Pelvic and breast ultrasound abnormalities and associated metabolic disturbances in girls with premature pubarche due to adrenarche.

OBJECTIVE: Premature adrenarche (PA) has been suggested as a risk factor for future health problems, such as metabolic syndrome and early menarche. However, not all girls with PA have these features and it is not certain who will develop them. We propose that these abnormalities might be identified earlier, even before they are visible. DESIGN: Case-control study. SETTING: Tertiary care hospital. PARTICIPANTS: Forty-eight girls with premature pubarche due to PA and age (mean age 7.6 ± 1.0 years), weight, body mass index (BMI), birth weight and gestational age-matched 49 girls with no palpable breast tissue. MEASUREMENTS: Early pubertal pelvic and breast ultrasonographic changes and their associations with obesity and metabolic parameters were evaluated. Blood samples were collected, breast and pelvic ultrasound examinations were performed and bone ages were assessed. RESULTS: Girls with PA were taller and their bone ages were higher (p = .049 and p = .005). Fasting blood glucose, insulin, triglycerides, high-density lipoprotein and low-density lipoprotein cholesterol were not different between the groups. Luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol were not different either. Ultrasonography revealed breast gland tissue in 30% of girls with PA and 5% of controls (p = .006). Uterine volume and endometrial thickness were higher in girls with PA (p = .03 and p = .04). Endometrial thickness was positively associated with serum insulin levels in the whole study group and after adjusting for age, diagnosis, BMI, mean ovarian volume and LH, FSH, estradiol levels, this association remained with a borderline p-value (R2 = 0.486, p = .050). CONCLUSIONS: We found early changes in uterus and breast glands of girls with PA and endometrial thickness was positively associated with insulin levels.

Evaluation of growth, puberty, osteoporosis, and the response to long-term bisphosphonate therapy in four patients with osteoporosis-pseudoglioma syndrome.

Osteoporosis-pseudoglioma syndrome (OPPG; MIM #259770) is a rare autosomal recessively inherited disease, characterized by early-onset osteoporosis and congenital blindness, caused by loss-of-function mutations in the LRP5 gene. Beneficial effects of bisphosphonate treatment in patients with OPPG are well known, while follow-up data on growth and pubertal parameters are limited. This article provides clinical follow-up data and long-term bisphosphonate treatment results in four OPPG patients from three unrelated families, ranging between 2.5 and 7 years of age at presentation. Clinical diagnosis was molecularly confirmed in all patients, with four different germline biallelic LRP5 mutations including a novel nonsense variant c.3517C>T (p.(Gln1173*)) in two siblings with marked phenotypic variability. Anthropometric and pubertal data and bone mineral density (BMD) measurements were evaluated retrospectively. Early puberty was observed in two patients. The bisphosphonate treatment duration of patients varied around 4-7 years and improvement in BMD z-scores with bisphosphonate treatment was demonstrated in all patients (z-score changes were +5.6, +4.0, +1.0, and +1.3). Although further research is needed to identify the possible association between early puberty and OPPG, all OPPG patients should be followed up with detailed endocrinological evaluation regarding pubertal status.

Growth and Pubertal Features in a Cohort of 83 Patients with Osteogenesis Imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a genetic disease characterized by fragile bones and variable short stature. METHOD: We performed a retrospective cohort study to evaluate demographic data, clinical findings, growth and pubertal characteristics, and medical treatment of 83 OI patients. RESULTS: 83 (31 female/52 male) patients were enrolled in the study. The median follow-up duration was 4.7 (0.6-17.7) years. 51 out of 83 patients (61.4%) received bisphosphonate therapy. The median Z-score of the bone mineral density improved in patients with OI-I and OI-III with the treatment. During follow-up, height-SDS significantly increased in both OI-I and OI-III on treatment; however, final adult height SDS of patients did not improve. The frequency of overweight and obesity was found to be increased at the last evaluation compared to the admission. The rate of precocious puberty (PP) and early puberty (EP) were 20 and 10% in girls, and they were 15.7 and 47.3% in boys, respectively. CONCLUSION: Reduced growth, significant weight gain over time due to impaired mobility, and high frequency of PP/EP require effective interventions to improve mobility and functional parameters as early as possible in children with OI.

Loss-of-function variants in SEMA3F and PLXNA3 encoding semaphorin-3F and its receptor plexin-A3 respectively cause idiopathic hypogonadotropic hypogonadism.

PURPOSE: Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by absent puberty and subsequent infertility due to gonadotropin-releasing hormone (GnRH) deficiency. IHH can be accompanied by normal or compromised olfaction (Kallmann syndrome). Several semaphorins are known potent modulators of GnRH, olfactory, and vomeronasal system development. In this study, we investigated the role of Semaphorin-3F signaling in the etiology of IHH. METHODS: We screened 216 IHH patients by exome sequencing. We transiently transfected HEK293T cells with plasmids encoding wild type (WT) or corresponding variants to investigate the functional consequences. We performed fluorescent IHC to assess SEMA3F and PLXNA3 expression both in the nasal region and at the nasal/forebrain junction during the early human fetal development. RESULTS: We identified ten rare missense variants in SEMA3F and PLXNA3 in 15 patients from 11 independent families. Most of these variants were predicted to be deleterious by functional assays. SEMA3F and PLXNA3 are both expressed along the olfactory nerve and intracranial projection of the vomeronasal nerve/terminal nerve. PLXNA1-A3 are expressed in the early migratory GnRH neurons. CONCLUSION: SEMA3F signaling through PLXNA1-A3 is involved in the guidance of GnRH neurons and of olfactory and vomeronasal nerve fibers in humans. Overall, our findings suggest that Semaphorin-3F signaling insufficiency contributes to the pathogenesis of IHH.

Growth and relationship of phenotypic characteristics with gonadal pathology and tumour risk in patients with 45, X/46, XY mosaicism.

OBJECTIVE: To evaluate the growth data, gonadal functions and tumour risk in children with 45, X/46, XY mosaicism. DESIGN: We reviewed retrospectively the records of 45 patients with 45, X/46, XY mosaicism or variants presented to our Unit from 1989 to 2019. RESULTS: The age at diagnosis ranged from 0.03 to 17.5 years. Twenty-eight patients had genital anomaly, 14 patients had female external genitalia and 3 patients had normal male genitalia. Patients showed normal height under 2 years of age. Mean height standard deviation score (HSDS) of 19 patients diagnosed before 2 years of age was -0.9 ± 0.6 and that of 26 patients diagnosed after 2 years of age was -2.6 ± 1.5. Ten patients diagnosed before 2 years of age showed growth deceleration after 2 years of age (HSDS decreasing from -0.6 ± 0.7 to -1.4 ± 0.9). Twenty-one patients reached adult height (AH). Growth hormone (GH) treatment was initiated in 10 patients. Although AHSDS of GH-treated patients was significantly greater than their mean HSDS before GH therapy (p =.013), it was not significantly different from AHSDS of the untreated group. Seventeen (37.8%) patients exhibited phenotypical features of Turner syndrome (TS) other than short stature. Two patients with genital anomaly had gonadoblastoma and germ cell neoplasia in situ, and one patient with female external genitalia had gonadoblastoma. CONCLUSIONS: GH therapy seems to improve AH of patients. Both patients with genital anomaly and female external genitalia have increased risk of germ cell tumours.

An evaluation of the knowledge and attitudes of school staff related to diabetes care at school: The 10th year of the "diabetes program at school" in Turkey.

The aim of this study was to measure the knowledge and attitudes of school staff regarding care in school for children with type 1 diabetes and to evaluate the contribution of the "Diabetes Program at School"(DPS). The data were collected through an online survey consisting of 55 questions, which included 39 knowledge and 16 attitude questions. The survey was delivered to the participating school staff via a link. A total of 55,677 people who completed 100% of the survey were included. Of the participants, 76% were teachers, 23% were school administrators and 0.1% were school nurses. 73% (40732) of the participants stated that they had heard about the "DPS". Of the participants who were aware of the DPS 75%, 50%, and 41% stated an increase in their knowledge level, self-confidence, and awareness respectively. Both scores were positively associated with being female and school nurse, having students with diabetes in the school, having been trained in childhood diabetes, being familiar with the program and being from the Western region of Turkey. The DPS is well known among school staff including teachers, school administrators, and school nurses. However, there are clear regional differences in the knowledge and attitude of school staff regarding diabetes care at school. Therefore, regional differences should be taken into account when planning the necessary interventions to prevent any further increase in the current inequalities. In addition, increasing the number of school nurses, together with strengthening the knowledge and attitude of school staff, can improve the level of diabetes care at school.

Evaluation of the Efficacy and Safety of 3 Different Management Protocols in Pediatric Diabetic Ketoacidosis.

OBJECTIVE: Management protocols for pediatric diabetic ketoacidosis (DKA) vary considerably among medical centers. The aim of this study was to investigate the efficacy and safety of 3 different fluid protocols in the management of DKA. METHODS: Fluid management protocols with sodium contents of 75, 100, and 154 mEq/L NaCl were compared. In all groups, after the initial rehydration, the protocols differed from each other in terms of the maintenance fluid, which had different rates of infusion and sodium contents. Clinical status and blood glucose levels were checked every hour during the first 12 hours. Biochemical tests were repeated at 2, 6, 12, 24, and 36 hours. RESULTS: The medical records of 144 patients were evaluated. Cerebral edema developed in 18% of the patients. The incidence of cerebral edema was lowest in the group that received fluid therapy with a sodium content of 154 mEq/L NaCl at least 4 to 6 hours and had a constant rate of infusion for 48 hours. The patients with cerebral edema had lower initial pH and HCO3 and severe dehydration with higher initial plasma osmolality. There was no significant difference between the groups in terms of the recovery times of blood glucose, pH, HCO3, and the time of transition to subcutaneous insulin therapy. CONCLUSIONS: Severity of acidosis and dehydration are associated with the development of cerebral edema. It can be concluded that fluid therapy with higher Na content and a constant maintenance rate may present less risk for the patient with DKA.

Superb Microvascular Imaging in the Evaluation of Pediatric Graves Disease and Hashimoto Thyroiditis.

OBJECTIVES: We aimed to investigate the differences between spectral Doppler and Superb Microvascular Imaging (SMI; Canon Medical Systems, Tokyo, Japan) findings in children with Hashimoto thyroiditis (HT) and Graves disease (GD) compared to healthy control participants. METHODS: The study included 34 patients with GD, 37 patients with HT, and 22 healthy volunteers. All patients with HT and 11 patients with GD were euthyroid; 23 patients with GD had symptoms of hyperthyroidism and had thyrotropin values of less than 0.5 mIU/L. Thyroid volumes, mean resistive indices, and peak systolic velocities along with vascularity indices (VIs) on Superb Microvascular Imaging were measured. RESULTS: Patients with GD had a significantly higher mean thyroid volume (P < .001; right lobe, 11.80 mL; left lobe, 9.10 mL) and peak systolic velocity (right, 32.5 cm/s; left, 30 cm/s) with a lower resistive index (right, 0.48%; left, 0.48%) compared to patients with HT (right, 8.78 mL, 20 cm/s, 0.55%; left, 7.41 mL, 20 cm/s, 0.55%, respectively) and also control participants (right, 4.59 mL, 15 cm/s, 0.56%; left, 3.52 mL, 15 cm/s, 0.54%). Patients with GD had a significantly higher median VI (right, 25%; left, 26%) compared to patients with HT (right, 11%; left, 13%) and control participants (right, 8%; left, 8%). When patients with GD were categorized as euthyroid and hyperthyroid based on thyrotropin levels and clinical symptoms, both euthyroid and hyperthyroid patients with GD had significantly higher thyroid volumes compared to patients with HT (P < .001). Hyperthyroid patients with GD had higher thyroid volumes compared to euthyroid patients with GD; however, the difference failed to reach statistical significance. A significant strong positive correlation with the VI and thyrotropin receptor autoantibody levels (r = 0.696) was found. The highest area under the curve was obtained for the right lobe VI (0.885), followed by the left lobe VI (0.872), right lobe volume (0.828), and peak systolic velocity (0.810). The optimal cutoff VI value for distinguishing between HT and GD was 17.35% with sensitivity, specificity, and diagnostic accuracy of 85.3%, 78.4%, and 81.7%, respectively. CONCLUSIONS: Superb Microvascular Imaging is a new method that can detect subtle vascularity changes with higher accuracy compared to spectral Doppler parameters in distinguishing between HT and GD.

Pituitary Iron Deposition and Endocrine Complications in Patients with ß-Thalassemia: From Childhood to Adulthood.

The endocrinological complications are a great concern in transfusion-dependent ß-thalassemia (ß-thal) patients. The pituitary iron deposition is regarded as the main cause of hormonal changes in thalassemic patients. In this study, our aim was to explore the association between endocrinological complications and pituitary iron overload by magnetic resonance imaging (MRI). Fifty transfusion-dependent thalassemia (TDT) patients were recruited for the study. Pituitary MRIs of patients were taken using a 1.5 Tesla Philips MRI machine. There was at least one clinical endocrine complication in two of three patients. The iron accumulation was moderate in the liver (60.0%) and was mild in hypophysis (16.0%) and in heart (8.0%). The hypogonadism and diabetes mellitus (DM) were not seen with a significantly increased pituitary iron burden. The hypogonadism was related to cardiac iron deposition (p = 0.04). The short stature was associated with a hepatic iron overload (p = 0.05). The conventional follow-up of patients with TDT might be inadequate and screening of patients with MRI of hypophysis along with heart and liver leads to better results.

A novel 3' untranslated region mutation in the SLC29A3 gene associated with pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus syndrome.

BACKGROUND: Pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) is one of the rare H syndrome diseases mainly characterized by hyperpigmentation, hypertrichosis, sensorineural hearing loss, cardiac complications, developmental delay, and diabetes mellitus (DM). Mutations in the coding regions of the SLC29A3 gene that encodes for an equilibrative nucleoside transporter (ENT3) have been reported to cause the phenotypic spectrum of the H syndrome. Disease-causing mutations in the untranslated regions (UTRs) of the SLC29A3 gene have not been previously described in the literature. The aim of the study is to describe and assess the pathogenicity of a novel 3'UTR mutation in the SLC29A3 gene associated with the PHID phenotype in two Turkish patients. METHODS: The mutation was identified by a targeted gene approach. To understand the pathogenicity of this 3'UTR mutation, RNA and protein expression studies were performed by using the quantitative real-time polymerase chain reaction method and western blotting, respectively, using fibroblasts cultured from the patients' skin biopsies. RESULTS: SLC29A3 and ENT3 expression levels were both decreased in the patients compared to controls matched for passage numbers, RNA, and protein extraction methods. CONCLUSIONS: A novel 3'UTR mutation in the SLC29A3 gene is associated with the PHID syndrome, highlighting a potentially new pathological mechanism for this disease. The involvement of the 3'UTR has not been previously established in any of the H syndrome disease cluster or in any complex syndrome of DM.

Determination of insulin resistance and its relationship with hyperandrogenemia,anti-Müllerian hormone, inhibin A, inhibin B, and insulin-like peptide-3 levels in adolescent girls with polycystic ovary syndrome

Background/aim: This study aims to investigate the association between polycystic ovary syndrome (PCOS) and obesity and insulin resistance (IR) with respect to anti-Müllerian hormone (AMH), inhibin A (INH-A), inhibin B (INH-B), and insulin-like peptide 3 (INSL3) levels, all factors which may have an impact on IR. Materials and methods: In this cross sectional study, 52 adolescent girls diagnosed with PCOS[groups:nonobese (NO), n = 23; overweight/obese (OW/O), n = 29] were included. Blood samples were obtained to measure AMH, INH-B, INH-A, and INSL3 levels, together with hormonal and biochemical assessments. Oral glucose tolerance test (OGTT) was performed and the indexes of IR [homeostasis model assessment: insulin resistance (HOMA-IR) and Matsuda index] were calculated. Results: Insulin resistance was 56.5% with OGTT and 30.4% with HOMA-IR in nonobese-PCOS girls. There was a correlation between INH-A and HOMA-IR even when controlled for body mass index (BMI). INH-B and FAI also had correlations with HOMA-IR which disappeared when controlled for BMI. In regression analyses, AMH (odds ratio = [0.903, P = 0.015) and FAI (odds ratio = 1.353, P = 0.023) are found to be contributors to IR. Their effect was BMI-independent. In ROC analysis, the cutoff value for FAI was 5.93 (sensitivity 71%) to define IR in PCOS girls. Conclusion: AMH and FAI may contribute to IR (defined by OGTT) in PCOS. FAI might be used as a supporting IR marker (defined by OGTT) in adolescent girls with PCOS.

Body mass index at the presentation of premature adrenarche is associated with components of metabolic syndrome at puberty.

The aim of this study was to analyze the relationship between premature adrenarche (PA) and metabolic syndrome (MeS) parameters at presentation and during puberty. This study comprised 47 girls with PA. Age- and puberty-matched 22 healthy girls without PA were the control group. Patients were evaluated at admission (first evaluation) and later in puberty (second evaluation). Anthropometric measurements, lipid levels, and hormonal parameters were studied and oral glucose tolerance test was performed. Indices for insulin resistance (IR) were calculated. The study group was divided in subgroups according to body mass index (BMI) and compared with the control group. The age of the PA group at first evaluation was 8.0 ± 1.1 years; mean height SDS and BMI SDS were 0.4 ± 1.2 and 0.6 ± 0.9, respectively. Age of PA group at the second evaluation was 12.9 ± 2.4 years. Frequency of obesity and overweight was 14.9 and 23.4%. Dyslipidemia ratio was 28.3%. PA group had significantly higher BMI than controls. Mean insulin concentration was higher and mean glucose and FGIR were lower in PA group and also dyslipidemia ratio was 5.3 times higher in PA than controls (p = 0.040). In PA group, overweight/obese subjects had still higher BMI at second evaluation and also higher fasting glucose, insulin, HOMA-IR. However, PA children with exaggerated DHEAS concentrations compared to those without had similar BMI SDS, insulin sensitivity, and secretion indices and lipid profile at second evaluation. BMI SDS at first evaluation was positively correlated with HOMA-IR at puberty; however, there is no correlation between DHEAS at first evaluation and HOMA-IR at puberty.Conclusion: BMI at adrenarche is more important than prepubertal adrogen concentrations such as DHEAS, while predicting the IR in puberty. Long-term follow-up of children supports the observation that PA per se may be related to IR; however, the risk increases with obesity. What is Known: • Premature adrenarche (PA) is receiving more attention as evidence emerges for a relation between early androgen excess and metabolic syndrome. • The onset of the adrenal androgen production before 8 years in girls defined as PA. Pubarche, axillary hair, apocrine body odor, acne are typical phenotypic features of PA. What is New: • Body mass index at adrenarche is an important risk factor for development of insulin resistance in pubertal ages. • Degree of dehydroepiandrosterone sulfate elevation was not shown as a risk factor for insulin resistance.

Determinants of Increased Aortic Diameters in Young Normotensive Patients With Turner Syndrome Without Structural Heart Disease.

Factors associated with aortic dilation and dissection in patients with Turner syndrome (TS) remain unclear. We assessed magnetic resonance imaging-based aortic diameters at nine predefined anatomic positions and examined associations of increased aortic diameters with B-type natriuretic peptide (BNP), A-type NP (ANP), growth hormone treatment, insulin-like growth factor 1 (IGF1), and estrogen status. Forty-seven patients with TS aged 7.3-21 years and 34 healthy peers were enrolled in this study. Aortic diameters were higher in patients with TS at three positions than in controls (p < 0.05). History of GH treatment, pubertal status, and serum estradiol levels were not associated with increased aortic diameters. Patients with TS had higher plasma BNP and ANP levels than controls. BNP and IGF1 were independently associated with the increase in aortic diameters in TS at three positions of the ascending aorta (R2 = 0.361-0.458, p < 0.05 for all). At two positions of the descending aorta, only BNP emerged as an independent variable (R2 = 0.130-0.139, p < 0.05). We conclude that young, normotensive patients with TS had greater aortic diameters at several positions than healthy controls. BNP and IGF1 were independently associated with increased aortic diameters in TS.

Two novel mutations in XYLT2 cause spondyloocular syndrome.

We report on two new patients with spondyloocular syndrome. Both patients harbor novel homozygous mutations in the XYLT2 gene. The patients present severe generalized osteoporosis, multiple fractures, short stature, cataract, and mild hearing impairment. XYLT2 mutations have been identified in spondyloocular syndrome, however only five mutations have been reported previously. These two patients with novel mutations extend the phenotypic and genotypic spectrum of spondyloocular syndrome.

The relationship between infancy growth rate and the onset of puberty in both genders.

BackgroundIn this study, we examined the hypothesis that weight gain and linear growth during the first years of life influence the onset of puberty both in girls and in boys.MethodsA cohort of 157 healthy children, aged 6-9 years, was evaluated and their growth patterns were analyzed retrospectively. Repeated measures mixed model was used to examine the longitudinal anthropometric data.ResultsGirls with pubertal signs were heavier than their peers starting at 9 months of age (P=0.02), and the difference became more evident over time (P<0.001). Accelerated weight gain between 6 and 15 months of age was found to increase the odds of having a pubertal sign at the study visit (odds ratio (OR)=34.5) after adjusting for birth weight, gestational age and current age, height, weight, and BMI (P=0.004). Anthropometric indices of boys with or without pubertal signs were not significantly different at the study visit, but boys with accelerated height gain between 9 and 15 months of age were more likely to have pubertal signs (OR=15.8) after adjusting for birth weight, gestational age and current age, height, weight, and BMI (P=0.016).ConclusionEarly growth acceleration might be important for the timing of puberty in both genders.

Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation.

Next-generation sequencing (NGS) enables analysis of the human genome on a scale previously unachievable by Sanger sequencing. Exome sequencing of the coding regions and conserved splice sites has been very successful in the identification of disease-causing mutations, and targeting of these regions has extended clinical diagnostic testing from analysis of fewer than ten genes per phenotype to more than 100. Noncoding mutations have been less extensively studied despite evidence from mRNA analysis for the existence of deep intronic mutations in >20 genes. We investigated individuals with hyperinsulinaemic hypoglycaemia and biochemical or genetic evidence to suggest noncoding mutations by using NGS to analyze the entire genomic regions of ABCC8 (117 kb) and HADH (94 kb) from overlapping ~10 kb PCR amplicons. Two deep intronic mutations, c.1333-1013A>G in ABCC8 and c.636+471G>T HADH, were identified. Both are predicted to create a cryptic splice donor site and an out-of-frame pseudoexon. Sequence analysis of mRNA from affected individuals' fibroblasts or lymphoblastoid cells confirmed mutant transcripts with pseudoexon inclusion and premature termination codons. Testing of additional individuals showed that these are founder mutations in the Irish and Turkish populations, accounting for 14% of focal hyperinsulinism cases and 32% of subjects with HADH mutations in our cohort. The identification of deep intronic mutations has previously focused on the detection of aberrant mRNA transcripts in a subset of disorders for which RNA is readily obtained from the target tissue or ectopically expressed at sufficient levels. Our approach of using NGS to analyze the entire genomic DNA sequence is applicable to any disease.

Increased arterial stiffness in young normotensive patients with Turner syndrome: associations with vascular biomarkers.

OBJECTIVES: Factors contributing to arteriopathy in patients with Turner syndrome (TS) remain unclear. We assessed arterial stiffness in young, normotensive patients with TS and correlated arterial stiffness with vascular biomarkers, GH treatment and oestrogen exposure. Sixty-one patients with TS (mean age, 12·6 years; range 6·6-21·3 years) were matched for age and sex with 61 healthy peers. Associations between arterial stiffness and high-sensitivity C-reactive protein (hsCRP), B-type natriuretic peptide (BNP), atrial NP (ANP), plasma aldosterone/plasma renin activity (PRA), IGF1 and IGFBP3 were examined after adjusting for well-established confounders of vascular disease. RESULTS: Carotid intima media thickness standard deviation score (SDS), arterial stiffness index SDS and incremental modulus of elasticity SDS were higher, and distensibility coefficient SDS was lower in patients with TS. The duration of GH treatment and oestrogen exposure was not associated with indices of arterial stiffness. TS patients had higher hsCRP, BNP and ANP. Plasma aldosterone/PRA, IGF1 and IGFBP3 were similar in patients and controls. Multivariable regression analyses (R(2) = 0·200-0·668, P < 0·01) showed that BNP was associated with all indices of arterial stiffness. We found that hsCRP was associated with distensibility coefficient SDS (ß = -0·16, P < 0·01). TS was independently associated with increased arterial stiffness (ß = 0·420-3·424, P < 0·001 for all, R(2) = 0·06-0·31). CONCLUSIONS: Young, normotensive TS patients had increased arterial stiffness than that of healthy peers. BNP, and possibly hsCRP, was independently associated with arterial stiffness in TS. Further research will determine any causal inference of these relationships.

A truncating TPO mutation (Y55X) in patients with hypothyroidism and total iodide organification defect.

UNLABELLED: Absract Purpose: Mutations in the TPO gene have been reported to cause congenital hypothyroidism (CH), and our aim in this study was to determine the genetic basis of congenital hypothyroidism in two affected children coming from a consanguineous family. METHODS: Since CH is usually inherited in autosomal recessive manner in consanguineous/multi case-families, we adopted a two-stage strategy of genetic linkage studies and targeted sequencing of the candidate genes. First we investigated the potential genetic linkage of the family to any known CH locus using microsatellite markers and then screened for mutations in linked-gene by Sanger sequencing. RESULTS: The family showed potential linkage to the TPO gene and we detected a non-sense mutation (Y55X) in both cases that had total iodode organification defect (TIOD). The mutation segregated with disease status in the family. Y55X is the only truncating mutation in the exon 2 of the TPO gene reported in the literature and results in the earliest stop codon known in the gene to date. CONCLUSIONS: This study confirms the pathogenicity of Y55X mutation and demonstrates that a nonsense mutation in the amino-terminal coding region of the TPO gene could totally abolish the function of the TPO enzyme leading to TIOD. Thus it helps to establish a strong genotype/phenotype correlation associated with this mutation. It also highlights the importance of molecular genetic studies in the definitive diagnosis and accurate classification of CH.

Blood levels of polychlorinated biphenlys and organochlorinated pesticides in women from Istanbul, Turkey.

The human body is not a chemically uncontaminated system. Every simple action that humans undertake, such as drinking water, eating, nursing, and even breathing air, puts the system under environmental xenobiotic exposure stress. Environmental chemicals have been shown to produce unwanted effects on health and remove the right to healthy living, starting from the first encounter in utero to geriatrics, throughout the lifespan. Organochlorine pesticides (OCPs) and polychlorinated biphenyl (PCB) levels, important members of the persistent organic pollutants (POPs), have been detected before in human breast milk and also in the adipose tissue of women from different regions of Turkey; however, there was no information about the blood levels of these chemicals. This study generated the first information that evaluates OCP and PCB contamination levels in the blood of the women living in Turkey. The current study measured the blood concentrations of OCPs and PCBs in 58 healthy women (age 20-41 years; mean age 28 years) who were living in Istanbul, Turkey, in the years 2010-2012. Samples were analyzed for 29 OCPs and 18 PCB congeners using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). PCB 153 was the predominant congener (643.2 pg/g lipid), followed by PCB 138 and PCB 180. 4,4'-DDE (24872.8 pg/g lipid) was the most common organochlorinated pesticide contaminant in studied blood samples. Results for analyzed chlorinated compounds were as follows: ∑PCB 2682 ± 3300 pg/g lipid; ∑DDT 25,938 ± 28,644 pg/g lipid; and ∑HCH 2930 ± 2222 pg/g lipid, respectively. The mean concentration of ∑WHOPCB-TEQ was 0.037 pg/g on a lipid basis. This information will be important base data during the assessment of the general health concerns of women, as well as for studies about how endocrine disruptors affect humans for forthcoming studies.

Pelvic ultrasound findings in prepubertal girls with precocious adrenarche born appropriate for gestational age.

BACKGROUND: Precocious adrenarche (PA) refers to the clinical onset of excess androgen in girls before the age of 8. It is associated with an increased risk of functional ovarian hyperandrogenism after puberty. PA may be associated with polycystic ovary syndrome (PCOS). We compared pelvic ultrasound (US) findings of girls with PA born appropriate for gestational age (AGA) to healthy body mass index (BMI)-matched peers to determine whether US findings in AGA-born PA girls are associated with PCOS antecedents. SUBJECTS AND METHODS: We conducted a cross-sectional study on 56 AGA-born girls with PA (6·9 ± 0·6 years) and 33 BMI-matched prepubertal AGA-born peers (7·1 ± 1·0 years). Hormonal data, homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISIcomp ) and pelvic US findings were compared. Associations of pelvic US findings with clinical and metabolic data were investigated. RESULTS: Precocious adrenarche girls had greater height and bone age-adjusted uterine length (UL; P = 0·01) and UL standard deviation score (SDS) (P = 0·02) than BMI-matched peers. Mean ovarian volume (MOV), MOV SDS, uterine volume, uterine cross-sectional area and ovarian morphology were similar between the groups (P > 0·05). MOV and MOV SDS correlated with ISIcomp (r = -0·683, P < 0·001; r = -0·760, P < 0·001; respectively). Correlations of pelvic US findings with other biochemical data did not reach significance (P > 0·05). Multivariate regression analysis revealed that in girls with PA, ISIcomp had the most significant effect on MOV SDS (R(2) = 0·731, ß = -4·784, P = 0·001). CONCLUSIONS: Appropriate for gestational age-born PA girls have greater UL measurements than AGA-born BMI-matched peers. In AGA-born girls with PA, decreasing insulin sensitivity is strongly and independently associated with an increase in MOV. Longitudinal follow-up of our cohort after menarche will allow us to establish how many AGA-born girls with PA will ultimately develop PCOS.