An Automated Risk Index for Diabetic Ketoacidosis in Pediatric Patients With Type 1 Diabetes: The RI-DKA.

Identifying patients at high risk for diabetic ketoacidosis (DKA) is crucial for informing efforts at preventive intervention. This study sought to develop and validate an electronic medical record (EMR)-based tool for predicting DKA risk in pediatric patients with type 1 diabetes. Based on analysis of data from 1,864 patients with type 1 diabetes, three factors emerged as significant predictors of DKA: most recent A1C, type of health insurance (public vs. private), and prior DKA. A prediction model was developed based on these factors and tested to identify and categorize patients at low, moderate, and high risk for experiencing DKA within the next year. This work demonstrates that risk for DKA can be predicted using a simple model that can be automatically derived from variables in the EMR.

A Comprehensive System for Identifying Patients With Type 1 Diabetes at Increased Risk for Diabetic Ketoacidosis at Texas Children's Hospital.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes a project at Texas Children's Hospital aimed at improving identification of patients with type 1 diabetes at high risk for diabetic ketoacidosis.

Patient and Caregiver Attitudes toward Disorders of Sex Development Nomenclature.

PURPOSE: The medical terminology applied to differences/disorders of sex development has been viewed negatively by some affected individuals. A clinical population of patients with differences/disorders of sex development and their caregivers were surveyed regarding current nomenclature, hypothesizing that those unaffiliated with support groups would have more favorable attitudes. MATERIALS AND METHODS: We recruited English and Spanish speaking patients 13 years old or older with differences/disorders of sex development and their caregivers at 5 national tertiary care clinics from July 2016 to December 2018. No diagnoses were excluded. Participants completed a survey rating terminology commonly applied to differences/disorders of sex development. Responses were compared between subgroups, including members vs nonmembers of a support group. RESULTS: Of 185 potential participants approached 133 completed the survey (72% response rate). Congenital adrenal hyperplasia (33%) was the most common diagnosis. "Variation of sex development" was the most liked term (37%) but was not liked more significantly than "disorders of sex development" (27%, p=0.16). No term was liked by a majority of respondents. "Disorders of sex development" (37%) and "intersex" (53%) were the only terms most frequently viewed unfavorably. Support group members were significantly more likely to dislike the term "intersex" (p=0.02) and to like "variation of sex development" (p=0.02). CONCLUSIONS: A clinical population of patients and their caregivers had generally neutral attitudes toward nomenclature applied to differences/disorders of sex development. Members of a support group had clearer terminology preferences. "Variation of sex development" was the most liked term, and "disorders of sex development" and "intersex" were the most disliked. No term was liked by most respondents, and no clear alternative to the present nomenclature was identified.

A Multidisciplinary Approach to Puberty and Fertility in Girls with Turner Syndrome.

Women with Turner Syndrome (TS) have a variety of medical needs throughout their lives; however, the peripubertal years are particularly challenging. From a medical perspective, the burden of care increases during this time due to growth optimization strategies, frequent health screenings, and puberty induction. Psychologically, girls begin to comprehend the long-term implications of the condition, including their diminished fertility potential. Unfortunately, clear guidelines for how to best approach this stage have not been established. It remains to be determined what is the best age to begin treatment; the best compound, dose, or protocol to induce puberty; how, when or what to discuss regarding fertility and potential fertility preservation options; and how to support them to accept their differences and empower them to take an active role in their care. Given the complexity of this life stage, a multidisciplinary treatment team that includes experts in endocrinology, gynecology, and psychology is optimal.

Intrauterine growth restriction and hypospadias: is there a connection?

Hypospadias is one of the most common congenital malformations of the genitourinary tract in males. It is an incomplete fusion of urethral folds early in fetal development and may be associated with other malformations of the genital tract. The etiology is poorly understood and may be hormonal, genetic, or environmental, but most often is idiopathic or multifactorial. Among many possible risk factors identified, of particular importance is low birth weight, which is defined in various ways in the literature. No mechanism has been identified for the association of low birth weight and hypospadias, but some authors propose placental insufficiency as a common inciting factor. Currently, there is no standardized approach for evaluating children with hypospadias in the setting of intrauterine growth restriction. We reviewed the available published literature on the association of hypospadias and growth restriction to determine whether it should be considered a separate entity within the category of disorders of sexual differentiation.

Assessing sex assignment concordance with genotype and phenotype.

OBJECTIVES: To catalogue patients with DSD and to assess the concordance of genotype and phenotype with sex assignment at birth compared to sex assignment before and following assessment by a Gender Medicine Team (GMT) at one institution, as an initial step in formulating standardized guidelines for management of these conditions. DESIGN: After obtaining IRB approval, a retrospective chart review was conducted patients seen in the Gender Medicine Clinic (GMC) between 2006-2009 at Texas Children's Hospital (TCH), Houston, Texas. McNemar's test and Kappa agreement provided associations of various factors with sex assignment at birth prior to GMT assessment and after GMT assessment. PARTICIPANTS: Forty-seven patients seen in the GMC with confirmed DSD. RESULTS: Forty-seven patients met the inclusion criteria. The mean age of the patients at the time of GMT evaluation was 9.1+/-6.1 years; 61.7% had male karyotype, and 38.3% had female karyotype; 51.1% had a male external phenotype, 42.6% had a female external phenotype, and 6.4% had phenotypic ambiguity. Sex assignment was concordant with genotype and phenotype in 63.8% and 86.4%, respectively of cases at the time of birth and in 76.6% and 97.7%, respectively, of cases after assessment by GMT. CONCLUSION: Long-term outcomes are needed to establish standardized practice guidelines for decision-making.

X-linked hypophosphatemic rickets associated with respiratory failure.

We report a 5-year-old girl who presented to our emergency room with respiratory arrest and limb deformities and was subsequently diagnosed with X-linked hypophosphatemic rickets. On normalization of the serum phosphorus concentration, her respiratory distress resolved, illustrating that untreated X-linked hypophosphatemic rickets can lead to life-threatening respiratory distress.

Rapid resolution of consumptive hypothyroidism in a child with hepatic hemangioendothelioma following liver transplantation.

We report a unique case of a 3-mo-old female with consumptive hypothyroidism and liver hemangioendothelioma who required pharmacological doses of thyroid hormones and was cured following liver transplantation. Liver hemangioendotheliomas are capable of producing an excess of the thyroid hormone inactivating enzyme, type-3 iodothyronine deiodinase. The increased tumoral enzyme activity leads to rapid degradation of thyroid hormones, resulting in consumptive hypothyroidism. Review of similar cases indicated variable outcomes. We focus on our patient's clinical course and describe in detail the thyroid hormone replacement therapy and a unique outcome of this rare type of hypothyroidism. This first example of a prompt and complete resolution of consumptive hypothyroidism in an infant after liver transplantation confirms the concept and the reversibility of consumptive hypothyroidism and provides novel insights into the rapidity of response of the infant's hypothalamic-pituitary-thyroid axis to thyroid hormone replacement.

A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents.

BACKGROUND: Short-term studies in adolescents have generally shown an enhancement of calcium absorption by inulin-type fructans (prebiotics). Results have been inconsistent; however, and no studies have been conducted to determine whether this effect persists with long-term use. OBJECTIVE: The objective was to assess the effects on calcium absorption and bone mineral accretion after 8 wk and 1 y of supplementation with an inulin-type fructan. DESIGN: Pubertal adolescents were randomly assigned to receive 8 g/d of a mixed short and long degree of polymerization inulin-type fructan product (fructan group) or maltodextrin placebo (control group). Bone mineral content and bone mineral density were measured before randomization and after 1 y. Calcium absorption was measured with the use of stable isotopes at baseline and 8 wk and 1 y after supplementation. Polymorphisms of the Fok1 vitamin D receptor gene were determined. RESULTS: Calcium absorption was significantly greater in the fructan group than in the control group at 8 wk (difference: 8.5 +/- 1.6%; P < 0.001) and at 1 y (difference: 5.9 +/- 2.8%; P = 0.04). An interaction with Fok1 genotype was present such that subjects with an ff genotype had the least initial response to fructan. After 1 y, the fructan group had a greater increment in both whole-body bone mineral content (difference: 35 +/- 16 g; P = 0.03) and whole-body bone mineral density (difference: 0.015 +/- 0.004 g/cm(2); P = 0.01) than did the control group. CONCLUSION: Daily consumption of a combination of prebiotic short- and long-chain inulin-type fructans significantly increases calcium absorption and enhances bone mineralization during pubertal growth. Effects of dietary factors on calcium absorption may be modulated by genetic factors, including specific vitamin D receptor gene polymorphisms.

Relationships among vitamin D levels, parathyroid hormone, and calcium absorption in young adolescents.

BACKGROUND: Evidence suggests that vitamin D status in adults, as assessed by serum 25-hydroxyvitamin D (25-OHD), is positively associated with calcium absorption fraction and inversely associated with serum PTH. Few comparable pediatric data exist. OBJECTIVES: The objective of this study was to evaluate the relationships among vitamin D status, PTH, and calcium absorption in midpubertal boys and girls. METHODS: Calcium absorption was measured as part of an evaluation of the effects of prebiotics (inulin-type fructans) using a stable isotope method in 93 young adolescents, 12.7 +/- 1.0 yr of age, receiving diets averaging approximately 900 mg/d calcium. RESULTS: A significant positive relation to calcium absorption was found for serum 1,25-dihydroxyvitamin D (P = 0.048) and PTH (P = 0.007), but not for 25-OHD (P = 0.77). PTH was significantly inversely related to 25-OHD and was positively related to serum 1,25-dihydroxyvitamin D and osteocalcin. PTH was marginally significantly inversely related to lumbar spinal, but not whole body, bone mineral density. CONCLUSIONS: These data suggest that in adolescents, especially in the presence of vitamin D insufficiency, PTH secretion increases to adapt to higher rates of bone formation associated with growth. This results in higher serum 1,25(OH)2D concentrations and increased calcium absorption results. Vitamin D status, as reflected by the serum 25-OHD level, is not closely related to calcium absorption. Whether adaptation to low serum 25-OHD is adequate under physiologically stressful situations, including those leading to very low serum 25-OHD levels, is unknown.

Vitamin D receptor Fok1 polymorphisms affect calcium absorption, kinetics, and bone mineralization rates during puberty.

UNLABELLED: Few studies of the VDR polymorphisms have looked at calcium metabolism or long-term effects. We measured bone mineralization and calcium metabolic parameters longitudinally in a group of 99 adolescents. We found a significant relationship between calcium absorption and skeletal calcium accretion and the Fok1, but not other VDR or related, genetic polymorphisms. It seems that the Fok1 polymorphism directly affects bone mineralization during pubertal growth through an effect on calcium absorption. INTRODUCTION: There are few data regarding the relationship between genetic markers for low bone mass and changes in calcium metabolism in childhood or adolescence. We sought to identify the effects of polymorphisms of the vitamin D receptor (VDR) on calcium and bone mineral metabolism in a longitudinal study of pubertal adolescents. MATERIALS AND METHODS: Adolescents (n = 99) received comprehensive stable isotope studies of calcium absorption, bone calcium kinetics, and bone mineralization. Studies were repeated 12 months later. Polymorphisms of putative genetic markers were determined and related to bone mineralization and calcium metabolic finding. Results were analyzed by ANOVA in which changes over time were determined using the initial value as a covariate. RESULTS: Polymorphisms of the Fok1 gene of the VDR were significantly related to calcium absorption (p = 0.008) and whole body BMC (p = 0.03) and BMD (p = 0.006). The Fok1 effect on whole body BMD was significant for those with Ca intake >800 mg/day (p < 0.001), whereas for those with Ca intake < or = 800 mg/day, the Fok1 genotype did not have a significant effect on whole body BMD (p = 0.40). The Fok1 genotype was significantly related to the changes during the year in whole body calcium accretion, with the ff genotype having a 63 +/- 20 mg/day deficit compared with the FF genotype (p = 0.008). CONCLUSIONS: The Fok1 polymorphism of the VDR receptor seems to directly affect bone mineral accretion during pubertal growth through an effect on calcium absorption. The relationship between different genetic polymorphisms and bone mineral metabolism may vary by life stage as well as diet.

Pubertal girls only partially adapt to low dietary calcium intakes.

UNLABELLED: We evaluated the effects of low calcium in the diets of young adolescent girls. We measured calcium absorption and excretion using stable isotopes. We found partial adaptation to low intakes but a persistent large deficit relative to recommended intakes. Low calcium intakes pose a substantial risk of inadequate calcium retention. INTRODUCTION: A substantial number of adolescent girls in the United States have habitual calcium intakes <500 mg/day (about 40% of the current recommended intake). The ability to adapt to these very low intakes by increasing calcium absorption and decreasing calcium excretion is not known. We sought to determine the effects of recommended (REC-Ca) versus very low (LO-Ca) calcium intakes on calcium absorption and excretion in white and black girls. MATERIALS AND METHODS: Pubertal, but premenarcheal girls, were adapted to low or recommended calcium intakes for at least 2 weeks before each study. Calcium absorption (n = 51) and endogenous fecal calcium excretion (n = 36 of the 51) were determined by dual-tracer stable isotope studies. Subjects were then switched to the other diet for at least 6 weeks, and the study was repeated. RESULTS: Calcium intake was 389 +/- 10 mg/day on LO-Ca and 1259 +/- 35 mg/day on REC-Ca diets. Fractional absorption increased from 44.9 +/- 1.9% on REC-Ca to 63.4 +/- 1.7% on LO-Ca (p < 0.01), but the net calcium absorption remained less than one-half the value on LO-Ca as on REC-Ca. Despite decreases in both endogenous fecal calcium excretion and urinary calcium excretion, net calcium balance was much lower on LO-Ca compared with REC-Ca1 (131 +/- 14 versus 349 +/- 32 mg/day, respectively; p < 0.001). We found significantly lower urinary calcium excretion but not calcium absorption in black girls compared with white girls. CONCLUSIONS: Very low calcium intakes are only partially adapted to by increased absorption and decreased excretion. Very low calcium intakes place both white and black pubertal girls at substantial risk for inadequate calcium retention.