Elpis Vlachopapadopoulou

Herpes virus antibodies seroprevalence in children with autoimmune thyroid disease

Background Elevated titers of antibodies against different herpes virus antigens have been reported in some immunodeficient and systemic autoimmune disorders. Objective To examine if Herpes Simplex Virus (HSV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) IgG and IgM antibodies are detected more frequently in children with autoimmune thyroid disease (AITD) compared to controls. Subjects and methods Thirty-four children with AITD, aged 9.62xa0±xa02.35xa0years, and 31 matched controls, aged 9.24xa0±xa02.98xa0years, were studied. Results The percentage of EBV IgG+ children with AITD was statistically higher than the percentage of EBV IgG+ controls (82.35% versus 51.61%, Pxa0=xa00.008). The percentage of EBV IgG+ children with AITD and hypothyroidism was statistically higher than the percentage of EBV IgG+ children with AITD, without hypothyroidism (100% versus 70%, Pxa0=xa00.024). No other statistically significant differences were observed in HSV−1+2, and CMV IgG or IgM antibodies between the subgroups of children studied. Conclusions EBV seroprevalence is higher in children with AITD compared to controls and the underlying pathology remains to be elucidated.

Evolution of sonographic appearance of the thyroid gland in children with Hashimoto's thyroiditis.

BACKGROUNDnAlthough thyroid ultrasound is a valuable tool for the diagnosis and follow-up of patients with Hashimotos thyroiditis (HT), classical sonographic findings are not always present.nnnAIMnTo calculate the time needed for children with HT and normal ultrasound at diagnosis to develop characteristic sonographic findings.nnnPATIENTS AND METHODSn105 children (23 male and 82 female) with HT (mean age 9.4 +/- 2.9 years) were studied. Physical examination and measurements of TSH and fT4 levels were performed at diagnosis, at 3-month intervals for the first year, and twice yearly thereafter. Thyroid ultrasound was performed at diagnosis and twice yearly thereafter. The median follow-up duration was 18 months (range: 6-61 months).nnnRESULTSnThe time needed for 30%, 50%, and 70% of children to demonstrate an abnormal thyroid sonographic pattern was 4, 7, and 14 months, respectively. Important factors accelerating sonographic changes were goiter (p = 0.023), hypothyroidism (p = 0.0255), and seropositivity for both thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg) autoantibodies (p = 0.0005).nnnCONCLUSIONnSonographic findings of HT are present in 37% of children at diagnosis. Fifty percent of children with normal initial thyroid US will develop changes within 7 months; however, characteristic findings may not develop for over 4 years.

Testicular microlithiasis in siblings: clinical implications

Testicular microlithiasis is a relatively uncommon condition in children. It is characterized by the presence of microcalcifications within the testicular parenchyma. Although it is a benign finding, underlying diseases and other conditions must be ruled out because testicular microlithiasis has been found in association with both benign and malignant lesions in the testes and other tissues. We present two brothers with testicular microlithiasis, and highlight the prevalence, natural history, associated malignant conditions and follow-up recommendations of children diagnosed with testicular microlithiasis.

Malignant Insulinoma in Childhood

Pancreatic tumors constitute a rare surgical problem in infancy and childhood. Insulinomas are rare in all age groups with an estimated incidence of one per 250,000 person-years and even rarer in childhood. We report a 10 year-old girl with malignant insulinoma. The presenting symptom was hypoglycemic attacks. Laboratory investigation demonstrated that the hypoglycemia was due to hyperinsulinism. MRI of the abdomen revealed a mass at the tail of the pancreas. Distal pancreatectomy with splenectomy was performed. Histological examination showed malignant insulinoma with peripancreatic lymph node metastases. One month later abdominal MRI revealed the existence of multiple small metastatic foci in the liver, which were confirmed by In111 octreoscan. Treatment with octreotide was started and the disease is stable after 12 months of therapy.

Gonadal function of young patients with beta-thalassemia following bone marrow transplantation

Bone marrow transplantation (BMT) can induce short- and long-term impairment of gonadal function. Patients with beta-thalassemia represent a special group, as their primary diagnosis and its treatment modalities are responsible for gonadal dysfunction. To address the effect of BMT on puberty and gonadal function, we investigated 25 patients (12 males) with thalassemia who received allogenic BMT during childhood or adolescence and at the post-transplant evaluation were at an age that the pubertal process should have started. Pubertal stage by Tanner of breast and pubic hair, as well as testicular volume were assessed pre-BMT once and post-BMT at least twice. Menstrual history was recorded. FSH, LH, testosterone and estradiol levels were also determined. The impact of BMT appears to be different in the two sexes. Males seem to have higher tolerance, as all males who were pubertal at the time of BMT had normal testosterone, and all but one normal gonadotropin levels. From those who were prepubertal at BMT, 62% proceeded to normal pubertal development. Post-menarcheal females seem to be an extremely sensitive group to the deleterious effect of the transplantation process, as 100% of the post-menarcheal females exhibited amenorrhea and elevated gonadotropin levels. These findings are important for pre- and post-BMT counseling.

Utility and applicability of the “Childhood Obesity Risk Evaluation” (CORE)-index in predicting obesity in childhood and adolescence in Greece from early life: the “National Action Plan for Public Health”

AbstractEarly identification of infants being at high risk to become obese at their later childhood or adolescence can be of vital importance in any obesity prevention initiative. The aim of the present study was to examine the utility and applicability of the “Childhood Obesity Risk Evaluation (CORE)” index as a screening tool for the early prediction of obesity in childhood and adolescence. Anthropometric, socio-demographic data were collected cross-sectionally and retrospectively from a representative sample of 5946 children, and adolescents and were combined for calculating the CORE-index score. Logistic regression analyses were performed to examine the associations of the CORE-index score with obesity by gender and age group, and cut-off point analysis was also applied to identify the optimal value of the CORE-index score that differentiates obese from non-obese children. Mean CORE-index score in the total sample was 3.06 (sd 1.92) units (range 0–11xa0units). Each unit increase in the CORE-index score was found to be associated with a 30xa0% (95xa0% C.I. 1.24–1.36) increased likelihood for obesity in childhood or adolescence, while the optimal cut-off value of the CORE-index score that predicted obesity with the highest possible sensitivity and specificity was found to be 3.5.n Conclusion: The present study supports the utility and applicability of the CORE-index as a screening tool for the early identification of infants that are potentially at a higher risk for becoming obese at their childhood and adolescence. This tool could be routinely used by health professionals to identify infants at high risk and provide appropriate counselling to their parents and caregivers so as to maximize the effectiveness of early obesity prevention initiatives.What is known?• Childhood obesity has reached epidemic proportions worldwide.• Certain perinatal and socio-demographic indices that were previously identified as correlates of childhood obesity in children were combined to develop the CORE-index, a screening tool that estimates obesity risk in 9–13xa0year-old children.What is new?• The utility and applicability of the CORE-index as screening tool can be extended to the age range of 6–15xa0years.• The CORE-index is a cost-effective screening tool that can assist health professionals in initiating obesity preventive measures from early life.

Tumor necrosis factor-α levels in short children

Growth hormone has been suggested to modulate the release of cytokines, such as tumor necrosis factor-alpha (TNFalpha) and interleukin-1 (IL-1). Moreover, TNFalpha synthesis has been shown to be decreased in hypophysectomized rodents. The aim of this study was to evaluate the influence of GH status on TNFalpha levels in a group of 44 short prepubertal children. Among them, 13 children aged 9.8 +/- 3.5 years were growth hormone (GH) deficient and the other 31 short children had normal growth velocity, normal GH response to provocative testing, and did not suffer from any chronic disease, thus this group was diagnosed as having idiopathic short stature (ISS). A group of 40 age- and sex-matched healthy children was used as controls. No significant differences in basal TNFalpha levels (pg/ml) were found between the GH deficient, ISS children and healthy controls. Furthermore, there was no correlation between TNFalpha and basal serum concentrations of GH or peak GH levels after stimulation. Similarly, TNFalpha values did not correlate with either IGF-I or IGFBP-3 serum concentrations.

A Randomized Phase 2 Study of Long-Acting TransCon GH vs Daily GH in Childhood GH Deficiency

ContextnTransCon Growth Hormone (GH) (Ascendis Pharma) is a long-acting recombinant sustained-release human GH prodrug in development for children with GH deficiency (GHD).nnnObjectivenTo compare the pharmacokinetics, pharmacodynamics, safety, and efficacy of weekly TransCon GH to that of daily GH in prepubertal children with GHD.nnnDesignnRandomized, open-label, active-controlled study of three doses of weekly TransCon GH versus daily Genotropin (Pfizer).nnnSettingnThirty-eight centers in 14 European countries and Egypt.nnnPatientsnPrepubertal male and female treatment-naïve children with GHD (n = 53).nnnInterventionsnSubjects received one of three TransCon GH doses (0.14, 0.21, or 0.30 mg GH/kg/wk) or Genotropin 0.03 mg GH/kg/d for 26 weeks.nnnMain Outcome MeasuresnGH and insulinlike growth factor-1 (IGF-1) levels, growth, adverse events, and immunogenicity.nnnResultsnBoth GH maximum concentration and area under the curve were similar following TransCon GH or Genotropin administration at comparable doses. A dose response was observed, with IGF-1 standard deviation scores increasing into the normal range for all three TransCon GH doses. Annualized mean height velocity for the three TransCon GH doses ranged from 11.9 cm to 13.9 cm, which was not statistically different from 11.6 cm for Genotropin. Adverse events were mild to moderate, and most were unrelated to the study drug. Injection site tolerance was good. One TransCon GH subject developed a low-titer, nonneutralizing antibody response to GH.nnnConclusionsnThe results suggest that long-acting TransCon GH is comparable to daily Genotropin for GH (pharmacokinetics) and IGF-1 (pharmacodynamics) levels, safety, and efficacy and support advancement into phase 3 development.

Resolution of Hematocolpos in Adolescents Affected with Graft vs Host Disease

BACKGROUNDnBone marrow transplantation is a lifesaving procedure for a range of serious benign or malignant hematological conditions. A proportion of patients, however, will develop graft vs host disease (GVHD), acute or chronic, with serious long-term sequalae.nnnCASESnWe present 2 cases of hematocolpos that developed in adolescence because of vaginal synechiae due to GVHD. The condition was initially asymptomatic, resolved spontaneously at first and recurred. In 1 girl blunt lysis of the adhesions was performed with the patient under general anesthesia, followed thereafter by local hydrocortisone and estriol treatment.nnnSUMMARY AND CONCLUSIONnGenital symptoms might not be readily reported by adolescents after bone marrow transplantation. Physicians should be aware of possible late effects of GVHD on genitalia, inquire about symptoms, and be acquainted with addressing complications, such as vaginal obstruction.

Cortisol response to adrenocorticotropin testing in non-classical congenital adrenal hyperplasia (NCCAH).

Abstract Background: The adequacy of cortisol response in non-classical congenital adrenal hyperplasia (NCCAH) has not been fully elucidated. The aim was to evaluate cortisol response to adrenocorticotropin (ACTH) stimulation test in children and adolescents with NCCAH and heterozygotes for CYP21A2 gene mutations. Methods: One hundred and forty-six children and adolescents, mean age 7.9 (0.7–17.5) years with clinical hyperandrogenism, were evaluated retrospectively. Thirty-one subjects had NCCAH, 30 were heterozygotes for CYP21A2 gene mutations, while 85 showed normal response to ACTH test. Results: Baseline cortisol levels did not differ among NCCAH, heterozygotes, and normal responders: 15.75 (5.83–59.6) μg/dL vs. 14.67 (5.43–40.89) μg/dL vs. 14.04 (2.97–34.8) μg/dL, p=0.721. However, NCCAH patients had lower peak cortisol compared to heterozygotes and control group: 28.34 (12.25–84.40) vs. 35.22 (17.47–52.37) μg/dL vs. 34.92 (19.91–46.68) μg/dL, respectively, p=0.000. Peak cortisol was <18 μg/dL in 7/31 NCCAH patients and in one heterozygote. Conclusions: A percentage of 21.2% NCCAH patients showed inadequate cortisol response to ACTH stimulation. In these subjects, the discontinuation of treatment on completion of growth deserves consideration.