Metabolic and bone profile in postmenopausal women with and without type 2 diabetes: a cross-sectional study.

INTRODUCTION: Current studies support the implication of metabolic changes associated with type 2 diabetes in altering bone metabolism, structure and resistance. OBJECTIVE: We conducted a cross-sectional study on postmenopausal women aimed to analyze the differences in metabolic and bone profile in patients with and without type 2 diabetes Methods. We analyzed the metabolic and bone profile in postmenopausal women with and without type 2 diabetes (T2DM). Clinical, metabolic, hormonal parameters, along with lumbar, hip and femoral bone mineral density (BMD) and trabecular bone score (TBS) were evaluated. RESULTS: 56 women with T2DM(63.57±8.97 years) and 83 non-T2DM (60.21±8.77 years) were included. T2DM patients presented a higher value of body mass index (BMI) and BMD vs. control group (p = 0.001; p = 0.03-lumbar level, p = 0.07-femoral neck and p = 0.001-total hip). Also, BMI correlated positively with lumbar-BMD and glycated hemoglobin (HbA1c) (r = 0.348, p = 0.01; r = 0.269, p = 0.04), correlation maintained even after age and estimated glomerular filtration rate (eGFR) adjustment (r = 0.383, p = 0.005; r = 0.237, p = 0.08). Diabetic patients recorded lower levels of 25(OH)D(p = 0.05), bone markers (p ≤ 0.05) and TBS(p = 0.07). For the entire patient group we found a negative correlation between HbA1c level and bone markers: r = -0.358, p = 0.0005-osteocalcin, r = -0.40, p = 0.0005-P1NP, r = -0.258, p = 0.005-crosslaps. CONCLUSIONS: Our results indicate the presence of altered bone microarchitecture in T2DZ patients according to the TBS score, combined with lower levels of bone markers, with a statistically significant negative correlation between HbA1c level and bone markers.

Cribriform-morular variant of papillary thyroid carcinoma at pediatric age - case report and review of the literature.

Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare tumor, which exceptionally occurs at pediatric age. CMV-PTC may develop in patients with familial adenomatous polyposis (FAP) or may be a sporadic tumor. The authors present a case of CMV-PTC in a 10-year-old girl patient without FAP history, who presented with a left neck mass. The patient underwent total thyroidectomy with central compartment neck dissection. Histopathological diagnosis was compatible with cribriform-morular variant of papillary thyroid carcinoma and Hashimoto's thyroiditis. Immunostaining was positive for thyroglobulin, ß-catenin, CD10 and p53. Molecular test showed the absence of BRAF, K-RAS mutations, deletions or duplications of APC (adenomatosis polyposis coli) gene and showed the presence of RET÷PTC (rearranged during transfection÷papillary thyroid carcinoma) rearrangements. At 32 months follow-up, the patient was without signs of recurrence. This particular form of thyroid carcinoma should raise suspicion of a possible familial cancer syndrome, therefore early diagnosis and thoroughly evaluation, which includes colonoscopy and genetic screening are mandatory.

Expression and characterization of androgen receptor coregulators, SRC-2 and HBO1, during human testis ontogenesis and in androgen signaling deficient patients.

Androgen receptor (AR) is essential for testicular physiology and spermatogenesis. SRC-2 and HBO1 are two AR coregulators yet their expression and roles in human testis are unknown. For the first time, we studied by immunohistochemistry and RT-PCR, the expression and distribution of these two coregulators during human testicular ontogenesis, in patients with altered AR signaling (Androgen insensitivity syndrome, AIS) and evaluated the functional impact of SRC-2 and HBO1 on AR signaling in a Sertoli cell context. SRC-2 was present in Sertoli cells at all developmental stages. HBO1 was barely or focally detected in the fetal testis yet its expression, in Sertoli and germ cells, drastically increased postnatally from early infancy to adulthood. In transient co-transfection studies we showed that SRC-2 induced, while HBO1 inhibited AR-mediated transactivation of reporter constructs in murine Sertoli SMAT1 cells. HBO1, but not SRC-2, expression was reduced in testes of patients with AIS compared to normal testes.

Adipocytokine profile and insulin resistance in childhood obesity.

BACKGROUND: Adipose tissue is a veritable "endocrine organ" due to its adipocytokines secretion implied in insulin sensitivity modulation and cardiovascular complications. OBJECTIVE: To identify the adipocytokines' plasmatic profile (adiponectin, leptin, resistin, IL-6, TNFα) in obese children and adolescents and to assess their relationship with "classic" clinical/paraclinical markers of metabolic syndrome and insulin resistance. MATERIAL AND METHODS: A case-control study comparing a study group of 38 obese children and adolescents (age 13.5±2.3 years) to a normal weight age matched control group of 24 children.We measured body mass index (BMI) and waist circumference (WC), systolic and diastolic blood pressure (BP). The classical metabolic parameters (fasting glycemia, total cholesterol and its fractions, serum triglycerides) were measured in both groups. Insulin sensitivity was evaluated using fasting insulinemia, HOMA-index and insulin-resistance summary score (IRS). Adiponectin, leptin, resistin, IL-6 and TNFα were measured using ELISA method. OUTCOMES: Serum levels of leptin, resistin and IL-6 were signficantly higher (42.42±22.58 ng/ml versus 14.4±14.49 ng/ml, p <0.001; 9.69±3.47 ng/ml versus 7.92±2.13ng/ml, p = 0.029 and 2.66 ±2.87 pg/ml versus 0.89 ± 1.16 pg/ml, p = 0.006 respectively), while adiponectin levels were significantly lower (9.05±4.61 µg/ml versus 15.93±9.24 µg/ml, p <0.001) in the obese group compared to control group. TNFα was not statistical different between groups.In multivariate regression analysis adiponectin was negatively and significantly correlated with WC (r = - 0.463, p = 0.003); leptin was positively and significantly related to WC, diastolic BP, fasting insulinemia and resistin (r = 0.775, p <0.001); resistin was positively related to leptin and IL-6 (r = 0.499, p <0.001), IL-6 was positively and significantly related to diastolic blood pressure (r = 0.333, p = 0.008). CONCLUSIONS: Serum levels of adiponectin, leptin, resistin and IL-6 are significantly different in obese children compared to normal weight controls; leptin was the only adipokine correlated with insulin resistance in children. There are significant correlations between plasmatic levels of leptin, resistin and IL-6.Simple plasmatic determination of TNFα is not a marker of the degree of obesity or its metabolic complications in pediatric population.

Postmenopausal women with osteoporosis: experience when treated with teriparatide in clinical practice.

OBJECTIVE: To observe and compare back pain and health-related quality of life (HRQoL) in postmenopausal women with a prior unsatisfactory response to antiresorptive therapy, treated with teriparatide (TPTD) or alternative treatments in normal clinical practice. RESEARCH DESIGN AND METHODS: Prospective, observational, multicentre, 24-month study of postmenopausal women with osteoporosis. A back pain and HRQoL questionnaire (European Quality of Life Questionnaire, EQ-5D) including visual analogue scale (VAS) was completed at each visit. RESULTS: A total of 153 patients were enrolled, 105 patients started TPTD treatment during the study (TPTD cohort) and 48 patients did not take TPTD treatment at any time during the study (non-TPTD cohort). Four patients did not meet the inclusion criteria for the study. Of the patients in the non-TPTD cohort, 31 (68.9%) took antiresorptives during the study. The patients selected by the investigator for teriparatide treatment were distinctly different from those not selected. At baseline, the mean back pain VAS was greater in the TPTD than the non-TPTD cohort, 64 mm and 42 mm, respectively (p < 0.001). During the study, compared with baseline, the mean back pain VAS decreased in the TPTD cohort at all visits (p < 0.001). In the non-TPTD cohort, a transitory decrease in the mean after 12 months was observed (-10 mm, p = 0.023) only. After 24 months, the mean back pain VAS improved in the TPTD cohort (-36 mm, p < 0.001) while no change was observed in the non-TPTD cohort (-4 mm, p = 0.467). At baseline, the mean EQ-VAS was lower in the TPTD than in the non-TPTD cohort, 40.8 and 55.2, respectively (p < 0.001). After 24 months, EQ-VAS improved in both cohorts (TPTD 34, p < 0.001 and non-TPTD 9, p = 0.026). CONCLUSIONS: TPTD-treated patients had more back pain and lower HRQoL at baseline. In the TPTD cohort the mean value was consistently and significantly improved in back pain and quality of life. In the non-TPTD cohort, the mean improvement in back pain and QoL was inconsistent possibly due to the initially higher QoL and lower back pain leaving less room for improvement. These results should be interpreted in the context of limitations related to a non-randomised observational study.

The expression of the F-box protein Skp2 is negatively associated with p27 expression in human pituitary tumors.

The CDK inhibitor p27 plays a pivotal role in controlling cell proliferation during development, and has been implicated in tumorigenesis. Previous studies have demonstrated changes in p27 protein expression, but not in mRNA levels, in human pituitary tumors. It seems probable that the fall in p27 is due to increased degradation through the ubiquitin-proteasome pathway. Skp2 (S-phase kinase-interacting protein) is a specific F-box protein that allows the recognition and binding of phosphorylated p27 to the ubiquitin complex. The aim of our study was thus to investigate the possible role of Skp2 in pituitary tumorigenesis. A total of 59 human pituitary samples, 7 normal and 52 adenomas, were assessed for transcriptional expression of Skp2; 51 pituitary samples were assessed for protein expression. Real-time RT-PCR was performed on cDNA of reverse-transcribed mRNA for relative quantification of the Skp2 transcript. Immunostaining was performed using mouse monoclonal anti-Skp2 antibody. Skp2 mRNA and protein was detectable in every sample studied. Our results showed no significant difference between the pituitary tumors and normal pituitary tissue in Skp2 mRNA or nuclear protein expression. Individual tumor types had similar mRNA expression and variable protein expression. However, samples with high p27 protein expression showed significantly less Skp2 expression than samples with low p27 staining. Our data suggest that increased p27 degradation through the ubiquitin-proteasome pathway could be regulated in pituitary tumors by changes in Skp2 expression, although other factors probably also play a role.