I. David Schwartz

Predictors of Insulin Regimens and Impact on Outcomes in Youth with Type 1 Diabetes: The SEARCH for Diabetes in Youth Study

OBJECTIVES To describe the insulin regimens used to treat type 1 diabetes mellitus (T1DM) in youth in the United States, to explore factors related to insulin regimen, and to describe the associations between insulin regimen and clinical outcomes, particularly glycemic control. STUDY DESIGN A total of 2743 subjects participated in the SEARCH for Diabetes in Youth study, an observational population-based study of youth diagnosed with T1DM, conducted at 6 centers. Data collected during a study visit included clinical and sociodemographic information, body mass index, laboratory measures, and insulin regimen. RESULTS Sociodemographic characteristics were associated with insulin regimen. Insulin pump therapy was more frequently used by older youth, females, non-Hispanic whites, and families with higher income and education (P = .02 for females, P < .001 for others). Insulin pump use was associated with the lowest hemoglobin A1C levels in all age groups. A1C levels were >7.5% in >70% of adolescents, regardless of regimen. CONCLUSIONS Youth using insulin pumps had the lowest A1C; A1C was unacceptably high in adolescents. There is a need to more fully assess and understand factors associated with insulin regimens recommended by providers and the influence of race/ethnicity, education, and socioeconomic status on these treatment recommendations and to develop more effective treatment strategies, particularly for adolescents.

Anastrozole Increases Predicted Adult Height of Short Adolescent Males Treated with Growth Hormone: A Randomized, Placebo-Controlled, Multicenter Trial for One to Three Years

CONTEXT The process of epiphyseal fusion during puberty is regulated by estrogen, even in males. OBJECTIVE Our objective was to investigate whether anastrozole, a potent aromatase inhibitor, could delay bone age acceleration and increase predicted adult height in adolescent boys with GH deficiency. METHODS Fifty-two adolescent males with GH deficiency treated with GH were randomized to cotreatment with anastrozole or placebo daily for up to 36 months. RESULTS Fifty subjects completed 12 months, 41 completed 24 months, and 28 completed 36 months. Linear growth was comparable between groups; however, there was a significantly slower increase in bone age advancement from baseline in the anastrozole group vs. placebo group after 2 yr (+1.8+/-0.1 vs. +2.7+/-0.1 yr, P<0.0001) and after 3 yr (+2.5+/-0.2 vs. +4.1+/-0.1 yr, P<0.0001). This resulted in a net increase in predicted adult height of +4.5+/-1.2 cm in the anastrozole group at 24 months and +6.7+/-1.4 cm at 36 months as compared with a 1-cm gain at both time points in the placebo group. Estradiol and estrone concentrations increased less in the anastrozole group compared with placebo group. All boys on the aromatase inhibitor had normal tempo of virilization. Safety data, including glucose, and plasma lipid concentrations were comparable between groups. CONCLUSIONS Anastrozole increases adult height potential of adolescent boys on GH therapy while maintaining normal pubertal progression after 2-3 yr. This treatment offers an alternative in promoting growth in GH-deficient boys in puberty. Long-term follow up is needed to elucidate fully the safety and efficacy of this approach.

Familial Short Stature Caused by Haploinsufficiency of the Insulin-Like Growth Factor I Receptor due to Nonsense-Mediated Messenger Ribonucleic Acid Decay

BACKGROUND IGF-I, essential for normal human growth in utero and postnatally, mediates its effects through the IGF-I receptor (IGF1R), a widely expressed, cell surface tyrosine kinase receptor. Five cases of heterozygous mutations in the IGF1R gene have been identified in patients with varying degrees of intrauterine and postnatal growth retardation. OBJECTIVE The objective of the study was the analysis of the IGF1R gene in a short-statured patient and his affected family members. PATIENT The male patient, with a height of -3.1 sd score (SDS; aged 12 yr), had normal circulating levels of GH binding protein, IGF-I, and IGF binding protein-3. His mother (-4.6 SDS), one of his siblings (-1.94 SDS), and several other maternal family members were also short statured. RESULTS The patient, his mother, and the short-statured sibling carry a novel heterozygous 19-nucleotide duplication within exon 18 of the IGF1R gene, which introduces a premature termination codon at codon 1106 of the IGF1R open reading frame on one allele. Analyses of the primary dermal fibroblasts derived from the patient and family members indicated that the IGF1R mRNA expressed from the mutant allele was degraded through the nonsense-mediated mRNA decay pathway, resulting in reduced amount of wild-type IGF1R protein and, subsequently, diminished activation of the IGF1R pathway. CONCLUSIONS The mutation results in haploinsufficiency of IGF1R protein due to nonsense-mediated mRNA decay and is associated with familial short stature.

Congenital sucrase-isomaltase deficiency presenting with failure to thrive, hypercalcemia, and nephrocalcinosis

BackgroundDisaccharide Intolerance Type I (Mendelian Interance in Man database: *222900) is a rare inborn error of metabolism resulting from mutation in sucrase-isomaltase (Enzyme Catalyzed 3.2.1.48). Usually, infants with SI deficiency come to attention because of chronic diarrhea and nutritional evidence of malabsorption.Case PresentationWe describe an atypical presentation of this disorder in a 10-month-old infant. In addition to chronic diarrhea, the child displayed severe and chronic hypercalcemia, the evaluation of which was negative. An apparently coincidental right orbital hemangioma was detected. Following identification of the SI deficiency, an appropriately sucrose-restricted, but normal calcium diet regimen was instituted which led to cessation of diarrhea, substantial weight gain, and resolution of hypercalcemia.ConclusionsThis case illustrates that, similar to congenital lactase deficiency (Mendelian Interance in Man database: *223000, Alactasia, Hereditary Disaccharide Intolerance Type II), hypercalcemia may complicate neonatal Sucrase-Isomaltase deficiency. Hypercalcemia in the presence of chronic diarrhea should suggest disaccharide intolerance in young infants.

Mediators of Psychological Adjustment in Children and Adolescents with Short Stature

Short stature is defined as growth below the fifth percentile for chronological age, or as height greater than 2 standard deviations (SDS) below the mean height for chronological age (1,2). Approximately 5 percent of all children (1.27 million) have significant short stature (SS) in the United States (2,3). Many posttreatment studies of children and adults treated for growth hormone deficiency (GHD) as children have shown these individuals to have poorer psychological and social adjustment than their normally developing peers (4-7). Higher unemployment rates (5), lower marriage rates (5), and increased incidents of psychiatric disorders and social phobia are reliably reported (7,8).

Effect of Acid-Phosphate Vs Neutral-Phosphate on Urine Acidity, Acid-Base Balance and Mineral Homeostasis in Children with Familial Hypophosphatemic Rickets (XLH)

Effect of Acid-Phosphate Vs Neutral-Phosphate on Urine Acidity, Acid-Base Balance and Mineral Homeostasis in Children with Familial Hypophosphatemic Rickets (XLH)

RECOMBINANT ERYTHROPOIETIN (rEPO) INDUCED ELEVATION IN GLYCOSYLATED HEMOGLOBIN (GHb) DUE TO INCREASED SYNTHESIS OF HEMOGLOBIN F (HgbF) IN END-STAGE RENAL DISEASE (ESRD). 2201

RECOMBINANT ERYTHROPOIETIN (rEPO) INDUCED ELEVATION IN GLYCOSYLATED HEMOGLOBIN (GHb) DUE TO INCREASED SYNTHESIS OF HEMOGLOBIN F (HgbF) IN END-STAGE RENAL DISEASE (ESRD). 2201