ACTA ENDOCRINOLOGICA (BUC)

Context. Intermedin (IMD) is the member of calcitonin gene-related peptide family, and tightly associated with type 2 diabetes mellitus (T2DM). The change of plasma IMD levels in T2DM is still unknown. Objective. We aimed to investigate the plasma levels of IMD in patients with T2DM. Design. Fortyone patients with T2DM who were hospitalized in the endocrinology department of Civil Aviation General Hospital from January 2012 to June 2015 were enrolled, and 44 volunteers were selected as the control group. Subjects and Methods. Plasma level of IMD was detected by ELISA. Diagnostic value of IMD was analyzed by area under the receiver operating characteristic (ROC) curve (AUC). Results. The plasma level of IMD in T2DM group was higher than that in the healthy control group, whereas smoking or cardiovascular complications did no influence the IMD levels. IMD levels were correlated with BMI, DBP, triglyceride, uric acid, urea nitrogen, fasting and 2 hours postprandial blood glucose, and HbA1C. The greatest value of AUC for IMD was only 58.73%. Conclusions. Although plasma levels of IMD were increased in patients with T2DM, the very low diagnostic value of IMD for T2DM might not be used for the disease diagnosis.

Background. To evaluate iodine status and the prevalence of thyroid disorders in different populations of Zhoushan Island, China.\r\nMethods. A total of 3284 inhabitants of Zhoushan Island were surveyed, including 1389 urban residents, 737 salt workers, 502 peasants, 362 fishermen, and 294 monks from Mount Putuo. All subjects, except for salt workers, consumed iodized salt. A thyroid ultrasound was performed and serum levels of\r\nthyroid hormones and thyroid peroxidase antibody were measured.\r\nResults. The median urinary iodine concentration was significantly higher in subjects who consumed iodized salt than in those who consumed non-iodized salt. No significant differences were noted in the prevalence of thyroid ultrasound abnormalities and functional thyroid disorders between subjects who consumed non-iodized and iodized salt except between salt workers and monks from Mount Putuo. The prevalence of thyroid ultrasound abnormalities differed\r\nsignificantly between males and females and was positively correlated with advanced age (r=0.212, P<0.001).\r\nConclusions. Iodine intake is considered adequate, more than adequate, or excessive amongst the study populations. The\r\nprevalence of both thyroid ultrasound abnormalities and functional thyroid disorders is extremely high in Zhoushan Island. Advanced age and female gender are significant predictors of thyroid ultrasound abnormalities.

No inheritance of early-onset female-related type 2 diabetes was reported within Chinese families. In this study, we aim to describe the inheritance pattern of type 2 diabetes in a 3-generation family and identify the gene responsible for type 2 diabetes. Genome-wide multipoint parametric linkage analysis revealed a maximum multipoint logarithm of odds (lod) score of 2.1 for a locus being associated with type 2 diabetes in this family on chromosome 20p11.2-12 between 23.5~30.8cM. Type 2 diabetes may be transmitted as an autosomal dominant trait with a high female-related penetrance in this family. Here we describe the first genetic locus for type 2 diabetes at chromosome 20p11.2-12. This region contains 8 known or predicted genes (PLCB1, PLCB4, LAMP5, PAK7, ANKEF1, SNAP25, SLX4IP, and JAG1). Gene SNAP25 which linked to energy or glucose homeostasis associated phenotypes may play a role in the development of type 2 diabetes in this family.

Background. The purpose of this study was to observe the effects of denosumab on bone mineral density (BMD), bone turnover markers and serum calcium in patients with primary hyperparathyroidism (PHPT) and osteoporosis. Methods. Seven consecutive patients with PHPT were administered a single subcutaneous injection of denosumab, 60 mg. The subjects were followed up to 6 months: serum calcium on days 1,3,7,14,30 and at 3 months and 6 months; serum intact parathyroid hormone (iPTH), C-telopeptide (CTX) and N-mid osteocalcin at baseline, 3 months and 6 months. BMD by DXA, at the femoral neck (FN) and lumbar spine (LS), were measured at baseline and at 6 months. Results. The patients (mean age= 69.8 yrs, range 62-81) had mild PHPT (mean total calcium = 10.8 mg/dL; mean PTH = 148.9 pg/mL); all had osteoporosis and four were currently treated with various bisphosphonates (BP). After 6 months mean LS BMD increased significantly by 4.5 % (p = 0.04) and mean FN BMD by 2.4% (p= 0.09 two-tailed; p = 0.047 one-tailed). Serum CTX decreased significantly by 90% at 3 months (p = 0.04), and by 48% at 6 months (p = 0.02); the similar changes for serum osteocalcin were 41% and 42% (p = 0.07, onetailed), respectively. In the first two weeks, serum total Ca variably decreased vs. baseline (0.5 to 2.8 mg/dL) in six out of seven patients. After 6 months mean total serum Ca nonsignificantly increased vs. baseline (11.4 mg/dL vs. 10.8 mg/dL, p = 0.1). Serum iPTH levels did not significantly change at both 3 and 6 months; after 6 months there was a trend toward decreased values (p = 0.03 onetailed). Conclusion. Denosumab increased BMD at both lumbar spine and femoral neck, and significantly decreased bone resorption in patients with PHPT. The effects on hypercalcemia were mild and transient, with a numerical increase after 6 months.

Context. Hyperparathyroidism-jaw tumour (HPTJT) syndrome is a rare autosomal dominant cause of familial hyperparathyroidism associated with ossifying fibromas (OF) of the maxillofacial bones and increased risk of parathyroid carcinoma, caused by inactivating germline mutation of the cell division cycle 73 (CDC73) gene. Objective. To report the first Romanian family with HPT-JT and genetic screening of CDC73 gene. Subjects and Methods. Mutational analysis of the CDC73 gene and genetic screening of the family of a proband with HPT-JT. Histological diagnosis of parathyroid tumors (WHO criteria) and immunohistochemistry (parafibromin) were performed. Results. Three of the six screened family members had evidence of PHPT and surgically proven parathyroid tumours. Two of the three affected members had parathyroid carcinomas and one had two parathyroid adenomas. Genetic screening of CDC73 gene revealed that 4 of 6 patients showed a heterozygous germline deletion of one nucleotide: c.128-IVS1+1 delG. All the three affected patients, resulted to be carriers of the CDC73 mutation, but each one bearing a different CDC73 polymorphism. Conclusions. We identified a new CDC73 germline mutation in a Romanian family of HPT-JT. Analysis of clinical phenotypes in the four mutated individuals confirmed the incomplete penetrance and the variable clinical expression of the disease.

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Objective. To study the effect of diethylhexyl phthalate (DEHP) alone or in combination with genistein (GEN) on the reproductive system of offspring rats, focus on the induction of reproductive outcomes. Method. 180 Wistar rats were divided in 6 groups (30 animals per group): DEHP 250 mg/kg/day group, DEHP 1000 mg/kg/day group, DEHP 2500 mg/kg/day group treated with DEHP 2500 mg/kg/day, DEHP (2500 mg/kg) + GEN (50 mg/kg) group, DEHP (2500 mg/kg) + GEN (500 mg/kg) group and control group treated with the same quantity of corn oil. The differences in sperm quality and reproductive organs were observed. Results. After DEHP administration we observed an increase in rat’s abestrus, metaestrus and all estrus cycle (P < 0.05), a decrease in rat testicle’s organ coefficient and relative energy of testis Sertoli cells and an increase in the early, late and total apoptotic rate of testicular Sertoli cells in a dose dependent manner (P < 0.05). When combine DEHP with GEN the sperm density, sperm quality, the cell activity rate and testis tissue’s changes will decrease compared with the group that receive only DEHP in a dose dependent manner. Conclusion. DEHP exposure induces cryptorchidism in offspring rats and this is aggravated by adding GEN.

Context. Data are conflicting concerning risk for Alzheimer’s disease (AD) and 5,10-methylenetetrahydrofolate reductase genetic variant (MTHFR C677T). Objective. The aim of the study was to investigate the associations of MTHFR C677T and risk of developing AD. Design and Methods. We searched the relevant articles by using Medline, web of science, and abstracts of conference proceedings. The meta-analysis and statistical analyses were performed using Stata. Results. In 33 included studies which provided 4518 cases and 5476 controls, the analysis for investigating the association between C677T allele T and the risk of developing AD relative to the allele C revealed no heterogeneity (p=0.088, I2=26.1%) between the 33 studies; the random effects (RE) pooled OR was significant: [RE OR=1.13(1.05-1.22)]. In subgroup analysis, we only observed the significant results in Asian populations. The pooled analysis for MTHFR 677 CT+TT vs. 677CC revealed a significant result [fixed effect (FE) OR=1.22(1.10-1.34)]. However, we did not observe significant associations in Europeans when comparing MTHFR 677 CT+TT with 677CC in subgroup analysis. The pooled analysis for MTHFR 677 TT vs. 677CC+CT did not reveal significant results: [FE OR=1.08(0.95-1.22)]. Conclusion. The risk allele T of MTHFR C677T is associated with high risk of AD in Asian populations, but not in Europeans.

Context. Results concerning the relationship between the risk of developing diabetic retinopathy (DR) and methylenetetrahydrofolate reductase genetic variant (MTHFR C677T) are inconclusive. Objective. The aim of the present analysis was to investigate the associations of DR with MTHFR C677T. Design and Methods. We searched the relevant articles by using Medline, web of science, and abstracts of conference proceedings. The meta-analysis was performed using Stata. Results. The included 7 studies provided 535 cases of DR and 759 controls. The main analysis for investigating the association between MTHFR 677 TT and the risk of developing DR relative to the 677 CC did not reveal significant heterogeneity (p=0.227, I2=27.6%) between the studies; the fixed effects (FE) pooled OR was significant: FE OR=1.84(1.30-2.61). The analysis for the association between MTHFR 677 TT and the risk of developing DR relative to the 677 CC+CT revealed heterogeneity (p=0.082, I2=48.9%) between the studies; the random effects (RE) pooled OR was significant: RE OR=1.72(1.07-2.76). In addition, T carriers have 31% higher risk of developing DR compared with homozygotes for C [OR=1.31(1.03-1.66)]. Conclusions. The present metaanalysis suggested an association between MTHFR C677T and DR and provided evidence that the TT genotype of the MTHFR C677T contributes to susceptibility to DR.

Background. Unexplained high bone mass (HBM) (Bone Mineral Density-BMD Z-score at the lumbar spine or hip of ≥+3.2 SD, or a combined spine and hip Z score ≥4 SD) after routine bone densitometry occurs with a prevalence of approximately 2 out of 1.000 and is currently believed to be a mild form of skeletal dysplasia (1). Results. We present the case of a patient with unexplained HBM (Z-scores at L3, L1-L4, total hip and radius total were +3, +2.7, +2 and +1.8, respectively) and concurrent symptomatic primay hyperparathyroidism (total serum calcium 11.9 mg/dL, serum Parathyroid Hormone - PTH 189.3 pg/mL) of long duration. There were no significant BMD changes at any skeletal site after the surgical cure of hyperparathyroidism. Testing for LRP (low density lipoprotein receptor-related proteins) 5 gene mutations was negative. Conclusions. We presented an unusual case of the association of a HBM with primary hyperparathyroidism with resistance to the catabolic action of PTH. In spite of the negative result of LRP5 testing we do believe that a mutation of a gene involved in the Wnt pathway in bone is responsible.