Band 26, Heft 9-10

Objective: A systematic review to assess the efficacy of tamoxifen in the management of idiopathic pubertal gynecomastia. Data sources: Searches were conducted using the databases of Medline (search engine PubMed) and Web of Science ® . Study selection: Studies reporting the use of Tamoxifen for the treatment of gynecomastia in adolescents. Outcome measure: Resolution of gynecomastia. Results: A total of 164 publications were found; 59 were selected for retrieval and six were included in the review. There were no randomized controlled studies; the studies found have methodological flaws but show promising results. No clinical side-effects were reported or observed. Conclusion: Tamoxifen may be effective for the treatment of pubertal gynecomastia, and it seems safe to use. Randomized controlled studies are necessary to confirm this indication.

Background: A typical peak timing in the glucagon stimulation test has been reported as an indication of growth hormone (GH) deficiency. Other stimulation tests have not been evaluated. Objective: To evaluate the clinical usefulness of peak timing in the arginine stimulation test (AST) for growth hormone deficiency. Methods: Retrospective review of 199 ASTs from one center. Outcomes included correlation of peak times with (a) frequency of deficient peak; (b) growth velocity standard deviation scores (GVSDSs); (c) other evidence of pituitary pathology; (d) results of confirmatory clonidine test; and (e) response to GH treatment. Results: The peak in 83/109 (76.14%) sufficient tests occurred at typical times vs. 45/72 (62.5%) deficient tests (p<0.05). GVSDS on GH treatment was greater among patients with typical timing in the AST compared with atypical timing (2.67±0.59 vs. 0.46±1.17, p=0.021). No other variable correlated significantly with AST timing. Conclusions: Timing of peak in the AST is not a clinically useful parameter.

Background and aim: The pathogenesis of short stature in celiac disease (CD) is unknown. Obese children are generally taller than their non-obese peers; however, the role of adiposity on stature in CD is unclear. Our aim was to determine the association between adiposity and stature in CD. Subjects and methods: We compared the anthropometric characteristics of prepubertal children of ages 3–12 years, with biopsy-proven CD (n=40) and who were not on gluten-free diet, to same aged, prepubertal non-CD children (n=50). Body mass index (BMI) was calculated using the formula weight/height 2 . Sex-adjusted midparental target height (MPTH) standard deviation score (SDS) was calculated using National Children Health Statistics data for 18-year-old adults. Data were expressed as mean±standard deviation. Results: CD subjects had significantly lower BMI SDS than controls (0.61±1.22 vs. 1.28±1.60, p=0.027) but were not significantly shorter than the controls (–0.05±1.21 vs. 0.21±1.71, p=0.41). When the patients were subdivided into the normal-weight and overweight/obese groups, the normal-weight CD patients were of similar height as the normal-weight controls (p=0.76) but were significantly shorter than both the overweight/obese controls (p<0.001) and overweight/obese CD children (p<0.001). Interestingly, the overweight/obese CD children were significantly taller than the normal-weight controls (p=0.003). The MPTH SDS did not differ between the groups. Conclusions: Overweight/obese prepubertal children with CD were taller than both their normal-weight CD peers and the normal-weight controls, but were of similar height as the overweight/obese control subjects.

Micronutrient deficiencies are common consequences of the plant-based diet in children from developing countries which may affect their linear and ponderal growth. The aim of the study was to investigate the association between micronutrient status and growth indices in Indian girls. In cross-sectional studies (2006–2010), data on weight, height and diet were collected on 1302 girls (2–18 years) from Pune city, India. Fasting hemoglobin was measured on 1118 girls and serum zinc was measured on 695 girls. Height-for-age Z-scores (HAZ) and body mass index for age Z-score (BMIZ) were computed using contemporary Indian references. HAZ >–1 was observed in 54% girls, and 18.1% were short (HAZ <–2). BMIZ was within the reference range (–2<BMIZ<2) in majority (82.4%) of the girls. Average HAZ and BMIZ were significantly higher in higher socioeconomic (HSE) than in middle (MSE) and lower (LSE) socioeconomic groups (p<0.05). Girls in all age groups had calcium, zinc, iron and vitamin intakes of <50% of Indian recommended dietary intakes. Mean nutrient intakes were significantly higher in HSE than in MSE and LSE girls (p<0.05). Girls with short stature (HAZ <–2) had significantly lower intakes of calcium, zinc, iron, β-carotene, riboflavin, niacin, folate and ascorbic acid (p<0.05). Higher levels of serum zinc and hemoglobin were observed in girls with HAZ >–1 than in short girls even after adjusting for socioeconomic status (SES). The mean serum zinc level of thin girls (BMIZ <–2) was significantly lower than those of both normal and overweight girls after adjusting for SES. Micronutrient sufficiency is of paramount importance for adequate growth in Indian girls.

Aim: Some cases of idiopathic short stature (ISS) may be caused by defects in the modulation of the negative feedback regulation of the growth hormone receptor (GHR)/ Janus kinase (JAK)2/signal transducers and activators of transcription (STAT)5 signaling pathway. The cytosolic tyrosine phosphatases, protein tyrosine phosphatase 1B (PTP1B) and Src homology 2 (SH2) domain-containing protein-tyrosine phosphatase-1 (SHP-1), the later which translocates to the nucleus after activation, interact with JAK2 in a GH-dependent manner. The possible contribution of PTP1B and SHP-1 to GH signaling in fibroblasts from ISS patients has not been studied. Methods: We determined the basal protein content of PTP1B and SHP-1 in the presence of recombinant human GH (rhGH) for 24 h in skin fibroblast cultures, obtained from patients with ISS, and were compared with a normal height control children group. JAK2 activation was determined in both groups. Results: JAK2 activation was delayed in fibroblasts from ISS patients compared to controls. Under basal conditions, the protein content of SHP-1 was lower in ISS, and after incubation with rhGH, it decreased in the non-nuclear and nuclear fraction of controls, but not in ISS patients. The protein content of PTP1B, however, increased in a similar fashion in fibroblasts from both ISS and control children. Conclusion: The delayed activation of JAK2 and the lack of response of SHP-1 after incubation with GH in fibroblasts from ISS patients, suggests that the growth retardation observed in some of these children may be mediated in part by this phosphotyrosine phosphatase.

Objective: This study investigated the relation between salivary cortisol and the metabolic syndrome (MetSyn) score in young girls. Methods: Twenty-three girls (8.4±0.9 years) had a fasting blood draw to measure high-density lipoprotein (HDL), glucose, and triglyceride concentrations. Waist circumference and blood pressure were also measured. Saliva samples were collected three times (upon waking, 30 min post-waking, and in the evening) at home to measure cortisol levels. A continuous MetSyn score was created from blood pressure, waist circumference, HDL, triglyceride, and glucose values. Correlations examined the unadjusted associations between cortisol values, MetSyn score, and its related components. Regression analysis examined the relation between cortisol values, the MetSyn score, and its related components adjusting for breast development. Results: The MetSyn score was not related with cortisol values; however, HDL was negatively related with 30-min post-waking, evening, and area under the curve cortisol levels. Triglycerides were positively related to the 30-min post-waking and area under the curve values. These relations existed after adjusting for breast development. Conclusion: While the MetSyn score was not related, specific MetSyn components were related to salivary cortisol levels. Cortisol may be involved in the development of some MetSyn components.

Background and Objective: We aimed to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) and anthropometric indicators of adiposity among Korean preadolescent children aged 7–9 years. Subjects and Methods: Children aged 7 to 9 from the Ewha Birth & Growth Cohort were followed up from July to August 2011. Serum 25(OH)D concentration was measured using radio immunoassay. We assessed the magnitude of cross-sectional association with vitamin D concentrations and indicators of adiposity [body mass index (BMI), waist circumference (WC), mid-arm circumference (MAC), body fat mass (BFM), percent body fat (PBF), and triceps skinfold thickness (TSF)] using multiple linear and logistic regression analyses adjusted for sex, age, birth order, maternal education, and fruit/fruit juice intake. Results: Thirty-two (16%) out of a total of 205 children showed an optimal level of serum 25(OH)D, but most children did not reach a sufficient level (<30 ng/mL) even in summer. The level of 25(OH)D was inversely associated with BMI ( β =–0.10, p<0.01), WC ( β =–0.28, p<0.01), and BFM ( β =–0.12, p=0.02) after adjusting for confounding factors and showed marginal boundary with PBF ( β =–0.20, p=0.06) and TSF ( β =–0.11, p=0.08). Regarding the risk of overweight, a 13% protective effect per 1 ng/mL increase of 25(OH)D was shown even after adjusting for relevant confounding factors (adjusted odds ratio=0.87, 95% confidence interval 0.78–0.98). Conclusions: We found that the 25(OH)D concentrations were inversely associated with adiposity indices in preadolescent children. This study suggests that adequate vitamin D intake in growing children is crucial to maintain an optimal vitamin D level to prevent obesity and obesity-related health problems later in life.

Aim: To investigate the association of serum resistin levels with metabolic syndrome (MS) and early atherosclerosis in obese children. Methods: A total of 176 obese children and 88 healthy children were enrolled in this study, and were gender and age matched. Obesity was defined as a body mass index (BMI) of ≥ the 95th percentile for age and sex. All children had a physical examination and routine hematology testing for fasting blood glucose, insulin, and lipids profile. Homeostasis model of assessment of insulin resistance (HOMA-IR) was calculated, as insulin resistance has a central role in the pathophysiology of MS. Non-invasive ultrasound measurement was obtained to investigate carotid intima-media thickness (IMT) as the markers of early atherosclerosis. Path analysis was used to evaluate the value of resistin levels to early atherosclerosis. Results: The resistin levels were higher in obese children compared to healthy children (23.14±7.35 vs. 17.1±5.7 ng/mL, p<0.05), and it is positively correlated with BMI, waist circumference, systolic blood pressure, fasting insulin, HOMA-IR, IMT and high sensitive CRP (Hs-CRP), but not related to diastolic blood pressure, blood lipids and fasting glucose. A positive linear correlation was observed between resistin and the number of MS components. Path analysis indicated serum resistin can directly (β=0.304, p=0.001), and indirectly via HOMA-IR (β=0.085, p=0.008) and Hs-CRP (β=0.047, p=0.029), contribute to early atherosclerosis. Conclusion: Resistin not only play a certain role in the presence of MS, but also indirectly via insulin resistance and Hs-CRP to contribute to early atherosclerosis in obese children.

Background: Infants of diabetic mothers (IDMs) are at risk of hypoglycaemia in the neonatal period. The prediction of which of these infants are at higher risk of developing hypoglycaemia is complex. Aims: To determine the characteristics of infants of diabetic mothers who are more likely to need an admission to the neonatal intensive care unit to manage their hypoglycaemia. Methods: Retrospective chart review of maternal and infant characteristics of ‘at-risk’ infants. Electronic patient records and neonatal and obstetric database accessed to obtain data. Results: A total of 326 infants were identified in a study period accessible to electronic patient records. Macrosomia was present in 15% of the infants. Hypoglycaemic episodes occurred in 109 (33.4%) infants. Maternal diabetes type, HbA 1c , prematurity, macrosomia, and temperature instability were identified as risk factors most commonly associated in infants who actually went on to develop hypoglycaemia. Conclusions: A weighted risk score to predict hypoglycaemia in this at-risk population may serve to rationalise admission to the neonatal unit and management of IDMs.

Background: The strains of type 1 diabetes mellitus in children and adolescents pose a challenge to the minor and his/her parents. Objective: The objective of this study was to identify parental dyadic coping patterns and explore their relation to psychosocial and disease variables. Subjects: Parents (n=44 dyads) of children/adolescents with type 1 diabetes. Methods: Cluster analysis employing Ward’s method was conducted as a multivariate classification procedure without predetermined cluster centers. Results: Three parental coping clusters were identified and labeled: avoiders, negotiators, and doers. Although not reaching statistical significance, the HbA 1c levels of children/adolescents with parental dyads exhibiting the negotiator coping pattern were consistently lower than the levels of children with parents classified as avoiders or doers. Conclusions: Parental dyads were distinguishable based on their dyadic coping patterns with a substantial proportion employing avoidant coping and suboptimal communication strategies. These parental dyads may benefit from minimal psychosocial intervention.

Mutations in SLC29A3 lead to pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) and H syndromes, familial Rosai-Dorfman disease, and histiocytosis-lymphadenopathy plus syndrome. We report a new association of PHID syndrome with severe systemic inflammation, scleroderma-like changes, and cardiomyopathy. A 12-year-old girl with PHID syndrome presented with shortness of breath, hepatosplenomegaly, and raised erythrocyte sedimentation rate and C-reactive protein. An echocardiogram showed biventricular myocardial hypertrophy, and cardiac magnetic resonance imaging showed circumferential late gadolinium enhancement of the myocardium. No systemic amyloid deposits were observed on a whole-body serum amyloid P scintigraphy scan. Abdominal ultrasound revealed intra-abdominal fat surrounding the solid organs, suggesting a possibility of evolving lipodystrophy with visceral adiposity. PHID syndrome is a novel monogenic autoinflammatory syndrome (AIS) associated with severe elevation of serum amyloid. Lipodystrophy, cutaneous sclerodermatous changes, and cardiomyopathy were also present in this case. In contrast to other AIS, blockade of interleukin-1 and tumor necrosis-α was ineffective.

Background and objective: The issue of insulin-like growth factor 1 (IGF-1) and diabetes in adults and type 2 diabetes has been well investigated. A few studies have investigated the serum IGF-1 level at the onset of type 1 diabetes mellitus (T1DM) in children. In the present study, we investigated the IGF-1 level of T1DM children before and after insulin therapy. Subjects and methods: Between August 2011 and October 2012, 62 children with newly diagnosed T1DM were recruited. Serum IGF-1 levels were compared before and 1 month after insulin therapy between diabetic ketoacidosis (DKA) and non-DKA patients. Results: Thirty-one patients without DKA (18 girls and 13 boys, mean age 8.8±3.01 years) and 31 patients with DKA (18 girls and 13 boys, mean age 8.3±3.7 years) were studied. The mean IGF-1 in the DKA group was lower than that in the non-DKA group; however, this difference was not statistically significant (p=0.10). Serum IGF-1 levels increased significantly 1 month after insulin therapy in both the DKA (p<0.001) and non-DKA (p<0.001) groups. Conclusion: Serum IGF-1 level is reduced in new-onset T1DM children. A significant increase in serum IGF-1 level can occur with insulin therapy in both DKA and non-DKA children.

Objectives: To investigate the prevalence of genetic mutations in steroid 5α-reductase-2 ( SRD5A2 ), androgen receptor ( AR ) and steroidogenic factor-1 ( SF-1 ) in Chinese children with hypospadias, and to also explore the possible underlying molecular mechanisms of this disease. Methods : A total of 52 boys with hypospadias were enrolled. Mutational analyses of the SRD5A2 , AR and SF-1 genes were performed by direct sequencing. Results : SRD5A2 gene mutations were found in 13.5% (7/52 cases), including five compound heterozygotic and two homozygotic mutations. One novel heterozygotic SF-1 gene mutation was identified in a patient with perineal hypospadias and cryptorchidism, the patient’s mother also had the same mutation. No mutation was found in the AR gene. The clinical manifestations of patients with mutations in SRD5A2 or SF-1 varied. Conclusions: In Chinese patients, SRD5A2 gene mutations were, relatively, frequently associated with hypospadias. The SF-1 gene may be another candidate gene for hypospadias. In contrast, AR gene mutations are not commonly associated with this condition.

The objective of the study was to evaluate whether or not sexual development differs between boys with prepubertal obesity and boys of normal weight. We enrolled healthy obese and normoweight schoolboys from Shenyang City, Liaoning, China. Eligible boys were at Tanner stage 1 and 8 years of age at baseline. We measured testosterone and estradiol concentrations in the saliva and assessed auxology annually for 4 years. In all 56 obese and 56 normoweight boys, the height, weight, body composition, and sex organ volume increased with age. The percentages of body fat, fat mass, and lean mass were all higher in obese than in normoweight boys. The mean testicular volume was smaller in obese boys than in normoweight boys. The sex hormone concentrations increased with age, except for testosterone in obese boys in year 3 of follow-up. In year 4, estradiol concentrations were significantly higher in obese boys than in normoweight boys. Excessive adiposity in prepubertal boys might affect testicular volume, possibly because of high estradiol and low testosterone concentrations.

A 6-day-old female patient suddenly died of congestive heart failure, hepatomegaly and hypoglycemic encephalopathy. Tandem mass spectrometry (MS) analysis revealed a possibility of carnitine deficiency. However, many of the clinical symptoms had not yet occurred at that time, and the clinical data was incomplete. We aim to derive a systematic procedure of identifying pathogenic mutations for similar patients. Physicians could save patients’ lives with effective treatment at a much earlier stage. Direct sequencing of the exons and exon–intron boundaries of GAA , SLC25A5 , CPT1 , CPT2 , SLC25A20 and MUT genes were performed on the parents of the patient. DNA from the blood spots of the patient was analyzed for the MUT gene. The results revealed that the patient was a compound heterozygote with MUT. c. 729_730insTT and c. 1677-1G>A. cDNA sequence demonstrated MUT c. 1677-1G>A resulting in the deletion of eight nucleotides and the introduction of 13 novel amino acids before premature termination.

Complete androgen insensitivity syndrome (CAIS) associated with Müllerian remnant is rare during childhood. The Müllerian system usually regresses because of the presence of the anti-Müllerian hormone (AMH) originating from the Sertoli cells of the gonads. Rarely, residual Müllerian structures may exist. We present two cases from the same family, raised as females. They were 12 and 18 years old, respectively, and they had Tanner V breast development but Tanner I-II pubic hair. The older patient had primary amenorrhea. Both have a 46,XY genotype. Pelvic ultrasonography revealed no uterus and ovaries. The patients underwent bilateral laporoscopic gonadectomy. Both had residual Müllerian structures. Mutation analyses were performed, and both patients were found to be carrying a point mutation in exon 4 of the AR gene consisting of a G nucleotide deletion at position c.1890delG, followed by a frame-shift mutation and a stop codon. This mutation has not been described yet in the literature. Although the association with CAIS and Müllerian remnant is rare, no genetic defect specific to androgen insensitivity with Müllerian remnants has been identified so far.

There are few reports of adults with disorders of sexual development (DSD). Here we describe the clinical profile and results of psychological assessment of three siblings with 46, XY DSD caused by partial androgen insensitivity syndrome (PAIS). The elder sibling (aged 22 years) was reared as female, while the middle and youngest siblings (17 and 18 years of age), were reared as males. The gender identity was concordant with the sex of rearing. There was no gender dysphoria. The psychological distress that our patients experienced was due to the limitations placed on them by their medical condition. It did not permit them to experience various facets of being either male or female completely. The younger siblings reared as males had additional problems of gynecomastia and lack of male secondary sexual development.

48, XXYY is a very rare sex chromosome aneuploidy, characterized by both an extra X and Y chromosome with a prevalence of 1:18,000–1:40,000. Most patients are diagnosed prenatally by cytogenetic examination of amniotic fluid, or during the first years of life because of severe developmental delay, cognitive impairment and behavioural disorders. This syndrome shares two findings with Klinefelter syndrome, namely tall stature and hypergonadotropic hypogonadism but at this time no genital anomalies have been reported in patients with this tetrasomy. We describe a 48, XXYY neonate and a clinical picture characterized by small penis, bifid scrotum, scrotal hypospadias and testes palpable in the labioscrotal folds.

Gonadal dysfunction is a complication following stem cell transplantation (SCT). There have been no reports of gonadal function in stem-cell-transplanted thalassemic survivors who received a reduced intensity conditioning regimen (RIC). We evaluated gonadal function in 47 β-thalassemic patients following SCT with either myeloablative or reduced intensity regimen. Thirty-six patients received a myeloablative regimen, the remaining 11 patients had an RIC regimen. Their median (range) age was 13.2 (5.9–25.8) years. There were 29 patients (62%) with gonadal dysfunction (26 with primary gonadal dysfunction and three with gonadotropin deficiency). Comparisons between patients who received myeloablative and RIC regimens, revealed no differences in gonadal dysfunction (56% vs. 82%, p=0.113, respectively). In conclusion, our study demonstrated high frequency of gonadal dysfunction in these patients. Even after receiving RIC, gonadal dysfunction was very common. To our knowledge, this study is the first to report gonadal function in children and adolescents with β-thalassemia disease who were pre-transplanted with RIC.

We report a testicular enlargement that mimics precocious puberty in a boy aged 6.5 years with monorchism and testicular microlithiasis.

Rett syndrome is an X-linked dominant disorder frequently caused by the mutations in the methyl-CpG-binding protein 2 gene (MECP2). Its prevalence in the population is 1/15,000–20,000. Patients with Rett syndrome present apparently normal psychomotor developments during the first 6–18 months of life. Subsequently, they show a short period of developmental stagnation followed by a rapid regression in language and motor development. Precocious puberty is characterized by premature breast and pubic hair development, and advanced bone age development at 8 years of age. We present a case of Rett syndrome and precocious puberty in a 6-year-old girl. At the age of 6, the first signs of precocious puberty appeared (Tanner stage 3). Laboratory measurements were detected as follows: luteinizing hormone (LH), 0.2 mIU/mL; follicle-stimulating hormone (FSH), 1.1 mIU/mL; estradiol, 36 pg/mL; bone age, 9 years. The response to luteinizing hormone releasing hormone (gonadotropin-releasing hormone stimulation test) was characteristic for true precocious puberty (LH, 32 mIU/mL; FSH, 26 mIU/mL). This is the first reported case of precocious puberty related to Rett syndrome.

The high prevalence of vitamin D deficiency in relation to diabetes mellitus is well reported in the literature. However, type I diabetes mellitus (T1DM) in association with resistant rickets is extremely rare and reported in only one previous case. The authors describe here a case of type II vitamin D-dependent rickets (VDDR type II) in a 10-year-old Indian girl who presented with diabetic ketoacidosis (DKA). DKA as a presenting manifestation of T1DM in a patient with VDDR type II has never been reported before in worldwide literature.

Hyperglycemia is seldom described in young patients with pituitary gigantism. Here, we describe the case of a 17-year-old Taiwanese boy who developed depressive mood disorder and diabetic ketoacidosis (DKA) at the presentation of pituitary gigantism. The boy complained of lethargy and dysphoric mood in June 2008. He presented at the emergency department with epigastralgia and dyspnea in January 2009. Results of laboratory tests suggested type 1 diabetes mellitus with DKA. However, serum C-peptide level was normal on follow-up. Although he had no obvious features of acral enlargement, a high level of insulin-like growth factor 1 was detected, and a 75 g oral glucose suppression test showed no suppression of serum growth hormone levels. A pituitary macroadenoma was found on subsequent magnetic resonance imaging. The pituitary adenoma was surgically removed, followed by gamma-knife radiosurgery, and Sandostatin long-acting release treatment. He was then administered metformin, 500 mg twice daily, and to date, his serum glycohemoglobin has been <7%.

We report an 18-year-old Japanese male with a lack of secondary sex characterization and growth failure caused by a rare association between Rathke’s cyst and hypophysitis. He was referred to us because of delayed secondary sex characterization. Endocrinological examination showed panhypopituitarism, and the replacement of hydrocortisone, levothyroxine, and desmopressin acetate (DDAVP) was initiated. Brain magnetic resonance imaging (MRI) showed a suprasellar region and a swollen pituitary stalk. The mass was partially resected using the transsphenoidal approach. The pathological diagnosis was hypophysitis and Rathke’s cyst. Follow-up MRI performed 1 year after surgery showed that the size of sellar region had not changed. After surgery, in addition to pre-operative hormonal replacement, growth hormone and testosterone were initiated. Two years later, the size of sellar region remains unchanged. In conclusion, while an association between Rathke’s cyst and hypophysitis is rare, we suggest that this condition should be included in differential diagnosis of the sellar region, even in adolescents.

There are different opinions concerning changes in glucose metabolism in patients with Laron syndrome. In this paper we discuss the treatment results of our patient with Laron syndrome who developed diabetes during late adolescence. A 19-year-old boy with Laron syndrome was referred to our clinic for follow-up. He had been diagnosed with Laron syndrome (LS) at 4 years old and rIGF-1 therapy was initiated. After 4 months the treatment was discontinued. At the age of 17, rIGF-1 therapy was restarted. A height gain of 8.8 cm. was observed during the 2-year treatment period. He was admitted to our hospital at the age of 19 years following discontinuation of the therapy. At that time, his height was 142 cm, and weight for height was 136%. His blood glucose was 85 mg/dL (4.72 mmol/L), insulin was 26.39 pmol/L, and HbA 1c was 5.4%. At the age of 20, when he has not been receiving IGF-1 therapy for 1 year, his weight for height was 143 cm. Laboratory evaluation revealed that fasting blood glucose was 176 mg/dL (9.77 mmol/L), fasting insulin was 29.86 pmol/L, and HbA 1c was 7.5%. Primary insulin therapy was then initiated. His parents both had a diagnosis of type 2 diabetes. Insulin therapy was switched to oral antidiabetic (OAD) therapy at the end of the second year because of a normal C-peptide level of 0.8 nmol/L under insulin therapy. After 6 months of OAD, HbA 1c was 5.7%. The treatment was then switched to IGF-1 therapy, but his blood glucose profile was impaired and OAD therapy was restarted. In conclusion, we observed that genetic susceptibility and abdominal obesity caused type 2 diabetes in this patient. We believe that oral antidiabetic agents and life-style changes may be the appropriate approach when diabetes is developed in LS patients.

Wegener granulomatosis (WG) is a cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA)-associated, multi-system, necrotizing granulomatous vasculitis. Inflammation of the nasal or oral mucosa, and lung and kidney involvements are typical in the course of the disease. In rare cases, pituitary involvement may occur and cause panhypopituitarism. Pituitary involvement is very rare, and only two pediatric case reports have been published to date out of a total of 24 cases. This is a case report of an adolescent patient who presented with panhypopituitarism symptoms and was later diagnosed with WG. A 16-year-old female patient complained of fever, headache, purulent nasal discharge and severe muscle and joint pain. Additionally, she had polyuria and polydipsia. Investigations revealed a pituitary mass and panhypopituitarism. Positivity of c-ANCA and renal biopsy result compatible with WG confirmed the diagnosis.

Acquired autoimmune hypothyroidism is common in late childhood and adolescence but is very rare in the first 3 years of life. We report on three cases of autoimmune thyroiditis (AT) in young children who presented with constipation, decreased appetite, and increased hours of sleep. Our cases highlight that AT may remain undiagnosed for a long time in young children owing to the rarity of the disease.

Background: Adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome (CS) in the presence of leukemic central nervous system infiltration is very rare. Case: A 3.8-year-old girl who had been treated for B-cell acute lymphoblastic leukemia (ALL) for 1.5 years was admitted to our hospital with excessive weight gain and depression for the last 2 months. Prior to her admission, she was on maintenance with the ALL-BFM95 study protocol for 10 months that does not contain corticosteroids. On physical examination, central obesity and moon face appearance were determined. Laboratory tests revealed high morning ACTH, cortisol level, and 24-h urinary free cortisol level. Morning cortisol level was 33.94 nmol/L after a 2-day (4×0.5 mg) dexamethasone suppression test. A lumbar puncture revealed leukemic cells in the cerebrospinal fluid. No pituitary adenoma was detected on magnetic resonance imaging. We diagnosed the patient with ACTH-dependent CS related to leukemic infiltration of the central nervous system. Conclusion: Central nervous system infiltration should be considered in leukemic patients who have developed CS. We believe increased leukemia inhibitory factor levels may be a factor for CS in our patient with ALL.

Mutation of the Wilms tumor gene ( WT1 ) is associated with two well-described syndromes called Denys-Drash (DDS) and Frasier (FS). Both are associated with nephropathy and ambiguous genitalia and have overlapping clinical and molecular features. The known risk of Wilms tumor in DDS and gonadoblastoma (GB) in FS patients requires tumor surveillance. The literature reports the occurrence of GB in DDS as lower than FS. This case highlights a very early presentation of bilateral GB in DDS and the consideration of early prophylactic gonadectomy at the time of diagnosis with DDS.

Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder of branched-chain amino acid metabolism caused by the defective function of branched-chain α-ketoacid dehydrogenase complex (BCKDH). It is characterised by increased plasma leucine, isoleucine, and valine levels, and mutations can be detected in any one of the BCKDHA , BCKDHB , and DBT genes. In this study, we describe the molecular basis of a novel mutation found in one MSUD Malay patient from consanguineous parents. A homozygous mutation has been detected in this patient whose both parents carried a heterozygous mutation at DNA coding region c.431G>T in exon 4, which resulted in a substitution of serine to isoleucine at codon 144 (p.S144I). In silico analysis predicted S144I to be potentially damaging. The mutation was located on the alpha helical region of the BCKDHA protein, and it is predicted to affect the stability of protein due to the loss of various polar interactions between local secondary structures. Homology analysis revealed that this mutation occurred in a highly conserved region (100%). This result indicates that S144I mutation is likely pathogenic and may contribute to the classic form of MSUD in this patient.

Androgen replacement therapy for male hypogonadism may be prescribed utilizing intramuscular, oral or more recently, topical formulations. With topical formulations, there is a risk of person-to-person transmission if appropriate precautions are not taken. We describe two cases of virilization in pre-pubertal children following passive transfer of paternal topical testosterone. A 21 month old male was referred with a 6 week history of pubic hair, phallic growth, and linear growth spurt. Genital examination revealed Tanner stage 2 pubic hair and Tanner stage 3 phallic development, which was discordant with the pre-pubertal testicular size (2 mL bilaterally). A 3 year 8 month old girl was referred for a 2 month history of increasing pubic hair development. Examination revealed Tanner stage 2 pubic hair and Tanner stage 1 breast development. Both of these patients had fathers who had been diagnosed with hypogonadism and were being treated with topical androgen gel therapy, which they applied to their arms and chest before bed. In addition, both patients often slept with their parents resulting in skin-to-skin contact. Investigations were consistent with gonadotropin independent virilization with both patients demonstrating elevated testosterone levels. Testosterone levels returned to normal pre-pubertal levels with no further development of secondary sexual characteristics following discontinuation of exposure to topical testosterone. Precautions must be taken to prevent person-to-person transfer of topical steroids. With the increasing popularity of topical steroids for the treatment of low testosterone, it is imperative that these therapies be prescribed and utilized judiciously to prevent harm, specifically gonadotropin-independent virilization.

Objectives: Camurati-Engelmann disease (CED) is a rare form of progressive bone dysplasia due to mutations in the transforming factor gene TGFB1 on chromosome 19q13.1-q13.3. Endocrine complications such as osteoporosis, vitamin D deficiency, delayed puberty and hypogonadotrophic hypogonadism may be present. Methods and results: Genetic analysis of the TGFB1 gene revealed a heterozygous missense mutation p.R218C in exon 4 of chromosome 19q13.1-q13.3 in a 14-year-old girl who presented with typical symptoms of CED, hyperprolactinaemia and menstrual irregularity. The patient responded well to prednisone 5 mg/kg per day as well as calcium and vitamin D supplements. Conclusions: The role of p.R218C in TGFB1 on the mechanism of the disease itself and the complications of it in bones and endocrine glands remain unclear. Early recognition as well as a detailed understanding of the pathogenesis of the disease is important for future treatment options and better quality of life of such patients.

Accumulation of ceramides within tissues induces insulin resistance. Moreover, adiponectin exerts its beneficial metabolic effects at least partially through ceramide catabolism. We hypothesized that specific plasma ceramide subspecies are elevated in obese children and adolescents with type 2 diabetes (T2D), and that they inversely correlate with adiponectin and measures of insulin sensitivity. This was a cross-sectional study. Participants included 14 obese female subjects with T2D, ages 10–17, and 14 lean healthy controls of the same age and gender. Fasting plasma ceramide subspecies were measured by quantitative tandem mass spectrometry. Subjects with T2D had higher concentrations of C22:0 and C20:0 ceramides, with a 2-fold increase in C18:0 ceramide and C24:1 dihydroceramide (p<0.05). C22:0, C20:0 and C18:0 ceramide correlated with decreased adiponectin concentrations, increased HOMA-IR, BMI Z-score, triglyceride and fasting blood glucose concentrations (p<0.05). Plasma levels of C18:0, C20:0 and C22:0 ceramide, as well as C24:1 dihydroceramide, were elevated in obese female children and adolescents with T2D. This may be a reflection of tissue insulin resistance and could be a result of low adiponectin levels.

Our aim was to determine whether small for gestational age (SGA) neonates exhibit reduced left ventricular contractility and diastolic dysfunction, through the assessment of tissue by Doppler imaging and investigation of the stress-velocity relationship (SVR). The study subjects were limited to 37 neonates just after birth. These patients were grouped into 14 SGA neonates with birth weights below the 10th percentile (aged 29–36 weeks, birth weight 860–2066 g) and 23 appropriate for age (AGA) neonates with birth weights between the 10th–90th percentile (aged 20–36 weeks, birth weight 954–2945 g). Although there were no significant differences in the SVR or diastolic function between the SGA and AGA neonates, wall stress correlated significantly and inversely with birth weight in all subjects with a higher E/Ew ratio by tissue Doppler imaging. In conclusion, there were no significant differences in cardiac function between SGA and AGA neonates. By contrast, the relationship between wall stress, diastolic dysfunction, and birth weight may be due to physiological alterations in neonates, including those with low birth weights, just after birth.