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Background/Aims: We report data from the EU Increlex® Growth Forum Database (IGFD) Registry, an ongoing, open-label, observational study monitoring clinical practice use of recombinant human insulin-like growth factor-1 (rhIGF-1) therapy in children. Methods: Safety and effectiveness data on rhIGF-1 treatment of 195 enrolled children with growth failure were collected from December 2008 to September 2013. Results: Mean ± SD (95% CI) height velocity during first year of rhIGF-1 treatment was 6.9 ± 2.2 cm/year (6.5; 7.2) (n = 144); in prepubertal patients naïve to treatment, this was 7.3 ± 2.0 cm/year (6.8; 7.7) (n = 81). Female sex, younger age at start of rhIGF-1 therapy, and lower baseline height SDS predicted first-year change in height SDS. The most frequent targeted treatment-emergent adverse events (% patients) were hypoglycemia (17.6%, predictors: young age, diagnosis of Laron syndrome, but not rhIGF-1 dose), lipohypertrophy (10.6%), tonsillar hypertrophy (7.4%), injection site reactions (6.4%), and headache (5.9%). Sixty-one serious adverse events (37 related to rhIGF-1 therapy) were reported in 31 patients (16.5%). Conclusion: Safety and effectiveness data on use of rhIGF-1 in a ‘real-world' setting were similar to those from controlled randomized trials. Severe growth phenotype and early start of rhIGF-1 improved height response and predicted risk of hypoglycemia.

This study assessed the epidemiologic characteristics of acute viral gastroenteritis in hospitalized children. A stool sample obtained from each child was analyzed for the presence of astrovirus, calicivirus, rotavirus, adenovirus, enterovirus, and digestive bacteria. Of the 438 stool samples obtained, 138 tested positive foror =1 pathogen during the winters of 1997-1998 and 1998-1999 (P.001). Virologic tests revealed rotavirus in 17.3% of samples, calicivirus in 7.3%, astrovirus in 6.8%, adenovirus in 0.7%, andor =1 virus in 5.4%. Median age was higher for patients with rotavirus gastroenteritis than it was for those with astrovirus or calicivirus gastroenteritis (P=.014). Mean duration of hospitalization was statistically significantly lower for children with rotavirus gastroenteritis (P=.022), despite the more-frequent dehydration observed among children with rotavirus versus those with astrovirus or calicivirus gastroenteritis (P=.007). In contrast, enteral rehydration was more rapidly achieved in patients with gastroenteritis due to rotavirus.

CONTEXT: Serum IGF-I levels are often low in patients with short stature (SS) without defined etiology. Hence, genetic investigations have focused on the GH-IGF-I axis.OBJECTIVE: Our objectives were to characterize IGF-I axis status and search for a broader range of genetic associations in children with SS and normal GH.DESIGN AND SETTING: We conducted a prospective, cross-sectional, epidemiogenetic case-control study in 9 European countries (2008-2010).PARTICIPANTS: Children (n = 275) aged ≥2 years with SS without defined etiology (≤-2.5 height SD score [SDS]) and ≥1 peak GH ≥7 μg/L) were recruited.METHODS: Serum IGF-I, IGF-binding protein-3 (IGFBP-3), and acid-labile subunit (ALS) levels were measured in a central laboratory. Candidate gene exome sequencing was performed in this cohort and ethnicity-matched controls.RESULTS: Serum IGF-I, IGFBP-3, and ALS levels were highly correlated, but there was a discrepancy between prevalence of IGF-I, IGFBP-3, and ALS deficiencies (53%, 30%, and 0.8%, respectively). An insertion-deletion (Indel) on the IGF1 gene (P = 1.2 × 10(-5), Bonferroni-corrected; case vs control frequency: 0.04 vs 0.112), an Indel on NFKB1 (P = 1.36 × 10(-10); case vs control frequency: 0.464 vs 0.272), and 2 single-nucleotide polymorphisms on ZBTB38 (P < 2.3 × 10(-6)) were associated with SS. At P < 10(-4), single-nucleotide polymorphisms on genes related to protein kinase regulation, MAPK, and Fanconi pathways were also associated with SS.CONCLUSIONS: IGF-I deficiency is a common feature in SS without defined etiology; an Indel in the IGF1 gene was associated with SS. However, genes involved in transcriptional regulation (NFKB1 and ZBTB38) and growth factor signaling were also associated, providing further candidates for genetic investigations on individual patients.

The strategy currently used to investigate thyroid nodules in most cases involves measurement of calcitonin to exclude the possibility of medullary thyroid cancer (MTC). Techniques used to measure calcitonin have become more reliable, sensitive, and easy to perform. Automated nonisotopic techniques now exist, such as the Advantage® system. We found that some children have particularly high calcitonin. Previous reports also have shown that calcitonin is higher in young children (1)(2)(3)(4)(5)(6)(7)(8)(9), but most of these studies are now outdated and are based on immunoradiometric or even radioimmunologic (RIA) methods, which sometimes involve an extraction step. These techniques are also not very sensitive or specific (interference by procalcitonin). Because most studies addressing this subject investigated specific populations (premature infants, newborns, or hypotrophic or hypocalcemic children), we concluded that it would be useful to determine reference intervals for blood calcitonin in children with the Advantage system. Because the manufacturer (Nichols Institute Diagnostics) found a significant difference between men and women, we also evaluated this finding. The Advantage is an automated multiparametric random-access system that uses an acridinium ester chemiluminescence technique and a magnetic separation step (10)(11). The monoclonal antibodies used recognize the 11–23 (capture monoclonal antibody) and 21–32 (labeled monoclonal antibody) fragments of human calcitonin. …