Search

Objective: Increased prevalence of celiac disease (CD) and autoimmune thyroid disorders (ATD) in patients with Type 1 diabetes mellitus (T1D) has been widely reported. Such an association may lead to adverse effects on the growth, bone metabolism and fertility, and response to therapy may become difficult. The aim of this study was to evaluate the clinical findings and HLA typing results in patients with T1D associated with CD or ATD. Methods: The association of CD and ATD was evaluated in 38 children with T1D aged 1.5−16.8 years who had been followed for 48.3±28 months. Diagnosis of CD was based on positivity for serum endomysial IgA antibody and histopathological findings of intestinal biopsy specimens. Thyroid autoimmunity was assessed by antithyroglobulin and antithyroid peroxidase antibodies and with diagnostic ultrasonographic findings. Results: ATD was detected in 31.5%, and CD−in 7.8% of T1D patients. Subjects with CD showed either no symptoms or suggestive problems such as short stature, hepatosteatosis, pubertal delay and difficulties in the control of diabetes. Patients with ATD had no clinical symptoms. DQ8 was the most prominent finding in CD. Conclusions: It is essential that patients with T1D, regardless of presence or absence of symptoms, should be investigated for CD and ATD. Conflict of interest:None declared.

We present ultrasonographic and magnetic resonance imaging findings of intratesticular adrenal rests in a 16-year-old patient with congenital adrenal hyperplasia. Scrotal ultrasonography showed bilateral well-delineated homogenous hypoechoic lesions located around the mediastinum testis, which were highly vascularized on power Doppler ultrasonography. Relative to normal testicular parenchyma the lesions were iso- or hyperintense on T1-weighted and hypointense on T2-weighted images. T2-weighted images also showed a target-like appearance caused by a more hypointense peripheral halo around the lesions. The lesions enhanced remarkably on post-contrast images. This case suggests that radiological evaluation of testes, even in the presence of normal physical examination findings, should be included in periodical follow-up of patients with congenital adrenal hyperplasia. Magnetic resonance (MR) imaging is useful in demonstrating the lesions, because the contrast resolution better than with ultrasonography.

Context: The central clinical feature of GH insensitivity (GHI) is severe growth failure associated with elevated serum concentrations of GH and abnormally low serum levels of IGF-I. GHI can be the result of an abnormality in the GH receptor or aberrancies downstream of the GH receptor. Objective: We investigated the GH-IGF-I axis in a young female GHI subject who presented with a height of 114 cm (−7.8 sd score) at age 16.4 yr. Patient: The subject, from a consanguineous pedigree, had circulating levels of GH and GH-binding protein that were normal to elevated, whereas IGF-I (7.2 ng/ml; normal, 242–600), IGF-binding protein-3 (543 ng/ml; normal, 2500–4800), and acid-labile subunit (1.22 μg/ml; normal, 5.6–16) levels were abnormally low and failed to increase during an IGF-I generation test. Design: Dermal fibroblast cultures were established with the consent of the patient and family. Immunoblot analysis of cell lysates and DNA sequencing of her signal transducer and activator of transcription 5b (STAT5b), a critical intermediate of the GH-IGF-I axis, were performed. Results: Sequencing of the STAT5b gene revealed a novel homozygous insertion of a single nucleotide in exon 10. The insertion resulted in a frame shift, leading to early protein termination and consequent lack of immunodetectable STAT5b protein. Conclusion: The identification of a second case of severe growth failure associated with STAT5b mutation implicates a unique and critical role for STAT5b in GH stimulation of IGF-I gene expression and statural growth.

Background: To evaluate the growth hormone reserve and the growth hormone response to recombinant human growth hormone (GH) in prepubertal thalassemic children with growth retardation. Methods: Twenty thalassemic patients with short stature and delayed bone age were studied. Patients were randomized into GH-treated (n=10) and non-GH treated (control; n=10) groups. The GH-treated group received recombinant human (rh)-GH (Genotropin) at the dose of 0.7 IU/kg per week for 12 months. Results: There was a significant discordance between GH response to pharmacologic stimuli and physiological secretion of GH/GHRH testing. Following the administration of rhGH, growth velocity increased from 2.47~0.48 cm/year to 6.27~0.76 cm/year (P=0.005), whereas there was not a similar change in the non-GH-treated group. The height velocities of the two groups during the 1 year follow-up period were significantly different (6.27~0.76 vs 3.99~0.34 cm/year; P=0.025). There were significant differences between the height velocity improvements and height velocity standard deviation scores of the two groups as well. Conclusion: The present study has demonstrated that rhGH is a safe and efficacious mode of treatment in thalassemic children.

Background: 45,X Turner syndrome (TS) female subjects have visuospatial skill and social cognition deficits that may arise from X-linked imprinting. The aim of the present study was to compare phenotypic characteristics and neurocognitive pattern of 12 monosomic TS girls, according to X-linked imprinting. Methods: Microsatellite markers were used to determine the parental origin of the missing chromosome X. Wechsler Intelligence Scale for Children–Revised (WISC-R) was administered as measures of general intellectual functioning. The results were compared in TS patients with maternally derived X chromosome (Xm) and paternally derived X chromosome (Xp). Results: Six out of 12 patients (50%) had Xm, and the other six (50%) had Xp chromosome. There was no difference in the total, verbal and performance IQ score between the TS subgroups with Xm and Xp. When the WISC-R subtest score patterns were compared, the mean arithmetic scores were significantly poorer in the Xm TS than in the Xp TS. Conclusion: In monosomic TS cases, paternal imprinting may predict arithmetic ability, on the other hand, reductionist consideration defined by genetic imprinting is not sufficient to confirm this. Further studies should be undertaken to clarify this situation.

Neonatal diabetes mellitus (NDM) is defined as hyperglycemia occurring in the first few weeks of life. It can be either transient (TNDM) or permanent (PNDM). A 25 days old newborn was brought to the hospital with restlessness, respiratory depression and cyanosis. He was born at term with a birth weight of 2,000 g. There was no consanguinity between his parents. His physical examination findings were as follows: Weight and height were under 3th percentile, he was hypoactive and dehydrated. Serum glucose level was 800 mg/dl; C-peptide was 0.41 ng/ml. Upon investigation for dyslipidemia in association with his neonatal diabetes, hyperchylomicronemia was found both in the patient and his father. Pancreatitis, anemia and cholestasis were also observed. Insulin treatment was started for his diabetes together with a special diet for dyslipidemia. At the end of 28 months of follow-up, dyslipidemia has resolved but the need for insulin therapy was still existing. However, TNDM was considered in differential diagnosis because he was small for gestational age (SGA) at birth and his symptoms had started at the 25th day of the neonatal period. Delayed recovery from insulin dependency brought out the possibility of PNDM. Furthermore, neonatal diabetes combined with hypechylomicronemia is a rare clinical picture. Reported cases of NDM with different clinical evaluation will help to better understanding of this disorder.

The management of children with congenital adrenal hyperplasia (CAH) remains a challenge, especially with regard to their growth potential. We aimed to determine the correlation of the final height of Turkish children with classical CAH to their genetic height potential and to determine the effect of hydrocortisone replacement therapy on the final height. A total of 24 CAH (16 simple virilizing and 8 salt-wasting form) were included in this retrospective longitudinal study. The final height (FH), final height standard deviation score (FHSDS), target height (TH), target height standard deviation score (THSDS), corrected height for target height (CHSDS), weight, and body mass index (BMI) were calculated for all patients. We evaluated the adult height taking into consideration the correlation with the genetic height potential and the country standards. The average follow-up time was 14.2 +/- 3.1 years and the average daily hydrocortisone dose was 19.7 +/- 2.9 mg/m2. The mean FH and FHSDS were 152.2 +/- 7.2 cm and -1.0 +/- 1.1 SD, respectively, in females and 163.1 +/- 6.6 cm and -1.2 +/- 1.0 SD, respectively, in males. The CHSDS was found to be -0.73 +/- 0.9 SD. FH was below the TH in 79.1% of our cases. In 20.8% of our patients, FH was less than the third percentile for the standard height for our country. Interestingly, the FH showed no correlation with the dosage of hydrocortisone. Thirteen of our cases (54.2%) reaching FH were obese/overweight. A positive correlation was detected between hydrocortisone treatment and the BMI. The observations that 79.1% of our classical CAH cases receiving an average daily hydrocortisone dose of 19.7 +/- 2.9 mg/m2 ended up with an adult height below the TH and that 54.2% of the cases were overweight/obese lead us to believe that we should be using the lowest possible dose for treatment.

Diabetes is an important problem encountered in thalassemic patients. The severity and type of glucose disturbances vary greatly in different studies. Also the pathogenesis seems to be complex; either insulin deficiency or insulin resistance may mediate the glucose disturbances. In a group of thalassemic patients glucose homeostasis was evaluated. Diabetes prevalence was 1.8%. Forty patients were investigated both with an oral glucose tolerance test and first-phase insulin response. Three patients had impaired fasting glucose, 1 patient had impaired glucose tolerance, and 2 patients had hyperinsulinism. Nineteen of 40 patients who were tested had low first-phase insulin response (47.5%) with below 10th centile. Age, BMI, height SDS, age at diagnosis, age at first blood transfusion, number of blood transfusions in a year, percentage of elevated liver enzyme, and hemoglobin and ferritin levels were not different between patients with low first-phase insulin response to patients with normal first-phase insulin response. Four patients are HCV infected, and only 1 of them had low first-phase insulin response. The study group showed a high rate of impairement in insulin secretion by first-phase insulin response to glucose overload, despite the low rate of insulin resistance. Defect of insulin secretion in thalassemic patients may develop earlier than insulin resistance, and then be accompanied by insulin resistance. Increasing insulin resistance with age and the occurrence of additional factors could lead to detoriation of glucose metabolism.

Premature pubarche can be benign, or it can be an early marker of insulin resistance in some girls. The aim of this study was to evaluate insulin resistance in prepubertal girls presenting with premature pubarche (n = 19; mean age = 6.93 +/- 1.78) as compared to age- and Tanner stage-matched controls (n = 10; mean age = 7.55 +/- 1.32) using indirect insulin resistance parameters. Two groups were compared by means of oral glucose tolerance test (OGTT), indirect insulin resistance (IR) parameters [homeostasis assessment (HOMA) models: HOMA-IR, glucose/insulin (G/I)] and serum lipid profiles. In the girls with premature pubarche, mean baseline insulin level and HOMA-IR value were significantly higher and G/I ratio was lower than in the control group. IR was observed in 42.1% and in 31.6% according to HOMA-IR value and G/I ratio, respectively. Even at diagnosis, IR was increased in a significant portion of the girls with premature pubarche.

The effect of parental rearing on gender identity development in children with ambiguous genitalia remains controversial. The present study aimed to address this issue by investigating the factors that may be associated with sex of rearing in children with male pseudohermaphroditism.The study included 56 children with male pseudohermaphroditism that were consecutively referred to a child psychiatry outpatient clinic. At the time of referral the age range of the sample was 6 months-14 years; 28 children had been raised as boys and 28 as girls. Demographic and biological information was obtained from patient charts. An intersex history interview was administered to the children and parents, whereas The Gender Identity Interview and the Draw-A-Person Test were administered only to the children. The children were observed during free play. Comparisons of biological, psychological and social variables were made with respect to gender of rearing.More children reared as boys were younger at time of referral, belonged to extended families, and had higher Prader scores. Although children's gender roles were appropriate for their gender of rearing, findings of the Gender Identity Interview and the Draw-A-Person Test suggested that some of the girls presented with a male or neutral gender self-perception.The relationships between age at the time of problem identification, age at the time of diagnosis, and gender of rearing indicate the importance of taking measures to ensure that the intersex condition is identified at birth and children are referred for early diagnosis, gender assignment, and treatment.

The most complicated group of sexual differentiation disorders is that of gonadal development. Disorders of gonadal development form a wide clinical, cytogenetic and histopathological spectrum. There are still some unsolved difficulties of diagnosis, development of malignancy and the sex rearing of these patients. We reviewed 23 cases of gonadal developmental disorders among 169 patients with ambiguous genitalia or delayed puberty. Among 169 patients, 87 patients were 46,XY disorders of sex development (DSD), 59 patients were 46,XX DSD without disorders of gonadal development and the remaining 23 patients had disorders of gonadal development. Nine of these 23 patients were diagnosed as 46,XY gonadal dysgenesis, 7 patients had ovotesticular DSD, 5 patients had 45,X/46,XY mixed gonadal dysgenesis. Fourteen patients with disorders of gonadal development had genital ambiguity, 5 patients had a female genital phenotype with a palpable gonad and/or delayed puberty. Four patients had the male genital phenotype. Disorder of gonadal development is a very important clinical problem with different aspects of diagnosis, treatment, rearing sex and prophylaxis. Each patient should be evaluated individually employing a multidiciplinary approach.

Background: Sex assignment decisions for children with disorders of sex development (DSD) should be based on integrative assessments of relevant biological and psychosocial characteristics. Aim: To investigate the factors that contributed to sex assignment decisions for children with 46,XY DSD. Patients: Sixty-one children recruited from a clinical sample were evaluated. Methods: Findings of endocrinological and psychiatric evaluations were entered into a logistic regression analysis. Results: Gender identity was the strongest correlate of assigned sex. External genital undervirilization, sex announced at birth and toy/ activity preferences were predominant predictors. Twelve children, six of whom were prepubertal, were reassigned to male sex. Conclusions: Psychological factors seem to be as influential on sex reassignment decisions as are endocrinological and social factors, especially if the disorder is diagnosed at an older age. Prepubertal gender conversion is possible, which implies the importance of follow-up during childhood.

Aims Functional ovarian hyperandrogenism (FOH) is considered to be a form of polycystic ovary syndrome (PCOS) at adolescence. There are almost no data in the prepubertal period, although one of the earliest manifestations of PCOS is premature pubarche. Prepubertal girls with obesity or insulin resistance are also at risk to develop the full PCOS phenotype after puberty. The aim of this study was to evaluate prepubertal girls with premature pubarche and/or obesity for PCOS or FOH. Methods Twenty-seven prepubertal girls with premature pubarche and/or obesity aged >6 years were evaluated. FOH was defined as abnormal ovarian 17OHP response to challenge with GnRH analog of >2 ng/ml after exclusion of adrenal dysfunction. All patients underwent a pelvic ultrasound examination. Results Sixteen patients had premature pubarche, seven were obese, and four had both premature pubarche and obesity. Eleven of 27 patients (40.7%) showed high (>2 ng/ml) 17OHP response to GnRH challenge. Three patients (11%) with FOH also showed PCO morphology on pelvic ultrasound examination. Conclusion In prepubertal girls who carry risk factors, including genetic polymorphisms and/or particular environmental factors, FOH/PCOS could develop at a high rate.

berberoglu, merih/0000-0003-3102-0242 WOS: 000236479400009 PubMed: 16607925 Objective: Long-term replacement treatment with high doses of steroids in congenital adrenal hyperplasia (CAH) is known to have a negative influence on growth. We evaluated the effects of long-term steroid treatment in patients with classical CAH on height development in relation to genetic height potential. Patients and Methods: Twenty-three patients with CAH (16 females, 7 males, mean age: 9.8 +/- 3.5 years) were included in this longitudinal study. The effect of steroid treatment on growth was determined by monitoring patients for 8.61 +/- 3.46 years (2-17 years) while they were treated with hydrocortisone at a mean dosage of 17.64 +/- 3.60 mg/m(2)/day. The height standard deviation scores (Ht-SDS), target Ht-SDS, and corrected Ht-SDS for target height was calculated for all patients. Predicted adult height according to bone age was calculated and it was determined whether height was developing according to the genetic height potential. In addition, patients were grouped as 'tight control' or 'poor control' according to their mean serum 17OH-progesterone or ACTH levels while on treatment. We evaluated whether height development was different for the tight and poor control groups. Results: The mean chronological age of our patients at the time of the study was 9.89 +/- 3.53 years, Ht-SDS -0.77 +/- 1.57, target height (TH) 161.03 +/- 6.54 cm, TH-SDS -0.60 +/- 0.90, predicted height (PH) 157.2 +/- 11.16 cm, PH-SDS -1.1 +/- 1.69, and corrected Ht-SDS -0.75 +/- 1.14. There was no significant difference between the actual Ht-SDS and TH-SDS of our patients (p > 0.05) but the corrected Ht-SDS was less than zero. Only 28.5% of our patients had normal height according to their genetic potential while 71.5% were shorter than their genetic height potential. While the Ht-SDS and corrected Ht-SDS were similar in the tight and poor metabolic control groups, the predicted height was significantly greater in the tight control group. Conclusion: We demonstrated that a hydrocortisone dose of 17.64 +/- 3.60 mg/m(2)/day in classical CAH had a negative influence on height development for genetic height potential in 8.5 years of follow-up and that it is necessary to use the lowest possible steroid dosage by individualizing the dose.

In endemic areas iodine deficiency, and in iodine sufficient regions autoimmune thyroiditis, is the first aetiological factor for goitre. The aims of this study were to determine the incidence of iodine deficiency and autoimmune thyroiditis in patients presenting with goitre, to compare clinical and ultrasonographic assessment of thyroid size and to investigate the relationship between iodine and autoimmune thyroiditis. Patients diagnosed with goitre clinically (n = 204) were evaluated by their anthropometric measurements, ultrasonographic examination of the thyroid gland, thyroid function and TRH stimulation tests, thyroid autoantibodies and morning urinary iodine measurements. Thyroid volumes were evaluated according to three different reference criteria. Incidences of iodine deficiency and autoimmune thyroiditis were 54% and 17%. The incidences of iodine deficiency and excess were not significantly different in the autoimmune group (n = 35) compared to the non-autoimmune group (n = 169). In the autoimmune group, urinary iodine concentration correlated positively with serum thyroid hormones (FT 3 r = 0.42, TT 3 r = 0.38, TT 4 r = 0.34) and negatively with serum TSH levels (r = 0.45). There were discrepancies between clinical and ultrasonographic evaluation of goitre, and between different reference criteria. This study revealed that iodine deficiency is still the first aetiological factor for goitre in our region and failed to show a relationship between iodine intake and autoimmune thyroid disease.

UNLABELLED Atherothrombotic complications in insulin resistance are partly attributed to impaired fibrinolysis caused by increased PAI-1 plasma levels, and 4G/5G promotor polymorphism of the PAI-1 gene may modulate PAI-1 transcription. OBJECTIVE To investigate PAI-1-675 4G/5G allele gene polymorphism and its relationship with obesity in children. CHILDREN AND METHOD: The study participants were 133 apparently healthy non-obese children, 24 probable exogenously obese without family history (Group I), 66 probable familial obese (Group II), and 44 obese children who were referred to the pediatric endocrinology department with any complication of obesity (Group III). Group I and Group II obese children were gathered from a school-based epidemiological study. RESULTS Incidence of obesity was 19% in a school with high socio-economic status, whereas it was 4% in a school with low socio-economic status. Frequencies of 4G/4G gene polymorphisms were 24.81%, 37.50%, 64.80% and 61.11% in the control group, and groups I, II, and III, respectively. In groups II and III, 4G/4G gene polymorphism, and in non-obese control children 5G/5G gene polymorphism, was common. In obese children in the presence of family history for obesity and metabolic syndrome (odds ratio [OR]: 4.48, 95% confidence interval [CI]: 1.26-15.82), carriage of the 4G allele either in heterozygous or homozygous state increased the risk of vascular disease (OR: 6.10, 95% CI 1.64-22.90). In patients with acanthosis nigricans, high HOMA-IR values, hypertriglyceridemia and elevated atherogenic index, 4G/4G genotype frequency was remarkably higher compared to patients with other features of metabolic syndrome. CONCLUSION The increasing prevalence of childhood obesity in high socio-economic status is associated with health risks. In obese children with family history of obesity and cardiovascular disease or type 2 diabetes mellitus and in obese children who had any feature of metabolic syndrome, frequency of 4G/4G genotype was more than the 4G/5G and 5G/5G genotypes in the PAI-1 gene. These patients can be at increased risk for developing vascular disease. Acanthosis nigricans, high HOMA-IR value, hypertriglyceridemia and high atherogenic index can also reflect the high risk of vascular disease in metabolic syndrome.

Optimal management of differentiated thyroid cancer in childhood is undetermined. During monitoring of thyroid carcinoma, serum thyroglobulin (hTG) levels provide valuable information. hTG levels not only increase in differentiated thyroid cancers but also in iodine deficiency because of compensation by the thyroid gland. A 14.6 year-old girl was diagnosed with nodular goiter, subclinical hypothyroidism and severe iodine deficiency. She had a very high hTG level. Despite benign fine-needle aspiration biopsy (FNAB), because the hTG level was still very high after treatment with LT4, thyroidectomy was undergone. Cytopathological examination showed minimally invasive follicular thyroid carcinoma. During follow-up, to exclude the presence of persistent/recurrent disease, the hTG level rose to an undesirably high level after withdrawal of TSH suppressive therapy, and radioiodine ablation therapy was applied. This report shows that even if there is an explanation for nodular goiter and high hTG levels, such as iodine deficiency, malignancy cannot be ruled out without thyroidectomy. FNAB is not reliable especially in iodine deficient areas. Serum hTG measurement is a valuable tool for both diagnosis and follow-up of differentiated thyroid carcinoma in children.

Background/Aim: The availability of sensitive thyrotropin (TSH) assays decreased the diagnostic value of thyrotropin-releasing hormone stimulation tests (TRH-ST) in subclinical hypothyroidism. In this study we aimed to evaluate the relation between basal and stimulated serum TSH levels on TRH-ST and to determine the prevalence of patients with normal basal serum TSH and exaggerated TSH responses. Methods: 179 patients (117 girls, 123 pubertal) with a median age of 12 (2.7–21.4) years who presented with goiter were enrolled and evaluated for their pubertal stage, height, thyroid autoimmunity, ultrasonography, thyroid function, and TRH-ST. Serum TSH concentrations were determined by sensitive assays. At TRH-ST, a peak serum TSH level >25 mIU/l was considered as an exaggerated response. Results: 30 (17%) patients had an exaggerated TSH response. In patients with serum TSH levels between 2 and 4.68 mIU/l (upper half the normal range), an exaggerated TSH response was observed in 19.5%. A positive correlation between basal and TRH-stimulated TSH levels was determined (r = 0.536, p < 0.01). In patients with an exaggerated TSH response, 23 had normal (discordant) and 7 had high basal TSH levels (concordant). The mean basal serum TSH level was lower in the discordant group compared to the concordant group (p < 0.01). Conclusion: Basal serum TSH levels might not be sufficient for diagnosing subclinical hypothyroidism. Stimulated TSH levels on TRH-ST are valuable, especially when serum TSH concentrations are in the upper half of the normal range.

Human chorionic gonadotropin (hCG) stimulation test is a reliable dynamic test for the evaluation of testicular function during childhood. Several protocols have been recommended but their reliability is controversial. In order to decide the best timing to measure stimulated testosterone levels in short- and long-term hCG protocols, we evaluated 83 prepubertal patients in two group. In group A, 34 patients with isolated micropenis and in group B, 49 inguinal cryptorchidic patients were enrolled. In group A short-term hCG protocol (3000 IU/m2/im/3 days) and in group B long-term hCG protocol (1500 IU/m2/im; thrice a week for 3 weeks) was administered. Blood samples were drawn at the initiation of the test and then at the 1st and 4th days after the last hCG injection. Each case's peak stimulated testosterone (Tmax) and the incremenet in plasma testosterone (deltaT) were calculated and compared with the 1st and 4th day responses within the group. In the short-term protocol the 4th day responses were higher than the 1st day responses (p0.01). Interestingly, while four patients had insufficient responses at the 1st day, three had sufficient Leydig cell response at the 4th day. In the long-term protocol group, in contrast to the short-term group, the 1st day responses were higher than the 4th day (p0.01). According to our results, while performing hCG test in a patient, if a short-term protocol is planned, it is more convenient to check the 4th day testosterone response. On the other hand, in a long-term protocol it is best to check the 1st day response. We suggest that even if a patient's 1st day response is inadequate, the 4th day response should be checked in order to avoid misdiagnosis.

Over the past 20 years, orally administered biphosphonates have been used extensively in the management of a number of common skeletal disorders of different etiology. Recently, in clinical practice, in a number of cases in whom oral therapy is insufficient or contraindicated, intravenous administration of pamidronate presents an alternative therapeutic option. In order to investigate the clinical and radiological effects of cyclic intravenous pamidronate administration in children with osteogenesis imperfecta, a prospective open study of pamidronate treatment was undertaken in a cohort of eight bed-bounded (3.6-13.8 years) patients with severe osteoporosis and vertebral deformities. Pamidronate was administered at a dose of 0.5 mg/kg/ day for three days. Tri-monthly cyclic intravenous infusions were performed over-one year. Bone density, verebral corpus heights, estimated volumetric bone density and biochemical measurements were analyzed. Side effects of the therapy were determined via questionnaire. Significant reductions in the number of bone fractures and pain were observed in all patients. Ambulation scores were significantly altered and seven of eight patients became independent. Serum alkaline phosphatase levels decreased significantly. Lumbar X-ray and densitometry showed a striking improvement by the end of the treatment period. Even spaced dense lines corresponding to infusion periods were observed on roentgenograms of the radio-ulnar region. Pubertal progression and growth velocity were not affected inversely during therapy. Although we did not observe any severe side effect, one patient's blood urea nitrogen level was altered slightly. In conclusion, one year cyclical pamidronate treatment seems to be effective and safe in improving bone mineralization and in reducing fracture incidence in severe osteoporosis.

OBJECTIVES 1. To evaluate the relationship between plasma leptin and TNFalpha concentrations in obese children and to assess the differences between hyperinsulinemic and normoinsulinemic groups. 2. To evaluate the relationship between plasma leptin and insulin levels in obese children. 3. To investigate the TNFalpha G308A mutation in obese children. METHODS Body mass index (BMI), fasting plasma glucose and insulin levels, oral glucose tolerance test results, homeostasis model assessment of insulin resistance (HOMA-IR) results, and plasma leptin and TNFalpha concentrations were evaluated in obese children (n = 45) and age- and gender-matched, lean healthy controls (n = 40). RESULTS In obese children the fasting insulin, HOMA-IR results, plasma leptin and TNFalpha concentrations were significantly higher than in controls (p

PubMedID: 16355808 Aim: To compare the growth response to growth hormone (GH) treatment in patients with idiopathic GH deficiency (IGHD) who were prepubertal with the response of those who were pubertal at the onset of GH therapy on an increased GH dose. Patients and methods: Among the Turkish patients enrolled in the Pfizer International Growth Study (KIGS) database with the diagnosis of IGHD, the growth data over 2 years of GH therapy were analyzed longitudinally of 113 (79 M) prepubertal (Group 1) and 44 (33 M) pubertal (Group 2) patients. Pubertal signs were reported to be present initially or to have appeared within 6 months of GH therapy in Group 2. Mean ± SD age at onset of therapy was 8.7 ± 3.5 and 13.5 ± 1.8 years; height SDS -4.2 ± 1.4 and -3.2 ± 1.1 (p

TPIT is a highly cell-restricted transcription factor that is required for the expression of the propiomelanocortin (POMC) gene and for terminal differentiation of the pituitary corticotroph lineage. Its exclusive expression in pituitary POMC-expressing cells has suggested that its mutation may cause isolated deficiency of pituitary ACTH. We present a neonate with the diagnosis of congenital early onset isolated ACTH deficiency (IAD) associated with a loss of POMC function as a result of a missense mutation in the TPIT gene. A 5 day-old male infant was admitted for hypoglycemia, limpness and conjugated hyperbilirubinemia. Laboratory investigations indicated low plasma cortisol concentration (0.1 μg/dl) accompanying a very low ACTH (

The effect of oral administration of desmopressin (DDAVP) solution was investigated in a very low birth weight premature infant with central diabetes insipidus that was associated with grade four germinal matrix hemorrhage. As an alternative to the nasal route, long-term successful management resulting in favorable growth and development during infancy was achieved using the oral route.

Seckel syndrome is a rare, recessively inherited disorder of severe growth retardation with low birth weight and distinct craniofacial, orodental and skeletal anomalies. In addition to these characteristics, some cardiovascular, hematopoietic, endocrine and central nervous system abnormalities have also been described. We report a patient with Seckel-like syndrome who has precocious puberty associated with non-classical congenital adrenal hyperplasia (NCCAH). She was admitted to our clinic three times. She was diagnosed as having Seckel-like syndrome and premature thelarche at the age of 8.9 years. At 10.9 years old she was admitted to our clinic with pubic hair and cliteromegaly. Hormonal findings revealed NCCAH and hydrocortisone therapy was offered but the patient was non-compliant. At 13.6 years she had acanthosis nigricans as an additional clinical finding and her pubertal stage was 4. She had irregular menses. On hormonal evaluation she had euglycemic hyperinsulinism accompanying mild hypertriglyceridemia and functional ovarian hyperandrogenism. Premature pubarche, hyper-insulinism, dyslipidemia, and hyperandrogenism, and some combinations of these, can be associated with reduced fetal growth. This is the first report of hyperinsulinism, and probably NCCAH, in association with Seckel syndrome.

Objective The aim of this study was to investigate the nutritional status of children on continuous ambulatory peritoneal dialysis (CAPD) and to relate it to the dose of dialysis and serum levels of inflammatory cytokines and insulin-like growth factor-1 (IGF-1). Patients 17 CAPD patients (8 girls, 9 boys; mean age 13.1 ± 3.5 years, median 15 years) were included in the study. Anthropometric measurements and serum albumin levels were used in the evaluation of nutritional status. Serum interleukin (IL)-1β, IL-6, tumor necrosis factor α, and IGF-1 levels were determined in all CAPD patients and in a healthy control group. Weekly Kt/V and creatinine clearance (CCr) were measured to determine adequacy of dialysis. Results The mean dialysis period was 23.7 ± 15.2 months (median 23 months). Anthropometric measurements and serum albumin level were as follows: height 130.2 ± 15.6 cm, height standard deviation score (HtSDS) -4.2 ± 2.4, body mass index (BMI) 16.3 ± 1.6 kg/m2, body mass index standard deviation score (BMISDS) -0.8 ± 0.9, triceps skinfold thickness (TST) 4.2 ± 1.4 mm, midarm circumference (MAC) 16.21 ± 2.3 cm, upper arm muscle area (AMA) 1799.1 ± 535.7 mm2, upper arm fat area (AFA) 334.5 ± 143 mm2, and serum albumin 3.1 ± 0.7 g/dL. The BMI was above the fifth percentile in all patients; TST and MAC were below the fifth percentile in 14 patients (82.4%) and 10 patients (58.8%) respectively. The AMA was below the fifth percentile in 8 patients; however, the AFA was below the fifth percentile in all patients. Mean serum albumin level was under 3.5 g/dL in 70.5% of the children. We found significant positive correlations between BMI and Kt/V ( r = 0.69, p < 0.01), CCr ( r = 0.64, p < 0.05), and IL-6 ( r = 0.61, p < 0.01). There was an inverse correlation between BMISDS and dialysis period ( r = -0.58, p < 0.05); and between IL-6 and serum albumin ( r = -0.49, p < 0.05). A significant positive correlation between BMISDS and serum IGF-1 level ( r = 0.62, p < 0.01) was noted. We also found a significant positive correlation between serum IGF-1 level and both HtSDS ( r = 0.57, p < 0.05) and TST ( r = 0.52, p < 0.05). Significant positive correlations between AFA and CCr and IGF-1 were also noted (both r = 0.56, p < 0.05). Conclusion Although many factors may be responsible for malnutrition and growth retardation, we found that prolonged period of dialysis, inadequate dialysis, and low IGF-1 levels are the most important risk factors in CAPD patients.

Latent autoimmune diabetes mellitus in adults (LADA) is characterized by clinical presentation as type 2 diabetes mellitus after 25 years of age, initial control achieved with oral hypoglycemic agents for at least 6 months, presence of autoantibodies and some immunogenetic features of type 1 diabetes mellitus. An 8.3 year-old girl was referred to our pediatric endocrinology department because of incidental glucosuria. She did not complain of polyuria, polydipsia, or weight loss. Her body mass index (BMI) was at the 80th percentile. Fasting glucose was 126 mg/dl, and OGTT glucose level at 120 min was 307 mg/dl. Although C-peptide levels were normal, her first phase insulin response (FIR) was lower than the 1st percentile. Anti-insulin antibody (AIA), islet cell antibody (ICA), and anti-glutamic acid decarboxylase (antiGAD) were negative. According to the clinical and laboratory findings, she was diagnosed as having type 2 diabetes mellitus. She was started with oral anti-diabetic treatment for a period of 1 year. Insulin had to be initiated for worsening of HbA1c levels. In the fourth year of follow-up, she was admitted to our hospital with diabetic ketoacidosis although she was on an intensive insulin regimen. At this time, C-peptide levels were low, antiGAD and AIA were positive with HLA DR3/DQ2 haplotype. In addition, her thyroid peroxidase antibody and endomysium antibody were found to be high at follow-up. Small intestinal biopsy revealed celiac disease. This patient may represent the first case of latent autoimmune diabetes mellitus in children (LADC) with autoimmune thyroiditis and celiac disease.

BACKGROUND AND AIM Normal growth in children is regulated to a great extent through the actions of the GH/IGF-I axis, a system consisting of GH and its mediators (ternary complex) that modulate growth in many tissues. The ternary complex (IGF-I/IGFBP-3/ALS) provides an acute regulatory mechanism in which IGF-I may be mobilized from the circulating reservoir of 150 kDa complexes to the tissues. Acute exercise is known to be a stimulus for GH secretion. The beneficial effects of scheduled exercise on body composition are also well established. However, the impact of strenuous exercise on the pubertal development of child athletes is still not well understood. The first goal of this study was to assess the acute effects of high intensity exercise training on GH-dependent ternary complex components in female rhythmic gymnasts compared to age-matched healthy female controls with normal physical activity. The second goal was to explore the influence of these exercise-induced changes on skeletal and pubertal growth in the same group prospectively over a period of 4 years. SUBJECTS AND METHODS Seventeen female rhythmic gymnasts, aged 11.4 +/- 0.9 years, who had 10 h per week intense exercise for at least 4 months volunteered to participate in this study. Anthropometric measurement of height (Height SDS for chronological age [HtSDS(CA)], parentally adjusted height, predicted adult height), bone age and weight (BMI) were made using standard techniques in gymnasts and controls (aged 12.5 +/- 3.0 years, n = 12). Gymnasts were followed up to 4 years to observe growth velocity and pubertal progression. In order to determine the acute impact of exercise on levels of GH and GH-dependent ternary complex component (IGF-I, IGFBP-3, ALS, IGF-I/IGFBP-3 molar ratio), blood samples were obtained from gymnasts after a routine 2-h high-intensity training program and then after a 2-day rest period. These results were compared with age-matched controls with no scheduled sports activity. RESULTS Despite the significant increment in serum GH and GH-dependent components immediately following the exercise, serum GH/IGF-I levels showed a significant decrement (p < 0.01) after a 2-day rest in gymnasts, to a nadir as low as those of the control subjects' baseline levels (p < 0.01). There was no difference in anthropometric characteristics of gymnasts and controls except BMI; gymnasts were leaner than controls. During a 4-year follow up, there were no differences between the gymnasts and controls in regard to skeletal growth and reaching their predicted height. However, in gymnasts there was a delay in pubertal tempo but not in growth. CONCLUSION Intense exercise induces an acute rise in GH levels, but this acute elevation rapidly normalizes after a 2-day rest in female rhythmic gymnasts. These fluctuations in serum GH and GH-dependent ternary complex components had no reflection on the skeletal growth patterns in gymnasts over the 4-year follow up but there was a delay in their pubertal progression.

To describe the presence of dysregulations in steroid biosynthesis and the risk of functional ovarian hyperandrogenism (FOH) and polycystic ovary syndrome (PCOS)-like development in children with hyperandrogenism, 28 girls were studied. Adrenal steroidogenic profile was defined by basal and ACTH-stimulated levels of 17OHP, cortisol, DHEAS and androstenedione, and delta precursor/delta product ratios. Ovarian hyperandrogenism was defined by 17OHP response to LHRH stimulation, and pelvic ultrasonography (US) was performed to evaluate ovarian morphology. Basal and ACTH-stimulated hormonal results revealed non-classical 21-hydroxylase deficiency-like status in one patient (3.6%), and 21-hydroxylase deficiency heterozygote carrier-like state in four patients (14.3%), while the other 23 patients (82.1%) had functional adrenal hyperandrogenism (FAH). Among these patients with FAH, 47.83% had FOH; when these patients were evaluated by pelvic US, 30.4% had morphological changes which were not concordant with their age. We suggest that even mild forms of hyperandrogenism must be considered seriously and dysregulations of the steroidogenic pathway and ovarian abnormalities must be evaluated carefully to determine the risk of FOH/PCOS.

The aim of this study was to compare vertebral bone mass values of patients with central precocious puberty (CPP) with healthy age and puberty matched controls and to determine the effect of gonadotropin releasing hormone (GnRH) analogs on bone mass in patients who had been treated at least for 1 year. Girls with idiopathic CPP, 11 pretreatment, 14 post-treatment, and 19 pubertal girls as controls were enrolled in the study. The mean ages of the controls and the patients with CPP pre- and post-treatment were 10.25 +/- 1.06, 8.23 +/- 1.11, and 10.36 +/- 1.82 years, respectively. Leuprolide acetate (Lucrin) 3.75 mg was administered s.c. monthly. Bone measurements were performed by dual energy X-ray absorptiometry (DEXA) (Norland) at the anterior-posterior vertebrae (L2-L4). The post-treatment group's mean BMD value was 0.66 +/- 0.12; Z scores according to CA and BA were 0.32 +/- 10 and 0.30 +/- 1.1, respectively. In the study group, BMD values compared to the control group were normal. No significant change in BMD values was observed after treatment. Neither osteopenia nor osteoporosis was observed in patients taking GnRH analog.

Deficiency of carbonic anhydrase II (CA II) isoenzyme produces metabolic disorders of bone, kidney and brain. In this report we describe the clinical, radiological, pathological and genetic findings in three brothers who were affected with the autosomal recessive syndrome of osteopetrosis, renal tubular acidosis (RTA) and cerebral calcification. The RTA was hybrid type, but urinary concentration ability was intact. Additional features were severe mental retardation, stunted growth, microcephaly, dental malocclusion, high-arched palate, and broad thumbs. Previous reported patients with this syndrome were predominantly from the Middle East and Mediterranean region. This is the first report with CA II deficiency from the Turkish population. The presence of mental retardation and relative infrequency of skeletal fractures in our patients resembles the clinical course of patients with the Arabic mutation of the CA II gene, but this mutation was not found in our patients.

We report an 11 month-old infant with severe hypercalcemia associated with hyperlipidemia following bolus vitamin D administration. At the time of admission, serum concentration of calcium was 5.5 mmol/l (22 mg/dl); total cholesterol, high density lipoprotein cholesterol (HDL-C), very low density lipoprotein (VLDL), low density lipoprotein cholesterol (LDL-C), and triglyceride levels were respectively: 6.37 mmol/l (246 mg/dl), 0.77 mmol/l (30 mg/dl), 1.37 mmol/l (54 mg/dl), 4.1 mmol/l (162 mg/dl), 3 mmol/l (271 mg/dl). Physical examination revealed dehydration and irritability that was inappropriately mild according to the serum calcium level. On the 16th day of therapy that consisted of intravenous fluids with furosemide (sodium diuresis), steroid, calcitonin, magnesium sulfate, and phosphorus, serum calcium level declined below 3 mmol/l (12 mg/dl). The hyperlipidemia resolved gradually with a concomitant decline in serum calcium. This report is interesting in that hypercalcemia was associated with transient hyperlipidemia that disappeared with normocalcemia, which might suggest protection against hypercalcemic symptoms.

The concurrence of ambiguous genitalia, nephropathy and predisposition to Wilms' tumor are characteristics of Denys-Drash syndrome. Some of the reported patients do not express the full spectrum of the syndrome, while the occurrence of nephropathy has become a generally accepted common feature of this syndrome. We report an infant with male pseudohermaphroditism due to partial gonadal dysgenesis and nephropathy without Wilms' tumor but with a Wilms' tumor suppressor gene (WT1) mutation. The high risk of Wilms' tumor mandates regular surveillance and the use of prophylactic bilateral nephrectomy as a treatment is not yet clear.

Familial glucocorticoid deficiency (FGD) or unresponsiveness to ACTH at the receptor level is a rare autosomal recessive hereditary syndrome characterized by a low cortisol level despite high serum ACTH concentration. Aldosterone levels are normal. The clinical entity generally presents in the first year of life with skin hyperpigmentation and hypoglycemic convulsions. Cortisol response to exogenous ACTH is also absent. Unresponsiveness to ACTH may be due to a mutation in the ACTH receptor; sometimes no mutation is found. We discuss the clinical and laboratory findings and genetic studies in six patients with a diagnosis of FGD. A homozygous V142L mutation was detected in three of the patients and a homozygous D103N mutation was detected in two patients.

INTRODUCTION The purpose of this study was to determine the pancreas reserve in siblings of diabetic patients by screening islet cell antibodies (ICA), insulin auto antibodies (IAA), reduced C-peptide levels, first-phase insulin release and the derangement of cellular immunity (reduction of natural killer cells, abnormality of the T cell subpopulations). METHODS AND RESULTS Twelve siblings (aged 9.3 +/- 2.8 years) of diabetic children were evaluated and results were compared with the control group (12.1 +/- 3.5 years). For siblings of the diabetic children, fasting, post-prandial and glucagon response C-peptide mean values were 2.2 +/- 1.2, 7.2 +/- 7.1 and 5.3 +/- 3.6 ng/mL, respectively, while in the control group they were 1.5 +/- 0.8, 3.6 +/- 2.0 and 5.1 +/- 2.9 ng/mL, respectively. There were no differences between the two groups. In 33%, postprandial C-peptide, and in 11% of the siblings, glucagon response C-peptide values were exaggerated. In siblings the first phase insulin release (FPIR) during an intravenous glucose tolerance test was 128.5 +/- 96.6 (above the 50th percentile) and stimulated insulin release (SIR) was 103.8 +/- 92.5 (above 25th percentile). Sibling values were significantly lower than the control group (FPIR 152.4 +/- 42.5, P = 0.01; SIR 134.9 +/- 38.2, P = 0.01). Values for FPIR (in two children) and SIR (three cases) were below the 5th percentile. In one, FPIR and SIR levels were both below the 1st percentile. Islet cell antibodies and IAA were also present in this subject. Treatment with nicotinamide was started in the cases with FPIR and SIR below the 5th percentile. We did not observe overt diabetic symptoms during the follow-up period of more than 3 years. CONCLUSION We recommend that borderline insulin secretion be tested annually in siblings who show insufficient FPIR.

Amac: Obezite vucutta asiri yag depolanmasi ile ortaya cikan enerji metabolizmasi bozuklugudur. Cocukluk caginda baslayan obezitenin eriskin donemde de devam etmesi ve saglik icin risk olusturmasi soz konusudur. Gerec ve yontem: Bu arastirmada Ankara ili Mamak ilcesine bagli bir ilkogretim okulunda ve lisede 6-17 yas grubundaki 1510 cocugun boy ve agirliklari olculerek vucut kitle indeksi (VKI) ve relatif vucut kitle indeksi (RVKI) hesaplanmis, obez olanlarin gunluk beslenmeleri ve aktiviteleri bir anket formu ile degerlendirilmistir. Bulgular: RVKI degerlerine gore tum cocuklarin % 4.8’i obezdi. Obezlerin % 81.9’unda RVKI 121- 140, digerlerinde ise 140’tan buyuktu. Obez cocuklarin % 55.6’sinin kiz cocuk oldugu goruldu. Obezite sikligi 6-12 yas arasindaki cocuklarda % 4.4, 12-17 yas arasindaki cocuklarda % 5.4 olarak saptandi. Ayrica antropometrik olcumler Neyzi standartlarina gore degerlendirildiginde erkek cocuklarin % 1.9’unun, kiz cocuklarin ise % 3.7’sinin agirlik persentillerinin 97’nin uzerinde oldugu saptandi. RVKI degerlerine gore obezite tanisi konan ogrencilerin % 90.3’unde ailede obezite oykusu, % 82.3’unde ailede kalp hastaligi, diabet, hipertansiyon gibi hastaliklar vardi. Anketin analizinde obez cocuklarin aktivite duzeylerinin dusuk oldugu ve hatali beslenme aliskanliklarina sahip olduklari belirlendi. Sonuc: Bu arastirma obezitenin okul cocuklarinda onemli bir sorun oldugunu, genetik yatkinligin yaninda beslenme aliskanliklarinin ve fizik aktivitelerindeki yetersizligin de obezite olusumunda etken olabilecegini gostermistir.