ACTA ENDOCRINOLOGICA (BUC)

Context. Advanced skin cancers have high mortality and morbidity, and early detection is crucial for prognosis. Information regarding the patterns of skin self-examination and tumor early detection in the Central and Eastern Europe is scarce. Objective. Analyze the gender differences in the practices and attitudes related to skin cancer early detection of skin cancer patients in Romania. Methods. Prospective questionnaire- based survey of patients with confirmed diagnosis of skin cancer, registered in a university reference center for dermatooncology between 2011-2012. Results. 122 skin cancer patients completed the survey (response rate 72%). Female skin cancer patients reported lower level of education and likelihood to receive a medical full skin examination. Women were more likely to check their own skin and to detect suspicious lesions on themselves and their partners than men. They delayed longer the presentation to a physician after noticing a suspicious lesion (11.4 months vs. 6.4 months median). 90.76% of all skin cancer patients were not warned by any doctor about their skin cancer risk; 30% of them never check their skin. Conclusions. Women tend to be more concerned about their skin than men, but receive less medical attention and delay longer the diagnosis. Our study also signaled an urgent need of improving the patients and physicians education for skin cancer early detection in Romania.

Context. Different polymorphisms of the endothelial nitric oxide synthase gene (NOS3) have been related to diabetic kidney disease. Objective. To evaluate the association between advanced diabetic chronic kidney disease (ACKD) and the rs1799983 and rs2070744 poymorphisms of NOS3 in a population from the Gran Canaria island. Design. Cross-sectional case-control study. Subjects and methods. Polymorphisms were genotyped in 152 subjects with ACKD secondary to type 2 diabetes [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2], 110 subjects with type 2 diabetes for 20 or more years since diagnosis without ACKD (eGFR ≥45 mL/ min/1.73m2 and albumin/creatinine ratio <300 mg/g and/or 24-h urinary albumin excretion <300 mg) and 292 healthy controls. Association between both polymorphisms and established coronary heart disease (CHD) was also analyzed in both groups with diabetes. Results. A greater proportion of homozygous individuals for the risk allele C of rs2070744 was found among subjects with ACKD. Association between ACKD and rs2070744 was observed in a recessive genetic model, both for comparison to subjects with diabetes but no ACKD [OR 2.17 (95% CI: 1.17-4.00), p=0.014] and for comparison to healthy controls [OR 1.61 (1.03-2.52), p=0.036]. The frequency of the C allele was significantly higher among subjects with CHD, but only in the group with ACKD. No associations were found for rs1799983. Conclusions. NOS3 rs2070744 is associated with ACKD in population with type 2 diabetes from Gran Canaria. A link between this genetic variant and CHD in Canarian subjects with type 2 diabetes could be restricted to cases with ACKD.

Context. In HIV+ patients, several factors related to patient and antiretroviral therapy (ART) could determine early onset of bone mineral density (BMD) disturbances. Objective. Evaluation of bone quality according to gender in patients from the HIV Romanian cohort. Design. A cross-sectional study in “Prof. Dr. Matei Balș” National Institute for Infectious Diseases, Bucharest between 2016-2018. Subject and Methods. We collected data regarding HIV infection, ART history, viral hepatitis co-infections and we calculated patients body mass index (BMI). CD4 cell count, HIV viral load (VL), vitamin-D levels were determined. Dual-energy X-ray absorptiometry (DXA) scans were used to evaluate BMD. Results. We enrolled 97 patients with the median age of 26 years. According to the DXA T-scores, 10 males and 8 females had osteopenia and 4 males and 4 females had osteoporosis. According to Z-scores 2 males and 1 female had osteoporosis. Hip DXA T-scores revealed osteopenia in 6 males and 9 females, whereas T and Z-scores showed osteoporosis in 2 males and 3 females. Lumbar spine (LS) T-score diagnosed osteopenia in 9 males and 6 females, while T and Z-scores revealed osteoporosis in 3 males and females. In males, low T-scores were associated with decreased BMI; low LS DXA Z-scores with low vitamin-D levels; low T and Z-scores and LS-BMD with high VL. Conclusions. Evaluating bone quality in patients with a long history of HIV infection, multiple factors should be taken into account.

Background and aim. The goals of bariatric surgery are to improve the quality of life by lowering body mass index (BMI) but also to treat obesity comorbidities. The aim of our study was to evaluate the impact of laparoscopic sleeve gastrectomy (LSG) on metabolic parameters. Methods. 85 obese patients treated by bariatric surgery LSG procedure were included in the study. Basal, 6 and 12 months after surgery serum glucose levels and lipid fractions were measured. Metabolic syndrome criteria according to IDF 2006 were evaluated at baseline and after bariatric surgery. Results. Our group included 61.2 % female patients, the mean age was 40.2 ±10.2 years and the metabolic syndrome criteria at baseline were confirmed in 69.4% of the study group. At twelve months after the intervention, the mean excess weight loss (%EWL) was 72%, with age and BMI subgroups variations. We found significant improvements of serum concentrations for triglycerides (P-value = 0.001, decreased by 30%), HDL-cholesterol (P-value = 0.017, increased by 26%), total cholesterol (P-value = 0.043, decreased by 12%) and glucose (P-value = 0.007, decreased by 12%). Conclusions. The positive effect of bariatric surgery was confirmed for lipid fractions and fasting glucose levels, also the metabolic syndrome prevalence was significantly reduced, all these changes contribute to lower cardiovascular risk together with significant weight loss.

49, XXXXY karyotype syndrome has an incidence of between 1/85 000 and 1/100 000 live births. Typical clinical features include hypogonadism, mental retardation with severe learning difficulties, craniofacial and skeletal abnormalities, but also congenital heart disease. We report on a 4 year-old boy diagnosed with severe generalized hypotonia during his first year of life. Behavioural and cognitive profiles of the case are presented. MRI shows apart from global volume loss and atrophy, scattered punctate foci of T2 signal hyperintensity in the white matter. Endocrine investigations revealed impaired GH concentration during clonidine test, low IGF-1 concentration and cryptorchidism. Long term follow-up of patients with polysomy X by a team of specialists in pediatric neurology, endocrinology and cardiology is mandatory.

Context. Papillary thyroid carcinoma(PTC)s are the indolent progressive tumours. Survivin is a unique bifunctional protein with cell cycle regulation and apoptosis inhibition. The expression of this protein has been shown to be increased in thyroid tumours correlated with aggressive behavior from well differentiated to anaplastic. Objective. In this study, we aimed to investigate the relationship between immunohistochemically survivin expression and tumour-associated prognostic factors in papillary thyroid carcinomas. Design. In patients with thyroidectomy, we compared the clinicopathological findings and immunohistochemical positivity for survivin. Subjects and Methods. In 109 patients, sex, age, tumour size, histological tumour variant, tumour focality, tumour border pattern, tumour peripheral/intratumoural lymphocytic and stromal response, intraglandular spread, extrathyroideal spread, lymph node metastases, lymphocytic tiroiditis and relationships of these findings with survivin positivity were investigated. Results. When we indicated the tumour size and compared it with survivin expression, tumour size correlates with, survivin expression (p = 0.016). Survivin expression was correlated statistically significant with lymphovascular invasion, without stromal response and with intraglandular extension respectively (p<0.001, p = 0.043, p<0.001). No significant correlation was found between other clinicopathological parameters and survival. Conclusion. Few studies have investigated the relationship of survivin expression with prognosis in thyroid papillary carcinomas and showed that survivin was a poor prognostic marker. If its expression is detected in preoperative cytology smears, it may affects the surgical treatment strategy. When it is detected in the tissue, postoperative radioactive iodine treatment plan may be modified and the need for more aggressive follow-up may be considered.

Objective. This study aims to investigate the factors affecting development of acute kidney injury (AKI) in patients with severe hypothyroidism. Methods. This retrospective observational study involved patients with primary hypothyroidism and thyroid stimulating hormone (TSH) levels of more than 50 mIU/L at their review in the endocrinology outpatient clinic, between January 2015 and April 2021. Factors affecting the development of AKI were examined by logistic regression analysis. Results. A total of 100 patients, 20 (11 male (M), 9 female (F)) in the AKI (case) group and 80 (23 M, 57 F) patients in control group, were included in our study. The median age of the case group (56 years, interquartile range (IQR) 44.3–68.5) was significantly higher than the control group (49 years, IQR 32.3–60; p = 0.027), and the ratio of males to females was significantly higher in the case group (p = 0.001). Multivariate logistic regression analyses showed that hypothyroidism diagnosed after the age of 60 years (odds ratio (OR) 59.674, 95% confidence intervals (CI) 5.955–598.031; p = 0.001), free triiodothyronine (FT3) < 1.3 pg/mL (OR 17.151, 95% CI 2.491–118.089; p = 0.004) and creatine kinase (CK) > 1000 U/L (OR 1.522, 95% CI 1.602– 82.848; p = 0.015) were predictors for the development of AKI in patients with severe hypothyroidism. Conclusion. We recommend close follow-up and monitoring of patients with AKI caused by severe hypothyroidism if patients who are diagnosed at age > 60 years, CK > 1000 U/L or FT3 < 1.3 pg/mL.

Background. Heterozygous gain-of-function mutations in the glucokinase (GCK) gene cause hyperinsulinaemic hypoglycaemia (GCK-HI), while lossof- function mutations lead to a monogenic type of diabetes (GCK-MODY). We, herein, report a heterozygous GCK gene mutation in a large family with GCK-MODY and insulinoma in one individual from the same family. Patients and methods. The proband, an 11-yearold male, was referred for asymptomatic mild hyperglycemia (fasting glucose:121 mg/dL) and HbA1c of 6.1%. Segregation analysis of the family revealed multiplex members with asymptomatic fasting hyperglycaemia or non-insulindependent diabetes and 33-year-old maternal uncle of the proband case had a history of distal pancreatectomy due to the diagnosis of insulinoma. His preoperative investigations were revealed fasting glucose of 31 mg/dL, insulin: 7μU/ mL, C-peptide: 2.6 mg/dL, and a low HbA1c(4.0%) which was suggestive for recurring hypoglycaemia episodes. Postpancreatectomy he developed mild fasting hyperglycemia (115-136 mg/dL). Results. Genetic analysis revealed heterozygous p.Ser453Leu(c.1358C> T) mutation in the GCK gene in the proband. In segregation analysis, the identical heterozygous p.Ser453Leu(c.1358C> T) GCK gene mutation was detected in all of the other affected family members for whom a DNA analysis was applicable. The maternal uncle was first diagnosed with insulinoma and underwent a pancreatectomy. He also had an identical mutation in a heterozygous state. Conclusion. We, to the best of our knowledge, firstly identified these two entirely distinct phenotypes of glucose metabolism, GCK-MODY and GCK-HI, due to an identical heterozygous p.Ser453Leu (c.1358C> T) mutation in the GCK. Further studies required to elucidate this new phenomenon and understanding the genotype-phenotype relationship of GCK gene mutations.

Background. There have been a number of reports on the relationship between the PPARγ2 Pro12Ala genotype and the development of obesity. Objective. A case-control survey was designed to investigate the potential association between a Pro12Ala polymorphism in the PPARγ2 gene and obesity and/or obesity-related phenotypes in a population from Turkey. Materials and methods. The polymerase chain reaction and restriction enzyme digestion were used to genotype the Pro12Ala polymorphism of the PPARγ2 gene in 149 unrelated obese and 105 non-obese control subjects from Turkey. The data were analyzed statistically. Results. We found that the overall minor allele frequency was 0.12 in cases and 0.095 in controls. In terms of genotype distribution and allele frequencies among the cases versus controls in the population studied, only the genderstratified analysis revealed a significantly higher frequency of Pro/Ala genotype within males. The polymorphism was associated with significantly higher weight, height, waist circumference, central adiposity (waist-to-hip ratio, WHR), lean body weight as well as dry body weight, but not overall adiposity (total body fat percentage, TBF) in cases carrying Ala allele (Pro/Ala or Ala/Ala). However, in the subjects carrying Ala allele of the control group, WHR values were found significantly lower. Conclusion. Our results showed that the Pro12Ala polymorphism in the PPARγ2 gene is associated with obesity in the studied adult population from Turkey. These data suggest that the Pro12Ala polymorphism in PPARγ2 may be a potential genetic risk factor for central obesity.

A 20-year-old woman was studied because of lack of spontaneous pubertal development and primary amenorrhea. At the moment of examination in the Medical Genetics Department she had normal height, sparse axillary and pubic hair, but breasts were well developed (she already had some estrogen therapy). She had normal but infantile external genitalia, normal vagina and small uterus. Laparoscopic investigation suggested the presence of gonadoblastoma in the dysgenetic gonads and histopathologic examination confirmed the diagnosis. The karyotype revealed a 46, XY chromosome constitution in lymphocytes, without structural defects of X or Y chromosomes. Because of the risk of malignancy, gonadectomy was performed.