T Follicular Helper Cell-Dependent Clearance of a Persistent Virus Infection Requires T Cell Expression of the Histone Demethylase UTX.

Epigenetic changes, including histone methylation, control T cell differentiation and memory formation, though the enzymes that mediate these processes are not clear. We show that UTX, a histone H3 lysine 27 (H3K27) demethylase, supports T follicular helper (Tfh) cell responses that are essential for B cell antibody generation and the resolution of chronic viral infections. Mice with a T cell-specific UTX deletion had fewer Tfh cells, reduced germinal center responses, lacked virus-specific immunoglobulin G (IgG), and were unable to resolve chronic lymphocytic choriomeningitis virus infections. UTX-deficient T cells showed decreased expression of interleukin-6 receptor-α and other Tfh cell-related genes that were associated with increased H3K27 methylation. Additionally, Turner Syndrome subjects, who are predisposed to chronic ear infections, had reduced UTX expression in immune cells and decreased circulating CD4(+) CXCR5(+) T cell frequency. Thus, we identify a critical link between UTX in T cells and immunity to infection.

Cleft palate and hypopituitarism in a patient with Noonan-like syndrome with loose anagen hair-1.

Noonan syndrome (NS), the most common of the RASopathies, is a developmental disorder caused by heterozygous germline mutations in genes encoding proteins in the RAS-MAPK signaling pathway. Noonan-like syndrome with loose anagen hair (NSLH, including NSLH1, OMIM #607721 and NSLH2, OMIM #617506) is characterized by typical features of NS with additional findings of macrocephaly, loose anagen hair, growth hormone deficiency in some, and a higher incidence of intellectual disability. All NSLH1 reported cases to date have had an SHOC2 c.4A>G, p.Ser2Gly mutation; NSLH2 cases have been reported with a PPP1CB c.146G>C, p.Pro49Arg mutation, or c.166G>C, p.Ala56Pro mutation. True cleft palate does not appear to have been previously reported in individuals with NS or with NSLH. While some patients with NS have had growth hormone deficiency (GHD), other endocrine abnormalities are only rarely documented. We present a female patient with NSLH1 who was born with a posterior cleft palate, micrognathia, and mild hypotonia. Other findings in her childhood and young adulthood years include hearing loss, strabismus, and hypopituitarism with growth hormone, thyroid stimulating hormone (TSH), and gonadotropin deficiencies. The SHOC2 mutation may be responsible for this patient's additional features of cleft palate and hypopituitarism.

Growth hormone therapy in Turner syndrome.

Short stature is the single most common physical abnormality in Turner syndrome (TS) with adult stature averaging 20 cm shorter than that of the general population. Randomized, placebo-controlled studies to final adult height have proven that GH therapy is effective in increasing stature in TS. Recently, randomized, controlled studies have demonstrated that adjunctive therapies with low-dose estrogen or low-dose oxandrolone enhance stature further. These therapies may provide benefits beyond height augmentation.

Prevention of Growth Failure in Turner Syndrome: Long-Term Results of Early Growth Hormone Treatment in the "Toddler Turner" Cohort.

INTRODUCTION: In the randomized "Toddler Turner" study, girls who received growth hormone (GH) starting at ages 9 months to 4 years (early-treated [ET] group) had marked catch-up growth and were 1.6 ± 0.6 SD taller than untreated (early-untreated [EUT]) control girls after 2 years. However, whether the early catch-up growth would result in greater near-adult height (NAH) was unknown. Therefore, this extension study examined the long-term effects of toddler-age GH treatment on height, pubertal development, and safety parameters. METHODS: Toddler Turner study participants were invited to enroll in a 10-year observational extension study for annual assessments of growth, pubertal status, and safety during long-term GH treatment to NAH for both ET and EUT groups. RESULTS: The ET group was taller than the EUT group at all time points from preschool to maturity and was significantly taller at the onset of puberty (p = 0.016), however, the difference was not significant at NAH. For the full cohort (ET + EUT combined, n = 50) mean (± SD) NAH was 151.2 ± 7.1 cm at age 15.0 ± 1.3 years. NAH standard deviation score (SDS) was within the normal range (>-2.0) for 76% of ET and 60% of EUT subjects (68% overall) and correlated strongly with height SDS at GH start (r = 0.78; p < 0.01), which in turn had a modest inverse correlation with age at GH start (i.e., height SDS declined with increasing age in untreated girls [r = -0.30; p = 0.016]). No new safety concerns arose. CONCLUSION: Although the ET group was taller throughout, height SDS at NAH was not significantly different between groups due to catch-down growth of ET girls during lapses in GH treatment after the Toddler study and similar long-term GH exposure overall. Early initiation of GH by age 6 years, followed by uninterrupted treatment during childhood, can prevent ongoing growth failure and enable attainment of height within the normal range during childhood, adolescence, and adulthood.

Turner syndrome: language profile of young girls at 12 and 24 months of age.

BACKGROUND: Turner syndrome (TS) is a genetic disorder associated with complete or partial absence of an X chromosome affecting approximately 1/2000 live female births. Available evidence suggests that, in the school-age years, girls with TS often require speech and language services; however, little is known about the language development of infants and toddlers. METHOD: This study (N = 31) explored the language profiles of 12- and 24-month-old girls with TS, as well as the percentage of girls who might be "at risk" for language delays. We also followed a subset of 12-month-old girls with TS to 24 months of age to determine the stability of the 12-month findings. RESULTS: Although all mean scores were within the average range at both time points, results revealed a higher prevalence of 24-month-old girls with TS "at risk" for receptive language difficulties. In addition, expressive language skills significantly exceeded receptive language skills at both time points. We found 12-month-old girls to be "at risk" for social and symbolic difficulties based on clinical assessment; only symbolic difficulties were significant based on caregiver report. At 24 months, clinical assessment indicated greater use of speech sounds and words than normative expectations. Caregivers reported greater use of speech sounds, and also, greater use of gestures. Although some changes occurred over a 1-year time span (12 to 24 months), all mean test scores remained within the average range and the changes in the percentage of girls manifesting "at risk" status on either the PLS-4 or CSBS-DP were non-significant. CONCLUSIONS: Although within normal limits, receptive language skills were found to be significantly lower than expressive language skills at both ages. Social and symbolic communication skills also were in the average range, with both showing significant improvement from 12 to 24 months based on clinical assessment. Caregiver report found that use of gestures and production of speech sounds not only improved from 12 to 24 months, but also exceeded normative expectations. Findings suggest the presence of relatively intact speech and language abilities during the first 2 years of life, with perhaps some emergent concerns for receptive language development. Ongoing developmental surveillance will be important.

Early Development of Infants with Turner Syndrome.

OBJECTIVE: To examine the early cognitive, temperament, and adaptive functioning of infants and toddlers with Turner syndrome (TS). METHODS: Cognitive abilities were measured using the Mullen Scales of Early Learning at 1 year of age for 31 girls with TS and compared with neurotypical female (N = 53) and male (N = 54) control groups. Temperament (Carey Toddler Temperament Scales) and adaptive functioning (Vineland Adaptive Behavior Scales-Second Edition) were measured at 1 year of age and compared with normative data. An exploratory analysis of cognitive/developmental trajectories was also conducted comparing age 12-month to 24-month time points for 22 TS subjects. RESULTS: Infants with TS performed largely within the average range for adaptive behavior, temperament, and early cognitive development with some increased risk for delays in language and significant increased risk for delays in motor skills (p < 0.001). Although exploratory, there was some suggestion of slower rates of progression in fine-motor and visual reception skills from 12 to 24 months of age. CONCLUSIONS: Infants and toddlers with TS exhibit a relatively positive neurodevelopmental profile overall, with some indication of an increasing gap in function in fine-motor and visual perceptual abilities as compared to neurotypical peers. It is unclear whether these apparent differences represent normal variability in this very young population or, perhaps, are early precursors of later phenotypic characteristics of TS in the school-age and young adult years.

Moving toward an understanding of hormone replacement therapy in adolescent girls: looking through the lens of Turner syndrome.

Turner syndrome (TS) is a relatively common disorder of phenotypic females caused by loss of all or part of the second sex chromosome. Most individuals with TS have short stature and gonadal dysgenesis and are at risk for many other medical and learning problems. In the 45,X ovary, germs cells multiply quite normally during fetal development, but there is accelerated atresia of oocytes in the second half of pregnancy that produces gonadal insufficiency by birth. In girls with other karyotypes, especially those mosaic for 45,X/46,XX, gonadal function may be normal or near-normal. In this chapter, management goals for gonadal insufficiency in girls with TS are presented. The effects of estrogen deficiency and its replacement on three specific problems associated with TS-short stature, cardiovascular disease, and developmental differences in brain structure and function-are explored. General guidelines for estrogen replacement therapy using transdermal estrogen, the most physiologic option, are provided and future research goals are outlined.

Growth hormone treatment of early growth failure in toddlers with Turner syndrome: a randomized, controlled, multicenter trial.

CONTEXT: Typically, growth failure in Turner syndrome (TS) begins prenatally, and height sd score (SDS) declines progressively from birth. OBJECTIVE: This study aimed to determine whether GH treatment initiated before 4 yr of age in girls with TS could prevent subsequent growth failure. Secondary objectives were to identify factors associated with treatment response, to determine whether outcome could be predicted by a regression model using these factors, and to assess the safety of GH treatment in this young cohort. DESIGN: This study was a prospective, randomized, controlled, open-label, multicenter clinical trial (Toddler Turner Study, August 1999 to August 2003). SETTING: The study was conducted at 11 U.S. pediatric endocrine centers. SUBJECTS: Eighty-eight girls with TS, aged 9 months to 4 yr, were enrolled. INTERVENTIONS: Interventions comprised recombinant GH (50 mug/kg.d; n = 45) or no treatment (n = 43) for 2 yr. MAIN OUTCOME MEASURE: The main outcome measure was baseline-to-2-yr change in height SDS. RESULTS: Short stature was evident at baseline (mean length/height SDS = -1.6 +/- 1.0 at mean age 24.0 +/- 12.1 months). Mean height SDS increased in the GH group from -1.4 +/- 1.0 to -0.3 +/- 1.1 (1.1 SDS gain), whereas it decreased in the control group from -1.8 +/- 1.1 to -2.2 +/- 1.2 (0.5 SDS decline), resulting in a 2-yr between-group difference of 1.6 +/- 0.6 SDS (P < 0.0001). The baseline variable that correlated most strongly with 2-yr height gain was the difference between mid-parental height SDS and subjects' height SDS (r = 0.32; P = 0.04). Although attained height SDS at 2 yr could be predicted with good accuracy using baseline variables alone (R(2) = 0.81; P < 0.0001), prediction of 2-yr change in height SDS required inclusion of initial treatment response data (4-month or 1-yr height velocity) in the model (R(2) = 0.54; P < 0.0001). No new or unexpected safety signals associated with GH treatment were detected. CONCLUSION: Early GH treatment can correct growth failure and normalize height in infants and toddlers with TS.

Visuospatial executive function in Turner syndrome: functional MRI and neurocognitive findings.

Turner syndrome is a genetic disorder that results from an abnormal or missing X chromosome in females and is typically associated with impairments in visuospatial, but not verbal, information processing. These visuospatial processing impairments may be exacerbated with increased task demands, such as those engaged during working memory (WM). While previous studies have examined spatial WM function in Turner syndrome, none have directly compared the neural correlates of spatial and verbal WM processes across the encoding, maintenance and retrieval phases. We employed both neurocognitive assessments and functional MRI (fMRI) to examine the neural circuitry underlying both verbal and visuospatial WM functions in individuals with Turner syndrome and normal controls. We furthermore examined the vulnerability of task-related fMRI activation to distracters presented during WM maintenance. Fifteen healthy female volunteers and eight individuals with Turner syndrome performed a delayed-response WM task during fMRI scanning. Neurocognitive tests revealed impaired performance across both verbal and spatial domains in Turner syndrome, with greater impairment on tasks with WM demands. Frontoparietal regions in controls showed significantly sustained levels of activation during visuospatial WM. This sustained activation was significantly reduced in the group with Turner syndrome. Domain-specific activation of temporal regions, in contrast, did not differ between the two groups. Sensory distraction during the WM maintenance phase did not differentially alter frontoparietal activation between the two groups. The results reveal impaired frontoparietal circuitry recruitment during visuospatial executive processing in Turner syndrome, suggesting a significant role for the X chromosome in the development of these pathways.

Differences in follicle-stimulating hormone secretion between 45,X monosomy Turner syndrome and 45,X/46,XX mosaicism are evident at an early age.

CONTEXT: Little information exists regarding FSH values in very young girls with Turner syndrome (TS). OBJECTIVES: The objective of the study was to evaluate the pattern, natural progression, and karyotype-related differences in FSH secretion in young, prepubertal girls with TS. STUDY DESIGN: FSH was measured at study entry and annually for 2 yr. SETTING: The Toddler Turner study was conducted at 11 U.S. pediatric endocrine centers. STUDY PARTICIPANTS: Eighty-eight girls with karyotype-proven TS aged 9 months to 4 yr participated in the study. MAIN OUTCOME MEASURES: By-karyotype differences in FSH concentration and age-related changes in FSH were measured. RESULTS: Mean (+/- SD) FSH was markedly elevated in the 45,X (n = 56: 68.3 +/- 36.0 IU/liter) and Other groups [n = 15 (excluding three subjects with Y-containing karyotypes): 52.7 +/- 50.8 IU/liter] but was minimally elevated in girls with 45,X/46,XX mosaicism (n = 14: 10.1 +/- 13.5 IU/liter, P < 0.005 both comparisons). Over the 2-yr period, FSH declined in the 45,X group (-13.4 IU/liter.yr, P < 0.0001). Nonetheless, only three of 159 FSH values fell within normal range for age at any time during the 2-yr study. FSH decline was similar in the Other group (-14.3 IU/liter.yr, P = 0.0032). In contrast, no significant decrease in FSH with age was observed in the 45,X/46,XX group. CONCLUSIONS: In contrast to the original report of FSH concentrations in individuals with TS, this study demonstrates distinct differences in patterns of FSH secretion between young girls with monosomy TS, who have persistent elevation of FSH to age 6 yr, and those with 45,X/46,XX mosaicism, whose FSH values suggest retained ovarian function in the majority. These findings have implications for patient management and family counseling.

Evidence for early initiation of growth hormone and transdermal estradiol therapies in girls with Turner syndrome.

Results from the first randomized, controlled trial of growth hormone (GH) therapy in girls with Turner syndrome (TS) followed to final height firmly establish that GH increases final adult stature. It is widely believed that the efficacy of GH is dependent upon the duration of therapy and dosing (longer duration and higher dose give taller final height). In a recent observational study involving more than 1500 French girls with TS, multivariate analyses demonstrated that the age at initiation of GH therapy accounted for a large percentage of the variance (44%) in response. Age at initiation of estrogen therapy was the second most important factor in determining GH effect (later initiation, taller final height), accounting for 22% of the variance. Overall, 0.3 cm in adult height was gained for every year that estrogen therapy was delayed. However, analyses of the French data restricted to patients with induced puberty revealed that those treated with percutaneous estradiol attained a height 2.1cm taller than those using oral estradiol or other estrogen preparations. In another study, girls receiving GH therapy (n=14) who were randomized to receive intramuscular (IM) depot estradiol early (12.0-12.9 years) attained at least as much height as those who initiated it late (14.0-14.9 years). These results are consistent with the observations in adult women that oral estrogens decrease IGF-I serum levels and suppress the IGF-independent metabolic effects of GH, while transdermal estrogens do not. Taken together, these studies suggest that girls with TS should begin GH therapy as soon as growth failure is demonstrated and that puberty should be induced with transdermal or IM estradiol. Girls for whom height is normalized with GH therapy in early childhood have the opportunity to undergo puberty at an age-appropriate time and still achieve a normal adult stature.

Central obesity, the metabolic syndrome, and plasminogen activator inhibitor-1 in young adults.

PURPOSE: To determine the association of central obesity with the components of the metabolic syndrome (i.e., hyperinsulinemia, hypertension, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol [HDL-C]) and plasma levels of plasminogen activator inhibitor-1 (PAI-1) in young adults. We hypothesized that central obesity as determined by waist circumference would be predictive of components of the metabolic syndrome and of PAI-1. DATA SOURCES: Participants in this descriptive study consisted of 85 healthy young adults aged 19-22 years, 62% women who fasted for 12 h prior to data collection in the General Clinical Research Center at a major university hospital medical center in the southeastern United States. CONCLUSIONS: The majority of the participants had one or more components of the metabolic syndrome (n= 43, 51%). Central obesity was present in 14.1% and was more common in women than men (chi(2)= 5.11; p= 0.021). Central obesity was significantly and positively correlated with elevated blood pressure (BP) and levels of insulin and PAI-1 while being negatively correlated with HDL-C. In multiple regression analyses, diastolic BP, insulin, and HDL-C were predictors of waist circumference (R(2)= 0.615). In a separate multiple regression, PAI-1 was predicted by waist circumference (R(2)= 0.331). IMPLICATIONS FOR PRACTICE: Many otherwise healthy young adults have one or more components of the metabolic syndrome. Assessment and institution of preventative measures for obesity and the components of the metabolic syndrome should begin in childhood. Furthermore, determination of waist circumference especially in young women may aid the practitioner to identify those at risk for the metabolic syndrome earlier in their disease trajectory. Furthermore, insulin resistance is believed to occur initially in the trajectory of the metabolic syndrome, making it a principal contender for suitable interventions to reduce risk for both type 2 diabetes and cardiovascular disease (CVD). Homeostatic model assessment for insulin resistance was used to assess for insulin resistance among the euglycemic participants. Recording the presence of insulin resistance will aid the practitioner in determining if a low-risk patient is in peril for development of type 2 diabetes and/or CVD. Early cardiovascular risk recognition is vital to clinical practice as it allows more time for the practitioner to counsel patients for the essential planning needed to make lifestyle changes.

Prevalence of pilomatricoma in Turner syndrome: findings from a multicenter study.

IMPORTANCE: The absence of data on the prevalence of pilomatricoma among patients with Turner syndrome served as the catalyst for this multicenter investigation. OBJECTIVES: To ascertain the prevalence of pilomatricoma among patients with Turner syndrome and to determine any association between the development of pilomatricomas and the use of exogenous hormones in patients with Turner syndrome. DESIGN: A retrospective medical record review from January 1, 2000, through January 1, 2010, was performed of all patients with Turner syndrome. Data on pilomatricomas and the use of hormone therapy were collected. SETTING: University of California-Davis Medical Center, University of Nebraska Medical Center, and The University of North Carolina at Chapel Hill. PARTICIPANTS: Patients with a diagnosis of Turner syndrome. MAIN OUTCOME MEASURES: Prevalence of concomitant pilomatricoma and diagnosis of Turner syndrome. Secondary outcome measures included the use of the exogenous hormones estrogen or recombinant human growth hormone (rhGH). RESULTS: In total, 311 patients with Turner syndrome were identified from these 3 institutions. Among them, 8 patients (2.6%) were diagnosed as having pilomatricomas. Before the development of pilomatricomas, 5 patients had been treated with rhGH but not estrogen, 1 patient had received estrogen but not rhGH, and 2 patients did not receive either therapy. CONCLUSIONS AND RELEVANCE: Although the prevalence of pilomatricoma among the general population is unknown, this study demonstrates a high prevalence (2.6%) of pilomatricomas among patients with Turner syndrome. No apparent relationship was noted among our patients or in the literature between the use of rhGH and the development of pilomatricomas.

Approach to the patient with Turner syndrome.

Turner syndrome (TS) occurs in about 1:4000 live births and describes females with a broad constellation of problems associated with loss of an entire sex chromosome or a portion of the X chromosome containing the tip of its short arm. TS is associated with an astounding array of potential abnormalities, most of them thought to be caused by haploinsufficiency of genes that are normally expressed by both X chromosomes. A health care checklist is provided that suggests screening tests at specific ages and intervals for problems such as strabismus, hearing loss, and autoimmune thyroid disease. Four areas of major concern in TS are discussed: growth failure, cardiovascular disease, gonadal failure, and learning disabilities. GH therapy should generally begin as soon as growth failure occurs, allowing for rapid normalization of height. Cardiac imaging, preferably magnetic resonance imaging, should be performed at diagnosis and repeated at 5- to 10-yr intervals to assess for congenital heart abnormalities and the emergence of aortic dilatation, a precursor to aortic dissection. Hypertension should be aggressively treated. For those with gonadal dysgenesis, hormonal replacement therapy should begin at a normal pubertal age and be continued until the age of 50 yr. Transdermal estradiol provides the most physiological replacement. Finally, nonverbal learning disabilities marked by deficits in visual-spatial-organizational skills, complex psychomotor skills, and social skills are common in TS. Neuropsychological testing should be routine and families given support in obtaining appropriate therapy, including special accommodations at school.

Growth hormone treatment does not affect incidences of middle ear disease or hearing loss in infants and toddlers with Turner syndrome.

CONTEXT: No randomized, controlled, prospective study has evaluated the effect of growth hormone (GH) on the rates of middle ear (ME) disease and hearing loss in girls with Turner syndrome (TS). DESIGN: A 2-year, prospective, randomized, controlled, open-label, multicenter, clinical trial ('Toddler Turner Study'; August 1999 to August 2003) was carried out. SETTING: The study was conducted at 11 US pediatric endocrine centers. SUBJECTS: Eighty-eight girls with TS, aged 9 months to 4 years, were enrolled. INTERVENTION: The interventions comprised recombinant GH (50 microg/kg/day, n = 45) or no treatment (n = 43) for 2 years. MAIN OUTCOME MEASURES: The outcome measures included occurrence rates of ear-related problems, otitis media (OM) and associated antibiotic treatments, tympanometric assessment of ME function and hearing assessment by audiology. RESULTS: At baseline, 57% of the girls (mean age = 1.98 +/- 1.00 years) had a history of recurrent OM, 33% had undergone tympanostomy tube (t-tube) insertion and 27% had abnormal hearing. There was no significant difference between the treatment groups for annual incidence of OM episodes (untreated control: 1.9 +/- 1.4; GH-treated: 1.5 +/- 1.6, p = 0.17). A quarter of the subjects underwent ear surgeries (mainly t-tube insertions) during the study. Recurrent or persistent abnormality of ME function on tympanometry was present in 28-45% of the girls without t-tubes at the 6 postbaseline visits. Hearing deficits were found in 19-32% of the girls at the annual postbaseline visits. Most of these were conductive deficits, however, 2 girls had findings consistent with sensorineural hearing loss, which was evident before 3 years of age. CONCLUSIONS: Ear and hearing problems are common in infants and toddlers with TS and are not significantly influenced by GH treatment. Girls with TS need early, regular and thorough ME monitoring by their primary care provider and/or otolaryngologist, and at least annual hearing evaluations by a pediatric audiologist.

Gonadotropin secretion in girls with turner syndrome measured by an ultrasensitive immunochemiluminometric assay.

BACKGROUND/AIM: Gonadotropin levels measured by radioimmunoassays are high in girls with Turner syndrome (TS), but overlap significantly with those of normal girls. We hypothesized that gonadotropin levels would be above the normal range in TS when measured by ultrasensitive assays. METHODS: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured in 68 TS, and 133 control girls using ultrasensitive immunochemiluminometric assays (ICMA). RESULTS: FSH levels in TS and normal girls were highest in early childhood (56.0 +/- 39.7 and 2.3 +/- 1.8 IU/l, respectively), declined at 6-10 years of age (11.3 +/- 13.1 and 1.8 +/- 0.9 IU/l, respectively), and then increased again (104.4 +/- 68.9 and 4.9 +/- 2.4 IU/l, respectively). FSH was in the normal range on 11 of 27 occasions in TS girls with ages 5-10 years, and on 3 of 44 occasions in >10 years. Although average LH values were higher than those of controls, they often overlapped the normal range. CONCLUSION: A significant number of TS girls have normal gonadotropins by ICMA. Spontaneous gonadotropin levels are not an adequate screening test for the diagnosis of TS but may prove useful for predicting the gonadal function and determining the appropriate timing of estrogen replacement therapy.

Continuous subcutaneous glucose monitoring in children with type 1 diabetes mellitus: a single-blind, randomized, controlled trial.

BACKGROUND: Tight glycemic control delays the long-term complications of type 1 diabetes mellitus (T1DM) but increases the risk for hypoglycemia. The continuous glucose-monitoring system (CGMS) provides blood glucose (BG) readings every 5 min, and its accuracy and reliability has been established in adults. However, there are limited data on its efficacy and safety in children. The purpose of this study was to determine if CGMS use improves metabolic control in children with T1DM. METHODS: Twenty-seven children (12 male) with T1DM participated in this single-blind, randomized, controlled trial. Participants (age: 11.4 +/- 3.7 (mean +/- SD) yr, range: 7-17 yr) were randomized to an intervention group (n = 18) or a control group (n = 9). Both groups wore the CGMS for 72-h periods at 0, 2, and 4 months. Adjustments in therapy for the intervention group were based on both CGMS and self-monitoring of BG (SMBG) data, while only SMBG data were used for the control group. Hemoglobin A1c (HbA1c) was determined at 0, 2, 4, and 6 months. The change in HbA1c from 0 to 6 months (HbA1c(Delta1-4)) and mean daily area under the CGMS curve for glucose <70 mg/dL area under the curve (AUC(<70)) were compared between groups. RESULTS: At study entry, HbA1c levels were similar in the intervention and control groups (8.4 +/- 0.98 and 8.8 +/- 0.86%, respectively; p = 0.12) but were significantly lower in the intervention group compared with the control group at study completion (7.8 +/- 0.88 and 8.6 +/- 0.95%, respectively; p = 0.02). The decrease in HbA1c of 0.61 +/- 0.68% in the intervention group was statistically significant (p = 0.03), whereas the decrease in HbA1c of 0.28 +/- 0.78% in the control group was not. Nonetheless, the differences in HbA1c(Delta1-4) between groups did not reach statistical significance (p = 0.13). There was no statistically significant difference in AUC(<70) between study groups (p = 0.18). CONCLUSION: CGMS use may improve metabolic control in children with T1DM without increasing the risk for hypoglycemia.

Health supervision for children with Turner syndrome.

This report is designed to assist the pediatrician in caring for the child in whom the diagnosis of Turner syndrome has been confirmed by karyotyping. The report is meant to serve as a supplement to the American Academy of Pediatrics' "Recommendations for Preventive Pediatric Care" and emphasizes the importance of continuity of care and the need to avoid its fragmentation by ensuring a medical home for every girl with Turner syndrome. The pediatrician's first contact with a child with Turner syndrome may occur during infancy or childhood. This report also discusses interactions with expectant parents who have been given the prenatal diagnosis of Turner syndrome and have been referred for advice.