Sleep Disorders and Obesity in Childhood: A New Component in Solving Obesity.

Sleep disorders have been widely reported in obese individuals. Previous studies have shown that together with an increase in obesity prevalence, so does sleep duration in children and adolescents decrease. By contributing to energy imbalances, hormonal changes occurring with reduced sleep quality may cause weight gain and obesity. Current evidence shows that short sleep duration has effects on body weight and weight gain. Compared to individuals sleeping for a normal duration, insulin sensitivity is lower in those who sleep less. Lack of sleep increases the desire for food and has a direct effect on physical activity. Further studies are required to determine the contribution of sufficient sleep to obesity treatment.

Isolated hyperthyrotropinemia in childhood obesity and its relation with metabolic parameters.

PURPOSE: The aim of the presented study was to evaluate the prevalence of isolated hyperthyrotropinemia (IH) in obese children and the relation between anthropometric and metabolic parameters. METHODS: Hospital records of the children, who presented to the Pediatric Endocrinology outpatient clinic of our institution with obesity, and age and gender-matched healthy children, who had undergone thyroid function test for any reason were retrospectively reviewed. RESULTS: The prevalence of IH was significantly higher in the obese group than in the controls (9.2 and 3.8 %, respectively). Body mass index-standard deviation score (BMI-SDS), thyroid-stimulating hormone (TSH), lipid parameters were significantly different in the obese group than in the control group. A positive correlation between TSH and BMI-SDS and negative correlation between TSH and free T4 (fT4) levels were found in obese subjects. Stepwise multiple linear regression analysis confirmed that BMI-SDS, fT4 and triglyceride levels were the strongest independent variables correlated with TSH level in obese subjects (r (2) = 0.046, p = 0.001). CONCLUSIONS: IH prevalence is higher in obese children as compared to healthy children and the increase in TSH level correlates negatively with serum fT4 and positively with BMI-SDS and triglyceride levels in obese children.

Quantification of overnight urinary gonadotropin excretion predicts imminent puberty in girls: a semi-longitudinal study.

PURPOSE: We explored the alternative of using overnight fold change in gonadotropin levels by comparing the last-night-voided (LNV) and first-morning-voided (FMV) urine concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as a conceptual analogy to the invasive gonadotropin-releasing hormone (GnRH) stimulation test setting. METHODS: We investigated the nocturnal changes in the immunoreactivity levels of urinary gonadotropins between early and late prepubertal stages as well as between early and late pubertal stages in FMV and LNV urine samples from 30 girls, of whom those who were prepubertal were further investigated through follow-up visits within the 1-year period from the start of the study. RESULTS: ROC analysis revealed that the FMV total U-LH and FMV U-FSH concentrations at or above 0.3 IU/L and 2.5 IU/L, respectively, were excellent predictors of forthcoming onset of puberty within 1 year (100% sensitivity, 100% specificity, AUC: 1.00, and n = 10, for both). FMV total U-LH concentration at or above 0.8 IU/L represented the cut-off for clinical signs of puberty. FMV/LNV total U-LH and FMV/LNV U-FSH ratios at or below 4.11 and 1.38, respectively, were also good predictors of the onset of clinical puberty within 1 year. An overnight increase (FMV/LNV ratio) in total U-LH concentrations and in the U-LH/U-FSH ratio at or below 1.2-fold in pubertal girls was associated with the postmenarcheal pubertal stage. CONCLUSION: FMV total U-LH and U-FSH above 0.3 IU/L and 2.5 IU/L, respectively, can be used as cut-off values to predict the manifestation of the clinical signs of puberty within 1 year. FMV total U-LH concentrations 0.3-0.8 IU/L and 0.6 IU/L may represent the range and the threshold, respectively, that reflect the loosening of the central brake on the GnRH pulse generator. An overnight increase of 20% or less in total U-LH concentrations and in the U-LH/U-FSH ratio in an early pubertal girl may serve as an indicator of imminent menarche, a presumed timing of which can be unraveled by future longitudinal studies.

Clinical and diagnostic characteristics of hyperprolactinemia in childhood and adolescence.

Pituitary adenoma is the most common cause of hyperprolactinemia, which is a rare endocrine disorder encountered in pediatric patient care. Epidemiological and clinical information about hyperprolactinemia in childhood and adolescence is limited. Clinical signs of hyperprolactinemia are very heterogeneous. In girls, disturbances in menstrual function and galactorrhea may be seen, whereas in boys, headache, visual disturbances, delayed pubertal development and hypogonadism are often present. Owing to the ease of ordering a serum prolactin measurement, an evidence-based, cost-effective approach to the management of this endocrine disorder is required. Before a diagnosis of hyperprolactinemia is made, drug use, renal insufficiency, hypothyroidism, and parasellar tumors should be excluded. The main objectives of treatment are normalization of prolactin level, adenoma shrinkage, and recovery from clinical signs related to hyperprolactinemia. In patients with microadenoma, invasive or non-invasive macroadenoma, and even in patients with visual field defects, dopamine agonists are the first-line treatment. Surgical treatment is indicated in patients who are unresponsive or intolerant to medical treatment or who have persistent neurological signs. Radiotherapy should be considered as a supportive treatment for patients in whom surgery fails or medical response is not achieved.

Vitamin D in childhood cancer: a promising anticancer agent?

Children diagnosed and treated for cancer are vulnerable to Vitamin D deficiency depending on many factors. The Vitamin D status in children with cancer has been mostly regarded as a contributory factor for skeletal pathologies so far. However, the calcitriol was found to promote cell differentiation, inhibit malignant proliferation, and exhibit antiinflammatory, proapoptotic and antiangiogenic properties. In addition to this, numerous epidemiological studies link Vitamin D and cancer and indicate to possible role of Vitamin D in cancer pathogenesis and progression. This article aims to provide an overview of the possible role of Vitamin D deficiency in childhood cancer in terms of prevention and treatment.

Urine Sampling Protocol Recommendations for Reliable Determination of Total Urinary Luteinizing Hormone Immunoreactivity in the Pediatric Population.

This study investigates day-to-day variations in urinary luteinizing hormone (U-LH) concentrations in children, focusing on potential minimization or correction methods. 95 children and adolescents (51 boys, 44 girls, ages 5-17) provided daytime and evening urine samples for U-LH determinations over three consecutive days. No consistent day-to-day differences in U-LH levels were observed, although random variations, particularly in adolescents aged 13 or older, were noted. The net inter-assay CV% for U-LH changes over three days showed high variability, averaging 24.6% to 28.0% for boys and 21.6% to 27.3% for girls, independent of sex, collection time, or U-LH level. To reliably determine total urinary luteinizing hormone immunoreactivity in the pediatric population, it is advisable to collect multiple first-morning voided samples for at least three consecutive days as an interim solution, pending the development of a standardized protocol or correction method for varying urine composition. Strict adherence, especially for adolescents aged 13 or older, is vital.

The negative impact of levothyroxine treatment on urinary luteinizing hormone measurements in pediatric patients with thyroid disease.

Objectives: Previous studies suggest urinary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements by immunofluorometric assays (IFMA) as noninvasive alternatives to serum assays for puberty assessment. However, these studies excluded patients with other endocrine disorders and those taking medications. Besides, the recent discontinuation of IFMA manufacturing is a concern. We explored the utility of luminometric assays (LIA) for urinary gonadotropins and thyroid-stimulating hormone (TSH) determinations in euthyroid patients with thyroid pathologies. Methods: We used LIA and IFMA assays to measure serum and first-morning-voided (FMV) urine LH, FSH, and TSH concentrations in euthyroid patients with various thyroid disorders. Of the 47 euthyroid patients with normal serum TSH (S-TSH) levels, 14 were receiving levothyroxine therapy. Results: FMV total urinary LH (U-LH) concentrations correlated significantly with those measured in serum using either LIA (r=0.67, P<.001) or IFMA (r=0.83, P=.003) in patients not receiving levothyroxine treatment; however, no significant correlation could be detected in patients receiving levothyroxine regardless of the assay method (for LIA: r=0.50, P=.08 and IFMA r=0.44, P=.15). Urinary TSH (U-TSH) concentrations correlated poorly with those in serum in both the untreated and the treated groups (r=-0.13, P=.49, and r=-0.45, P=.11, respectively). Conclusion: FMV total U-LH determinations by LIA can be used to assess pubertal development in patients with thyroid pathology, provided the euthyroid patient is not on levothyroxine treatment. U-TSH measurements by LIA cannot replace invasive S-TSH measurements at least in patients with normal S-TSH levels. Further research may reveal the utility of U-TSH determinations in patients with elevated S-TSH levels.

Hyperprolactinemia in children: clinical features and long-term results.

Hyperprolactinemia is a rare endocrine disorder in childhood, which may result from hypophyseal adenoma. We aimed to review the etiologic reasons and clinical features in hyperprolactinemia patients retrospectively. The mean age of 11 female patients at diagnosis was 14.2 ± 1.3 years. Five patients had microadenoma, four patients had macroadenoma, and two patients were diagnosed with idiopathic hyperprolactinemia. The most frequent symptoms were menstrual disorders, headache, and galactorrhea, and one-third of the patients had obesity at diagnosis. There was no anterior pituitary hormone deficiency. All patients received bromocriptine as initial therapy; only two patients with macroadenoma and one patient with microadenoma were switched to cabergoline. Transsphenoidal surgery was performed for a patient with macroadenoma, who had cavernous sinus invasion and visual field defect. Medical treatment should be the first-line treatment option in both microadenoma and macroadenoma cases without any neurological signs. Surgery should be employed with limited indications.

Clinical profile and etiologies of children with central diabetes insipidus: a single-center experience from Turkey.

AIM: The aim of this study is to evaluate the clinical, anthropometric, hormonal, and radiological characteristics of children with central diabetes insipidus (DI). METHODS: Case records of 34 children (22 boys and 12 girls) with documented central DI referred to the Pediatric Endocrinology and Adolescent Clinic of Dokuz Eylul University Faculty of Medicine were reviewed. The mean age at diagnosis was 6.4 +/- 5.6 years (range, 0.08-16 years). All patients underwent anterior pituitary function assessment and magnetic resonance imaging of pituitary at diagnosis. The median duration of follow-up was 7.9 +/- 4.5 years. RESULTS: The etiology of central DI was organic in 22 (64.7%) patients, trauma in 2 (5.9%) patients, and idiopathic in 10 (29.4%) patients. Organic causes consisted of craniopharyngioma in 7 patients, Langerhans cell histiocytosis in 4 patients, germinoma in 4 patients, holoprosencephaly in 3 patients, astrocytoma in 1 patient, cavernous hemangioma in 1 patient, Rathke's cleft cyst in 1 patient, and autoimmune polyendocrinopathy in 1 patient. Anterior pituitary hormone deficiencies were documented in 18 (53%) patients. Organic central DI group had a greater prevalence of anterior pituitary hormone deficiency when compared with the idiopathic group (66% and 10%, respectively; p = 0.007). The final height of patients with organic etiology were significantly lower than the idiopathic group (155 and 178, cm respectively; p = 0.021). CONCLUSIONS: Etiological diagnosis is possible in a significant proportion (70.6%) of children with central DI. Findings of this study suggest that accompanying anterior pituitary hormone deficiencies and short stature may be considered as indicators of organic etiology.

Urinary gonadotropin measurements by enhanced luminometric assays (LIA) for the evaluation of pubertal development.

OBJECTIVES: Determination of LH in urine has proved to be a reliable method for evaluation of pubertal development. The human LH assay based on time-resolved immunofluorometric (IFMA) technology (AutoDELFIA, PerkinElmer, Wallac) has been found to be suitable for this purpose thanks to its high sensitivity but other assays have not been evaluated. We have analyzed our data obtained by another potentially sensitive detection technique, enhanced luminometric assay (LIA) with the objective of finding a viable alternative to IFMA since these may not be available in the future. METHODS: LIA was used to measure LH and FSH in serum and urine samples from 100 healthy subjects of each Tanner stage and both genders, whose pubertal development has been determined. RESULTS: Urinary gonodotropin concentrations measured by LIA correlated well with Tanner stage [(r=0.93 for girls, r=0.81 for boys; p<0.01 for LH) and (r=0.81 for girls, r=0.73 for boys; p<0.01 for FSH)]. LIA determinations revealed the increase in U-LH concentrations during the transition from Tanner stage 1-2 in both girls and boys (p<0.001), whereas U-FSH and S-LH were able to detect the increase from Tanner stage 1-2 only in boys or girls, respectively (both p<0.001). CONCLUSIONS: Measurement of urinary gonadotropin concentrations by LIA may be useful for the evaluation of overall pubertal development and also in the detection of transition from prepuberty to puberty.

Nutritional rickets and vitamin D deficiency in infants, children and adolescents.

Nutritional rickets continues to be a public health problem in many countries despite the presence of cheap and effective means of preventing the disease. Deficiency of vitamin D is associated with rickets in growing children and osteomalacia in adults. Vitamin D deficiency is attributed to a variety of causes including diet, atmospheric pollution, religious practices that restrict sunlight exposure (clothing), geographic latitude and altitude, season, and time of the day. The clinical findings of rickets can vary among stages of the disease. It is recommended that healthy infants, children and adolescents take at least 400 IU vitamin D per day to prevent rickets and vitamin D deficiency. Pediatricians and other healthcare professionals should try to ensure that children and adolescents receive daily vitamin D requirements appropriate for their risk factors, traditions, and customs. Additionally, it is important to use every opportunity to ensure that effective preventive strategies are put in practice.

A comparison of multiple daily insulin therapy with continuous subcutaneous insulin infusion therapy in adolescents with type 1 diabetes mellitus: a single-center experience from Turkey.

AIM: To compare the long-term outcomes of continuous subcutaneous insulin infusion (CSII) pump therapy with the clinical and metabolic parameters recorded during multiple daily insulin (MDI) therapy. PATIENTS AND METHODS: CSII pump was used by volunteer adolescents, who had a duration of diabetes mellitus (DM) longer than one year, regularly attended periodic examinations for the last year, measured and recorded blood glucose levels on average 3 to 4 times a day, and did not achieve the preferred metabolic control even though the use of MDI therapy. Carbohydrate counting and flexible MDI therapy was taught to these patients before CSII pump implantation. The metabolic and clinical parameters of the patients for the post-CSII pump period were compared with the data of flexible and non-flexible MDI periods. RESULTS: The mean CSII pump implantation age of the 17 adolescents enrolled in the study was 15.53 +/- 1.8 years, duration of DM 6.77 +/- 4.05 years, flexible MDI injection duration 0.70 +/- 0.20 years, and duration of CSII pump use 2.07 +/- 1.12 years. A decrease was detected in HbA(1c) levels of the patients with transition to CSII pump compared to flexible and non-flexible MDI injection periods; however, this decrease was not statistically significant (7.71%, 8.21%, and 8.71%, respectively, p = 0.105). No statistically significant difference was detected in frequency of hypoglycemia, lipid profiles, total daily insulin requirement, and BMI SDS values of the patients when data of the post-CSII pump state were compared with that of flexible and non-flexible MDI therapy groups. CONCLUSION: In adolescents, it was found that CSII pump therapy is efficient and safe without any increased risk for weight gain and hypoglycemia compared to flexible and non-flexible MDI injection periods. The present study also demonstrated that flexible MDI injection therapy might be efficiently and safely used in patients who cannot receive CSII pump therapy due to social and/or financial factors.

Characterization of GH-1 mutations in children with isolated growth hormone deficiency in the Turkish population.

Isolated growth hormone deficiency (IGHD) is defined as a medical condition associated with growth failure due to insufficient production of growth hormone (GH) or lack of growth hormone action. It occurs with an incidence of between 1/4,000 and 1/10,000 live births. Most cases are sporadic and idiopathic but 5-30% of growth hormone deficiency (GHD) has genetic etiology. Mutations in the GH encoding gene (GH-1) have been detected in patients with IGHD. The purpose of this study was to characterize mutations of the GH-1 gene in children with IGHD in the Turkish population. We found four missense mutations (E33G, N47D, T-24A and A13S), one nonsense mutation (W-7X), one insertion and two deletions in nine patients out of seventy-five patients with IGHD. The missense mutation A13S, GAAA insertion at intron 1 (+178A), and the deletions of +83C in intron 1 and deltaF166 in exon 5 are novel mutations.

Endocrine disrupters - with special emphasis on sexual development.

The impact of environmental pollutants in increasingly observed alterations in wildlife is obvious. Many laboratories and a number of human studies have revealed that human beings are not resistant to these contaminants. We briefly discuss the findings of animal and human studies regarding the effects of endocrine disrupting chemicals relevant to clinical problems encountered in child care, namely, premature and delayed sexual development and disorders of male genital development.

The effect of growth hormone treatment on bone mineral density in prepubertal girls with Turner syndrome: a multicentre prospective clinical trial.

BACKGROUND: Patients with Turner syndrome (TS) are treated with GH to increase adult height. Although it is well established that GH promotes longitudinal bone growth, the effects of GH treatment on bone density are less clear. OBJECTIVE: To determine how GH treatment affects trabecular bone mineral density (BMD) in girls with TS at prepubertal ages in a prospective multicentre study. PATIENTS AND METHOD: Twenty-two patients with TS in the prepubertal period with a mean age of 9.8 +/- 2.5 (range 3.6-12.8) years were included in the study. All girls with TS underwent measurement of areal BMD using dual-energy X-ray absorptiometry (DXA) to obtain pretreatment anteroposterior (AP) lumbar spine values at L1-L4. Patients received GH (Genotropin) subcutaneously for 1 year at a dose of 0.05 mg/kg/day. Height and weight were measured at 3-monthly intervals. The AP lumbar spine areal BMD was remeasured using the same technique after 1 year of treatment. Lumbar spine BMD Z-scores and volumetric BMD (vBMD) Z-scores were calculated using national standards. RESULTS: The height SDS of our cases showed a significant increase with GH therapy. The pretreatment lumbar spine (L1-L4) BMD Z-score was -1.2 +/- 1.2 SD and the vBMD Z-score was -0.8 +/- 1.6 SD. There were no significant changes in these values after 1 year of GH treatment. Prepubertal TS girls more than 11 years of age had lower vBMD Z-scores (-1.7 +/- 1.7 SD) than the girls aged less than 11 (-0.1 +/- 1.0 SD) (P < 0.05) at the onset of therapy. No significant changes were observed in these values after 1 year of GH therapy. CONCLUSIONS: Osteopaenia becomes apparent in prepubertal TS patients as they reach pubertal age. BMD evaluation may be necessary in these prepubertal TS girls at diagnosis. Short-term GH therapy in these TS patients does not have a significant effect on bone density when measured at a site with a predominance of trabecular bone.

A Synopsis of Current Practice in the Diagnosis and Management of Patients with Turner Syndrome in Turkey: A Survey of 18 Pediatric Endocrinology Centers

Objective: A comprehensive survey was conducted to evaluate the shortcomings of clinical care in patients with Turner syndrome (TS) in Turkey. Methods: A structured questionnaire prepared by the Turner study group in Turkey, which covered relevant aspects of patient care in TS was sent to 44 pediatric endocrinology centers. Results: Eighteen centers (41%) responded to the questionnaire. In the majority of the centers, diagnostic genetic testing, screening for Y chromosomal material, protocols regarding the timing and posology of growth hormone (GH) and estrogen, thrombophilia screening, fertility information and screening for glucose intolerance, thyroid, and coeliac diseases in patients with TS were in line with the current consensus. Thirteen centers (72.2%) performed GH stimulation tests. Only four centers (22.2%) used oxandrolone in patients with TS with very short stature. The majority of the centers relied on bone age and breast development to assess estrogen adequacy, though together with variable combinations of oestrogen surrogates. Two centers (11.1%) reported performing serum estradiol measurements. Eight centers (44.4%) routinely conducted cardiac/thoracic aorta magnetic resonance imaging. Screening for hearing, dental and ophthalmologic problems were performed by thirteen (72.2%), six (33.3%) and ten (55.6%) centers, respectively. Psychiatric assessments were made by four centers (22.2%) at diagnosis, with only one center (5.6%) requiring annual reassessments. Conclusion: Although we found some conformity between the current consensus and practice of the participating centers in Turkey regarding TS, further improvements are mandatory in the multi-disciplinary approach to address co-morbidities, which if unrecognized, may be associated with reduced quality of life and even mortality.

Clinical significance of the parental origin of the X chromosome in turner syndrome.

CONTEXT: The phenotype in Turner syndrome (TS) is variable, even in patients with a supposedly nonmosaic karyotype. Previous work suggested that there were X-linked parent-of-origin effects on the phenotype. HYPOTHESIS: The TS phenotype is influenced by the parental origin of the missed X chromosome. DESIGN: This was a multicenter prospective study of TS patients and both their parents, determining parental origin of the X-chromosome, and characterizing the clinical phenotype. PATIENTS AND METHODS: Eighty-three TS patients and their parents were studied. Inclusion criteria were TS with karyotype 45,X or 46Xi(Xq). Four highly polymorphic microsatellite markers on the X-chromosome DMD49, DYSII, DXS1283, and the androgen receptor gene and three Y chromosome markers, SRY, DYZ1, and DYZ3. OUTCOME MEASURES: The study determined the correlation between the parental origin of the X chromosome and the unique phenotypic traits of TS including congenital malformations, anthropometry and growth pattern, skeletal defects, endocrine traits, education, and vocation. RESULTS: Eighty-three percent of 45,X retained their maternal X (X(m)), whereas 64% 46Xi(Xq) retained their paternal X (X(p), P < 0.001). Kidney malformations were exclusively found in X(m) patients (P = 0.030). The X(m) group had lower total and low-density lipoprotein cholesterol (P < 0.003), and higher body mass index sd score (P = 0.030) that was not maintained after GH treatment. Response to GH therapy was comparable. Ocular abnormalities were more common in the paternal X group (P = 0.017), who also had higher academic achievement. CONCLUSIONS: The parental origin of the missing short arm of the X chromosome has an impact on overweight, kidney, eye, and lipids, which suggests a potential effect of an as-yet-undetermined X chromosome gene imprinting.

Effects of growth hormone on growth, insulin resistance and related hormones (ghrelin, leptin and adiponectin) in Turner syndrome.

BACKGROUND: Concomitant evaluation of the metabolic and growth-promoting effects of growth hormone (GH) therapy in Turner syndrome (TS) may be used in the prediction of the growth response to GH therapy. AIM: To evaluate the metabolic effects of GH therapy in TS and correlation with the short-term growth response. PATIENTS: 24 prepubertal children with TS, aged 9.4 +/- 2.6 years were followed for auxology and IGF-I, IGFBP-3, leptin, ghrelin, adiponectin, lipids and OGTT results in a prospective multicenter study. INTERVENTION: GH (Genotropin) in a dose of 50 microg/kg/day for 1 year. RESULTS: Height standard deviation score (SDS) increased from -3.9 +/- 1.5 to -3.5 +/- 1.4 (p = 0.000) on therapy. BMI did not change. IGF-I SDS increased from -2.3 +/- 0.4 to -1.6 +/- 1.1 at 3 and 6 months (p = 0.001) and decreased thereafter. Serum leptin decreased significantly from 2.3 +/- 3.9 to 1.7 +/- 5.3 ng/ml (p = 0.022) at 3 months and increased afterwards. Serum ghrelin decreased from 1.2 +/- 0.8 to 0.9 +/- 0.4 ng/ml (p = 0.005) with no change in adiponectin. Basal and stimulated insulin levels also increased significantly. Delta height SDS over 1 year showed a significant correlation with Delta IGF-I(0-3 months) (r = 0.450, p = 0.027). CONCLUSION: IGF-I may be considered as a marker of growth response in TS at short term. Leptin shows a decrease at short term but does not have a correlation with growth response. The decrease in ghrelin in face of unchanged weight seems to be associated with increase in IGF-I and insulin levels. The unchanged adiponectin levels in spite of an increase in insulin levels indicates that adiponectin is mainly affected by weight, not insulin.

A non-endocrine cause of testicular enlargement mimicking precocious puberty: testicular microlithiasis.

Untimely bilateral testicular enlargement greater than 3 ml is suggestive of precocious puberty, in which an underlying organic disease is more common in boys than in girls. We describe a 7 1/2 year-old boy presenting with testicular enlargement due to testicular microlithiasis. Following hormonal tests, diagnosis was based on ultrasonographic findings. Three years follow-up of the patient revealed normal pubertal progress and no malignant evolution. Testicular microlithiasis is a rare cause of testicular enlargement and pediatricians should take this disease into account in the differential diagnosis of suspected precocious puberty.