Naveen Uli

Treatment of childhood obesity

Purpose of reviewTo provide an overview of treatments for childhood obesity, highlighting recent advances and recommendations. Recent findingsThe three main treatment modalities are lifestyle interventions, medications, and bariatric surgery. Recent data support the short-term effectiveness of lifestyle interventions, and show that continued behavioral intervention increases the likelihood of a sustained effect for up to 2 years. New studies and regulatory decisions on medications for obesity (including orlistat, sibutramine, and metformin) are discussed. Emerging data suggest substantial weight loss after bariatric surgery in morbidly obese adolescents but also indicate adverse effects. An expert panel recently provided guidelines that alter definitions of obesity and offer a framework for obesity management. These guidelines are compared with others, and integrated recommendations presented. SummaryWhile primary prevention of childhood obesity is important, broadly effective methods to do so are not yet available. Given the large population of obese children and the risks they face, an emphasis on treatment is also critical. We suggest a staged approach, emphasizing early intervention and lifestyle changes. We also suggest limiting bariatric surgery to selected adolescents in Institutional Review Board-approved research studies. Health-policy interventions can facilitate both prevention and treatment of childhood obesity.

Pharmacotherapy in pediatric obesity: current agents and future directions.

Childhood obesity is emerging as a major public health threat, with adverse implications on the health of individuals and long-term costs to society. Family-based lifestyle interventions with behavioral modification, diet and exercise form the mainstay of treatment. Pharmacologic treatment may be considered in selected subjects, especially in the presence of significant and severe comorbidities, when lifestyle intervention has failed to achieve weight reduction. Orlistat and sibutramine are FDA-approved for treatment of pediatric obesity; metformin may be considered in the presence of clinically significant insulin resistance. Evidence is lacking on the appropriate duration of medical therapy and optimal combination with lifestyle intervention. Lack of coverage of medications by insurance and high out-of-pocket costs may be limiting factors to some families. Adverse effects necessitate careful monitoring and may lead to discontinuation of medication. Pharmacologic agents with novel mechanisms of action offer hope of improved efficacy, tolerability and safety.

Idiopathic Short Stature: Decision Making in Growth Hormone Use

Short stature is a common concern in pediatrics. Several ambiguities and controversies persist, especially with regard to criteria, cost, medical necessity and outcomes of growth hormone (GH) therapy for idiopathic short stature (ISS). Due to these ambiguities and controversies, a series of decisions by primary care physicians (whether to refer the short child to a pediatric endocrinologist), pediatric endocrinologist (whether to recommend GH treatment), families (whether to raise concern about short stature and whether to agree to undertake treatment), and third party payers (whether to cover the costs of GH therapy) influence which individual short children will receive GH in the US. Together, these decisions determine overall GH use. Apart from child’s growth characteristics, several non-physiological factors drive the critical decisions of these stakeholders. This article focuses on current ambiguities and controversies regarding GH therapy in ISS, discusses the decision-makers involved in GH therapy, and explores the factors influencing their decisions.

Progressive Central Puberty in a Toddler with Partial Androgen Insensitivity

A male infant was diagnosed with partial androgen insensitivity caused by a novel mutation in the androgen receptor. At 3.5 months of age, he received 100 mg of testosterone intramuscularly over the course of 3 months to increase phallic size. He developed pubic hair after 5 months and signs of progressive central precocious puberty when re-examined at 17.5 months, which subsequently was suppressed with depot leuprolide.

Challenges in the diagnosis and management of disorders of sex development

Disorders of sex development (DSD) represent a spectrum of uncommon but very complex disorders with medical, psychosexual, and family implications for those affected by them. The diagnosis and management of these disorders requires a coordinated team of multiple specialists. Following an international conference in Chicago in 2005, a consensus statement was created and presented, which has resulted in a new paradigm in the nomenclature, classification, and management of DSDs. Since that time, many improvements have been forthcoming, most notably in the area of molecular genetic technologies. These developments have advanced our understanding of the specific etiologies underlying many of these conditions. In this article, we present an overview of the physiology of sex development, a few clinical vignettes highlighting specific pathologic conditions, discussions regarding the evaluation and management of these disorders, and some thoughts on future directions in this field. Birth Defects Research (Part C) 108:293-308, 2016.

Physical Activity Self-Efficacy and Fitness: Family Environment Relationship Correlates and Self-Esteem as a Mediator among Adolescents Who Are Overweight or Obese

BACKGROUND Little is known regarding how dimensions of the family social environment relate to fitness levels and physical activity self-efficacy (PASE) among adolescents who are overweight or obese and whether these relationships are mediated by self-esteem. METHODS Potential associations were evaluated between relationship subdomains (cohesion, conflict, expressivity) of the Family Environment Scale (FES), self-esteem (Rosenberg Self-Esteem Scale, RSES), and PASE and fitness, using recovery heart rate [RHR, beats per minute (bpm)] from a 3-minute submaximal step test at baseline. Participants were 108 adolescents who were overweight or obese and were seeking weight-loss treatment as part of the Healthy Kids, Healthy Weight 12-week multidisciplinary pediatric weight management program. Structural equation modeling (SEM) was used to simultaneously evaluate paths between these variables and test for mediation. RESULTS In multivariable models, higher FES cohesion (β = -2.18, s.e. = 0.98; p = 0.02), expressivity (β = -1.97, s.e. = 0.99; p < 0.05), and PASE (β = -0.64, s.e. = 0.33; p < 0.05) scores were associated with lower RHR, which represents higher fitness. Furthermore, higher FES conflict scores were associated with lower RSES scores (β = -0.83, s.e. = 0.29; p < 0.01), and FES conflict (β = -0.63, s.e. = 0.22; p < 0.01) and RSES (β = 0.33, s.e. = 0.07; p < 0.01) were associated with PASE scores. In a good-fitting multivariate SEM [Comparative Fit Index (CFI) = 1.00; Standardized Root Mean Square Residual (SRMR) = 0.02; Tucker-Lewis index (TLI) = 1.22; Root Mean Squared Error of Approximation (RMSEA) <0.01], RSES mediated the relationship between FES conflict and PASE (sum of indirect paths: β = -0.30, s.e. = 0.11; p < 0.01) scores. CONCLUSIONS Our results highlight the importance of the relationship domain of the family environment on self-esteem, PASE, and physical fitness in adolescents who are overweight or obese.

Introduction: “Sex Development”

A common question asked after the birth of a child is “Is it a girl or a boy?” For parents of children with Disorders/ Differences in Sex Development (DSD), the question can provoke great anxiety. With an ever expanding and evolving understanding of sex development and determination, parents of patients with DSD have greater access to the support they need to answer that question rapidly and sensitively. Children born with ambiguous genitalia and their parents greatly benefit from a team approach to clinical management. The decisions made are critical because of the complexity of factors in sex development and the psychological and societal impact of these key decisions. The team could include endocrinologists, obstetriciangynecologists, psychiatrists, psychologists, surgeons, urologists, sociologists, as well as the primary care pediatrician and family members. In this special issue of Birth Defects Research Part C: EMBRYO TODAY Reviews, the review articles explore, through the distinct lenses of authors from all over the world with their different scientific, cultural and societal backgrounds, how we achieve one of the defining features of human identity, namely sex; whether we are male or female or somewhere in between. The authors bring us up to date on a range of issues in our understanding of sex development and disorders that arise prenatally and postnatally. They aim to answer the questions: What genes are involved in sex development, and how and when? How is DSD diagnosed? How is the progress in technology for diagnosis and discovery improving and expanding our understanding of DSD etiology? What can happen to a child with DSD? What are the practical clinical steps in dealing with DSD? Are there sex specific responses of embryos and fetuses to environmental exposures? How might society and cultural environments impact individuals with DSD? What do I do if my child has DSD? For such a charged topic as sex, terms are absolutely critical to consider. Among clinicians and investigators, the term Disorders of Sex Development (DSD) has been used for many years replacing intersex. Others contend that variant sex development is not a disorder at all, but represents a continuum of a biologic variant. Because of the negative connotation of the word “disorder”, especially long-lasting psychological impact, it has been suggested that it be replaced by “differences.” For now, “differences” has been accepted and DSD is often defined as disorders/ differences in sex development. An enormous amount of research has been conducted to elucidate the complex steps in sex development that are presented in the reviews within this issue, but there are still many mysteries and gaps. One very significant gap lies in our understanding of how sex development affects brain development and behavior. The social issues related to sex development are evolving rapidly and with much social discourse on these issues currently. Stay tuned for the next leaps in this field. There are now a number of websites to support the DSD community with clear information and these include www.dsdfamilies.org and the newly created http://www. dsdteens.org. In the early 1950’s George William Jorgensen, Jr. went to Denmark and metamorphosed into Christine Jorgensen. She became an Instant media sensation. Since then celebrities including Chaz Bono and Caitlyn Jenner have publicly revealed their desire to change their sex and have done so. Our current society may be more enlightened about accepting transgender individuals, but the current heated public discourse on subjects such as the use of bathrooms by transgender individuals continues. These discussions bring us to question whether sex is binary or continuous. Part and likely most of the answers lie in what happens in the womb. The reviews clearly show that the relationship between molecular pathways and gonadal phenotypes in DSD are being clarified. What a few of these reviews touch on but what is still very unclear is how sex development affects neural development and behavior. Most transgender individuals do not have DSD as currently defined. New advances in assaying brain function may help in filling this huge gap in our understanding.