Obesity, in childhood or in adulthood, remains to be a global health problem. The worldwide prevalence of obesity has increased in the last few decades, and consequently, the women of our time suffer more gestational problems than women in the past. The prevalence of obesity is greater in older women than in younger ones and in women with low educational level than in their counterparts with a higher level of education. Maternal obesity during pregnancy may increase congenital malformations and neonatal morbidity and mortality. Maternal obesity is associated with a decreased intention to breastfeed, decreased initiation of breastfeeding, and decreased duration of breastfeeding. We discuss the current epidemiological evidence for the association of maternal obesity with congenital structural neural tube and cardiac defects, fetal macrosomia that predisposes infants to birth injuries and to problems with physiological and metabolic transition, as well as potential for long-term complications secondary to prenatal and neonatal programming effects compounded by a reduction in sustained breastfeeding.

Objective: What initiates the pubertal process in humans and other mammals is still unknown. We hypothesized that gene(s) taking roles in triggering human puberty may be identified by studying a cohort of idiopathic hypogonadotropic hypogonadism (IHH).
Methods: A cohort of IHH cases was studied based on autozygosity mapping coupled with whole exome sequencing.
Results: Our studies revealed three independent families in which IHH/delayed puberty is associated with inactivating SRA1 variants. SRA1 was the first gene to be identified to function through its protein as well as noncoding functional ribonucleic acid products. These products act as co-regulators of nuclear receptors including sex steroid receptors as well as SF-1 and LRH-1, the master regulators of steroidogenesis. Functional studies with a mutant SRA1 construct showed a reduced co-activation of ligand-dependent activity of the estrogen receptor alpha, as assessed by luciferase reporter assay in HeLa cells.
Conclusion: Our findings strongly suggest that SRA1 gene function is required for initiation of puberty in humans. Furthermore, SRA1 with its alternative products and functionality may provide a potential explanation for the versatility and complexity of the pubertal process.

Objective: The rs2479106 and rs10818854 polymorphisms in the DENND1A gene have been reported to be extensively associated with risk of polycystic ovary syndrome (PCOS). However, the results from these studies remained inconclusive and conflicting. To detect a true association of rs2479106 and rs10818854 polymorphisms with PCOS risk, a single study may be underpowered, particularly for those studies with inadequate sample size. Therefore, we performed a meta-analysis of all available studies to explore this association.
Methods: All studies published up to March 2015 on the association were identified by searching electronic databases PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure. Studies containing available genotype frequencies of those 2 polymorphisms were chosen, and the odds ratios and associated 95% confidence intervals were calculated using fixed- or random- effects models.
Results: A total of 8 studies about s2479106 polymorphism (8185 cases and 28675 controls) and 5 studies about rs10818854 polymorphism (6638 cases and 27443 controls) met the inclusion criteria for the meta-analysis. Overall, significant increase of PCOS risk was found between DENND1A-rs10818854 and PCOS susceptibility. In addition, we also found an increased risk of PCOS in rs2479106 allele model, heterozygote variant genetic model, and dominant genetic model.
Conclusion: This meta-analysis suggested that rs2479106 and rs10818854 polymorphisms in the DENND1A gene were associated with increased risk of PCOS. To validate the association between these polymorphisms and PCOS susceptibility, further large and well-designed studies are needed.

Objective: The frequency of mutations in the short stature homeobox (SHOX) gene in patients with idiopathic short stature (ISS) ranges widely, depending mostly on the mutation detection technique and inclusion criteria. We present phenotypic and genotypic data on 38 Turkish patients with ISS and the distinctive features of 1 patient with a SHOX deletion.
Methods: Microsatellite markers (MSMs) DXYS10092 (GA repeats) and DXYS10093 (CT repeats) were used to select patients for fluorescent in situ hybridisation (FISH) analysis and to screen for deletions in the SHOX gene. The FISH analysis was applied to patients homozygous for at least one MSM. A Sanger sequencing analysis was performed on patients with no deletions according to FISH to investigate point mutations in the SHOX gene.
Results: One patient (2.6%) had a SHOX mutation.
Conclusion: Although the number of cases was limited and the mutation analysis techniques we used cannot detect all mutations, our findings emphasize the importance of the difference in arm span and height when selecting patients for SHOX gene testing.

Objective: In the current study, we aimed to investigate whether thyroid autoimmunity (TA) had any effect on carotid intima-media thickness (cIMT) and enhanced the risk of cardiovascular disease (CVD) independent of thyroid function (TF) in pubertal girls with Hashimoto’s thyroiditis (HT).
Methods: Sixty-six newly diagnosed euthyroid girls with HT with a mean age of 14.4±2.4 years were included in the study. The control group consisted of 41 age- and body mass index (BMI)-matched healthy girls. At enrollment, all sub-jects underwent physical examination including blood pressure, standing height, weight, waist circumference (WC), and hip circumference measurements. The lipid profile, highsensitivity C-reactive protein (hs-CRP), ho-mocysteine, blood glucose, insulin, TF, and thyroid antibodies were measured, and thyroid ultrasound and cIMT were performed.
Results: There were no significant differences in anthropometric variables between the two groups, but the patients with HT had significantly higher waist-to-hip ratio (WHR). Thyroid hormones, insulin, homocysteine, and homeostatic model assessment-insulin resistance were not different between the two groups. Serum hs-CRP levels were significantly higher in patients than controls (3.4 ng/mL vs. 2.03 ng/mL), (p<0.001). Patients were also characterized by significantly higher total cholesterol (166.4±27 mg/dL vs. 151±22 mg/dL), (p<0.01) and low-density cholesterol (95.8±24.4 mg/dL vs. 82.6±20.7 mg/dL), (p<0.01) levels. Patients, regardless of TF, had significantly increased cIMT compared with controls [0.28 mm vs. 0.25 mm, (p<0.001)], and cIMT was correlated with weight-standard deviation score (SDS), BMI SDS, WCSDS, and WHR. This increase in cIMT was associated independently with BMI-SDS and hs-CRP levels.
Conclusion: TA may be related to chronic inflammation, which may cause endothelial dysfunction, a promoter of atherosclerosis in girls with HT. cIMT is a good tool for the early detection and the monitoring of early atherosclerosis in euthyroid patients with HT. Early detection of risk factors of CVD, may be helpful for planning treatment and interventions, so as to prevent complications from the disease in adulthood.

Objective: In obese subjects, slight increases have been observed in thyrotropin [thyroid-stimulating hormone (TSH)] levels, but data in children are scarce. The aim of this study was to evaluate whether thyroid function and autoimmunity vary with weight status in a healthy population of children and adolescents and to determine whether hyperthyrotropinemia is associated with any cardiovascular risk factor.
Methods: This cross-sectional epidemiological study was conducted in Almería (Spain) on a representative sample of 1317 healthy subjects aged 2-16 years. Thyroid function, thyroid autoimmunity and cardiovascular risk factors were measured. Chi-square test, analysis of variance and multiple linear regression were used in the statistical analyses.
Results: The obese children and adolescents had thyrotropin levels (mean ± standard deviation) of 3.12±2.44 mU/L. These levels were higher than those of overweight subjects (2.79±1.51 mU/L) and of normal weight subjects (2.73±1.30 mU/L) (p=0.02). Levels of free thyroxine and urinary iodine did not differ significantly between the groups. The prevalence (95% confidence interval) of thyroid autoimmunity was lower in the individuals with normal weight (2.9%; 2.0-4.2) than in the overweight (6.3%; 3.9-9.9) and obese subjects (5.6%, 2.5-11.3) (p=0.02). TSH levels were associated with obesity (ß=0.36; p<0.001) and thyroid autoimmunity (ß=1.10; p<0.001). They were not associated with any cardiovascular risk factor
Conclusion: Obese children and adolescents had higher levels of thyrotropin than those who were overweight and of normal weight. The differences among the groups were of very little clinical significance and could possibly be linked to the higher prevalence of thyroid autoimmunity in obese subjects. The hyperthyrotropinemia in these subjects was not associated with any cardiovascular risk factor.

Objective: Deficiency of sex steroids has a negative impact on bone mineral content. In studies conducted on postmenopausal women and animal studies, elevated follicle-stimulating hormone (FSH) levels were found to be correlated with a decrease in bone mineralization and osteoporosis. The aim of the present study was to evaluate bone mineral density (BMD) in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism and also to investigate the correlation between FSH level and BMD.
Methods: The study group included 33 adolescent girls with hypogonadism (14 with hypogonadotropic hypogonadism and 19 with hypergonadotropic hypogonadism). FSH, luteinizing hormone, estradiol levels, and BMD (using dual energy x-ray absorptiometry) were measured.
Results: There were no statistically significant differences between the chronological age and bone age of the two patient groups, namely, with hypogonadotropic and hypergonadotropic hypogonadism. There was also no significant difference between BMD z-score values obtained from measurements from the spine and the femur neck of patients in the two groups (p-values were 0.841 and 0.281, respectively). In the hypergonadotropic group, a moderately negative correlation was detected between FSH level and BMD z-score measured from the femur neck (?=-0.69, p=0.001), whilst no correlation was observed between FSH levels and height adjusted BMD-z scores measured from the spine (?=0.17, p=0.493). FSH level was not found to be an independent variable affecting BMD z-score.
Conclusion: BMD z-scores were detected to be similar in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism, and FSH levels were not found to have a clinically relevant impact on BMD.

Objective: Prevalence of congenital hypothyroidism (CH) in Turkey at birth was reported to be as high as 1: 650 in 2008-2010. Incidence rates of permanent and transient CH separately are unknown due to lack of follow-up data. We aimed to evaluate the impact of transient hypothyroidism on increasing incidence of CH and to determine the natural course and the clinical, biochemical, and imaging characteristics of transient CH.
Methods: Baseline and follow-up data of the infants with CH detected at screening in six provinces in the Black Sea Region were analyzed retrospectively during a time period covering the years 2008-2010.
Results: Among 138 cases (48% female), 16 (12%) showed transient hyperthyrotropinemia which resolved without intervention. Of the treated 122 cases, 63 (52%) had transient CH. While its frequency was 35% in 2008, it increased to 56% in 2009-2010, following a lowering of the thyroid stimulating hormone cutoff value. The frequency was higher in inland provinces than in coast (67% vs. 43%; p=0.01).Clinical characteristics of permanent and transient cases were similar except female-to-male sex ratios (1.5: 1 vs. 0.6: 1; p=0.02). L-thyroxine was discontinued in 70% of transient cases before 3 years of age at a median age of 19 (2-36) months. The only indication for early discontinuation of treatment was a low L-thyroxine dose, which was 1.25±0.27 µg/kg/day at withdrawal time.
Conclusion: Our regional follow-up data showed that more than half of newborns with primary CH had transient thyroid dysfunction. In the majority of cases, discrimination between transient and permanent CH can be made before age 3 years, as indicated by cessation of L-thyroxine treatment.

Objective: Type 1 diabetes mellitus (T1DM) may lead to deficiencies in trace elements that have substantial functions in the human organism. Changes in serum magnesium (Mg), copper (Cu), and zinc (Zn) levels are correlated with metabolic control and diabetes complications. The aim of this study was to evaluate the intra-erythrocyte levels of trace elements and urinary Mg excretion following intravenous (iv) Mg tolerance testing in children with T1DM.
Methods: A total of 43 children aged 2-18 years with T1DM and age/gender-matched 25 healthy children were included in the study. The iv Mg tolerance test was performed following the measurement of intra-erythrocyte Mg (eMg1), Cu (eCu1), and Zn (eZn1) levels using the atomic absorption spectrophotometer method. The Mg retention ratio was estimated from measurements in 24 h urine samples.
Results: No statistically significant difference was found for eMg1, eCu1, and eZn1 levels between the patient and control groups (p>0.05). In the patient group, the eMg1, eCu1, and eZn1 levels measured after the iv Mg tolerance test significantly increased compared with the baseline levels (p<0.05), and the Mg excretion ratio measured from the urine collected after the iv MgSO4 infusion was >50%.
Conclusion: The increased retention value following the iv Mg tolerance testing indicates intracellular Mg deficiency in children with T1DM.

Objective: Thyroid-stimulating hormone (TSH) level in neonates is recommended as an indicator for presence of iodine deficiency (ID) at a population level and as a monitoring tool in programs of iodine supplementation. The purpose of this study, based on data from the National Newborn Screening Program (NNSP) for congenital hypothyroidism (CH) in 2014, was to analyze neonatal TSH levels to predict the current status of iodine nutrition in Turkey.
Methods: According to screening methodology, heel-prick blood samples of newborns were collected on filter paper cards usually on day 3-5 after birth (or shortly before discharge). Results of samples collected >48 h after birth were analyzed. The degree of severity of ID was assessed by using the epidemiologic criteria of the World Health Organization (WHO). Elevated TSH levels (>5 mIU/L) were processed and classified according to province, region, birth season, and sampling time.
Results: A total of 1,298531 newborns were registered in the NNSP for the CH database. Of those, 1,270311 newborns had screening results collected >48 h after birth and were included in the statistical analyses. The national prevalence of elevated TSH was 7.2%. While the Gaziantep sub-region had the highest TSH elevation rate (15.9%), the Tekirdað sub-region had the lowest rate (4.0%; p<0.001). Seasonal variations were also significant, and the elevated TSH prevalence rate was highest in winter (7.4%; p<0.001).
Conclusion: National CH screening results suggest that Turkey may still be mildly iodine deficient. Nationwide studies should be performed for direct assessment and monitoring of iodine status in vulnerable populations to confirm accuracy of our results.

Objective: Clinicians should show an awareness on the menstrual characteristics of adolescent girls which may differ from adults in some aspects. To define menstrual cycle features among high school girls residing in a city center in southeastern Turkey.
Methods: A cross-sectional survey was conducted on 1256 girls attending a high school located in the city center of Elazýð, Turkey. Data from 879 girls (median age, 16.2 years; range, 13.6-19.2 years) who agreed to participate in the study and had started to menstruate were evaluated.
Results: Mean age at menarche was 12.7±1.3 years (range, 8.2-17.3 years). The mean cycle duration was 28.7±4.4 days, and the mean menstrual flow lasted 5.9±1.3 days. Severe, moderate, and mild dysmenorrhea was reported in 29%, 43%, and 28% of the girls, respectively, and 52% used analgesics for dysmenorrhea. A total of 34% of the girls defined their menstrual cycle as irregular, and 32% reported school absenteeism due to menstruation-associated complaints (pain and/or heavy bleeding). Menstrual bleeding affected attendance to classes and other school activities, daily work, social, family, and friend relationships, as well as sports/exercise activities in 43%, 49%, 58%, 48%, 44%, and 60% of the participants, respectively. In total, 30% of the responders had a problem with menstruation, and 12% and 17% of these stated that they consulted a primary care physician or specialist, respectively.
Conclusion: Dysmenorrhea was found to be common in adolescent Turkish girls and to affect daily life in approximately half of the girls.

Objective: Mutations in the KATP channel genes is the most common cause of congenital hyperinsulinism (CHI) of infancy. Our aim was to report the clinical and genetic characteristics, treatment modalities, and long-term prognosis of patients with CHI.
Methods: Clinical and biochemical findings, operation procedures, and results of genetic analysis were retrospectively evaluated in 22 CHI patients from two pediatric endocrine centers in Turkey.
Results: Seven of the patients were born large for gestational age. Hypoglycemia was diagnosed within the first 24 hours of life in 9 patients and treatment with diazoxide (n=21) and/or somatostatin (n=8) had been attempted. Seven patients (31.8%) were unresponsive to medical treatment and underwent pancreatectomy. Histological examination of the pancreas confirmed diffuse disease in 6 patients. Diabetes developed in 3 patients following pancreatectomy (10 years, 2.5 years, and immediately after operation). The remaining four patients had neither recurrence of CHI nor of diabetes during the 3.67±0.7 years of follow-up. Sequence analysis identified mutations in 12 out of 19 patients (63%). Mutations in the ABCC8 gene were the most common finding and were found in 6 out of 7 patients who underwent pancreatectomy. Other mutations included a paternally inherited KCNJ11 mutation, a homozygous HADH mutation, and a heterozygous GLUD1 mutation.
Conclusion: Mutations in the ABCC8 gene were the most common cause of CHI in our cohort. These mutations were identified in 85% of patients who underwent pancreatectomy. The development of diabetes mellitus after pancreatectomy may occur at any age and these patients should be screened regularly.

Objective: The CYP19A1 gene product aromatase is responsible for estrogen synthesis and androgen/estrogen equilibrium in many tissues, particularly in the placenta and gonads. Aromatase deficiency can cause various clinical phenotypes resulting from excessive androgen accumulation and insufficient estrogen synthesis during the pre- and postnatal periods. In this study, our aim was to determine the clinical characteristics and CYP19A1 mutations in three patients from a large Turkish pedigree.
Methods: The cases were the newborns referred to our clinic for clitoromegaly and labial fusion. Virilizing signs such as severe acne formation, voice deepening, and clitoromegaly were noted in the mothers during pregnancy. Preliminary diagnosis was aromatase deficiency. Therefore, direct DNA sequencing of CYP19A1 was performed in samples from parents (n=5) and patients (n=3).
Results: In all patients, a novel homozygous insertion mutation in the fifth exon (568insC) was found to cause a frameshift in the open reading frame and to truncate the protein prior to the heme-binding region which is crucial for enzymatic activity. The parents were found to be heterozygous for this mutation. Additionally, all patients had hypoplastic ovaries instead of cystic and enlarged ovaries.
Conclusion: A novel 568C insertion mutation in CYP19A1 can lead to severe aromatase deficiency. Homozygosity for this mutation is associated with the development of hypoplastic ovaries. This finding provides an important genetic marker for understanding the physiological function of aromatase in fetal ovarian development.

Objective: To investigate the effects of treatment with gonadotropin-releasing hormone analog (GnRHa) on final height in girls who experienced moderately early puberty with symptoms beginning at 7-8.5 years of age.
Methods: Female cases diagnosed with moderately early puberty which had started between ages 7 to 8.5 years were included in the study. In the treatment groups, all cases with a bone age ?10.5 years constituted group 1 (n=18) and those with a bone age >10.5 years constituted group 2 (n=23). The 8 patients for which treatment approval could not be obtained constituted group 3. The 49 cases in all three groups were observed until they reached their final height.
Results: Target height, target height standard deviation score (SDS), final height, and final height SDS values were similar in all 3 groups. Final height showed a significant positive correlation with target height (p=0.000, r=0.54) and height at diagnosis (p=0.003, r=0.467) in all groups. Linear regression analysis revealed that a 1 cm longer height at diagnosis increased the final height 0.213 fold, and a 1 cm longer target height at diagnosis increased the final height 0.459 fold.
Conclusion: We found that GnRHa did not make a positive contribution to final height in cases of moderately early puberty.

Objective: Deficiency of steroid 5-alpha reductase type 2 (5?RD2) is a rare autosomal recessive disorder caused by mutations in the SRD5A2 gene. A defect in the 5-alpha reductase enzyme, which ensures conversion of testosterone into dihydrotestosterone, leads to disorders of sex development. This study presents the clinical and genetic results of patients with 5?RD2 deficiency.
Methods: 5?RD2 deficiency was detected in 6 different patients from 3 unrelated families. All patients were reared as girls. Two of the patients presented with primary amenorrhea, one with primary amenorrhea and rejection of female gender, and the others with masses in their inguinal canals. Chromosome and sex-determining region Y (SRY) gene analyses were performed in all patients. Additionally, five exons of the SRD5A2 gene were amplified with polymerase chain reaction in the obtained DNA samples and evaluated.
Results: While 46,XY was identified in 5 patients, 47,XXY was detected in one patient. The SRY gene was positive in all patients. The p.Ala65Pro (c193G>C) mutation and V89L polymorphism were observed in exon 1 of the SRD5A2 gene in all patients.
Conclusion: Identification of this mutation and polymorphism is a significant indicator of presence of 5?RD2 deficiency in Southeastern Turkey, a geographical region where consanguineous marriages are also highly common.

The coexistence of mutations in the dual oxidase maturation factor 2 (DUOXA2) and dual oxidase 2 (DUOX2) genes is rarely identified in congenital hypothyroidism (CH). This study reports a boy with CH due to a novel splice-site mutation in the DUOXA2 gene and a missense mutation in the DUOX2 gene. A four-year-old boy was diagnosed with CH at neonatal screening and was enrolled in this study. The DUOXA2, DUOX2, thyroid peroxidase (TPO), and thyrotropin receptor (TSHR) genes were considered for genetic defects screening. Genomic DNA was extracted from peripheral blood leukocytes, and Sanger sequencing was used to screen the mutations in the exon frag-ments. Family members of the patient and the controls were also enrolled and evaluated. The boy harbored com-pound heterozygous mutations including a novel splice-site mutation c.554+5C>T in the maternal DUOXA2 allele and c.2654G>A (p.R885Q) in the paternal DUOX2 allele. The germline mutations from his parents were consistent with an autosomal recessive inheritance pattern. No mutations in the TPO and TSHR genes were detected. A novel splice-site mutation c.554+5C>T in the DUOXA2 gene and a mutation p.R885Q in the DUOX2 gene were identified in a 4-year-old patient with goitrous CH.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is considered as the second most common type of hereditary HI. Correlation of genotype and phenotype in HI/HA syndrome has been described in several studies. We present three Serbian patients with HI/HA syndrome with emphasis on a possible correlation between genotype and clinical manifestations. Patient 1 was heterozygous for a de novo mutation p.S445L in the GLUD1 gene, while patients 2 and 3 (son and mother) both carry the p.R221C mutation. Early onset of hypoglycaemia with generalized seizures was recorded in infancy in all three patients. The two male patients had mild developmental delay, while the female patient presented with epilepsy. Analysis of Serbian patients with HI/HA syndrome confirms the association of p.S445L and p.R221C mutations with hypoglycaemic seizures noted within the first three months of life and with subsequent risk for cognitive impairment and/or epilepsy.

Partial androgen insensitivity syndrome (PAIS) typically presents with micropenis, perineoscrotal hypospadias, and a bifid scrotum with descending or undescending testes and gynecomastia at puberty. It is an X-linked recessive disorder resulting from mutations in the androgen receptor (AR) gene. However, AR gene mutations are found in less than a third of PAIS cases. A 16-year-old boy was admitted with complaints of gynecomastia and sparse facial hair. Family history revealed male relatives from maternal side with similar clinical phenotype. His external genitalia were phenotypically male with pubic hair Tanner stage IV, penoscrotal hypospadias, and a bifid scrotum with bilateral atrophic testes. He had elevated gonadotropins with a normal testosterone level. Chromosome analysis revealed a 46,XY karyotype. Due to the family history suggesting a disorder of X-linked trait, PAIS was considered and molecular analysis of AR gene was performed. DNA sequence analysis revealed a novel hemizygous mutation p.T576I (c.1727C>T) in the AR gene. The diagnosis of PAIS is based upon clinical phenotype and laboratory findings and can be confirmed by detection of a defect in the AR gene. An accurate approach including a detailed family history suggesting an X-linked trait is an important clue for a quick diagnosis.

Deficiency of steroid 5-alpha reductase-2 (5ARD2) is an inborn error of metabolism causing a disorder of sexual differentiation. It is caused by a mutation in the SRD5A2 gene in which various mutation types have been reported. Affected individuals have a broad spectrum of presentation ranging from normal female-appearing genitalia, cliteromegaly, microphallus, hypospadias, to completely male-appearing genitalia. We report an extended Emirati family with 11 affected members. The family displayed various phenotypes on presentation leading to different sex of rearing. Some family members were reassigned gender at various stages of life. The index case was born with severe undervirilization with bilaterally palpable gonads and was raised as male from birth. He had a 46,XY karyotype and a high testosterone/dihydrotestosterone ratio. Genetic investigation revealed a novel homozygous deletion of exon 2 of the SRD5A2 gene. Both parents were found to be carriers for the gene deletion. The patient had masculinizing surgery and a course of topical dihydrotestosterone. No beneficial effect of the hormone application was noted over 3 months and the treatment was discontinued. The findings on this kindred indicate that deletion of exon 2 in the SRD5A2 gene causes various degrees of genital ambiguity leading to different sex of rearing in affected family members. Gender reassignment may be done at various ages even in conservative communities like the Gulf region.

Thyroid dyshormonogenesis is responsible for 10-15% of all cases of congenital hypothyroidism and is usually inherited. We report a 26-year-old German-Thai male with congenital hypothyroidism caused by a compound heterozygous mutation in the thyroid peroxidase (TPO) gene. He was diagnosed with congenital goitrous hypothyroidism at 4 months of age and had been treated with levothyroxine replacement therapy. His goiter size had increased due to poor compliance to treatment. Ultrasonography of the thyroid gland showed a pattern suspicious for malignancy. The patient later underwent near-total thyroidectomy. Pathologic examination results were consistent with a multinodular goiter and no malignancy. Genetic analyses by direct sequencing of the entire exons and flanking regions of the TPO gene were performed in the index case and family members. The analyses revealed a compound heterozygote of novel TPO mutation of c.1727C>T in exon 10 resulting in amino acid substitution (p.Ala576Val) and c.2268_2269insT in exon 13 causing a frameshift mutation which introduced a stop codon after the insertion site. The latter has been reported in Chinese subjects. However, there is no previous report of c.1727C>T mutation in the literature. We found the allele contained a novel exon 10 mutation inherited from the patient’s German mother and an exon 13 mutation from his Thai father. Analysis using two bioinformatic software programs indicated that this variant was likely to cause damage in the resulting protein molecule. The present report emphasizes the importance of regular follow-up and patient compliance to levothyroxine replacement in patients with goitrous congenital hypothyroidism to avoid prolonged stimulation of thyroid tissue by thyroid-stimulating hormone.

Mitchell-Riley syndrome is a genetic disorder characterized by neonatal diabetes, pancreatic hypoplasia, intestinal atresia and/or malrotation, biliary atresia, and gallbladder aplasia or hypoplasia. It was considered a variant of the Martinez-Frias syndrome with similar phenotypic characteristics, except for neonatal diabetes and tracheoesophageal fistula. However, the genetic mutation in (regulatory factor X on chromosome 6) RFX6 was only detected in babies who had diabetes, making it different from the previously known mutations for the disease. This is the first reported case of a classical Mitchell-Riley syndrome in the Arab peninsula along with additional features and novel mutations in the RFX6 gene.

Weight loss surgery (WLS) is efficacious for long-term weight reduction and decreases overall mortality in severely obese patients. The mechanisms implicated in long-term weight loss are not fully understood. Proposed mechanisms include changes in gut hormones and brain regulation of appetite and satiety. We aimed to investigate the long-term ghrelin and leptin profiles and changes in food preference and eating behavior after WLS in adolescent patients. Two obese females aged 15 years and 14 4/12 years, who did not respond to lifestyle changes, including dietary intervention and physical exercise in combination with medical therapy, underwent robotic-assisted gastroplication. Anthropometric measurements, food habits and eating behavior, as well as metabolic and hormonal changes during long-term post-surgical follow-up were monitored. Long-term weight reduction was obtained in both patients, with a significant decrease in waist circumference. Resting energy expenditure showed a decrease over time, with a respiratory quotient that increased showing a shift from oxidation of a high-fat diet before surgery to oxidation of a mixed diet two and three years later. Both subjects improved their eating habits and lifestyle. Co-morbidity resolution was also noted. Increased pre-prandial ghrelin levels as well as higher post-prandial ghrelin and a leptin drop compared with pre-surgery values were observed in both patients. Persistent weight loss after gastroplication is associated with a favorable change in gut hormones and food preferences. The role of hormonal and sensory components in long-term results seems crucial. Particularly in adolescent patients, a multidisciplinary approach and continuous nutritional care is mandatory for weight maintenance and consolidation of changes.