Band 27, Heft 3-4

Aims: To describe the development of weight in children and adolescents with type 1 diabetes in Germany. Methods: We analyzed the body mass index (BMI) of the most recent treatment year of each patient with diabetes in the Pediatric Quality Initiative (DPV) database. BMI SD score (SDS) was calculated based on pooled historical German normative data (AGA) and based on healthy children from the CrescNet database. Thus, 25,762 children and adolescents with diabetes were compared with more than 75,000 healthy controls. Results: BMI-SDS was 0.49±0.88 and 0.26±0.79 when children and adolescents, respectively, with diabetes were compared with AGA reference or with CrescNet controls from the same year. In both analyses, female patients (0.57±0.89 and 0.30±0.79) had significantly higher BMI-SDS than male patients (0.41±0.86 and 0.22±0.78; p<0.0001). Analysis of different age groups showed highest BMI-SDS in patients below 6 years (0.61 and 0.56, respectively). After adjustment for metabolic control, center, and insulin treatment, BMI-SDS was significantly influenced by diabetes duration, age, and female gender. Conclusions: BMI of children and adolescents with type 1 diabetes is higher compared with healthy children measured in the same year. Especially, very young children and adolescent girls are at risk for overweight independent of annual trends.

Background: Data regarding sexual maturation in Thai boys are limited to only one 1999 study done in Bangkok which found that the ages of onset of Tanner 2 testicular enlargement and pubic hair were 10.8 and 12.4 years, respectively. Objective: To determine the age of onset of pubertal maturation and the physical growth of Thai boys at Hat Yai municipality, southern Thailand, in the year 2012. Methods: A cross-sectional study was conducted in 1320 healthy boys, aged 6–19 years, during June 2011 to March 2012. Testicular volume and pubic hair development were assessed according to the Tanner staging method. Probit analysis was used to calculate the median age of different stages of testicular enlargement and pubic hair development. Results: The median ages of boys having Tanner 2 testicular enlargement and Tanner 2 pubic hair were 10.6 [95% confidence interval (CI), 10.4–10.7] and 12.0 (95% CI, 11.8–12.2) years, respectively. The youngest ages of boys who had Tanner 2 testicular enlargement and Tanner 2 pubic hair were 8.2 and 9.7 years, respectively. The final height was attained at age 18 years at 170.3 cm, 3.3 cm greater than the 167.0 cm final height of Hat Yai boys studied in 1994. Conclusions: The age of onset of puberty in Hat Yai schoolboys in 2012 was 0.2 years earlier than that of Bangkok schoolboys in 1999. The final adult height of Thai boys increased 3 cm during the two decades.

Background: Plasma adipocytokines are associated with metabolic profile and cardiovascular risk in obese children. Objective: To investigate the association of plasma leptin and adiponectin concentrations with cardiometabolic risk profile and systemic inflammation in non-obese children. Subjects: We studied 170 healthy, non-obese children (86 males, mean age 10±2 years). Methods: Children’s current body mass index (BMI), plasma leptin and adiponectin concentrations, lipid profile, fasting plasma glucose and high sensitivity C reactive protein (hsCRP) were measured. Results: After adjustment for age, gender and BMI, plasma leptin concentrations were positively associated with hsCRP (t=2.72, p=0.009) and fasting plasma glucose (t=4.27, p<0.0001); plasma adiponectin concentrations were negatively associated with hsCRP (t=–3.31, p=0.0016); and positively with high density lipoprotein cholesterol (t=2.32, p=0.02). Children in the highest quartile of leptin/adiponectin (L/A) ratio demonstrated significantly higher BMI, systolic blood pressure, hsCRP, triglycerides and fasting glucose and the lowest high density lipoprotein (HDL) compared to lower L/A ratio quartiles. Conclusions: Alterations in plasma leptin and adiponectin may help to reclassify non-obese children, detecting those with more unfavorable risk profiles independent of BMI status.

Objective: The aim of this study was to examine height-gain response in relation to predicted good or poor response during first-year low or high growth hormone (GH) dose in short prepubertal children born small for gestational age. Patients and methods: The OPTIMA (Optimization of GH Treatment in Short Children Born Small for Gestational Age Based on a Growth Prediction Model) randomised study evaluated 12-month height standard deviation score (SDS) changes in patients receiving GH dose: fixed high (FH; 0.067 mg/kg/day) or 0.035 mg/kg/day individually adjusted (IA) after 3 months according to the Cologne early growth prediction. Results: Predicted 12-month height SDS gain was <0.75 for 21/89 FH-dose patients, considered poor responders; 11/21 reached a 12-month height SDS gain of ≥0.75. In IA-dose poor responders, increasing GH dose at 3 months maintained mean height velocity (HV), with 73.7% reaching a 12-month height SDS gain of ≥0.75 vs. 73.8% in IA-dose good responders who continued on low GH dose, where mean HV decreased after the initial 3-month period. Conclusion: GH dose increase at 3 months in patients with predicted poor response maintained catch-up growth. Even when on FH dose, some patients did not achieve a good response.

Background: QT-wave abnormalities have been detected in type 1 diabetes mellitus (T1DM). Prolongation of the heart rate corrected QT interval (QTc) has been associated with cardiovascular mortality. We evaluated how often QT/QTc abnormalities are present in youth with T1DM and if they are associated with disease parameters. Methods: Sixty-two T1DM youngsters and equal age- and gender-matched controls were studied. Demographic, anthropometric, and laboratory data were determined. QT was measured on a 12-lead resting electrocardiogram. QTc was calculated using Bazett’s formula. Results: T1DM patients had significantly longer QT/QTc than controls, but significance disappeared after adjustment for confounders. Abnormally prolonged QTc≥440 ms was observed six times more frequently in those with T1DM. QT was correlated with age, age at disease onset, but not with glycated hemoglobin or diabetes duration; QTc was only correlated with pubertal stage. Conclusions: T1DM youths have a sixfold increased risk for QT/QTc prolongation and should have regular follow-up for cardiac autonomic dysfunction.

The aim of this study was to investigate the effect of 1-year micronutrient supplementation on the height velocity of underprivileged premenarchal girls in comparison with the natural growth of apparently healthy girls from an affluent class. A 1-year cluster-randomisation intervention trial was conducted in 119 premenarchal girls (8–12 years) from two schools catering to the lower socioeconomic strata (LSES) in Pune, India. Three classes of age-matched girls were randomly allocated to any one of the three intervention groups: (i) Ca+MZn+D group (C1: zinc, 15 mg/day+multivitaminscalcium, 500 mg/day; vitamin D, 30,000 IU/3 months); (ii) Ca+D group (C2: calcium, 500 mg/day; vitamin D, 30,000 IU/3 months); and (iii) M+D group (C3: multivitamins; vitamin D, 30,000 IU/3 months). Height, weight, and Tanner stage were assessed at baseline and endline. A total of 119 age-matched, apparently healthy school girls from a higher socioeconomic group (HSES) were assessed for their growth after 1 year without any supplementation. At baseline, mean height-for-age Z-scores and weight-for-age Z-scores by Indian references were >–2 in 99% of HSES girls and 28% of LSES girls had height-for-age Z-scores <–2. Post-intervention, increase in height-for-age Z-scores adjusted for Tanner stage was significantly higher in the Ca+MZn+D group (0.32±0.06) than in the respective age-matched controls (C1 group) (–0.02±0.05) (p<0.05) as well as in both the Ca+D group (0.18±0.06) and the M+D group (0.14±0.04) (p<0.05). After adjusting for Tanner stage, height velocity was significantly higher for the Ca+MZn+D group (6.7±0.4 cm/year) than for the M+D group (6.1±0.2), Ca+D group (5.6±0.5) as well as age-matched controls (C1 group) (5.0±0.3) (p<0.05). Supplementation with calcium+vitamin D, zinc and multivitamins may be effective in improving stature in underprivileged Indian premenarchal girls.

Objective: This work aimed to assess glucose metabolism and insulin sensitivity in young adults born small for gestational age (SGA) as well as to measure the body composition and adipocytokines of these subjects. Methods: A total of 108 out of 342 SGA-born participants were invited for reexamination from the former Bavarian Longitudinal Study (BLS), in which 7505 risk-newborns of the years 1985 to 1986 were prospectively followed. Of these, 76 (34 female/42 male) participants at the age of 19.7±0.5 years were enrolled. Clinical examination and oral glucose tolerance testing (oGTT) was performed with assessment of insulin resistance indices, HbA1c, body mass index (BMI), adipocytokines, and body composition by bioimpedance analysis (BIA). Results: A total of 25 out of 76 (32.9%) patients had abnormal fasting and/or glucose-stimulated insulin levels. Glucose values measured during oGTT showed no abnormalities, except one participant who had impaired glucose tolerance. Homeostasis model assessment insulin resistance index (HOMA-IR) was 1.92±4.2, and insulin sensitivity index by Matsuda (ISI Matsuda ) showed mean values of 7.85±4.49. HOMA-IR>2.5 was found in 8 patients (10.5%), and 20 patients (26.3%) had an ISI Matsuda <5, both interpreted as insulin resistant. No alterations of adipocytokines were found. Fat mass (FM) measured by BIA was within the normal range for both genders and correlated significantly with BMI (r=0.465, p<0.001) and leptin (r=0.668, p>0.001), but not with adiponectin. Insulin resistance correlated with change in weight-for-height Z-score during the first 3 months of age, indicating that weight gain during that early phase might be a risk factor for the development of insulin resistance in children born SGA. Conclusions: A high percentage of insulin-resistant subjects were reconfirmed in a large German cohort of young adults born SGA. Therefore, regular screening for disturbances in glucose metabolism is recommended in these subjects.

Obesity is a metabolic disorder defined as excessive accumulation of body fat, which is made up of genetic, environmental, and hormonal factors and has various social, psychological, and medical complications. Childhood obesity is a major indicator of adult obesity. The aim of this study is to evaluate the cardiac functions via electrocardiography (ECG), echocardiography (ECHO), and treadmill test in childhood obesity. A patient group consisting of 30 obese children and a control group consisting of 30 non-obese children were included in the study. The age range was between 8 and 17 years. Anthropometric measurements, physical examination, ECG, ECHO, and treadmill test were done in all patients. P-wave dispersion (PD) was found to be statistically significantly high in obese patients. In ECHO analysis, we found that end-diastolic diameter, end-systolic diameter, left ventricle posterior wall thickness, and interventricular septum were significantly greater in obese children. In treadmill test, exercise capacity was found to be significantly lower and the hemodynamic response to exercise was found to be defective in obese children. Various cardiac structural and functional changes occur in childhood obesity and this condition includes important cardiovascular risks. PD, left ventricle end-systolic and end-diastolic diameter, left ventricle posterior wall thickness, interventricular septum thickness, exercise capacity, and hemodynamic and ECG measurements during exercise testing are useful tests to determine cardiac dysfunctions and potential arrhythmias even in early stages of childhood obesity. Early recognition and taking precautions for obesity during childhood is very important to intercept complications that will occur in adulthood.

Objective: Adiponectin (APN) may play a role in adapting energy metabolism at the maternal-fetal unit. The aim of the study was to investigate the relationship between placental APN mRNA expression, maternal serum APN concentration and umbilical cord serum APN concentration in full-term healthy newborns. Methods: Serum APN levels were compared in 46 samples (23 from healthy newborns; gestational age 37.0 to 41.5 weeks) and their mothers (n=23). The APN concentration was measured using enzyme linked immunosorbent assay (ELISA). We analyzed the mRNA expression profile of APN in 22 placenta tissue samples using real time polymerase chain reaction (RT-PCR). Results: The highest APN serum concentrations were found in umbilical cord blood, these were significantly higher than maternal APN levels (mean concentration±SD; 38.48±12.8 vs. 6.6±2.3 μg/mL, p<0.001). Otherwise, there were no significant correlation between maternal APN and umbilical cord APN concentration. APN gene expression was very low and only found in 8 out of 22 placentas. There were no significant correlation between placental APN mRNA and umbilical cord serum APN or maternal serum APN concentration. Umbilical cord APN concentrations were positively associated with birth weight (r=0.535; p=0.012) and gestational age (r=0.559; p=0.013). Maternal APN concentration revealed a negative correlation between maternal body weight (r=–0.623; p=0.009) and body mass index (BMI) (r=–0.634; p=0.008) at delivery. Additionally, no significant correlation was found between newborn birth weight and maternal weight. Conclusions: This study suggests that high serum APN concentrations in umbilical cord blood are not regulated by placental APN mRNA gene expression. The high concentration of APN in cord blood is independent from maternal APN concentration, suggesting an important physiological role of APN and implicating that umbilical APN concentration reflects its exclusive production by fetal tissues.

Introduction: The objectives of this study were to demonstrate the presence of low bone mineral density (BMD) and to examine the association of known risk factors for low BMD in patients with beta thalassaemia major in Sri Lanka. Method : Thirty-eight patients were studied. Their examination and laboratory investigation findings were recorded (haematology, biochemistry, hormonal profile, COL1A1 rs1800012G>T genotype, dual energy X-ray absorptiometry (DXA) scanning). Results: Mean age was 10.95 years (range 5–21.4). 20 (52.6%) were male. BMD was low (z score ≤–2.0) in 12 (31.5%). Regression analysis of BMD on known risk factors (age, sex, pubertal stage, ferritin level, average pre-transfusion haemoglobin, serum calcium level and COL1A1 rs1800012G>T genotype) controlling for confounding factors on each comparison, showed that only age was significantly associated with low BMD (p=0.005). Conclusions: Approximately one-third of patients had a low BMD. Only age was significantly associated with a low BMD.

Objective: To evaluate health-related quality of life (HRQoL) in a group of girls with Turner syndrome (TS) and determine its relation to key features of the condition. Methods: HRQoL was assessed with the short-form health survey (SF-36). Results: Of the 35 girls, 32 [mean (SD) age: 16.7 (2.61) years], of whom 28 (87.6%) received growth hormone therapy, agreed to participitate. Compared with the general population, girls with TS have lower scores in the physical functioning domain of HRQoL. However, they have similar HRQoL as their peers in other dimensions. There was a negative and significant association between the postmenarchal status and the social functioning domain of HRQoL. Age at growth hormone treatment initiation has a negative impact on the general health domain. Age at growth hormone initiation, bone mineral apparent density (BMAD) and the prevalence of skeletal anomalies negatively influence the vitality domain. HRQoL scores in the physical function domain were negatively associated with BMAD and positively associated with height. Conclusion: Compared with the general population, Irish girls with TS have similar HRQoL in most of domains as their peers. Postmenarchal status, height, age at growth hormone initiation, BMAD and skeletal anomalies showed significant association with at least one domain of HRQOL.

Aim: To investigate the etiology and clinical characteristics of hypothalamic syndrome in Chinese children. Methods: Thirty-three cases of hypothalamic syndrome were analyzed for etiology, initial symptoms, and clinical characteristics. Results: All of the 33 patients manifested symptoms of hypothalamic dysfunction and disorders of the hypothalamus-hypophysis-target gland axis. Fourteen patients were diagnosed with an intracranial tumor by magnetic resonance imaging (MRI) examination, four patients had postoperative intracranial tumors, one had received radiotherapy for suprasellar germinoma, one was hypothalamic-pituitary dysplasia, one had a history of viral encephalitis, and in 12 patients, the cause was unknown. The most common presenting symptoms were polydipsia/polyuria and eating disorders. Conclusion: Intracranial tumor is an important cause of hypothalamic syndrome in children, with germinoma the most common. Polydipsia, polyuria, and eating disorders are typical presenting symptoms. Long-term follow-up is needed for patients presenting with central diabetes insipidus, eating disorders or hypothalamic syndrome of unknown etiology. In addition, periodic pituitary MRI scanning is necessary to find potential intracranial tumors that may arise at any time.

Purpose: The aim of this work is to determine if a relationship exists between thyroid dose and incidence of primary hypothyroidism (PH) in children undergoing craniospinal irradiation (CSI). Methods: A total of 22 patients received CSI with evaluable thyroid dose information. All patients received concurrent chemotherapy and 21 patients (95%) received adjuvant chemotherapy. Median follow-up was 42.9 months. Results: The incidence of PH in our cohort was 59% at a median time after radiotherapy of 3.5 years (range: 8 months to 7.5 years). Mean thyroid dose appeared to best predict for PH, with a median of 2080 cGy for patients with PH versus 1736 cGy for children without PH (p=0.057). There was no association between the rate of PH and sex, age, CSI dose, minimum thyroid dose and maximum thyroid dose. Conclusions: A relationship may exist between the mean thyroid dose and incidence of PH in patients undergoing CSI. Thus, new strategies to protect the thyroid gland may be warranted.

Background: Noonan syndrome (NS) is an autosomal dominant syndrome characterized by typical dysmorphic features, cardiac anomalies as well as postnatal growth retardation, and is associated with Ras-MAPK pathway gene mutations. The purpose of this study was to improve the diagnosis of Chilean patients with suspected NS through molecular analysis. Methods: We screened 18 Chilean patients with a clinical diagnosis of NS for mutations in PTPN11 by high resolution melting (HRM) and subsequent sequencing. Results: Three PTPN11 missense mutations were detected in 22% of analyzed patients. Of these, two (c.181G>A and c.1510A>G) were previously reported and one was the novel substitution c.328G>A (p.E110K) affecting the linker stretch between the N-SH2 and C-SH2 domains of SHP-2 protein. Conclusion: Molecular studies confirmed the clinical diagnosis of NS in 4 of 18 patients, which provided support for therapeutic decisions and improved genetic counseling for their families.

Objective: The combination therapy of gonadotropin-releasing hormone analogues (GnRHa) and recombinant human growth hormone (rhGH) has been used to increase growth in children with premature sexual maturation and attenuated growth. The aim of this report was to study the benefit over cost of combined treatment in girls with central precocious puberty (CPP) and poor height prognosis and in girls with idiopathic short stature (ISS) and early puberty. Should this expensive treatment be given to such patients? Subjects and methods: Two patient groups were included: five girls with central precocious puberty (CPP) who reached final height (FH) at 16.3±1.2 years and eight girls with ISS who reached FH at 14.7±0.8 years. Patients were treated for 3.5±0.6 years. Results: In both groups, FH improved significantly; in CPP from –1.3 to –0.5 standard deviation score (SDS) (p=0.030) and in ISS from –2.6 to –1.7 SDS (p=0.012). Only girls with CPP reached their target height (–0.5 vs. –0.6 SDS) (p=0.500). Conclusions: Both groups had a total height gain of 5 cm. Each centimetre cost about €2700 per patient. This treatment should be considered only in patients with extremely low height prediction and very early pubertal onset.

Background: The molecular mechanisms leading to the formation of the two thyroid symmetrical lobes, which are impaired in thyroid hemiagenesis (TH), are little known. Objective: The aim of this work was to search for mutations in thyroid developmental candidate genes HOXA3 , HOXB3 , HOXD3 and PITX2 . Methods: Total DNA from peripheral blood was extracted and then the entire coding region of all these genes was amplified by polymerase chain reaction and direct sequencing. Results: Herein we describe familial cases of TH in two generations (proband and his father), in addition to other two sporadic cases. We have found polymorphisms in the HOXB3 (rs2229304), HOXD3 (rs34729309, rs1051929, c.543-199G>T and c.543-34G>A; and a new synonymous variant, NP_008829.3:p.314;C>G) and PITX2 (c.45+76C>T) genes, but no deleterious mutations. Conclusion: These results suggest the existence of other left-right thyroid asymmetry candidate genes in humans such as classical Mendelian mutation-causing disease, as well as other etiopathogenic mechanisms such as epigenetic modifications, especially for sporadic hemiagenesis.

Mutations in DUOX2 have been reported to cause congenital hypothyroidism (CH), and our aim in this study was to determine the genetic basis of CH in two affected individuals coming from a consanguineous family. Because CH is usually inherited in autosomal recessive manner in consanguineous/multicase 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 genes by Sanger sequencing. The family showed potential linkage to DUOX2 locus and we detected a nonsense mutation (R434X) in both cases and the mutation segregated with disease status in the family. This study highlights the importance of molecular genetic studies in the definitive diagnosis and classification of CH, and it also suggests a new clinical testing strategy using next-generation sequencing in all primary CH cases.

Several monogenic defects have been reported to be associated with idiopathic short stature. Focusing on growth hormone receptor (GHR)-gene alterations, the heterozygosity of the same gene defect may be associated with a range of growth deficits. We found a heterozygous mutation (V144I) within exon 6 of the GHR gene in a patient with a low level of insulin-like growth factor I (IGF-I), normal level of GH, and severe short stature. Despite the lack of statistical difference, an overall tendency for reduced wt -GH-induction of GHR activation and Jak/Stat signalling in cells transiently expressing GHR-V144I alone or co-expressing wt -GHR compared to cells expressing only wt- GHR was found when GH doses were increased. Our results suggest that, although GHR sequence variants are responsible for some functional alterations commonly observed in children with idiopathic short stature, these changes may not explain all the height deficits observed in these subjects.

Objectives: Mutations in the CYP27B1 gene, which encodes vitamin D 1α-hydroxylase, are the genetic basis of vitamin D-dependent rickets type 1A (VDDR1A, MIM 264700). The aim of this study was to investigate a novel CYP27B1 mutation and its clinical manifestations. Methods: VDDR1A was diagnosed based on clinical presentation, a physical examination, bone characteristics on an X-ray, and laboratory results. A molecular model of the CYP27B1 protein was constructed using the SWISS-MODEL server and Swiss-PdbViewer. Results: We sequenced the CYP27B1 gene in a 5-year-old male child who presented with growth retardation and a history of frequent hand, leg, and perioral twitching since the age of 12 months. We identified a compound heterozygous mutation consisting of two missense mutations: one in exon 7 (R389C [c.1165C>T]) and one in exon 8 (R459C [c.1375C>T]). We used the wild-type CYP27B1 as a receptor and calcidiol as a ligand to predict the interaction between the R459 site and calcidiol. According to the predicted structure, the wild-type R459 residue localizes to the pocket where CYP27B1 binds to its ligand. Conclusions: According to the Human Gene Mutation Database, the compound heterozygous mutation identified in our patient is novel and has not yet been reported in the literature. This mutation provides a new basis for further research on VDDR1A and for the development of clinical diagnostics.

We report the case of a 12-year-old boy with a de novo mutation in the DAX1 gene (for dosage-sensitive sex reversal, congenital adrenal hypoplasia critical region on the X chromosome, gene 1; also called NROB1). He was born at term, Addison’s disease was diagnosed at 8 years with a salt-wasting syndrome, and then hydrocortisone substitution was taken; the child continued to develop normally. A reoccurrence of salt-wasting syndrome usually happened after an episode of an abrupt withdrawal of hydrocortisone substitution. Because of adrenal insufficiency without hypogonadotropic hypogonadism, he came to the clinic at 12 years of age and hypoplasia of adrenal glands was found by MRI scans. We proposed the diagnosis of congenital adrenal hypoplasia in this patient and identified a hemizygous mutation (c.999_1000insCTCA, p.Leu335ThrfsX389) in exon 1 of the DAX1 gene. To our knowledge, it is a de novo mutation that leads to a frame-shift, a premature stop codon. In conclusion, it is very important to identify mutation in the DAX1 gene for a boy with adrenal insufficiency of unknown etiology.

Hypercalcemia is rare in children with etiology different from adults. We report an 11.5-year-old boy with developmental delay that presented with difficulty in walking and vomiting. Laboratory investigations revealed hypercalcemia (Ca 13.8 mg/dL) with low serum parathormone, normal full blood count and no circulating blasts. Osteolytic lesions were discovered on radiological survey. Bone marrow examination was consistent with the diagnosis of common B acute lymphoblastic leukemia (ALL). Hypercalcemia was successfully treated with zoledronic acid. Hypercalcemia is a rare but well-recognized complication of ALL, usually present at the time of initial diagnosis. We reviewed the literature and analyzed the clinical and laboratory data in 36 cases of childhood ALL presenting with hypercalcemia. In conclusion, hypercalcemia alone or combined with osteolytic lesions can be the only presenting symptom of ALL in children.

Preterm ovarian hyperstimulation syndrome (POHS) is an uncommon disorder characterized by prematurity, hypogastric and upper leg swelling of various intensities, high serum estradiol and gonadotropin levels, and ovarian follicular cyst/cysts. In this paper, we present the first case of POHS presenting with vaginal bleeding. A female infant was born via spontaneous vaginal delivery at 25 weeks of gestation with a birth weight of 610 g. At 36 weeks of post-conception age, she developed breast enlargement, swelling of the clitoral hood, labia major and minor, hypogastrium and upper legs. Several weeks later, vaginal bleeding started and lasted 3 days. The vaginal bleeding continued to occur at monthly intervals. The elevated levels of gonadotropins and estrogens, vulvar swelling and cysts in both ovaries confirmed the diagnosis of preterm ovarian hyperstimulation syndrome.

Germinomas presenting with a pituitary stalk lesion and panhypopituitarism are rare in children, and their definite diagnosis is challenging. An invasive diagnostic approach, such as a transsphenoidal biopsy, is often required prior to establishing a treatment regimen. A 13-year-old female presented with 1 year of secondary amenorrhea, fatigue, and progressive thirst with polyuria. Laboratory work-up revealed panhypopituitarism (central hypothyroidism, hypogonadotropic hypogonadism, adrenal insufficiency and central diabetes insipidus). α-Fetoprotein and β-human chorionic gonadotropin were not elevated in serum nor in cerebrospinal fluid. The magnetic resonance imaging (MRI) of the pituitary region showed an enhancing infundibular lesion, extending into the hypothalamus, and infiltrating the pituitary gland. A transsphenoidal biopsy of the infundibular lesion confirmed the diagnosis of germinoma (germ-cell tumor). After appropriate hormone replacement therapy, chemotherapy and low-dose radiation therapy, the patient achieved complete resolution of the pituitary stalk lesion on the MRI.

There are various phenotypes of mutations in BCS1L which encode a mitochondrial inner membrane protein that facilitates the insertion of Rieske iron-sulfur protein into respiratory chain complex III. Herein we report the radiologic findings of a patient with bc1 synthesis-like ( BCS1L ) gene mutation who was presented with convulsions.

Mutations in the KCNJ11 gene are responsible for the majority of permanent neonatal diabetes mellitus (PNDM) cases. Some mutations in this gene, including p.Q52R, are associated with the developmental delay, epilepsy, neonatal diabetes (DEND) syndrome. We describe a patient with PNDM who had no neurological finding although she was determined to have a novel mutation (p.Q52L) in the same residue of the KCNJ11 as in the previously reported cases with DEND syndrome. This case suggests that not all Q52 mutations in the KCNJ11 gene are necessarily related to DEND syndrome.

Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea is caused by thyroid transcription factor 1 ( NKX2-1/TTF1 ) mutations. We report the clinical and molecular characteristics of four cases presenting with primary hypothyroidism, respiratory distress, and neurological disorder. Two of the four patients presenting with the triad of BLTS had NKX2-1 mutations, and one of these NKX2-1 [c.890_896del (p.Ala327Glyfs*52)] is a novel variant. The third patient without any identified NKX2-1 mutations was a carrier of mitochondrial mutation; this raises the possibility of mitochondrial mutations contributing to thyroid dysgenesis. Although rare, the triad of congenital hypothyroidism, neurological, and respiratory signs is highly suggestive of NKX2-1 anomalies. Screening for NKX2-1 mutations in patients with thyroid, lung, and neurological abnormalities will enable a unifying diagnosis and genetic counseling for the affected families. In addition, identification of an NKX2-1 defect would be helpful in allaying the concerns about inadequate thyroxine supplementation as the cause of neurological defects observed in some children with congenital hypothyroidism.

Excessive thyroid hormone production, as seen in Graves’ disease, stimulates osteoblast-mediated bone turnover in favor of bone resorption. Acute reversal of bone resorption can lead to hungry bone syndrome (HBS), a state of rapid calcium deposition into newly synthesized osteoid resulting in hypocalcemia. Hypocalcemia due to subsequent functional or relative hypoparathyroidism is a recognized complication of therapy for Graves’ disease. HBS is most recognized as an outcome of rapid correction of vitamin D deficiency or of acute hypoparathyroidism in cases of parathyroid gland function disruption after surgical removal of the thyroid. We report the case of an adolescent boy with Graves’ disease who presented with hypocalcemia after radioactive iodine ( 131 I) therapy due to HBS. Our report highlights the risk of HBS and severe hypocalcemia following treatment for Graves’ disease in pediatric patients and also underscores the importance of pretreatment assessment and intervention for coexistent vitamin D deficiency.

The most common congenital endocrine disorder is congenital hypothyroidism (CH), which can lead to mental retardation if untreated. Majority of the patients have been found to have defects in thyroid development and migration disorders (dysgenesis), and the remaining ones have thyroid hormone synthesis defects (dyshormonogenesis). One of the most common mechanisms to cause dyshormonogenesis is a defect in the thyroid peroxidase (TPO) enzyme. In familial cases, mutations in the TPO gene are fairly prevalent. To date, more than 80 mutations have been identified, which result in variably decreasing TPO bioactivities. Clinical manifestations of TPO defects are typically permanent CH and with or without goiter. In this report, we presented two children with CH who were born to consanguineous parents and were homozygous carriers of a missense (G319R) TPO mutation, the mutation segregated with the disease status in the families confirming its pathogenicity. G319R mutation seemed to be a common cause of CH in Turkish population, which could originate from a common founder ancestor. Moreover, our results also confirmed the phenotypic variability associated with different TPO mutations.