46,XY DSD and limb abnormalities in a female with a de novo LHX9 missense mutation.

Differences in sex development (DSD) are a group of rare conditions involving genes, hormones and reproductive organs, including genitals. Although these disorders are common, information about the molecular causes remain limited. Many genes have been identified in association with DSD but in many cases the causative gene could not be identified. The Lhx9 gene has been studied in mice and birds, and biallelic mutations in this gene have been found to cause 46,XY DSD and limb abnormalities. So far two variants of LHX9 have been identified in 46,XY individuals with testicular regression, micropenis and hypospadias. We report a de novo heterozygous missense variant in LHX9 in a girl with 46,XY DSD and finger and toe abnormalities. It was previously predicted that a mutation in LHX9 would not cause extragenital anomalies in light of prior animal studies, but our report adds to the limited knowledge of the phenotype observed in humans with a variant in LHX9. To the best of our knowledge this is the first reported case with this combination of abnormalities.

Role of Social Factors in Glycemic Control Among African American Children and Adolescents with Type 1 Diabetes.

OBJECTIVE: With the rising incidence of Type 1 diabetes (T1DM), it is important to recognize deficiencies in care and areas of improvement to provide better access to resources and education for T1DM patients. The objective of this study was to recognize social factors and compliance barriers affecting glycated hemoglobin (A1c) level in T1D patients among the minority population. METHODS: A total of 84 T1DM patients, ages 3 to 21 years, 49% males, 87% African American participated in the study. Study questionnaires assessing patient knowledge and other variables were distributed and patient charts were reviewed retrospectively to obtain relevant clinical data. T-tests, one-way ANOVA and spearman correlation were used for analysis. RESULTS: Mean A1c in our study was 10.5% and mean knowledge score was 10.1 out of 14. There was no significant correlation (r = 0.12, p = 0.26) between A1c and patients' knowledge scores. Patients with more frequent blood sugar (BS) monitoring (3-4 times/day) had 2 points lower A1c (9.6 vs 11.6 %, 95% CI 0.2-3.7, p = 0.03) than those with 2 or less times/day. No significant difference in A1c between 3-4 checks/day vs >4 checks/day BS checks. Most patients reported 'forgetfulness' (19%) followed by 'too time consuming' (17.9%) as barriers to daily BS monitoring. There was no significant difference in A1c between pen or pump users (10.5 vs 10.2 %, p = 0.55). Surprisingly, those with home supervision had higher A1c than those without (10.7 vs 9.6 %, p = 0.04) while there was no significant difference between those with or without nurse supervision at school (10.6 vs 9.8 %, p = 0.33). Those reporting happy mood interestingly had higher A1c than those with sad/depressed mood (10.7 vs 9.4 %, p = 0.04). On multiple linear regression analysis, frequency of BS checks, home supervision and mood were the most significant predictors of A1c and altogether explained 20% of the variability in A1c. CONCLUSION: Frequent BS monitoring is associated with lower A1c. Supervision at home and school did not improve A1c, but it was self-reported information. Mood did not affect A1c contrary to that reported in other studies.

Family Consumer Behaviors, Adolescent Prediabetes and Diabetes in the National Health and Nutrition Examination Survey (2007-2010).

BACKGROUND: Prediabetes or diabetes (characterized by hemoglobin A1c [HbA1c] levels ≥ 5.7 gm%) has been associated with numerous long-term complications. Family consumer behaviors are important risk factors that lead to impaired glucose tolerance or diabetes. However, few studies have studied the association between the family consumer environment and prediabetes and diabetes in adolescents. OBJECTIVE: The aim of this study was to examine the association between family consumer behaviors (healthy food availability and supermarket spending) and adolescent prediabetes and diabetes (ClinicalTrials.gov identifier #NCT03136289.) Methods: Data from a nationwide survey conducted by the Centers for Disease Control and Prevention (National Health and Nutrition Examination Survey [NHANES] 2007-2010 data) were used for these analyses. Adolescents aged 12-19 years were selected for this study. Bivariate analyses and logistic regression models assessed the relationship between family consumer behaviors and the prevalence of adolescent prediabetes and diabetes. Multivariable models adjusted for age, gender, ethnicity, physical activity, education, income, and household size. RESULTS: A total of 2520 adolescents were eligible for this study. Adolescents with healthier household food availability had negative odds (odds ratio [OR] = 0.74, 95% confidence interval [CI], 0.55-1.00), as did higher log supermarket spending (OR = 0.69; 95% CI, 0.57-0.85). Interaction models demonstrated that adolescent females had more negative odds of prediabetes/diabetes for both healthier food availability (OR = 0.79, 95% CI, 0.39-1.29) and for greater log supermarket spending (OR = 0.69, 95% CI, 0.57-0.85). CONCLUSION: This study shows that both healthy food availability and an increase in supermarket spending were associated with a decreased adjusted prevalence of prediabetes and diabetes in adolescents, with a greater effect in females. These results suggest the need for policy and dietary interventions targeting the consumer environment.

Differences between Metabolically Healthy vs Unhealthy Obese Children and Adolescents.

Obesity is on the rise worldwide. An obesity subtype, metabolically healthy obese (MHO), is resilient to unfavorable metabolic and cardiovascular effects. Factors predicting MHO phenotype are not well characterized. We aimed to identify MHO and metabolically unhealthy obese (MUO) children and adolescents with respect to metabolic factors, and to find predictors of MHO subtype. A retrospective chart review was done on children, ages 4-19 years, 99% African-American/Caribbean, with BMI ≥95th %tile. MUO was defined as meeting ≥1 of the following: fasting glucose ≥100 mg/dl, HbA1c >5.6%, BP ≥90th %tile, TG ≥150 mg/dl, or HDL <40 mg/dl. Study included 189 subjects, 37.6% were MHO and 62.4% MUO. MHO subjects were younger (mean ± SD, 11.6 ± 3.3 vs 12.9 ± 3.2 years; p < 0.009) and had lower BMI %tile (98.4 ± 1.4 vs 98.8 ± 2.1; p < 0.04), smaller waist (94.2 ± 15.2 vs 101.4 ± 17 cm; p < 0.003) and hip circumferences (105.3 ± 15.6 vs 113.5 ± 15.4 cm; p < 0.001), lower fasting insulin (18.5 ± 10.2 vs 24.2 ± 14.3 µU/ml; p < 0.022), and lower HOMA-IR (4.1 ± 2.4 vs 5.5 ± 3.6; p < 0.022). Acanthosis nigricans was noted less frequently in MHO than MUO (p < 0.005). In stepwise logistic regression, age and BMI %tile were significant predictors of MHO. We found that 38% of obese children are MHO. They are younger and have lower BMI %tiles. Lifestyle modification initiated at an early age may prevent metabolic abnormalities.

Comparison of A1C to Oral Glucose Tolerance Test for the Diagnosis of Prediabetes in Overweight and Obese Youth.

IN BRIEF This study reports performance of A1C against the oral glucose tolerance test (OGTT) in predicting prediabetes among overweight and obese African-American and Caribbean children. A retrospective chart review was completed for 230 children. Receiver operating characteristic curves were generated to find the predictive performances of different tests against the OGTT. A1C alone is a poor discriminator of prediabetes in our study population, with low sensitivity (70%) and specificity (48.8%). BMI z score, A1C, and homeostatic model assessment of insulin resistance are significant predictors of prediabetes and, when taken together, provide better discrimination for prediabetes.

Precocious Puberty and GnRH analogs: Current treatment practices and perspectives amongst US pediatric endocrinologists.

INTRODUCTION: GnRHas are used for treatment of precocious puberty. Over the last decade, several new formulations have been approved. METHODS: The Drugs & Therapeutics subcommittee of the Pediatric Endocrine Society (PES) undertook a review to ascertain the current treatment options, prescribing behaviors, and practices of GnRHas among pediatric endocrinologists practicing within the United States. The survey consisted of four main subsections: 1. Description of clinical practice; 2. Self-assessment of knowledge base of pediatric and adult GnRHa formulations; 3. Current practice for treating CPP; and 4. Utilization of healthcare resources. RESULTS: There were 223 survey respondents. Pediatric endocrine practitioners were most familiar with the pediatric one-monthly preparation, the three-month preparation, and the histrelin implant (Supprelin®) (61.9%, 71.7%, and 34.5%, respectively), with lower familiarity for 24-week triptorelin intramuscular (Triptodur®) and 22.9% and six-month subcutaneous leuprolide (Fensolvi®). Only 23% of the respondents reported being extremely familiar with the availability of adult formulations, and 25% reported being completely unaware of cost differences between pediatric and adult GnRHa preparations. The implant was the most preferred therapy (44.4%), but in practice, respondents reported a higher percentage of patients were treated with 3-month preparation. While family preference/ease of treatment (87%) was the key determinant for using a particular GnRHa preparation, insurance coverage also played a significant role in the decision (65.5%). Responses regarding assessment for efficacy of treatment were inconsistent, as were practices and criteria for obtaining an MRI. CONCLUSIONS: The survey indicated there is more familiarity with older, shorter-acting GnRHas, which are prescribed in greater numbers than newer, longer-acting formulations. There is lack of consensus on the need for CNS imaging in girls presenting with CPP between 6-8 years of age and use of laboratory testing to monitor response to treatment. Insurance requirements regarding CNS imaging and laboratory monitoring are highly variable. Despite having similar constituents and bioavailability there are substantial cost differences between the pediatric and adult formulations and lack of evidence for safe use of these formulations in children. The survey-based analysis highlights the challenges faced by prescribers, while reflecting on areas where further research is needed to provide evidence-based practice guidelines for pediatric endocrinologists.

Comparison of temporal artery thermometry and rectal thermometry in febrile pediatric emergency department patients.

OBJECTIVES: Fever is among the most common reasons for emergency department (ED) visits by children. This study compares temporal artery thermometry to rectal thermometry in febrile children in an ED. METHODS: This was a retrospective evaluation of children younger than 36 months treated consecutively in an urban medical center. Patients underwent triage with temporal artery thermometry, and after transfer to the pediatric ED, they underwent rectal thermometry. Fever was defined as rectal temperature of 100.4 °F (38 °C) or greater, and 147 patients met this definition. Data extraction from electronic charts obtained paired temporal artery and rectal temperatures, and these were compared by Bland-Altman analysis. Temperature points of 100.4 °F (38 °C) and 102.2 °F (39 °C) were evaluated to compare temporal artery thermometry with rectal thermometry sensitivity and specificity. RESULTS: A statistically and clinically significant difference between temporal artery and rectal temperature was found. Temporal artery thermometry was 53% sensitive detecting rectal temperature 100.4 °F (38 °C) or greater, and 27% sensitive detecting rectal temperature of 102.2 °F (39 °C) or greater. Mean rectal temperature was 102.36 °F (39.09 °C) (95% confidence interval [CI], 102.14 °F-102.58 °F); mean temporal artery temperature was 100.36°F (37.98 °C) (95% CI, 100.08 °F-100.65 °F), and mean difference between the two was 1.99 °F (1.11 °C) (95% CI, 1.75 °F-2.23 °F). CONCLUSIONS: Temporal artery thermometry is poorly sensitive detecting fever and does not accurately reflect rectal temperature. Temporal artery thermometry should not be used for clinical management of children younger than 36 months if detection of fever is of importance.

A Case of Growth Hormone Use in Dyggve-Melchior-Clausen Syndrome.

Short stature has many causes including genetic disease, skeletal dysplasias, endocrinopathies, familial short stature, and nutritional deficiencies. Recombinant growth hormone (rGH) therapy may be employed to improve stature based on the underlying etiology and growth velocity. Skeletal dysplasia in Dyggve-Melchior-Clausen (DMC) syndrome tends to be progressive, typically with hip involvement, and ultimately leads to bilateral dislocation of the hip joints. Here, we present a pediatric patient with short stature treated with rGH therapy, complicated by the development of debilitating, bilateral hip pain, and found to have DMC syndrome. Our patient had limited range of motion at several joints including the hips after receiving 6 months of rGH therapy. Given the timing of the patient's rGH therapy and the progression of her disease, it is difficult to determine if there were any benefits and instead, is concerning for worsening of her skeletal dysplasia with rGH therapy use. Consequently, patients with severe short stature should have a thorough workup for genetic causes like DMC syndrome, before initiating rGH therapy to determine any potential benefits or harms of treatment.

Case Studies in Pediatric Lipid Disorders and Their Management.

CONTEXT: Identification of modifiable risk factors, including genetic and acquired disorders of lipid and lipoprotein metabolism, is increasingly recognized as an opportunity to prevent premature cardiovascular disease (CVD) in at-risk youth. Pediatric endocrinologists are at the forefront of this emerging public health concern and can be instrumental in beginning early interventions to prevent premature CVD-related events during adulthood. AIM: In this article, we use informative case presentations to provide practical approaches to the management of pediatric dyslipidemia. CASES: We present 3 scenarios that are commonly encountered in clinical practice: isolated elevation of low-density lipoprotein cholesterol (LDL-C), combined dyslipidemia, and severe hypertriglyceridemia. Treatment with statin is indicated when the LDL-C is ≥190 mg/dL (4.9 mmol/L) in children ≥10 years of age. For LDL-C levels between 130 and 189 mg/dL (3.4-4.89 mmol/L) despite dietary and lifestyle changes, the presence of additional risk factors and comorbid conditions would favor statin therapy. In the case of combined dyslipidemia, the primary treatment target is LDL-C ≤130 mg/dL (3.4 mmol/L) and the secondary target non-high-density lipoprotein cholesterol <145 mg/dL (3.7 mmol/L). If the triglyceride is ≥400 mg/dL (4.5 mmol/L), prescription omega-3 fatty acids and fibrates are considered. In the case of triglyceride >1000 mg/dL (11.3 mmol/L), dietary fat restriction remains the cornerstone of therapy, even though the landscape of medications is changing. CONCLUSION: Gene variants, acquired conditions, or both are responsible for dyslipidemia during childhood. Extreme elevations of triglycerides can lead to pancreatitis. Early identification and management of dyslipidemia and cardiovascular risk factors is extremely important.

Premature Thelarche.

Premature thelarche is a benign condition that affects young girls and may be interpreted as a sign of central precocious puberty (CPP). Parental concern is common when breast development is noted in a young girl. It is important to differentiate premature thelarche from CPP, as the latter is a more serious disorder that may affect final adult height and menarcheal age, and may have psychological implications as well. Distinguishing between the two conditions clinically may help the patients avoid unnecessary testing. Pediatricians can play a pivotal role by providing reassurance to families and helping alleviate parental anxiety. This article reviews the clinical presentation of premature thelarche, its usual course, and implications. [Pediatr Ann. 2018;47(1):e12-e15.].

Williams Syndrome and 15q Duplication: Coincidence versus Association.

Williams syndrome is a multisystem disorder caused by contiguous gene deletion in 7q11.23, commonly associated with distinctive facial features, supravalvular aortic stenosis, short stature, idiopathic hypercalcemia, developmental delay, joint laxity, and a friendly personality. The clinical features of 15q11q13 duplication syndrome include autism, mental retardation, ataxia, seizures, developmental delay, and behavioral problems. We report a rare case of a girl with genetically confirmed Williams syndrome and coexisting 15q duplication syndrome. The patient underwent treatment for central precocious puberty and later presented with primary amenorrhea. The karyotype revealed 47,XX,+mar. FISH analysis for the marker chromosome showed partial trisomy/tetrasomy for proximal chromosome 15q (15p13q13). FISH using an ELN-specific probe demonstrated a deletion in the Williams syndrome critical region in 7q11.23. To our knowledge, a coexistence of Williams syndrome and 15q duplication syndrome has not been reported in the literature. Our patient had early pubertal development, which has been described in some patients with Williams syndrome. However, years later after discontinuing gonadotropin-releasing hormone analogue treatment, she developed primary amenorrhea.

Pubertal assessment: targeted educational intervention for pediatric trainees.

Background Timely and periodic pubertal assessment in children is vital to identify puberty related disorders. Pediatricians need to have working knowledge of puberty time and tempo. Pediatric residency is an important platform to acquire physical examination skills including pubertal assessment. Objective An educational intervention for teaching pubertal assessment was piloted on pediatric residents at our institution. Methods The intervention comprised of interactive lecture series, ID badge size Tanner stage cards and Tanner posters placed in residents' continuity clinics. Pre-intervention, post-intervention and 3 months post-intervention surveys for participating trainees were administered to determine the effectiveness of the intervention. Attitudes, practices, knowledge scores, and barriers to Tanner staging conduct were analyzed. Results Forty-three residents participated in the intervention. Knowledge scores of PGY1 (5.95 ± 1.6 vs. 7.47 ± 1.4, p < 0.01) improved right after the intervention, as did self-reported clinical practices of all trainees 3 months post- intervention with regards to conducting external genital examination and performing pubertal assessment. Confidence levels of pediatric trainees in conducting pubertal assessment and comfort levels in assessing the need for endocrine referral based on abnormal Tanner staging improved after the intervention, although the effect was not statistically significant. Conclusion Our intervention is a worthwhile technique for teaching pubertal assessment to residents as it is simple to conduct, easily reproducible, provides baseline knowledge needed for recognition of normal pubertal development and puberty related conditions, and instills confidence in residents.

Metformin Use in Children and Adolescents with Prediabetes.

With the increasing incidence of childhood obesity, clinicians need to understand its comorbidities and their management. The American Diabetes Association recommends pediatricians screen high-risk overweight and obese children. Identifying and treating prediabetic children and adolescents can help to reduce the burden of type 2 diabetes. Lifestyle interventions are pivotal. Metformin is the only oral medication approved for diabetes treatment in children. It has been studied in clinical trials in nondiabetic children and has been shown to have beneficial effects on body weight. Effects on diabetes prevention have not been studied and long-term data are limited in the pediatric population.

Pubertal assessment: a national survey of attitudes, knowledge and practices of the US pediatric trainees.

Background and objective Sex maturity rating (SMR), defines different levels of sexual maturity, based on the development of secondary sexual characteristics. Periodic assessment of pubertal maturation by physicians is crucial for timely identification of puberty-related disorders. With this pilot study, we aimed to assess the attitudes, knowledge and practices of pubertal assessment by current US pediatric trainees. Methods An anonymous online survey questionnaire was sent to categorical pediatric residents at different levels of training and pediatric chief residents across the US. Results We received responses from 2496 pediatric residents from all over the US. We found that 96% of trainees understand the importance of assessing SMR, 62% feel confident in assessing it and 55% feel comfortable assessing the need for an endocrinology referral. Only 33% of trainees performed external genital exams during all regular clinic visits while 26.9% never performed them during sick visits and 6% never assessed SMR during any of the patient visits. Higher levels of training and having completed an endocrinology rotation were associated with improvement in comfort level, practice and knowledge of trainees regarding pubertal assessment. Conclusion This study revealed that the current clinical practices of performing external genital exams and SMR among pediatric residents need improvement. Stronger reinforcement from continuity clinic preceptors and/or online and clinic based resources for SMR assessment for trainees may improve adherence to the recommended guidelines.