Preconceptional Counseling in Women with Hyperthyroidism.

Preconception evaluation of couples wishing to conceive is an important step toward a healthy pregnancy and it is especially important in people with a chronic condition or at genetic risk. The most common endocrine disorders in women at reproductive age are those involving the thyroid gland and it is well recognized that hyperthyroidism (HT), over-function of the thyroid gland, is associated with risks of maternal, fetal, and neonatal complications. The aim of this paper is to review the latest evidence regarding the components of preconception counseling in women with HT that contemplate a pregnancy. We also want to raise awareness among healthcare professionals about the importance of periconceptional counseling in improving pregnancy outcomes and avoid maternal and fetal complications related to thyroid dysfunction. In women with Graves' disease seeking pregnancy, it is essential to discuss all the treatment options along with the associated risks and benefits. Extensive prospective studies are still needed to understand the implications of current recommended strategies for the management of HT in preconception and during pregnancy.

DXA Android-to-Gynoid Ratio and Cardiovascular Risk Assessment in Age and BMI Propensity-Matched Early Postmenopausal Women.

Background and Objectives: The literature suggests that physiological menopause (MP) seems linked with increased adiposity with a preference for intra-abdominal fat accumulation, greater than what can be attributed only by aging, which could magnify this period's increased cardiovascular risk. Materials and Methods: We retrospectively analyzed two age and body mass index (BMI) propensity-matched subgroups each formed of 90 clinically healthy, 40-60-year-old postmenopausal women, within the first 5 and 5-10 years of MP. The 10-year ASCVD risk was assessed using medical history, anthropometric data, and lipid profile blood tests. The android-to-gynoid (A/G) ratio was computed using Lunar osteodensitometry lumbar spine and hip scans. Results: The A/G ratio was significantly higher for the subgroup evaluated in years 5-10 of MP than in the first 5 years of MP, even after controlling for BMI (1.05 vs. 0.99, p = 0.005). While displaying a significant negative correlation with HDL cholesterol (r = 0.406), the A/G ratio also had positive correlations with systolic blood pressure (BP) values (r = 0.273), triglycerides (r = 0.367), and 10-year ASCVD risk (r = 0.277). After adjusting for smoking, hypertension treatment, and type 2 diabetes, the 10-year ASCVD risk became significantly different for women in the first 5 years (3.28%) compared to those in years 5-10 of MP (3.74%), p = 0.047. Conclusions: In women with similar age and BMI, the A/G ratio appears to vary based on the number of years since menopause onset and correlates with either independent cardiovascular risk parameters like BP, triglycerides, and HDL cholesterol or with composite scores, such as 10-year ASCVD risk.

Uric Acid in Primary Hyperparathyroidism: Assessment of Surgical versus Conservative Approach.

Introduction: Although suggested in early papers, the association between primary hyperparathyroidism (PHPT) and hyperuricemia is still debated, as is the potential benefit of parathyroidectomy compared to conservative treatment in serum uric acid (SUA) metabolism. Material and Methods: Our retrospective study of 125 Caucasian PHPT patients with surgical criteria evaluated between 2017 and 2021 at Elias Emergency and University Hospital, Bucharest, Romania aims to describe the characteristics of hyperuricemia in PHPT patients and to assess the differences in SUA levels between 38 surgically cured and 41 conservatively managed patients. Results: Our hyperuricemic PHPT patients (N=34) had significantly higher levels of calcium (11.55[11.05;12.42] vs. 11.2[10.8;11.96], p=.039) than the normouricemic subjects (N=91). At baseline, SUA correlated with age, serum total calcium (p=.004, r=.328), creatinine, triglycerides, and magnesium levels. A linear regression model identified calcium as a covariate with unique contribution for SUA variability. After successful parathyroidectomy, the 38 cured patients showed significantly lower serum calcium (9.3[8.7;9.75] vs. 11.55[11;12.12], p .001) and SUA (4.95[3.52;6.3] vs. 5.65[4.49;7.45], p=.011) levels compared to baseline. Conclusions: Hyperuricemic PHPT patients have significantly higher levels of serum calcium, which is also an independent determinant of SUA variability. Patients who undergo successful parathyroidectomies show a significant decrease in SUA during 1 year of follow-up.

Preconception Counseling in Patients with Hypothyroidism and/or Thyroid Autoimmunity.

Preconception counseling is an essential tool for preventing adverse pregnancy outcomes associated with thyroid dysfunction. The high prevalence of thyroid disease among women of reproductive age, and the increased risk of adverse pregnancy outcomes associated with thyroid dysfunction, emphasize the necessity for well-established screening and treatment criteria in the preconception period. We therefore conducted a literature review for relevant information on the screening, diagnosis and treatment of subclinical and overt hypothyroidism in women seeking pregnancy. While screening for thyroid disease is recommended only in the presence of risk factors, iodine supplementation should be recommended in most regions, with higher doses in areas with severe deficiency. Known hypothyroid women should be counseled about increasing their levothyroxine dose by 20-30% in the case of suspected or confirmed pregnancy (missed menstrual cycle or positive pregnancy test). Treating subclinical hypothyroidism appears to be beneficial, especially in the presence of autoimmunity or in patients undergoing artificial reproductive techniques. Regarding the management of TPOAb negative SCH women or euthyroid women with positive TPOAb, further research is necessary in order to make evidence-based recommendations.

Rates and Causes of Death among Adult Diabetes Patients in Romania.

Aims: To study the age and sex-dependent mortality rates and causes of death in a large Romanian diabetes cohort as compared with the general population. Methods: All adult patients aged 20-64 years, receiving a free diabetes prescription in a major urban area during 2001-2008 were included and followed-up for death until December 31, 2011. Crude mortality rates and standardized mortality rate ratios (SMR) against general population (data from the National Institute of Statistics) were calculated. Years lost due to diabetes were computed assuming the general population mortality rates for ages below 20 and above 64 years. Results: During the 11 years study period, 49,328 diabetes patients (mean age at baseline 53.0 ± 8.8 years) contributed 297,370 person-years and 5,053 deaths. All cause mortality rates (per 1000 person years) increased with age and was 3.4 in 20-24 years age group and 25.7 in 60-64 year age group, while the corresponding SMR decreased from 6.0 to 1.5. Diabetes patients aged 20-24 years had a life expectancy of 48.6 years, which was 6.6 years less compared with the corresponding general population (55.2 years). The gap was 7.0 years in women and 5.8 years in men. Diabetes patients aged 20-24 years lost 196 minutes of life daily due to diabetes in women and 182 minutes in men. Conclusions: Mortality rates increased, while mortality rate ratios against general population decreased with age. Men had higher mortality rates, but women had higher mortality rate ratios in the gender analysis.

Stroke Mortality Rates and Trends in Romania, 1994-2017.

BACKGROUND AND AIM: Romanian national level stroke mortality data is relatively scarce. The current study investigated stroke mortality rates and trends in Romania. METHODS: All individual deaths registered in Romania during 1994-2017 were analyzed using an anonymized database, based on death certificates. Stroke crude mortality rates (CMR) and age-standardized mortality rates (ASMR) were calculated and expressed per 100,000 persons-year. RESULTS: Between 1994 and 2017, 6,281,873 persons died in Romania, stroke being registered as the underlying cause of death in 959,319 cases. The overall stroke CMR was 188.2 (199.3 for women and 176.5 for men). The CMR for hemorrhagic stroke (HEMS) was 32.4 and for ischemic stroke (ISCS) 10.9. There was a significant decrease in stroke ASMR from 344.4 (95% confidence interval [CI] 343.4-345.4) in 1994 to 192.1 (95% CI 191.5-192.7) in 2017, with an annual percent change (APC) of 2.53% per year (95% CI 2.50-2.55, P < .001). Although compared with men, women had higher CMRs, when those rates were age-standardized men had higher ASMR as compared with women. The decline in HEMS ASMR had an APC of 4.65% per year (95% CI 4.59-4.70, P < .001). ISCS ASMR showed an initial increase in ASMR during 1994-2005, with APC 6.39% per year (95% CI 6.09-6.70, P < .001), followed by a significant decrease until 2017, with APC 2.83% per year (95% CI 2.59-3.07, P < .001). CONCLUSION: There was a significant reduction in stroke ASMR during 1994-2017. The decline was slow until 2002 and became steeper after that, with significant differences in gender analysis.

Postoperative Hypoparathyroidism in Patients After Total Thyroidectomy - Experience of a Tertiary Center in Romania.

Background: Post-surgical hypoparathyroidism (PoSH) is a common long-term complication after thyroid surgery. The reported median (range) incidence rates of temporary and permanent PoSH was 27% (19 - 38%) and 1% (0 - 3%) respectively. Material and Methods: We retrospectively analyzed the files of 552 patients who underwent thyroidectomy in our surgery department between 2015- 2017 with the aim to assess the prevalence of PoSH and to identify patient and disease related factors associated with postoperative hypocalcemia. Results: 171 (30.97%) patients developed PoSH, 88.37% transient, 11.63% permanent. The median (IQR) duration of postoperative hypocalcemia was 60 (67.5) days. Preoperative biological parameters were similar in PoSH and the control group, except median (IQR) serum magnesium level that was significantly higher in PoSH group [2.04 (0.17) vs. 1.89 (0.28) mg/dl, p=0.005]. In the subgroup of patients with thyroid carcinoma the surgery duration was longer in PoSH patients compared to the control group [135 (60) vs. 110 (43) minutes, p=0.020]. In patients with PoSH, median post-operative serum calcium was significantly higher in patients with reported difficult surgery [8.2 (0.2) vs. 7.9 (0.6) mg/dl, p=0.043] and the mean serum calcium decrease was higher in patients with cervical neck dissection and lymphadenectomy (1.94 +-0.59 vs. 1.68 +-0.56 mg/dl, p=0.033). Conclusions: Our data show a high prevalence of PoSH that is likely to increase given the rising number of thyroid surgeries being performed. Further research is needed in order to better define this condition, to establish appropriate treatment and preventive measures.

All-cause and cardiovascular mortality associated with sulphonylurea and metformin therapy in type 2 diabetes.

PURPOSE: To test the hypothesis that cumulative exposure to sulphonylurea (SU) or metformin (MET) have different effects on mortality when taken as a replacement or add-on of one for the other. METHODS: All consecutive diabetes patients aged over 20 years were screened at their first diabetes outpatient visit between 2001 and 2008 (n = 79869). Only patients on MET (n = 11374) or SU (n = 18502) monotherapy were retained. All patients were followed up for death until December 31, 2011, but censored at first exposure to anything else besides MET/SU. Adjusted time-dependent Cox regression and competing risk regression analysis, with daily updates of treatment modalities were performed. RESULTS: Mean age was 62.1 ± 11.2 years and follow-up was 4.6 ± 3.2 years (138496 person-years). Adjusted all-cause and cardiovascular mortality rates were significantly higher in MET as compared with SU group. All-cause mortality hazard ratios (HR) for cumulative time exposure were as follows: HR 0.956 (95%CI 0.951-0.962, p < 0.001) for SU added to MET, HR 1.092 (95%CI 1.087-1.096, p < 0.001) for SU replacing MET, HR 0.979 (95%CI 0.975-0.983, p < 0.001) for MET added to SU, and HR 1.127 (95%CI 1.118-1.136, p < 0.001) for MET replacing SU. CONCLUSION(S): The effect on all-cause mortality was beneficial for MET+SU combined therapy, but deleterious for either SU replacing MET, or MET replacing SU. There were no major outcome differences when analyzing individual SU, or specific mortality.

Obesity and eating behaviors in school children and adolescents -data from a cross sectional study from Bucharest, Romania.

BACKGROUND: Epidemiological data on obesity prevalence are scarce in Romanian population. Consequently, the aim of our study was to evaluate the prevalence of obesity and unhealthy behaviors among school children and adolescents from Bucharest, Romania. METHODS: Cross-sectional study, 866 participants (53.2% girls, 46.8% boys, age range 6-18 years), selected by systematic sampling with probability-proportionate-to-size from all Bucharest's schools. MEASUREMENTS: height, weight and a questionnaire to collect information about life style and eating behavior. Nutritional status was established based on World Health Organization recommendations (WHO), International Obesity Task Force (IOTF), Center for Diseases Control (USA-CDC) cut off values and local standards, respective. RESULTS: The prevalence of overweight (including obese) and obesity alone based on different standards, was 31.6% and 11.4% (WHO), 24.6% and 6.2% respectively (IOTF), 25.2% and 10% (USA-CDC), 22.3% and 12.5% (local standards). When using local standards (weight only based), the obese subjects proportion among overweight children raised questions regarding the appropriateness of these standards. Overweight (including obese) prevalence was significantly higher among the boys versus girls: 36.2% vs. 27.6%, ( OR 1.5; 95% CI 1.12-2.03; p value = 0.006) and among the 6-10.9 years vs. 11-17.9 age group, (40.7% vs 26.6%). Almost all the participants (95%) reported at list one unhealthy eating behavior but no significant relationship was found with overweight or obesity only. CONCLUSIONS: This first epidemiological study of obesity prevalence in school children and adolescents showed that 11.4% of Bucharest's children and adolescents were obese by WHO classification, 6.1% by IOTF cut off values and 10% by CDC classification. Younger children and the boys were more affected no matter which standard we used. In spite of unsignificant relationship to the adiposity status, our data showed a high prevalence of unhealthy eating behaviors reported by the participants. Particular aspects of the overweight versus obesity prevalence, after applying local standards, suggests that international recognized algorithms should be used for constant epidemiological evaluation instead of establishing local criteria.

The clinical value of human leukocyte antigen HLA-DRB1 subtypes associated to Graves' disease in Romanian population.

The aim of this study was to identify the primary susceptibility HLA-DRB1 alleles associated with GD in Romanian population and to seek whether specific HLA-DRB1 haplotypes are associated with differences in the clinical presentation of GD at diagnosis. Molecular typing of HLA-DRB1 alleles was performed in 77 Romanian Caucasian GD patients and 445 racially matched controls. In GD patients, age, presence of eye disease, goiter grade, autoantibody status and titer, TSH, FT4, FT3, TT3 levels were recorded at diagnosis. The allelic frequencies of HLA-DRB1*03 (41.55% vs. 17.75%, p < 0.0001, χ(2) = 20.81) and DRB1*11 (42.85% vs. 30.56%, p = 0.045, χ(2) = 3.98)were higher, whereas those of HLA-DRB1*01(3.89% vs. 16.40%, p = 0.007, χ(2) = 7.281) and DRB1*15 (10.38% vs. 21.34%, p = 0.038, χ(2) = 4.309)were lower in GD patients than in controls. FT4/TT3 ratio (p = 0.015) and anti-thyroglobulin antibodies (p = 0.024) were higher in *03/11 patients compared to *X/X, *11/Z, *03/Y patients (where X is any other allele than *03 and *11, Y is any other allele than *11, Z is any other allele than *03). In conclusion, HLA-DRB1*03 and DRB1*11 may be the primary susceptibility HLA-DRB1 alleles associated with GD in Romanian population, whereas HLA-DRB1*01 and DRB1*15 seem to be protective. At diagnosis, HLA-DRB1*03/11 GD patients had higher FT4/TT3 ratio and anti-thyroglobulin antibody levels.

Takotsubo cardiomyopathy and transient thyrotoxicosis during combination therapy with interferon-alpha and ribavirin for chronic hepatitis C.

BACKGROUND: Thyroid dysfunction is a common complication of chronic hepatitis C (CHC) and its therapy. Takotsubo cardiomyopathy (TCM) is a multifactorial, stress related cardiomyopathy, rarely reported in association with thyrotoxicosis. Simultaneous occurrence of TCM and thyrotoxicosis due to hepatitis C and its treatment has never been reported. CASE PRESENTATION: A 47-year-old woman was admitted for acute chest pain, dyspnea, palpitations and diaphoresis. She had been diagnosed with CHC and had undergone 7 months of IFNα and Ribavirin therapy. At admission electrocardiogram (ECG) showed ST segment elevation, negative T waves and troponin was elevated suggesting ST segment elevation myocardial infarction (STEMI). Echocardiography demonstrated left ventricular apical akinesia and ballooning, with a left ventricular ejection fraction (LVEF) of 35%. Contrast angiography showed normal epicardial coronaries, yet a ventriculogram revealed left ventricular apical ballooning, consistent with TCM. Cardiac MRI showed left ventricle apical ballooning and no late enhancement suggesting the absence of any edema, scar or fibrosis in the left myocardium. She was diagnosed with non-autoimmune destructive thyroiditis: TSH=0.001 mU/L, free T4=2.41 ng/dl, total T3=199 ng/dl and negative thyroid antibodies. The thyroid ultrasonography showed a diffuse small goiter, no nodules and normal vascularization of the parenchyma. Following supportive treatment she experienced a complete recovery after a few weeks and she successfully completed her antiviral treatment, with no thyroid or cardiovascular dysfunction ever since. In patients treated with IFNα for CHC, the prevalence of thyroid dysfunction varies between 2.5-45.3% of cases. TCM is a stress related cardiomyopathy characterized by elevated cardiac enzymes, normal coronary angiography and an acute, transient, left ventricular apical dysfunction that mimics myocardial infarction. Most of the patients survive the initial acute event, typically recover normal ventricular function within one to four weeks and have a favorable outcome, as was the case with our patient. Thyrotoxicosis induced stress cardiomyopathy is rare and has been mostly reported in association with Graves' disease, thyroid storm, thyrotoxicosis factitia or following radioiodine therapy for toxic multinodular goiter. CONCLUSION: Routine thyroid screening should be done in patients receiving IFN-alpha and Ribavirin for CHC and thyrotoxicosis should be considered as a possible and treatable underlying cause of TCM.

Aggressive Primary Thyroid Mucoepidermoid Carcinoma with Extensive Pulmonary Involvement.

Mucoepidermoid carcinomas (MECs) represent the most common malignant neoplasms of the salivary glands, but they have also been described in other unusual sites. Primary MECs originating in the thyroid gland are exceedingly rare, accounting for less than 0.5% of thyroid tumors. Owing to their low to medium grade, they are usually associated with an indolent evolution and a good long-term prognosis, generally being managed surgically based on the extent of the disease. However, this does not always apply, as primary thyroid MECs may present as metastatic or locally advanced diseases. While several treatment options have been explored in such cases, no consensus currently exists on their optimal treatment plan, and they should be managed in a multidisciplinary fashion. We report the case of a 67-year-old patient with primary MEC of the thyroid, which behaved aggressively, with extensive pulmonary metastasis, ultimately leading to the rapid clinical deterioration and death of the patient.

Exploring the severity and early onset of familial type 1 diabetes in Romania: genetic and microbiota insights.

Type 1 diabetes mellitus (T1DM) is a chronic condition characterized by pancreatic autoimmunity and destruction of the insulin producing beta-cells. The risk of familial type 1 diabetes (FT1DM) is greater in families with paternal T1DM. The children with paternal FT1DM have a more severe form of the disease with diabetic ketoacidosis. Three families with FT1DM, out of which two with paternal diabetes and daughters diagnosed with this disease, and one family with sibling FT1DM were evaluated between 2019-2021 in the Pediatric Diabetes and the Diabetes, Nutrition and Metabolic Departments of a tertiary hospital. Clinical, biological, and genetic evaluations were performed, together with an assessment of the gastrointestinal microbiota. The Romanian children with FT1DM had a more severe onset, a median of age at onset of 9 years old and a genetic predisposition with positive HLA DR3/R4, DQB1*02:01. The protecting allele, DPB1*04:01, was found only in the siblings with FT1DM. A gastrointestinal dysbiosis, characterized by pro-inflammatory bacteria, with high levels of Enterobacteriaceae and Candida, was observed in the gut microbiota. This is the first case series of FT1DM in Romanian patients that shows the presence of genetic determinants but also a pathological microbiota which may determine a more severe and an early-age onset of disease.

Association of HLA Haplotypes with Autoimmune Pathogenesis in Newly Diagnosed Type 1 Romanian Diabetic Children: A Pilot, Single-Center Cross-Sectional Study.

BACKGROUND: The increasing incidence of autoimmune diseases in type 1 diabetes mellitus (T1DM) patients highlights the influence of human leukocyte antigen (HLA) haplotypes on their development. This study aims to determine genetic predisposition to autoimmune diseases in T1DM patients, including thyroid disease and celiac diseases, and explore its correlation with vitamin D deficiency. METHODS: A cross-sectional study involving thirty-six T1DM children was conducted. Typing was performed for the HLA A, B, C, DP, DR, and DQ loci. Regression analysis linked DR-DQ haplotypes to T1DM and the associated conditions. RESULTS: The most frequent predisposing alleles and haplotypes were HLA-DR3 (70.27%), DQ2 (70.27%), DR3-DQ2 (70.27%), DQB1*02:01 (70.27%), A02 (54.05%), whereas the most prevalent protecting allele was DPB1*04:01 (52.63%). Positive correlations were observed between positive anti-thyroid peroxidase antibodies and the absence of protective alleles (DPB1*04:02, p = 0.036; DPB1*04:01, p = 0.002). Associations were found between the absence of DPB1*04:01 and anti-thyroglobulin antibodies (p = 0.03). HLA allele DPB1*03:01 was linked with vitamin D deficiency (p = 0.021). Positive anti-transglutaminase antibodies correlated with C03:03 (p = 0.026) and DRB1*04:01-DQA1*03-DQB1*03:01 (p < 0.0001) and the lack of DQA1*01:03-DQB1*06:03-DRB1*13:01 (p < 0.0001). CONCLUSIONS: The predisposing T1DM haplotypes were associated with the presence of anti-transglutaminase and anti-thyroid antibodies, indicating a genetic predisposition to autoimmune diseases.

Degraded Bone Microarchitecture in Women with PHPT-Significant Predictor of Fracture Probability.

Introduction: Patients with primary hyperparathyroidism (PHPT) experience bone mineral density (BMD) loss and trabecular bone score (TBS) alteration, which current guidelines recommend assessing. Considering TBS alongside BMD for a 10-year fracture risk assessment (FRAX) may improve PHPT management. Design: Retrospective, cross-sectional study composed of 49 Caucasian females (62 ± 10.6 years, 27.7 ± 0.87 kg/m2) with PHPT and 132 matched control subjects (61.3 ± 10.5 years, 27.5 ± 0.49 kg/m2) evaluated in 3 years. We assessed lumbar spine (LS) and femoral neck (FN) BMD, T and Z scores (GE Healthcare Lunar Osteodensitometer) and TBS (iNsight 1.8), major osteoporotic fracture (MOF), and hip FRAX. Results: Patients with PHPT had statistically lower mean values for lumbar spine bone mineral density (LS BMD) (0.95 ± 0.25 vs 1.01 ± 0.14 g/cm2, P = .01), LS T-scores (-2 ± 0.2 vs -1.4 ± 0.1 SD, P = .009), LS Z scores (-0.9 ± 0.19 vs -0.1 ± 0.11 SD, P = .009), femoral neck bone mineral density (FN BMD) (0.79 ± 0.02 vs 0.83 ± 0.01 g/cm2, P = .02), FN T-scores (-1.8 ± 0.13 vs -1.5 ± 0.07 SD, P = .017), FN Z scores (-0.51 ± 0.87 vs -0.1 ± 0.82 SD, P = .006), and TBS (0.95 ± 0.25 vs 1.01 ± 0.14 g/cm2, P = .01) compared with control subjects. 22.4% of patients with PHPT had degraded microarchitecture (TBS < 1.2) vs. 7.6% in control group (χ2 = 0.008). PHPT proved to be a covariate with unique contribution (P = .031) alongside LS BMD (P = .040) in a linear regression model [R 2 = 0.532, F(4,16) = 4.543] for TBS < 1.2. TBS adjustment elevated MOF FRAX both for PHPT (4.35 ± 0.6% vs 5.25% ± 0.73%, P < .001) and control groups (4.5 ± 0.24% vs 4.7% ± 0.26%, P < .001) compared with BMD-bases FRAX, but also increased differently between the 2 study groups (1.1-folds for PHPT patients and 1.04 for control subjects, P = .034). Conclusion: Compared with control, TBS-adjusted FRAX provides significantly higher MOF risk than BMD-based FRAX in PHPT women.

Thyroid autoimmunity in 72 children with type 1 diabetes mellitus: relationship with pancreatic autoimmunity and child growth.

The aim of this study was to assess the association between pancreatic and thyroid autoimmunity (TA) and determine impact of thyroid antibodies on statural growth. Seventy-two children with type 1 diabetes mellitus (TIDM) and no clinical evidence of thyroid disorders were evaluated: glycated haemoglobin (A1c), thyroid peroxidase antibodies (TPOAb), glutamic acid decarboxylase antibody (GADA), tyrosine phosphatase antibodies (IA2A), and thyroid-stimulating hormone (TSH). The score of standard deviation for height (SDS) was calculated. There were 72 patients, 38 (52.7%) boys and 34 (47.2%) girls, with a mean age of 10.89 +/- 4.26 years and a mean duration of T1DM of 3.41 +/- 2.56 years. TPOAb were present in 23.6% of patients; 12.5% of subjects were positive for GADA and 41.6% for IA2A. Patients with TA had more prevalent GADA and IA2A (23.5% vs. 9%, p < 0.001, and 58.8% vs. 36.3%, p < 0.001, respectively). A1c was higher in patients with TA (9.7% +/- 2.05% vs. 8.6% +/- 2.11%, p = 0.05). TA was associated with lower SDS (0.26 vs. 0.98, p = 0.043). TSH was higher in patients with TA (3.39 vs. 2.15 microU/mL, p < 0.05). Logistic regression analysis revealed that a negative SDS for height was independently associated with duration of diabetes (p = 0.049) and TSH (p = 0.027) but not with birth weight, A1c, and TPOAb. In conclusion, TA was found in 23.6% TIDM children. Patients with TA had significantly higher prevalence of GADA and IA2A and significantly higher A1c vs. patients without TA. Our data suggest significant association between TA and height in children with T1DM. SDS was independently associated with diabetes duration and TSH.

Assessment of peripheral blood cells parameters as a valuable tool in patients with neuroendocrine neoplasms.

OBJECTIVES: Neuroendocrine neoplasms (NENs) are an extremely heterogeneous medical entity, representing a diagnostic and therapeutic challenge. Chronic inflammation, as is the case with other malignancies, plays a crucial role in NEN carcinogenesis. DESIGN: The complete blood count (CBC) is a reliable tool for monitoring patients with cancer. Quantifying the absolute count of neutrophils (N), lymphocytes (L), platelets (P), and the ratios that derive from these parameters (neutrophil-to-lymphocyte ratio - NLR, platelet-to-lymphocyte ratio - PLR, and inflammatory systemic index - SII calculated as N×P/L) proved their prognostic and predictive value in numerous malignancies. MATERIALS AND METHODS: We aimed to investigate the utility of these hematological parameters in 31 patients with NENs of various locations. Our study included the comparative analysis of pre-treatment hematological markers in NEN patients versus 21 age and gender matched healthy individuals. Additionally, for 26 out of the 31 patients included we analyzed and compared the inflammatory markers before and after treatment initiation. RESULTS: The results revealed a statistically significant higher median value of N, NLR, PLR and SII in the NENs group in comparison with the values obtained in the control group and higher values of N, NLR and SII in the pretreatment group. Furthermore, we observed a higher mean value of the post-treatment P in the pancreatic NENs as opposed to the values obtained for other tumor locations. CONCLUSIONS: The current study emphasizes the importance of the evaluation of CBC in the NENs setting thus adding value to prognostic models that can be useful for risk stratification and medical decision-making.

Insights into Epigenetic Changes Related to Genetic Variants and Cells-of-Origin of Pancreatic Neuroendocrine Tumors: An Algorithm for Practical Workup.

Current knowledge on the molecular landscape of pancreatic neuroendocrine tumors (PanNETs) has advanced significantly. Still, the cellular origin of PanNETs is uncertain and the associated mechanisms remain largely unknown. DAXX/ATRX and MEN1 are the three most frequently altered genes that drive PanNETs. They are recognized as a link between genetics and epigenetics. Moreover, the acknowledged impact on DNA methylation by somatic mutations in MEN1 is a valid hallmark of epigenetic mechanism. DAXX/ATRX and MEN1 can be studied at the immunohistochemical level as a reliable surrogate for sequencing. DAXX/ATRX mutations promote alternative lengthening of telomeres (ALT) activation, determined by specific fluorescence in situ hybridization (FISH) analysis. ALT phenotype is considered a significant predictor of worse prognosis and a marker of pancreatic origin. Additionally, ARX/PDX1 expression is linked to important epigenomic alterations and can be used as lineage associated immunohistochemical marker. Herein, ARX/PDX1 association with DAXX/ATRX/MEN1 and ALT can be studied through pathological assessment, as these biomarkers may provide important clues to the mechanism underlying disease pathogenesis. In this review, we present an overview of a new approach to tumor stratification based on genetic and epigenetic characteristics as well as cellular origin, with prognostic consequences.

Body Composition as a Modulator of Bone Health Changes in Patients with Inflammatory Bowel Disease.

BACKGROUND: Bone impairment of multifactorial etiology is a common feature in inflammatory bowel disease (IBD). Body composition parameters, which might be selectively modified in these patients, are important determinants of bone strength. Our aim was to investigate the relationship between components of body composition and bone parameters in IBD patients. METHODS: This is a cross-sectional, retrospective study including 80 IBD patients (43 women, 37 men). Lumbar spine (LS), femoral neck (FN) and whole body DXA scans were performed to analyze regional bone mineral density (BMD), as well as body composition, including appendicular skeletal muscle mass index (ASMI), total and visceral fat mass (VAT). Trabecular bone score (TBS) was assessed using iNsight Software. RESULTS: Twenty (25%) IBD patients had inadequate LS-BMD z scores (<=-2DS). Lean mass (LM) was a significant determinant of LS-BMD, after adjusting for age, gender, BMI and fat mass (p < 0.01), while fat mass% remained associated with FN-BMD (p < 0.01). TBS correlated positively with BMI (r = 0.24, p < 0.05), LS-BMD (r = 0.56, p < 0.001), ASMI (r = 0.34, p < 0.001) and negatively with VAT/total fat% (r = -0.27, p < 0.05). Multivariate analysis showed that ASMI, LS-BMD (positively) and VAT/total fat% (negatively) were independently associated with TBS. CONCLUSIONS: In IBD patients, skeletal muscle mass and fat percentage and distribution are important factors associated with bone health.

How Many Times Can One Go Back to the Drawing Board before the Accurate Diagnosis and Surgical Treatment of Glucagonoma?

Glucagonomas are neuroendocrine tumors (NETs) that arise from the alpha cells of the pancreatic islets. They are typically slow-growing tumors associated with abnormal glucagon secretion, resulting in one or more non-specific clinical features, such as necrolytic migratory erythema (NME), diabetes, diarrhea, deep vein thrombosis, weight loss, and depression. Here, we report the case of a 44-year-old male with a history of diabetes mellitus, presenting with a pruritic and painful disseminated cutaneous eruption of erythematous plaques, with scales and peripheral pustules, misdiagnosed as disseminated pustular psoriasis and treated for 2 years with oral retinoid and glucocorticoids. During this period, the patient complained of weight loss of 32 kg and diarrhea and developed deep vein thrombosis. These symptoms, together with an inadequate response to therapy of the skin lesions, led to the reassessment of the initial diagnosis. Laboratory tests confirmed elevated plasma glucagon levels (>1000 pg/mL) and computed tomography (CT) scans revealed a 35/44 mm tumor in the pancreatic tail. Due to considerable disease complications and the COVID-19 pandemic, the surgical removal of the tumor was delayed for nearly 2 years. During this time, somatostatin analogue therapy efficiently controlled the glucagonoma syndrome and likely prevented tumor progression. As in other functional pancreatic NETs, the early clinical recognition of hormonal hypersecretion syndrome and the multidisciplinary approach are the keys for best patient management.