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.

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.

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.

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.

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.

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.

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.

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.

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.

Perspectives on the diagnostic, predictive and prognostic markers of neuroendocrine neoplasms (Review).

Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare tumors with different types of physiology and prognosis. Therefore, prognostic information, including morphological differentiation, grade, tumor stage and primary location, are invaluable and contribute to the formulation of treatment decisions. Biomarkers that are currently used, including chromogranin A (CgA), serotonin and neuron-specific enolase, are singular parameters that cannot be used to accurately predict variables associated with tumor growth, including proliferation, metabolic rate and metastatic potential. In addition, site-specific biomarkers, such as insulin and gastrin, cannot be applied to all types of NENs. The clinical application of broad-spectrum markers, as it is the case for CgA, remains controversial despite being widely used. Due to limitations of the currently available mono-analyte biomarkers, recent studies were conducted to explore novel parameters for NEN diagnosis, prognosis, therapy stratification and evaluation of treatment response. Identification of prognostic factors for predicting NEN outcome is a critical requirement for the planning of adequate clinical management. Advances in 'liquid' biopsies and genomic analysis techniques, including microRNA, circulating tumor DNA or circulating tumor cells and sophisticated biomathematical analysis techniques, such as NETest or molecular image-based biomarkers, are currently under investigation as potentially novel tools for the management of NENs in the future. Despite these recent findings yielding promising observations, further research is necessary. The present review therefore summarizes the existing knowledge and recent advancements in the exploration of biochemical markers for NENs, with focus on gastroenteropancreatic-neuroendocrine tumors.

Platelet Activation and Inflammation in Patients with Papillary Thyroid Cancer.

BACKGROUND: The primary endpoint was to analyze the preoperatory inflammatory markers and platelet indices in papillary thyroid cancer (PTC) patients compared with patients with benign thyroid pathology. The secondary endpoints were to analyze the relationship between these markers and the pathological features of PTC and to compare their pre- and postoperative levels in PTC patients. METHODS: In this retrospective case-control study, we analyzed the files of 1183 patients submitted to thyroidectomy between January 2012 and December 2018. A total of 234 patients with PTC (mean age 51.54 ± 13.10 years, 84.6% females) were compared with an age-, gender- and BMI-matched control group of 108 patients with histologic benign thyroid disorders. RESULTS: PTC patients had higher platelet count (PLT) (p = 0.011), plateletcrit (PCT) (p = 0.006), neutrophil (p = 0.022) and fibrinogen (p = 0.005) levels. Subgroup analysis showed that PTC females had higher PLT (p = 0.006), PCT (p < 0.001) and erythrocyte sedimentation rate (ESR) (p = 0.005), while males had higher neutrophil (p = 0.040) levels. Papillary thyroid cancer patients under 55 years had higher PLT (p < 0.001) and PCT (p = 0.010), while patients over 55 years had higher mean platelet volume (p = 0.032), neutrophil-to-lymphocyte ratio (p = 0.013), ESR (p = 0.005) and fibrinogen (p = 0.019) levels. Preoperative values for platelet indices and inflammatory markers were similar to the postoperative determinations in PTC patients. Fibrinogen (AUROC = 0.602, p = 0.02; cut-off = 327.5 mg/dL, Se = 53.8%, Sp = 62.9%) and PLT (AUROC = 0.584, p = 0.012; cut-off = 223.5 × 103/mm3, Se = 73.1%, Sp = 42.6%) were independent predictors of the presence of PTC. CONCLUSIONS: Our data show that fibrinogen and platelet count could be promising, inexpensive, independent predictors for the presence of PTC when compared with benign thyroid disorders.

Assessment of bone quality with trabecular bone score in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) patients have a significant risk of developing bone loss. The trabecular bone score (TBS) is a relatively new parameter used to provide information on bone quality. The study cohort included 81 patients with IBD and 81 healthy controls. Blood tests, dual-energy x-ray absorptiometry (DXA), including TBS, were assessed. Harvey-Bradshaw Index (HBI) for Crohn's disease (CD) and the Partial Mayo Score for ulcerative colitis (UC) were used for evaluation of clinical disease activity. Compared with the healthy controls, the IBD patients had lower lumbar spine (LS) bone mineral density (BMD) (1.06 ± 0.18 vs. 1.16 ± 0.15 g/cm2, p < 0.005), hip BMD (0.88 ± 0.13 vs. 0.97 ± 0.13 g/cm2, p < 0.005) and TBS (1.38 ± 0.1 vs. 1.43 ± 0.1, p < 0.005) values. The patients with stricturing CD had lower TBS (1.32 ± 0.13 vs. 1.40 ± 0.9, p = 0.03) and LS BMD (0.92 ± 0.19 vs. 1.07 ± 0.1, p = 0.01) values compared with those with non-stricturing CD. Multivariate regression model analysis identified HBI as independent factor associated with TBS. Our results support that all DXA parameters are lower in patients with IBD than in healthy patients. Moreover, TBS is a valuable tool for assessment of bone impairment in active CD.

Bone Mineral Density Trends During the First Year After Laparoscopic Sleeve Gastrectomy-a Cohort Study on 241 Patients.

PURPOSE: Laparoscopic sleeve gastrectomy (LSG) is an effective weight loss procedure, but detrimental effects on bone health have been described. We aimed to assess the dynamics of regional and total bone mineral density (BMD) in a cohort of patients undergoing LSG and to capture gender differences in terms of evolution. MATERIALS AND METHODS: We conducted a retrospective study on 241 patients who underwent LSG to determine the regional and total BMD changes at 6 and 12 months after the intervention. RESULTS: One hundred ten males and 140 females (97 pre-, 43 postmenopausal) were included. Mean baseline body mass index (BMI) was 44.16 ± 6.11 kg/m2 in males and 41.60 ± 5.54 kg/m2 in females, reaching 28.62 ± 4.26 kg/m2 and 27.39 ± 4.2 kg/m2, respectively, at 12 months. BMD showed a continuous decline, with significant loss from 6 months postoperatively. There was a positive correlation between BMD and BMI decline at 12 months (r = 0.134, p < 0.05). Total BMD loss at 12 months was significantly greater in males than premenopausal females, independent of BMI variation and age. During the first 6 months, men lost significantly more bone mass than premenopausal and postmenopausal women (BMD variation was 2.62%, 0.27%, 1.58%, respectively). The second period (6-12 months) was similar in all three groups, revealing a further steady (~ 1.4%) BMD decline. CONCLUSIONS: Our results are consistent with previous findings that LSG negatively impacts BMD, stressing the importance of bone health-oriented measures in postoperative care. Moreover, the impact that seems more significant in males warrants future exploration, as it might change clinical practice.

Lean mass, magnesium, faecal calprotectin and glucocorticoid exposure as risk factors for low bone mineral density in inflammatory bowel disease patients.

BACKGROUND AND AIM: Low bone mineral density (BMD) is a common complication in patients with inflammatory bowel disease (IBD). However, debates are ongoing with regard to the other involved factors, especially in younger patients. This study aimed to evaluate the parameters that contribute to decreased BMD, focusing on premenopausal women and men aged <50 years. METHODS: This study included 81 patients with IBD and 81 age-, sex- and BMI-matched controls. Blood tests were conducted on IBD patients, and a dual-energy X-ray absorptiometry (DXA) scan was performed on both groups. RESULTS: Low BMD and fragility fracture were found to be more prevalent in IBD patients than in healthy subjects (49.3% vs 23.4%, P = 0.001 and 9.8% vs 1.2%, P = 0.01, respectively). Patients with low BMD were older, with a longer disease duration, higher faecal calprotectin (FC) levels and lower magnesium and lean mass (appreciated as appendicular skeletal muscle index (ASMI)). Multiple regression analysis revealed that ASMI, age and use of glucocorticoids were the independent parameters for decreased BMD. Although 91.3% of the patients had a 25-hydroxy vitamin D level of <30 ng/mL, it was not a statistically significant factor for decreased BMD. CONCLUSION: In our study, the levels of vitamin D did not seem to have an important impact on BMD. Conversely, FC, magnesium and lean mass are important factors, suggesting that good control of disease, adequate magnesium intake and increased lean mass can have a good impact on bone metabolism in patients with IBD.

Secondary thyroid malignancy - a rare clinical finding?

Metastases to the thyroid gland, while rarely seen in clinical practice, can pose a diagnostic and therapeutic challenge. Most commonly, they originate from lung, renal, and breast cancer, and are generally a sign of multiorgan metastatic disease. In most cases, metastases to the thyroid gland are diagnosed incidentally on imaging studies, since they are rarely symptomatic and often do not influence thyroid function tests. Thyroid ultrasonography and fine-needle aspiration biopsy play a pivotal role in their evaluation, as both classic immunocytochemical features, and more novel molecular markers can help in the differential diagnosis. Prognosis mainly depends on the biology of the primary tumor and its extension. Communication between clinicians is essential in such patients, in order to ensure that the treatment options are carefully balanced, thus raising the need for multidisciplinary teams in their management.

Somatostatinoma and Neurofibromatosis Type 1-A Case Report and Review of the Literature.

Somatostatinomas are rare neuroendocrine tumors (NET) that arise in the gastrointestinal (GI) tract. Because of their insidious growth, they are usually asymptomatic until late stages, presenting as malignant disease. We report the case of a 50-year-old woman who presented with epigastric abdominal pain, diarrhea and significant weight loss in the last two years. On clinical examination the patient met the criteria for neurofibromatosis type 1 (NF1). Abdominal CT and MRI revealed an infiltrative duodenal mass, with pancreatic invasion, locoregional enlarged lymph nodes and disseminated hepatic nodules. Microscopy and immunohistochemistry uncovered a neuroendocrine tumor, staining positive for chromogranin A (CgA), synaptophysin and somatostatin, with a Ki67 = 1%. Somatostatin receptors (SSTRs) type 2 were negative and SSTRs type 5 were positive in less than 50% of tumoral cells. Our patient was classified as a T3N1M1 stage IV metastatic duodenal grade 1 somatostatinoma and treatment with somatostatin analogues and chemotherapy with capecitabine and temozolomide was started, with so far abdominal imaging follow-up showing stable disease. When a patient is diagnosed with a rare NET, such as a somatostatinoma, it is of utmost importance to determine if it is a sporadic tumor or just a feature of a genetic disorder.

Hereditary leiomyomatosis and renal cell cancer syndrome - case report and review of the literature.

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is an exceptionally rare autosomal dominant condition caused by a germline heterozygous mutation of the fumarate hydratase gene. It manifests as multiple piloleiomyomas, associated with numerous, early-onset uterine leiomyomas in female patients, as well as a highly increased risk of renal cell carcinoma (RCC), most often type 2 papillary RCC. HLRCC has been described in association with adrenal cortical hyperplasia, pheochromocytoma, adrenal cortical carcinoma, and other solid tumors, but the exact relationship between these disorders has not yet been clarified. We present a case of HLRCC associated with bilateral adrenal cortical hyperplasia and discuss the pathogenesis, clinical and paraclinical features of HLRCC, as well as the adequate management of these patients.

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.

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.