Alice Albu

FTO gene associates to metabolic syndrome in women with polycystic ovary syndrome

The FTO (Fat mass and obesity associated) locus has recently been associated with obesity and type 2 diabetes (T2D) in humans. To understand the role of the FTO gene in polycystic ovary syndrome (PCOS) we genotyped single nucleotide polymorphism (SNP) rs1421085 (C/T) in women with PCOS (n=207) and controls (n=100) from a Central European population. The homozygous C/C genotype showed increased prevalence in PCOS patients either obese or with metabolic syndrome (MetS) compared to lean PCOS patients or controls (27.6%, 38.9%, 22.3%, and 16.3%, respectively). In logistic regression, this genotype strongly associated with MetS (P<0.0001, OR 3.2, 95% CI 1.8-5.7) and impaired fasting glucose (IFG) with P<0.0007, OR 7.7, 95% CI 2.1-28.6, independently of BMI or age, and to AUC(gluc) during OGTT (P<0.0001, alpha=0.99), indicating an influential role of the FTO gene in the glucose intolerance component of MetS.

Adiponectin, body mass index and hepatic steatosis are independently associated with IGF-I status in obese non-diabetic women.

OBJECTIVE Low IGF-I levels have been associated with obesity, insulin resistance, hepatic steatosis, and were shown to predict cardiovascular mortality. Adiponectin, on the other hand, was proved to have an important protective role against metabolic and cardiovascular diseases. This study investigates the relation between hepatic steatosis, adiponectin and IGF-I levels in a group of non-diabetic obese Romanian women. DESIGN This cross-sectional study included 201 obese non-diabetic women, with mean age of 41.1±11.9 years and mean body mass index (BMI) of 44.1±8.3 kg/m(2), consecutively admitted to the Endocrinology Department of a University Hospital to be evaluated as candidates for bariatric surgery. Main measured parameters included total adiponectin (detected by ELISA method), insulin, C reactive protein (CRP), and IGF-I (all by chemiluminescence methods). Insulin sensitivity was assessed using the Quantitative Insulin Sensitivity Check Index (QUICKI). Patients were considered IGF-deficient if IGF-I z score was ≤2 standard deviations from mean for age. Hepatic ultrasound was used to determine the presence of significant steatosis (SS+). RESULTS Significant steatosis was observed in 60.7% of our patients and this feature was associated with reduced total adiponectin levels (p<0.001) and lower IGF-I z scores (p<0.001). IGF-I z score negatively correlated with BMI (r=-0.283, p<0.001), alanine aminotransferase (ALT) (r=-0.130, p=0.032), gamma glutamyltransferase (GGT) (r=-0.158, p=0.018) and logarithmic transformed (log) CRP (r=-0.232, p=0.001) and positively correlated with QUICKI (r=0.148, p=0.023) and log adiponectin (r=0.216, p=0.003). The relationship between IGF-I z score and log adiponectin remained significant after adjusting for age, BMI, ALT, QUICKI and log CRP (r=0.183, p=0.012). IGF-I deficiency was present in 33.3% of these obese women. In multivariate logistic analysis, BMI (p<0.001), ALT (p=0.003), log adiponectin (p<0.001) and SS (p=0.043) proved to be independently associated with IGF-I deficiency. CONCLUSIONS Adiponectin is significantly correlated with IGF-I z scores and, along with BMI, ALT and significant steatosis, is independently associated with IGF-I deficiency in obese non-diabetic women.

Risk Factors Associated with Hypogonadism in β–Thalassemia Major Patients: Predictors for a Frequent Complication of a Rare Disease

Abstract Background: β-Thalassemia major (BTM) is a rare disease that challenges clinicians because of the high prevalence of complications despite progress in the development of new therapeutic methods. The aim of this study was to identify clinical and hematological parameters associated with hypogonadism, the most frequent iron overload-related complication found in Romanian patients. Methods: Patients with BTM were evaluated in the Endocrinology Department of Elias Hospital between February 2004 and December 2013. Only patients who provided written informed consent were included in the study. A complete physical and hormonal evaluation was performed on all patients, and data regarding treatment of the hematological disease were collected. Results: Of the evaluable patients, 85 were included in the study (median age, 21[10] years; range, 13–36 years). We found that 30.6% of the study participants (26 of 85) had normal gonadal status, 54.1% (46 of 85) had early forms of hypogonadism (delayed or arrested puberty), and 15.3% (n = 13) developed hypogonadism after complete sexual maturation. Patients with any form of hypogonadism were older (median age 22 vs 16.5 years, P = 0.047), had significantly lower average hemoglobin levels (P = 0.003), and had higher levels of serum ferritin (P = 0.006) versus patients without hypogonadism. Patients with delayed puberty were associated with increased average serum ferritin levels (P = 0.007), decreased hemoglobin levels (P = 0.001), and increased age at initiation of iron chelation therapy (P < 0.01). We found no significant differences between patients with early forms of hypogonadism and those with hypogonadism after complete sexual maturation, with respect to the analyzed parameters. Patients with adult hypogonadism were significantly older (median age 26 vs 16.5 years, P = 0.007) and tended to have higher serum ferritin levels (P = 0.056) compared with patients without hypogonadism. Conclusion: Our data show that hypogonadism is highly prevalent among Romanian patients with BTM, its presence being associated with higher iron overload and lower hemoglobin values. The late start of iron chelation therapy was particularly associated with pubertal abnormalities.

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

Abstract 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 (T1DM) 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 μU/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% T1DM 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.

Cardiovascular risk assessment in osteoporotic patients using osteoprotegerin as a reliable predictive biochemical marker

Osteoprotegerin (OPG), a member of the tumour necrosis factor receptor (TNFR) superfamily of proteins known to be involved in a large number of biological systems, plays a pivotal role in bone remodelling. In addition to the roles of OPG in bone metabolism, it has been reported to be associated with a high cardiovascular risk in patients with metabolic syndrome. In most cases, the exact functions of OPG remain to be established; however, the widespread expression of OPG suggests that this molecule may have multiple biological activities, mainly in the cardiometabolic environment. The aim of this study was to evaluate the value of OPG as a predictive marker for cardiovascular and metabolic risk in osteoporotic patients. The study group comprised patients with osteoporosis, in order to evaluate the association between OPG serum levels and cardiovascular pathology. Our results revealed significant correlations between classical biochemical bone and metabolic parameters, such as osteocalcin and parathyroid hormone with lipid and glucose biomarkers, sustaining the crosstalk between calcium and bone parameters and cardiovascular risk. The OPG serum level proved to have a significant and independent predictive value for metabolic syndrome (MetS) as a cardiovascular risk standard in osteoporotic patients. The OPG serum levels were increased in patients with MetS as a protective response against the atherosclerotic lesions. The serum levels of 25-hydroxy vitamin D had significant and independent predictive value for cardiovascular and metabolic risk in our subjects, sustaining the active role of vitamin D beyond the area of bone metabolism.

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, χ2 = 20.81) and DRB1*11 (42.85% vs. 30.56%, p = 0.045, χ2= 3.98)were higher, whereas those of HLA-DRB1*01(3.89% vs. 16.40%, p = 0.007, χ2 = 7.281) and DRB1*15 (10.38% vs. 21.34%, p = 0.038, χ2 = 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.

Association of serum adiponectin and insulin-like growth factor I levels with parameters of cardiac remodeling in severely obese patients

Background: Obesity is associated with various changes in cardiac geometry and this process involves both hemodynamic and non-hemodynamic factors, among which adipocitokines and growth factors may play an important role. The aim of this study was to identify the extent and pattern of cardiac remodeling in a group of severely obese patients and analyze the relationship between adiponectin, IGF-I and cardiac parameters reflecting obesity-associated structural changes. Subjects and methods: Our study included 344 patients (104 men) with severe obesity [mean body mass index (BMI)= 45.7±8.5 kg/m2], extensively evaluated clinically and biologically (complete metabolic tests, serum adiponectin, and IGF-I measurements). Left ventricular (LV) mass index (LVMI), left atrium (LA) size, and LV geometry were determined by means of cardiac ultrasound. Results: The most prevalent pattern of LV geometry was eccentric hypertrophy (28.7% of patients). In a gender-, age-, BMI-, diabetes- and hypertension-adjusted general linear model, patients with concentric or eccentric hypertrophy had significantly lower values of adiponectin than those with normal geometry (6.75±0.41, 6.96±0.53, vs 9.04±0.42 mg/l, p<0.05). In multivariate analysis, independent determinants for LVMI were BMI (β=0.364, p<0.001), systolic blood pressure (BP) (β=0.187, p=0.004), age (β=0.246, p<0.001), adiponectin (β=−0.151, p=0.012), and IGF-I z-score (β=0.134, p=0.025) while factors independently related to LA size were systolic BP (β=0.218, p<0.001), BMI (β=0.194, p<0.001), age (β=0.273, p<0.001), gender (β=−0.195, p<0.001), and adiponectin (β=−0.180, p=0.005). Conclusions: In patients with severe obesity, IGF-I z score and adiponectin correlate with parameters of cardiac remodeling independently of anthropometric, hemodynamic or metabolic factors.

Is growth hormone administration essential for in vitro fertilization treatment of female patients with growth hormone deficiency

ABSTRACT Available evidence suggests that the fertility of growth hormone deficient female patients could be decreased, although the responsible mechanisms are unknown. Taking into account the multiple effects of growth hormone on reproduction suggested by experimental and clinical studies in women without growth hormone deficiency, the growth hormone deficit by itself could contribute to infertility in these patients. However, the necessity of growth hormone administration and the profile of the infertile patients with growth hormone deficiency who would benefit from treatment are largely unknown. Growth hormone effects on oocyte quality is one of the possible mechanisms through which growth hormone could be involved in fertility of these patients. However, this hypothesis was not tested in patients with adequately diagnosed growth hormone deficiency. We present the case of a 29-year-old female patient with growth hormone deficiency and tubal infertility who was referred for in vitro fertilization treatment. The couple underwent two conventional in vitro fertilization procedures: the first one, without growth hormone treatment and, because no pregnancy was achieved, the second one after growth hormone (somatropinum) administration for 3 months. Although the number of the retrieved oocytes was the same, the quality of the oocytes was improved and their ability to evolve into good quality embryos after fertilization was increased after growth hormone administration. Consequently, the pregnancy was obtained after the second in vitro fertilization treatment and patient gave birth to a healthy boy. In conclusion, our case report suggests that adequate levels of growth hormone are essential for an adequate competence of the oocytes in infertile patients with growth hormone deficiency. Therefore, growth hormone administration should be taken into consideration for patients with this deficiency in order to optimize the results of infertility treatment. Abbreviations: GH: growth hormone; GHD: growth hormone deficiency; HCG: human chorionic gonadotropin; IVF: in vitro fertilization; IGF: insulin like growth factor

The relationship between anti-Müllerian hormone serum level and body mass index in a large cohort of infertile patients

PurposeTo evaluate the relationship between serum Anti-Müllerian hormone (AMH) level and body mass index (BMI) in infertile patients.MethodsMedical records of patients with infertility evaluated between January 2013 and February 2018 in the Reproductive Medicine Department of a private hospital were reviewed. Patients with the following criteria were excluded from the study: polycystic ovary syndrome, primary ovarian insufficiency, AMH values > 10 ng/mL, current oral contraceptive users and previous ovarian surgery or endometriosis, and anovulation of other causes, except decreased ovarian reserve.ResultsA total of 2204 infertile patients were included (mean age 34.58 ± 4.3 years, mean BMI 22.35 ± 3.6 kg/m2, and mean serum AMH 2.44 ± 2.17 ng/ml). In the entire group of patients, serum AMH level was positively correlated with BMI after adjustment for age (beta = 0.059, p < 0.005). When the association between serum AMH level and BMI was analysed in subgroups of patients, after adjustment for age, we found a positive correlation between the two parameters in patients ≤ 35 years old (< 0.05), of normal weight (p < 0.05) and with normal ovarian reserve (p < 0.05). After adjustment for age, BMI ≥ 25 kg/m2 was significantly associated with higher AMH values in comparison to normal weight patients.ConclusionsIn infertile patients, AMH is positively correlated with BMI, especially in patients younger than 35 years, of normal weight and with normal ovarian reserve. Moreover, the presence of mild excess adiposity seems to be associated with higher AMH values. Our data contradict the previous studies showing a negative impact of excess adiposity on AMH serum levels.

OC-70 Are children with isolated idiopathic growth hormone deficiency and idiopathic short stature responding differently to somatropinum administration?

Introduction Traditionally, children with idiopathic short stature (ISS) are considered to be partially resistant to growth hormone (GH), being, therefore less responsive to GH administration in comparison to children with GH deficiency (GHD). Moreover, the reimbursement policy for GH administration for short stature in children state that GH should be administrated for a more severe height deficiency in ISS (below −3 SD) in comparison to GHD (−2 SD). The aim of the study was to evaluate whether children with short stature due to idiopathic isolated GHD (IGHD) respond differently to somatropinum administration in comparison to ISS children. Material and methods patients were 155 children (age 2,9–12 years, 106 male/49 female) diagnosed with ISS (32 patients) and IGHD (123 patients) and treated according to the national protocol for 3,6 years. Standard deviation scores (SDS) for height were calculated at different time points and compared between the two groups. A favourable response to treatment was considered an increase in height with at least 0,5 SD year. Results SDS for height at the first evaluation was similar between groups (mean of −3,3 for ISS and −3,1 for IGHD). A similar proportion of patients had a favourable response to treatment during follow-up (71,5% of IGHD and 71,9% of ISS children, p=NS), with a mean recovered SDS for the height of 1,56±0,4 SD in IGHD and 1,48±0,52 SD in ISS group (p=NS). No statistically significant differences between the two groups were observed for the gain in SDS for height at 6, 12, 18 and 24 months of follow-up, the highest response occurring in the first 18 months. The doses of somatropinum administered were not statistically different in the two groups. Conclusion our study showed that the responsiveness to somatropinum administration is similar in patients with ISS and IGHD diagnosed based on current GH cut-offs. Therefore, readjustment of height deficit criteria for GH administration for these two categories of patients should be taken into consideration in order to improve cost efficiency.