Tyrimai rodo, kad Covid-19 pandemija 2021 metais turėjo reikšmingą įtaką ketoacidozės dažnio padidėjimui tarp vaikų iki 18 metų amžiaus. Metodika: Atliktas retrospektyvinis tyrimas, į kurį įtraukti vaikai iki 18 metų amžiaus, kurie 2018, 2021 ir/ar 2024 metais kreipėsi į LSMUL KK Vaikų Skubios pagalbos skyrių (SPS) dėl cukriniam diabetui būdingų simptomų ar jų paūmėjimo. Tyrimui gautas etikos komiteto leidimas (Nr. BE-10-6). Rezultatai: Analizuotu laikotarpiu į SPS kreipėsi 231 pacientas, tačiau į tyrimą įtraukti 93 pacientai (vidutinis tiriamųjų amžius - 10 metų; jauniausias pacientas - 1 m. amžiaus, o vyriausias - 17 m.), atitinkantys diabetinės ketoacidozės diagnostikos kriterijus, iš kurių 33 (35,5 %) pacientų kreipėsi jau turėdami 1 tipo CD diagnozę, o kiti pacientai - 60 (64,5 %) buvo nauji 1 tipo CD atvejai. 2021 metais, pandemijos piko metu, fiksuotas didžiausias diagnozuotų DKA pacientų skaičius - 39 pacientai (41,9 %) ir, palyginti su 2018 ir 2024 metais, kreipėsi daugiau sunkų DKA laipsnį turinčių naujai diagnozuotų CD pacientų. Vertinant rūšiavimo efektyvumų analizuotais laikotarpiais, pastebėta, kad iš 3 kategorijai priskirtų 62 pacientų: 19 buvo sunkios diabetinės ketoacidozės, 18 - vidutinio sunkumo ir 25 - lengvos formos DKA. Išvados: Dažniausiai į vaikų SPS kreipėsi pacientai, turintys sunkų diabetinės ketoacidozės (DKA) laipsnį. Tai pabrėžia būtinybę gerinti šios būklės klinikinį atpažinimų ir tobulinti pacientų rūšiavimo procesus skubios pagalbos skyriuose, siekiant užtikrinti savalaikę ir tinkamą pagalbą.

Context: Patients with congenital adrenal hyperplasia (CAH) often face challenges in achieving their target adult height. The QEPS growth model, previously used for assessing healthy and pathological growth patterns, has not been applied to individuals with CAH. Objective: To evaluate growth patterns in patients with CAH using the QEPS growth model and to compare their growth characteristics with a healthy reference population. Design: A retrospective longitudinal study analyzing growth data collected from 1986 to 2008.Setting: The study was conducted in a single tertiary care center. Patients: The study included 25 patients (13 girls) with CAH, subtyped into salt wasting (SW; 12 boys, 8 girls) and simple virilizing (SV; 5 girls). Growth data were compared with a healthy reference cohort. Interventions: All patients were treated with hydrocortisone, and patients with CAH-SW received mineralocorticoids. Main outcome measures: Growth patterns were analyzed using the QEPS model, which includes specific early life growth (E-function), basic childhood growth (Q-function), and specific pubertal growth (P-function). Final adult height was compared with the reference population and parental heights. Results: CAH-SW boys and girls were longer at birth, exhibited reduced early-life growth, and had reduced puberty-specific growth (lower Pmax), resulting in shorter adult height (1.7 SDS). CAH-SV girls had earlier pubertal growth onset, also leading to reduced adult height (−1.6 SDS). Both groups showed similar basic childhood growth. Conclusions: Patients with CAH-SW displayed distinct growth patterns, including longer birth length but reduced specific early and pubertal growth, resulting in shorter adult height compared with reference populations and parental heights.

TEMOS AKTUALUMAS Moterų lytinė funkcija yra daugialypis, sudėtingas ir dažnai nepakankamai įvertinamas sveikatos aspektas. Su amžiumi susiję fiziologiniai, hormoniniai ir psichosocialiniai pokyčiai gali reikšmingai paveikti lytinę funkciją ir neigiamai veikti moterų gyvenimo kokybę. Lytinę disfunkciją patiria apie 40-45 proc. moterų visame pasaulyje. Nepaisant to, šios problemos klinikinėje praktikoje dažnai lieka nepakankamai atpažįstamos ir aptariamos. Lietuvoje šios srities epidemiologinių duomenų trūksta, todėl būtini reprezentatyvüs tyrimai, padėsiantys kurti tikslingas intervencijas ir gerinti moterų seksualinę sveikatą visais gyvenimo etapais. DARBO TIKSLAS (-AI) Įvertinti Kauno miesto moterų populiacijos lytinę funkciją, naudojant FSFI klausimyną, ir jos sąsajas su amžiumi; [...].

Background/Objectives: Early nutrition is crucial for postnatal growth and metabolic status in preterm very low birth weight (VLBW) infants; however, the optimal macronutrient proportions remain unclear. We aimed to investigate how early nutrition influences long-term outcomes in extremely preterm (EP) and very/moderately preterm (VP) infants. Methods: We included 120 preterm infants in the prospective follow-up study. Anthropometric and metabolic parameters (fasting glycemia, insulin, and IGF-1) were assessed at birth, on the 28th day after birth, and once a year until 3–4 years (N = 65). Total daily parenteral and enteral nutrient intake was calculated. Standard deviation scores (SDS) for anthropometric measurements were calculated using Swedish growth reference data. Results: Although there was no difference in weight-adjusted macronutrient intake, EP newborns grew more slowly in the first 28 days than VP newborns. At the age of 1 year, the central-to-peripheral subcutaneous fat ratio was higher in children born EP compared to children born VP. No other anthropometric differences were found between groups at 1 year of age, and later between both groups. On the 28th day after birth, infants born EP had higher glucose and insulin levels, HOMA-IR, and lower IGF-1 levels compared to infants born VP. No relation was found between macronutrient intake and increases in weight SDS and height SDS in VP newborns. In the EP subgroup, carbohydrate and protein intake during the first 28 days were directly related to central-to-peripheral subcutaneous fat at 1 and 3–4 years. Conclusions: Early nutrition affects children’s growth up to 1 year of age, while later on, other factors seem to interfere. Higher protein and carbohydrate intake does not have a positive effect on the growth of preterm infants but is related to more central adipose tissue distribution.

Background: Pituitary tumor-transforming gene 1 (PTTG1) contributes to pituitary neuroendocrine tumour (PitNET) development through its roles in cell-cycle control, genomic instability, and angiogenesis. Although PTTG1 overexpression promotes tumor progression, the impact of PTTG1 genetic variants on PitNET size remains unclear. Objective: To investigate the impact of PTTG1 gene variants (rs1895320, rs2910200, and rs6882742) on PitNET size. Methods: This case-control study included PitNET patients and age- and gender matched controls. Diagnoses were made by imaging and/or histopathology. DNA was extracted from peripheral blood and three PTTG1 variants were genotyped using real-time PCR. Ki-67 and p53 expression was measured by immunohistochemistry. Statistical analyses included chisquare tests, logistic regression, and nonparametric tests. Results: The study enrolled 120 PitNET patients and 220 controls. Among patients, 65% had macroadenomas; 55.8% of tumors were hormonally active. Genotype and allele distributions for all three PTTG1 variants showed no statistically significant differences between patients and controls or between tumor size groups. However, logistic regression analysis revealed that the PTTG1 rs3811999 TT genotype was associated with a 2.5-fold increased risk of microadenoma occurrence (OR = 2.53, 95% CI: 1.17- 5.48, p = 0.018). PTTG1 rs1895320 G allele was observed more frequently in the >1% Ki-67 LI group (13.5%) compared with the ≤1% group (2.4%). Macroadenomas had statistically significantly higher p53 H-score compared to the microadenomas group (median (IQR): 27.34 (24.83) vs. 16 (16.83), p = 0.012). Conclusions: Our findings indicate that the PTTG1 rs3811999 TT genotype may contribute to microadenoma development and should be explored further in larger, independent cohorts.

Background Digital diabetes technologies support self-management, yet their real-world use and patient experience may differ between T1DM and T2DM. Methods A cross-sectional survey was conducted in Lithuania among adults with diabetes and parents of children with T1DM. Questionnaires assessed demographics, use of diabetes technologies, usability, professional support, and satisfaction. Data from 159 respondents (T1DM n=117, T2DM n=42) were included. Group comparisons were performed using descriptive statistics and chi-square tests. The study was a part of the project received funding from Research Council of Lithuania (LMTLT), agreement No S-THCS-25-1 under the frame of Transforming Health and Care Systems, THCS, (GA N° 101095654 of the EU Horizon Europe Research and Innovation Programme) Results Mean age was 38±12.8 years in T1DM and 62±9.9 years in T2DM. CGM use was significantly higher in T1DM than T2DM (43.6% vs 11.6%, p<0.001); insulin pumps were used only in T1DM (22.2%). Physical activity apps were more common in T1DM (17.9% vs 4.7%, p=0.037). Most T1DM participants felt comfortable using technologies (76.9% vs 20.9%, p<0.001) but more often considered discontinuation (14.5% vs 2.3%, p<0.001). Adequate professional support was reported more frequently by T2DM participants (88% vs 53%, p<0.001). The main perceived benefit was improved DM control in both groups, while the main barrier was a confusing user interface. Detail information in Table 1. Conclusions T1DM adults use advanced diabetes technologies more frequently but experience greater technology burden. T2DM adults report better professional support despite lower uptake. Improving usability and structured education may enhance sustainable technology use across diabetes types.