Timing and regimen of puberty induction in children with hypogonadism: a survey on the practice in Arab countries.

Objectives There are some variations in the practice of puberty induction between different regions; however, data from Arab countries are lacking. We aimed to survey the practice of pediatric endocrinologists in Arab countries on the timing and regimen for puberty induction in girls and boys with hypogonadism. Methods An online questionnaire was emailed to physicians registered in the Arab Society for Paediatric Endocrinology and Diabetes. Results In total, 106 replies from 17 countries were received. In non Turner syndrome (TS) girls, puberty was induced by 49.4% of participants at 12-13 years and by 32.5% at  ≥14 years. Ethinyl estradiol and conjugated estrogen were the most popular preparations used (29.7 and 16.6%, respectively). Of the participants, 60% introduce progesterone either at 2-3 years after starting estrogen or following a significant breakthrough bleeding on estrogen. In girls with TS, 84.2% of participants prescribed estrogen to those aged 11 years and older (51.5% at 11-12 years) and 5.3% prescribed it to those at the prepubertal age. In boys, 57.3% of participants induce at ≥14 years, 80.6% use intramuscular testosterone and 46.5% start with 50 mg/kg/month. Human chorionic gonadotropin is more used in non-Gulf Arab countries (18.2 vs. 2.9%; p 0.036) with a trend of using oral testosterone undecanoate in Gulf states (12.2 vs. 2.0%; p 0.051). Conclusions We describe the approach to puberty induction in boys and girls among pediatric endocrinologists in Arab countries. The observed variation in practice would be useful in developing regional consensus guidelines on puberty induction in children with hypogonadism.

Serum visfatin level as a noninvasive marker for nonalcoholic fatty liver disease in children and adolescents with obesity: relation to transient elastography with controlled attenuation parameter.

BACKGROUND: Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). Visfatin is an adipokine produced by visceral fat tissue and liver cells. Transient elastography with controlled attenuation parameter (CAP) noninvasively assesses liver fibrosis and steatosis. AIM: To measure visfatin level in 80 children and adolescents with obesity as a potential biomarker for NAFLD and assess its relation to transient elastography. METHODS: Abdominal ultrasound, liver stiffness and CAP measurements were performed for all patients. Fasting lipid profile, fasting blood glucose, insulin level, liver and kidney functions, coagulation profile and serum visfatin levels were assessed. RESULTS: Among patients with obesity, 31 (38.8%) had NAFLD and 16 (20%) patients had elevated alanine aminotransferase (ALT), while 9 (11.2%) had both NAFLD and elevated ALT. Transient elastography showed that 12.5% had fibrosis stage F1, 2.5% had F2 and another 2.5% had F3 while none had F4. Using CAP, 23.8, 13.8 and 17.5% had S1, S2 and S3, respectively. Serum visfatin levels were significantly elevated in all patients compared with nonobese controls. Higher visfatin levels were found among patients with dyslipidemia, NAFLD, elevated ALT and steatosis defined by CAP. Serum visfatin was related to the degree of fibrosis and steatosis. Visfatin cutoff value 18 ng/mL could significantly detect the presence of NAFLD with 83.9% sensitivity and 81.4% specificity. Serum visfatin was positively correlated to BMI, waist circumference, waist/hip ratio, ALT, total cholesterol, liver stiffness and CAP. CONCLUSIONS: Visfatin could be a promising serum biomarker for monitoring liver disease among pediatric patients with obesity.

Primary School Performance of Girls with Turner Syndrome: A Transcultural Assessment.

OBJECTIVES: We analyzed primary school performance of girls with Turner syndrome (TS) in two distinct countries to ascertain if the cognitive phenotype of TS causes selective learning difficulties. METHODS: The cohort comprised of 44 Czech and 50 Egyptian girls with TS who attended public schools. School reports from grades 1 to 9 were obtained retrospectively from Czech participants with TS. Only recent school reports were obtained from Egyptian participants. Two controls per participant were requested - biological sisters and/or female classmates. The results were converted into a 5-point scale (1-excellent; 5-unsatisfactory). RESULTS: Analysis of longitudinal Czech data displayed a strong time component in both subjects and controls. Showing better points in lower grades with its gradual worsening as the education complexity increased. In contrast, there was a strong statistically significant difference between groups in Mathematics (p=0.0041, p=0.0205 after Bonferroni correction) and this difference increased over time. The points for Mathematics did not differ in grades 1+2 (0.05 difference in mean grade between the two groups), however, they differed by 0.28 in grades 6+7 and by 0.32 in grades 8+9. While slightly different in character (cross-sectional vs. longitudinal), the Egyptian cohort data confirmed our findings, showing no difference in general school performance but having similar trends in Mathematics (grades 1+2: 0.11, grades 6+7: 0.54, grades 8+9: 0.68; p=0.0058, p=0.029 after Bonferroni correction). CONCLUSION: Excluding results in Mathematics, which showed pronounced worsening in relation to age in comparison with unaffected controls, girls with TS performed similarly to their controls.

Vitamin D status in prepubertal children with isolated idiopathic growth hormone deficiency: effect of growth hormone therapy.

Few studies, and with controversial results, analyzed vitamin D status in children before and after growth hormone (GH) treatment. Thus, we aimed to assess vitamin D status in prepubertal children with idiopathic growth hormone deficiency (GHD), and to evaluate the effect of GHD and GH treatment on vitamin D levels. Fifty prepubertal children with isolated GHD were compared with 50 controls. All were subjected to history, anthropometric assessment and measurement of 25 hydroxyvitamin D (25(OH)D), serum calcium, phosphorous, alkaline phosphatase and parathyroid hormone (PTH) at diagnosis and 1 year after GH therapy. Serum 25(OH)D levels <30 ng/mL and 20 ng/mL were defined as vitamin D insufficiency and deficiency, respectively. 25(OH)D was lower in cases than controls. Forty per cent of children with GHD were 25(OH)D insufficient and 44% deficient, while 16% were sufficient at baseline. There was a positive correlation between 25(OH)D and peak GH levels. Peak GH was a significant predictor of 25(OH)D levels. After 1 year of GH therapy, 25(OH)D increased (18.42±5.41 vs 34.5±10.1 ng/mL; P<0.001). Overall, 22% of cases remained insufficient and 24% deficient, with an increase in prevalence of children with normal levels (54%; P<0.001). 25(OH) correlated negatively with PTH (r=-0.71, P=0.01). In conclusion, hypovitaminosis D is prevalent in children with GHD and significantly improved 1 year after GH therapy. 25(OH)D should be assessed in children with GHD at diagnosis and during follow-up.

Nutritional rickets: vitamin D, calcium, and the genetic make-up.

BACKGROUND: The prevalence of vitamin D (vitD) deficiency presenting as rickets is increasing worldwide. Insufficient sun exposure, vitD administration, and/or calcium intake are the main causes. However, vitD system-related genes may also have a role. METHODS: Prospective study: 109 rachitic children completed a 6-mo study period or until rachitic manifestations disappeared. Thirty children were selected as controls. Clinical and biochemical data were evaluated at baseline in patients and controls and biochemistry re-evaluated at radiological healing. Therapy was stratified in three different protocols. Fifty-four single-nucleotide polymorphisms (SNPs) of five vitD system genes (VDR, CP2R1, CYP27B1, CYP24A1, and GC) were genotyped and their association with clinical and biochemcial data was analyzed. RESULTS: Therapy response was similar in terms of radiological healing although it was not so in terms of biochemical normalization. Only VDR gene (promoter, start-codon, and intronic genotypes) was rickets-associated in terms of serum 25-OH-D, calcium, radiological severity and time needed to heal. Eight patients with sufficient calcium intake and 25-OH-D levels carried a VDR genotype lacking minor allele homozygous genotypes at SNPs spread along the gene. CONCLUSION: Although patients presented epidemiologic factors strongly contributing to rickets, genetic modulation affecting predisposition, severity, and clinical course is exerted, at least in part, by VDR gene polymorphic variation.

Dietary fructose intake in obese children and adolescents: relation to procollagen type III N-terminal peptide (P3NP) and non-alcoholic fatty liver disease.

BACKGROUND: Excessive use of fructose has been incriminated as a risk factor for hepatic steatosis. Procollagen type III N-terminal peptide (P3NP) is a marker for steatohepatitis. Thus, we aimed to assess fructose intake in obese children and its relation to nonalcoholic fatty liver disease (NAFLD) and P3NP. METHODS: Fifty-five obese children were compared to 30 controls. All were subjected to dietary fructose and anthropometric assessment, fasting blood sugar (FBS), fasting insulin (FI) and homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, uric acid, alanine aminotransferase (ALT), P3NP and abdominal ultrasound. RESULTS: Patients had higher fructose intake which was associated with increased NAFLD grade. There was an increase in P3NP with increased NAFLD grade. P3NP correlated positively with fructose intake (processed sources and total) and caloric intake. CONCLUSIONS: High fructose intake is associated with NAFLD and P3NP may serve as a marker of NAFLD in obese children with a proposed cutoff value of 8.5 ng/mL.

Serum Pentraxin 3 Fragment as a Noninvasive Marker of Nonalcoholic Fatty Liver Disease in Obese Children and Adolescents.

BACKGROUND/AIMS: It was suggested that serum pentraxin 3 (PTX3) levels could differentiate obese children with nonalcoholic steatohepatitis (NASH) from those with simple steatosis. Thus, we aimed to evaluate the clinical utility of serum PTX3 fragment levels in the diagnosis of NASH and the assessment of its severity in obese children with suspected nonalcoholic fatty liver disease (NAFLD). METHODS: Fifty obese children were compared to 25 matched controls. All were subjected to history taking, anthropometric measurements, and abdominal ultrasonography, as well as laboratory assessments of liver functions, fasting lipid profile, fasting blood glucose, fasting insulin, homeostasis model assessment (HOMA) index, fasting glucose/insulin ratio, and serum PTX3. RESULTS: PTX3 was higher in obese cases than controls (p = 0.0001). Eighty percent of the cases had NAFLD with progressive increases in PTX3 levels as the severity of fatty liver increased (p = 0.0001). Moreover, PTX3 was higher in cases with elevated liver enzymes (3.205 ± 0.77 U/l) than those with normal liver enzymes (2.77 + 0.69 U/l, p < 0.0001). A cutoff value of 3.03 U/l differentiated fatty liver from NASH with a sensitivity of 89% and a specificity of 86%. CONCLUSION: Noninvasive monitoring of serum PTX3 fragment levels in obese patients with suspected NAFLD may be used as a reliable tool for differentiating NASH from simple fatty liver.

Anthropometric and nutritional parameters in Egyptian children and adolescents with osteogenesis imperfecta.

BACKGROUND/AIMS: Patients with osteogenesis imperfecta (OI) present with various degrees of short stature and nutritional disorders. Thus, we aimed to evaluate anthropometric and nutritional parameters in OI children and their variability among various types. METHODS: Eighty-four patients with OI (types I, II, and IV) were subjected to the following anthropometric measurements: standing height (Ht), sitting height (SH), arm span, weight (Wt), and head circumference (HC), with calculation of Ht, SH, Wt, body mass index (BMI), and HC standard deviation scores (SDSs), and relative arm span. Triceps skinfold thickness (TSFT), subscapular skinfold thickness (SSFT), and mid upper arm circumference (MUAC) were measured, as well as dietary intake of macronutrients and calcium; also, energy requirements were calculated. RESULTS: Ht SDS was reduced in OI-III and OI-IV compared to OI-I; SH SDS was reduced in OI-III compared to OI-I. HC SDS was more increased in OI-III than in OI-I and OI-IV. BMI SDS correlated with TSFT, SSFT, and MUAC. OI-III patients had the highest percentage of energy intake. The frequency of low macronutrient and calcium intake was highest in OI-III, while the frequency of low fat intake was highest in OI-I. CONCLUSIONS: Anthropometric and nutritional parameters differ among OI types. Assessment of anthropometric measurements and nutritional status in OI patients is important.

Dyslipidemia and hyperinsulinemia in children and adolescents with chronic liver disease: relation to disease severity.

BACKGROUND: Lipid metabolism is profoundly disturbed in chronic liver diseases (CLD). Moreover, patients with cirrhosis displayed chronically elevated serum insulin (SI) concentrations. OBJECTIVES: The aim of this work was to assess fasting lipid profile (FLP) and SI levels among Egyptian patients with CLD and their relation to severity of liver disease. METHODS: A total of 40 Egyptian children with CLD were compared with 30 age-, sex-, and pubertal stage-matched controls. All subjects were subjected to history and auxological assessment; their FLP, fasting blood glucose (FBG) and SI were measured; and their fasting glucose/insulin (G/I) ratios were calculated. RESULTS: Total cholesterol (TC, p=0.006), triglycerides (TG, p=0.03), low density lipoproteins (LDL, p=0.034), and SI (p<0.001) were significantly higher while high density lipoproteins (HDL, p<0.001) and G/I ratio (p<0.001) were significantly lower as serum albumin decreased; these were also lower among cases with a progressive decrease going from child A to C. Of the 40 studied cases, eight (20%) had hypercholesterolemia, 13 (32.5%) had hypertriglyceridemia, 17 (42.5%) had low HDL and 9 (22.5%) had high LDL, 32 (80%) had hyperinsulinemia (HI), and 11 (27.5%) had insulin resistance (IR). CONCLUSIONS: Dyslipidemia and HI were frequent findings in patients with CLD, which worsened with increased severity of CLD.

Penile length and genital anomalies in Egyptian male newborns: epidemiology and influence of endocrine disruptors.

This is an attempt to establish the normal stretched penile length and prevalence of male genital anomalies in full-term neonates and whether they are influenced by prenatal parental exposure to endocrine-disrupting chemicals. A thousand newborns were included; their mothers were subjected to the following questionnaire: parents' age, residence, occupation, contact with insecticides and pesticides, antenatal exposure to cigarette smoke or drugs, family history of genital anomalies, phytoestrogens intake and history of in vitro fertilization or infertility. Free testosterone was measured in 150 neonates in the first day of life. Mean penile length was 3.4±0.37 cm. A penile length <2.5 cm was considered micropenis. Prevalence of genital anomalies was 1.8% (hypospadias 83.33%). There was a higher rate of anomalies in those exposed to endocrine disruptors (EDs; 7.4%) than in the non-exposed (1.2%; p<0.0001; odds ratio 6, 95% confidence interval 2-16). Mean penile length showed a linear relationship with free testosterone and was lower in neonates exposed to EDs.

R620W polymorphism of protein tyrosine phosphatase PTPN22 in Egyptian children and adolescents with systemic lupus erythematosus: relation to thyroid autoimmunity.

BACKGROUND: Some studies showed associations of the minor T allele of the C1858T single nucleotide polymorphism (SNP) corresponding to the R620W amino acid substitution of protein tyrosine phosphatase (PTPN22) with multiple autoimmune diseases, including systemic lupus erythematosus (SLE). OBJECTIVES: To study the frequency of PTPN22 R620W polymorphism among Egyptian patients with SLE and to test the association of the T allele with autoimmune thyroid disease in such patients. METHODS: Clinical evaluation, measurement of thyroid hormones and antibodies, and genotyping of PTPN22 R620W polymorphism were done for 60 SLE patients and 60 age- and sex-matched healthy subjects. RESULTS: Nineteen SLE cases (31.67%) had thyroid dysfunction with subclinical hypothyroidism being the most frequent form of thyroid dysfunction (20%) followed by primary hypothyroidism (6.67%), subclinical hyperthyroidism (3.33%) and primary hyperthyroidism (1.67%). Autoimmune thyroid disease was detected in 36.67% of cases. Systemic lupus erythematosus disease activity index (SLEDAI) score did not differ between patients with thyroid dysfunction and euthyroid patients (p=0.061) nor with the frequency of positive thyroid peroxidise antibodies (TPOAb, p=0.092) and antithyroglobulin antibodies (ATGAb, p=0.1). T allele frequency did not differ between cases and controls (p=1.19) and was associated with autoimmune thyroid disease in Egyptian SLE patients (p=0.002). CONCLUSIONS: R620W polymorphism of the PTPN22 gene is not a major risk allele for SLE susceptibility among Egyptian SLE patients but appears to be a risk factor for concurrent autoimmune thyroid disease and SLE.

Uterine development in patients with Turner syndrome: relation to hormone replacement therapy and karyotype.

Our study aimed to assess uterine development in Turner syndrome patients and its relation to dose and type of estrogen therapy; and karyotype. Pelvic ultrasound was used to assess uterine size and shape, and ovarian volume in 40 Turner syndrome patients. Information on hormone replacement therapy was collected from patients' notes. Among the 40 patients studied, 57.5% started estrogen therapy and 30% were taking progestins. Sixty-five per cent had immature uterus, 17.5% had fully mature uterus and 17.5% had transitional uterus. Uterine volume was associated with age (p < 0.001), height (p = 0.002), weight (p = 0.001), years of estrogen use (p < 0.001), estrogen dose (p = 0.016), current estrogen use ( p =0.001) and Tanner breast stage ( p <0.001). Uterine volume was not affected by the type of estrogen used ( p =0.40) and karyotype ( p =0.40). Patients with Turner syndrome treated with estrogen (of adequate dose and duration) may attain a normal, mature uterine size and configuration, even at a late start of hormone replacement therapy and regardless of karyotype.