Diabetic Ketoacidosis at Onset of Type 1 Diabetes: Rates and Risk Factors Today to 15 Years Ago.

Diabetic ketoacidosis (DKA) is a serious, potentially lethal complication of type 1 diabetes mellitus that may be present at diagnosis. The aim of this study was to determine factors associated with presentation in DKA in new-onset youth and compare the rate of DKA and risk factors to a similar study 15 years prior. This study was a retrospective chart review of newly diagnosed patients with type 1 diabetes mellitus from 2010 to 2013. Of the 276 patients, 29% presented in DKA, compared with 38% 15 years prior (P < .002). Those with Medicaid, those misdiagnosed at initial encounter, and those not evaluated by a pediatrician initially were more likely to present in DKA (P = .002, P = .002, P < .001, respectively). The diagnosis of diabetes was not elicited in one third of patients who ultimately presented in DKA. Pediatricians should be reeducated to ask about polyuria and polydipsia in routine encounters. Furthermore, public awareness initiatives are needed to reduce late presentation in DKA.

Does initial dosing of levothyroxine in infants with congenital hypothyroidism lead to frequent dose adjustments secondary to iatrogenic hyperthyroidism on follow-up?

BACKGROUND: Congenital hypothyroidism (CH) is the most common preventable cause of intellectual disability. The recommended starting dose of levothyroxine (LT4) is between 10 and 15 µg/kg, an extremely wide range. We hypothesized that a sizable proportion of newborns treated for CH at the higher end of the dosage range become biochemically hyperthyroid at a follow-up visit. METHODS: This study is a retrospective chart review of infants with CH between 2002 and 2012. RESULTS: Of the 104 patients included in this analysis, the average age at diagnosis was 11 days and the average starting dose of LT4 was 12±2.5 µg/kg. At follow-up, 36.5% required a dose reduction because of iatrogenic hyperthyroxinemia, 51% required no dose adjustment and 12.5% required a dose increase due to an elevated thyroid stimulating hormone (TSH). The starting doses of LT4 for those requiring a dose reduction, those not requiring an adjustment and those requiring an increase in the dose were 13.2±2.4, 11.5±2.1 and 10.3±2.6 µg/kg/day, respectively (p≤0.0001). Of the 34% of infants treated with an initial dose of >12.5 µg/day, 57.1% required a dose reduction at follow-up, compared to 26.1% of those whose initial starting dose was ≤12.5 µg/kg/day (p=0.007). CONCLUSIONS: Following the guidelines for initiating therapy for CH, 36.5% of the infants required a dose reduction for iatrogenic hyperthyroxinemia. These infants received a higher dose of LT4 than the infants who either required no adjustment or required an increase in the dose. A narrower range for initial dosing in CH may be appropriate.

Prevalence and Determinants of True Thyroid Dysfunction Among Pediatric Referrals for Abnormal Thyroid Function Tests.

Background/Aims. Abnormalities in thyroid function tests (TFTs) are a common referral reason for pediatric endocrine evaluation. However, a sizable proportion of these laboratory abnormalities do not warrant therapy or endocrine follow-up. The objectives of this study were (a) to evaluate the prevalence of true thyroid dysfunction among pediatric endocrinology referrals for abnormal TFTs; (b) to identify the historical, clinical, and laboratory characteristics that predict decision to treat. Methods. This was a retrospective chart review of patients evaluated in pediatric endocrinology office during a weekly clinic designated for new referrals for abnormal TFTs in 2010. Results. A total of 230 patients were included in the study. Median age at referral was 12 years (range = 2-18); 56% were females. Routine screening was cited as the reason for performing TFTs by 33% patients. Majority was evaluated for hypothyroidism (n = 206). Elevated thyroid-stimulating hormone was the most common referral reason (n = 140). A total of 41 out of 206 patients were treated for hypothyroidism. Conclusions. Prevalence of hypothyroidism was 20%. Thyroid follow-up was not recommended for nearly one third of the patients. Among all the factors analyzed, an elevated thyroid-stimulating hormone level and antithyroglobulin antibodies strongly correlated with the decision to treat (P < .005).

Pediatric trainees' engagement in the online nutrition curriculum: preliminary results.

BACKGROUND: The Pediatric Nutrition Series (PNS) consists of ten online, interactive modules and supplementary educational materials that have utilized web-based multimedia technologies to offer nutrition education for pediatric trainees and practicing physicians. The purpose of the study was to evaluate pediatric trainees' engagement, knowledge acquisition, and satisfaction with nutrition modules delivered online in interactive and non-interactive formats. METHODS: From December 2010 through August 2011, pediatric trainees from seventy-three (73) different U.S. programs completed online nutrition modules designed to develop residents' knowledge of counseling around and management of nutritional issues in children. Data were analyzed using SPSS version 19. Both descriptive and inferential statistics were used in comparing interactive versus non-interactive modules. Pretest/posttest and module evaluations measured knowledge acquisition and satisfaction. RESULTS: Three hundred and twenty-two (322) pediatric trainees completed one or more of six modules for a total of four hundred and forty-two (442) accessions. All trainees who completed at least one module were included in the study. Two-way analyses of variance (ANOVA) with repeated measures (pre/posttest by interactive/non-interactive format) indicated significant knowledge gains from pretest to posttest (p < 0.002 for all six modules). Comparisons between interactive and non-interactive formats for Module 1 (N = 85 interactive, N = 95 non-interactive) and Module 5 (N = 5 interactive, N = 16 non-interactive) indicated a parallel improvement from the pretest to posttest, with the interactive format significantly higher than the non-interactive modules (p < .05). Both qualitative and quantitative data from module evaluations demonstrated that satisfaction with modules was high. However, there were lower ratings for whether learning objectives were met with Module 6 (p < 0.03) and lecturer rating (p < 0.004) compared to Module 1. Qualitative data also showed that completion of the interactive modules resulted in higher resident satisfaction. CONCLUSIONS: This initial assessment of the PNS modules shows that technology-mediated delivery of a nutrition curriculum in residency programs has great potential for providing rich learning environments for trainees while maintaining a high level of participant satisfaction.

Non-HDL-cholesterol in an adolescent diabetes population.

BACKGROUND: Screening for dyslipidemia poses some challenges. Nonfasting lipid profiles frequently have elevated triglycerides. In addition, in the standard lipid profile, low-density lipoprotein (LDL) cholesterol is a calculated value rather than a direct measurement and is triglyceride dependent. Non-high-density lipoprotein cholesterol (non-HDL-C) is an alternative method to assess for dyslipidemia and provides a single estimate of all atherogenic apolipoprotein B-containing lipoproteins. OBJECTIVE: To calculate the non-HDL-C in adolescents with diabetes and to evaluate risk factors associated with an elevated non-HDL-C and to compare the prevalence of dyslipidemia, defined by non-HDL-C, with the prevalence of dyslipidemia defined by LDL cholesterol in the SEARCH study. METHODS: Data were collected from 502 adolescent patients with diabetes and analyzed. Non-HDL-C was calculated and levels were categorized into normal, borderline, and high based on the National Cholesterol Education Program. RESULTS: Lipid profile was performed in 370 patients, 92% of whom had type 1 diabetes. In the 339 subjects with type 1 diabetes, mean hemoglobin A1c (HbA1c) of those with normal non-HDL-C (8.6%) was significantly lower than the HbA1c of those with high non-HDL-C (9.6%) (P = .005). Subjects with normal non-HDL-C had a lower body mass index (BMI) z-score (0.4 ± 0.8) than the group with borderline and high non-HDL-C (0.75 ± 0.9%), P = .002. In the 31 subjects with type 2 diabetes, the mean HbA1c of those with normal non-HDL-C (8.1%) and those with borderline non-HDL-C (7.0%) was significantly lower than the mean HbA1c of those with high non-HDL-C (11.8%) (P = .04, and P = .009, respectively). In addition, the subjects with normal non-HDL-C had a lower BMI z-score (1.3 ± 1.3) than the group with borderline and high non-HDL-C (2.2 ± 0.6%), P = .03. The prevalence of dyslipidemia using non-HDL-C was similar to prevalence rates using LDL-C in the SEARCH study. CONCLUSIONS: In adolescents with diabetes, non-HDL-C is increased with poorer diabetes control and higher BMI. It appears to be a superior nonfasting lipid screening test for adolescents with diabetes that can be readily calculated on a randomly obtained rather than fasting sample.

Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency.

Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation.

Pitfalls in the measurement of the nocturnal blood pressure dip in adolescents with type 1 diabetes.

OBJECTIVE: The purpose of this study was to screen adolescents with type 1 diabetes using ambulatory blood pressure monitoring (ABPM) to 1) test the hypothesis that using a preset sleep time results in an overdiagnosis of abnormal nocturnal dipping in systolic blood pressure and 2) assess the reproducibility of an abnormal nocturnal systolic blood pressure dip. RESEARCH DESIGN AND METHODS: For aim 1, ABPM from 53 adolescent patients with type 1 diabetes was reviewed. Nocturnal dips in systolic blood pressure calculated by actual sleep time were compared with those from a preset sleep time. For aim 2, blood pressure monitoring from 98 patients using actual reported sleep time was reviewed. Reproducibility of the nocturnal dip in systolic blood pressure was assessed in a subset of "nondippers." RESULTS: For aim 1, the actual mean +/- SE decline in nocturnal systolic blood pressure was 11.6 +/- 4.7%, whereas the mean decline in nocturnal systolic blood pressure calculated using the preset sleep time was 8.8 +/- 4.9% (P < 0.0001). For aim 2, 64% of patients had a normal nocturnal decline in systolic blood pressure (14.9 +/- 3.1% mmHg), whereas 36% had an abnormal dip (5.7 +/- 2.8% mmHg). Repeat ABPM performed in 22 of the 35 nondippers revealed that only 36% had abnormal systolic dipping confirmed on the repeat ABPM. CONCLUSIONS: The use of actual reported sleep time is required to accurately determine the nocturnal dip in systolic blood pressure. Repeating ABPM in nondippers is essential to confirm this abnormality.

Poor glycemic control is associated with abnormal changes in 24-hour ambulatory blood pressure in children and adolescents with type 1 diabetes mellitus.

INTRODUCTION: Twenty-four hour ambulatory blood pressure (ABPM) is emerging as a valuable tool to assess blood pressure (BP) changes in children with type 1 diabetes mellitus (DM1). Hypertension (HTN) is an important risk factor for, and may be an important indicator of diabetic nephropathy. Early accurate identification of HTN in DM1 may improve outcomes. AIM: To evaluate BP in adolescents with DM1 using 24-hour ABPM, and to identify risk factors associated with abnormal blood pressure. METHOD: The ABPM of 105 children with DM1 was reviewed. Mean systolic BP (sBP) percentile was determined from the National High Blood Pressure Education Program (NHBPEP) tables. The patients with abnormal sBP were compared to those with normal sBP with respect to age, race, sex, body mass index (BMI) percentile, duration of DM1, average hemoglobin A1c (HbA1c) over the preceding year, and family history of hypertension. RESULTS: Mean sBP was normal in 71%, whereas 23% had pre-hypertension, and 6% had stage 1 hypertension. Those who had abnormal sBP (pre-hypertension and stage 1 hypertension) had higher HbA1c (p = 0.023) and were more likely to be male (p = 0.03) than those with normal sBP. CONCLUSION: Stage 1 hypertension is present in 6%, and pre-hypertension in 23% of adolescents with DM1. Poor diabetes control and male gender appear to be risk factors for abnormal sBP as measured by 24-hour ambulatory blood pressure monitoring.

Impact on bone of an estrogen receptor-alpha gene loss of function mutation.

CONTEXT: The kindred described is the only known instance of a germ line loss of function mutation of estrogen receptor (ER)-alpha. OBJECTIVE: Our objective was to assess the impact of a loss of function mutation in the ER-alpha gene on histomorphometry, bone volumetric density, bone geometry and skeletal growth, and ER-alpha heterozygosity on spine density and adult height in an extended pedigree. DESIGN AND PARTICIPANTS: A longitudinal follow-up of the propositus with homozygous loss of function mutation of ER-alpha and single contact evaluation of the kindred were performed. MAIN OUTCOME MEASURES: Iliac crest bone biopsy and peripheral quantitative computed tomography of propositus with serial measures of areal spine bone mineral density (aBMD) by dual-energy x-ray absorptiometry and bone age were performed. Members of pedigree were evaluated for ER-alpha mutation carrier status and spine aBMD. RESULTS: Bone biopsy revealed marked osteopenia (cortex: 641 microm), low trabecular volume (10.6%), decreased thickness (76.2 microm), normal trabecular number, and low activation frequency (0.099/yr). Radial periosteal circumference was similar, endosteal circumference larger, and trabecular and cortical volumetric bone mineral density markedly lower (158 and 1092 mg/cm(3), respectively) than controls. Spine aBMD at age 28.5 yr (0.745 g/cm(2)) decreased to 0.684 g/cm(2) (Z score -3.85) in 3.5 yr. Bone age advanced from 15-17.5 yr. Kindred analysis revealed that gene carriers had spine aBMD Z scores less than zero (P = 0.003), but carriers and nonmutant members were similar (-0.84 +/- 0.26 vs. -0.64 +/- 0.16). CONCLUSION: Homozygous ER-alpha disruption markedly affects bone growth, mineral content, and structure but not periosteal circumference. ER-alpha heterozygosity appears to not impair spine aBMD.

Twenty-four hour ambulatory blood pressure monitoring in adolescents with type 1 diabetes: getting started.

Twenty-four hour ambulatory blood pressure monitoring (ABPM) is a valuable tool in the pediatric and adolescent population with type 1 diabetes. It provides useful information not readily available from sporadic clinic blood pressure (BP) measurements and a more reliable estimation of the subject's BP over an extended period of time. Ambulatory blood pressure monitoring is gaining popularity with clinicians and investigators alike. The American Heart Association has recently issued recommendations for the use of ABPM in children and adolescents. We have incorporated ABPM into our adolescent diabetes practice and present useful information for clinicians planning to initiate 24 h ABPM in their clinical practice.

Safety of medications and hormones used in pediatric endocrinology: adrenal.

Glucocorticoids have been prescribed for several decades in treating adrenal insufficiency of various etiologies. These drugs are also heavily used in treating non-endocrine disease. This article will focus on adverse side effects encountered in the chronic use of different types of glucocorticoids in children and young adults with endocrine causes of adrenal insufficiency. Dosing guidelines are discussed with a view toward minimizing the common co-morbidities of growth suppression, excess weight gain, and osteopenia, among others. This article also discusses the use of several inhibitors of adrenal steroid biosynthesis and one glucocorticoid receptor antagonist for the medical treatment of Cushing syndrome.

Identifying risk factors for the development of diabetic ketoacidosis in new onset type 1 diabetes mellitus.

To identify risk factors associated with the development of diabetic ketoacidosis (DKA) in new-onset type 1 diabetes mellitus, a retrospective chart review of 139 new onset type 1 diabetes patients from 1995 to 1998 was conducted. Categorical data were examined with contingency table analysis. Age range was 0.5 to 18 years. Overall, 38% of the patients presented in DKA. Sixty-two percent of the patients with either Medicaid or no insurance presented in DKA compared to 34% of the patients with private insurance, odds ratio 3.17 (92% CI 1.2-8.3) p = 0.03. Sixty-eight percent of patients in whom the diagnosis was missed (n = 25) presented in DKA (mean age, 5.4 +/- 4.4 years) compared to 32% in whom the diagnosis was not missed (mean age, 8.8 +/- 4.0 years) odds ratio 4.6 (95% CI 1.9-11.7), p = 0.0012; age p = 0.00019. Lack of private insurance, although a risk factor for the development of DKA, did not increase the likelihood of a missed diagnosis. Lack of private insurance (a proxy for socioeconomic status) and young age are apparent risk factors for the development of ketoacidosis. Misdiagnosis by the physician at initial patient encounter is especially prevalent in the young child but not related to insurance. Both increased public awareness and greater medical alertness are necessary to reduce the high rates of DKA in new-onset type 1 diabetic children.

Role of estrogen and androgen in pubertal skeletal physiology.

Since both estrogen and androgen are present in each sex, it has been difficult to discern the exact role that each sex steroid plays in skeletal physiology. However, studying clinical syndromes in which there is either only estrogen or androgen action has allowed us to gain insight into the unique role that each sex steroid plays in the growing skeleton. In complete androgen insensitivity syndrome (AIS) the only functional sex steroid receptor is that for estrogen. Effected XY females have a pubertal growth spurt that is typical of normal females, both in magnitude and timing. Individuals with AIS have a mild reduction in bone density but it is difficult to distinguish whether this is the result of androgen resistance or estrogen deficiency. These observations suggest that estrogen action only is sufficient to induce a normal pubertal growth spurt, epiphyseal maturation, and near normal bone mineral accretion in women. Until recently, the skeletal effects of estrogen were not thought to be of importance in the male. Conventional wisdom dictated that, in the male, testosterone mediated these skeletal changes. The notion that estrogen is of little importance in the male has been challenged by the recent discovery of two human syndromes in which estrogen action is lacking. In males with either estrogen resistance (inability to respond to circulating estrogen) or aromatase deficiency (inability to synthesize estradiol), as a result of the lack of estrogen action, a pubertal growth spurt does not appear to occur. Furthermore, complete epiphyseal maturation does not take place allowing for continued growth in adulthood and resultant tall stature. Finally normal bone mineral accretion does not take place resulting in severe osteoporosis. These findings indicate that estrogen plays a critical role in skeletal physiology of males as well as females.

Reversibility of growth stunting in early onset anorexia nervosa: a prospective study.

PURPOSE: To evaluate the growth of premenarchal patients with anorexia nervosa. METHODS: Growth parameters were measured semi-annually in 16 subjects with anorexia nervosa until 1 year post-menarche. RESULTS: Despite the accelerated growth that followed nutritional rehabilitation, the patients did not achieve their genetic height potential.