Isolated Central Hypothyroidism in an Adolescent With Narcolepsy.

Isolated central hypothyroidism (ICH) and narcolepsy are conditions rarely seen in the pediatric population which are usually characterized by delayed diagnosis and treatment due to their variable presentation and subclinical onset. We describe an unusual case of an adolescent male diagnosed with narcolepsy and central hypothyroidism. A 15-year-old obese boy presented with the complaint of excessive daytime sleepiness, fatigue, and snoring. Obstructive sleep apnea (OSA) was initially suspected as the underlying cause, but the sleep study was negative for OSA. However, the multiple sleep latency test was consistent with narcolepsy without cataplexy. He was then started on modafinil, but his symptoms persisted. Thyroid function tests were performed that were consistent with ICH. Thyroid replacement therapy was initiated with subsequent improvement in symptoms. A theoretical association exists between narcolepsy and ICH due to the involvement of the hypothalamus and pituitary gland. Nevertheless, clinical association, as seen in our case, is rare. Central hypothyroidism is a known etiology leading to fatigue and sleepiness. Narcolepsy without cataplexy can have overlapping symptoms with hypothyroidism, as seen in our patient. The presence of narcolepsy should prompt screening for hypothyroidism in appropriate clinical settings.

Assessment of Microvascular Function in Children and Adolescents with Diabetes and Obesity.

BACKGROUND: Endothelial dysfunction (ED) is a marker of vascular damage. Glycated hemoglobin (A1C) predicts vascular complications. The EndoPAT (peripheral arterial tonometry) device calculates the reactive hyperemic index (RHI), a measure of endothelial function. The greater the vasodilation, the higher the RHI. We hypothesized that children with poorly-controlled diabetes mellitus (DM) and non-diabetes mellitus (NDM) obese children have ED. METHODS: A cross-sectional study using the EndoPAT device was performed on children with poorly-controlled DM and NDM children. ANOVA, t-test, Mann-Whitney U test, multiple linear regression and Spearman correlation were used. RESULTS: Of 58 children that completed the study (aged 13.1 ± 3.42 years), 33 with type 1 diabetes (T1DM), 8 with type 2 diabetes (T2DM) and 17 were NDM obese children. Eighty-five percent were African-American, 60% were female and 79% entered puberty. The RHI of children with DM (1.42 ± 0.48) versus NDM obese group (1.40 ± 0.34) was not different (P = 0.86) regardless of the type of DM or body mass index. In the DM group, for every 1% increase in latest A1C, the RHI decreased by 0.097 (P = 0.01) after adjusting for age, gender, and type of DM. The RHI of DM patients with latest A1C of < 10% (1.70 ± 0.58) versus those with A1C ≥10% (1.21 ± 0.19) was statistically different (P = 0.02). In the total study population, males had significantly lower RHI (1.28 ± 0.36) when compared to females (1.51 ± 0.46), P = 0.04 but this difference disappeared when considering pubertal status and type of diabetes. CONCLUSIONS: Our data showed that patients with poorly-controlled DM as reflected by latest A1C of ≥ 10% had worse endothelial function as reflected by lower RHI score.

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.

Baseline IGFBP - 3 as the Key Element to Predict Growth Response to Growth Hormone and IGF - 1 Therapy in Subjects with Non - GH Deficient Short Stature and IGF - 1 Deficiency.

BACKGROUND: Short stature in children represents a heterogeneous group with different etiologies. Primary Insulin like growth factor 1 (IGF - 1) deficiency in short stature can present with normal or elevated growth hormone (GH) production. Currently there is no model that can reliably predict response to recombinant (r)GH therapy and/or rIGF - 1 therapy in children with non - GH deficient short stature. HYPOTHESIS: Baseline Insulin like growth factor binding protein 3 (IGFBP - 3) along with ∆ IGF - 1 in the first 3 months of GH therapy level can be a marker of growth response to the rGH and/or rIGF - 1 therapy in children with non - growth hormone deficiency short stature. OBJECTIVES: To study the relationship between baseline IGFBP - 3 and IGF - 1 levels and the response to rGH and rIGF - 1 therapy in children with short stature, normal GH secretion and low IGF - 1 SDS. METHODS: 43 children, age 9.07 ± 2.75 years with height -2.72 ± 0.7 SD and baseline IGF - 1 of -2.76 ± 0.58 SD, who passed the growth hormone releasing hormone (GHRH) stimulation test were included in a retrospective chart review. They were treated with rGH therapy with a mean dose of 0.46 ± 0.1 mg/kg/week. Growth velocity (GV), IGF - 1 and IGFBP - 3 levels were done at 3 and 6 months of therapy. Subjects with poor response to rGH after 6 months of therapy were switched to rIGF - 1 therapy at 0.24 mg/kg/day for the next 6 months. Subjects were divided according to their growth rate into responders to rGH (N = 23); non - responders to rGH, responders to rIGF - 1 (N = 14) and non - responders to rGH and rIGF-1 (N = 6). RESULTS: There was no correlation between GV and peak GH level at GHRH test. Growth velocity positively correlated with ΔIGF - 1 SD among subjects treated with rGH therapy. Height SD positively correlated with IGFBP - 3 SD. Baseline IGFBP - 3 also inversely correlated with GH peak during GHRH test. CONCLUSIONS: In subjects with short stature and low IGF - 1 level, baseline IGFBP - 3 levels can predict the growth response to rGH and/or rIGF - 1 therapy.

Screening for autoimmune thyroiditis and celiac disease in minority children with type 1 diabetes.

BACKGROUND: Hashimoto's thyroiditis (HT) and celiac disease (CD) are commonly associated with type 1 diabetes (T1DM). There is no consensus on screening, however, the American Diabetes Association (ADA) and the International Society for Pediatric and Adolescent Diabetes (ISPAD) recommend testing for thyroid function (TFT), thyroid antibodies and anti-tissue transglutaminase antibodies (TTG) IgA soon after diagnosis. TFT should be repeated every 1-2 years while TTG IgA should be tested for within 2 and 5 years. We hypothesize that the rate of HT and CD in our T1DM children is lower, so screening may need to be revised to reflect their underlying risk. METHODS: An Institutional Review Board (IRB)-approved retrospective chart review was conducted on children with T1DM in the past 10 years. Age, sex, race, A1C, TFT, thyroid and celiac antibodies were obtained. t-Tests, the Wilcoxon-Mann-Whitney test and stepwise regression were performed. RESULTS: Of 222 children with T1DM, with a mean age of 15.8±5.53 years, followed for 6.1±4.0 years, 53% female, mean A1C 11.1±1.9% and 87% African American (AA). Three had Graves' disease (1.3%), three had HT (1.3%) and 97% were euthyroid. TFT were assessed on average every 1.3 years and thyroid antibodies every 2.5 years. Positive thyroid antibody was found in 11%, negative in 57% and unknown in 32%. The positive antibody group had higher mean A1C and TSH. No biopsy confirmed cases of CD (0%) were found when screened every 2.3 years. CONCLUSIONS: The number of individuals who screened positive for hypothyroid HT and CD was lower than expected in our population. Further studies are needed to assess the optimal screening frequency for HT and CD in minority children with T1DM.

Improving paediatric residents' knowledge and perspectives regarding the insulin pump using a novel educational workshop.

OBJECTIVES: As a pilot study, we aimed to investigate the knowledge and perceptions of categorical paediatric residents (RES) at our institution regarding insulin pumps (IPs) and the impact following a targeted workshop. METHODS: All RES at our institution in attendance at a routine noon conference participated in a workshop, completing an anonymous survey before and right after the intervention to evaluate knowledge, attitudes and self-reported comfort regarding IPs. The workshop consisted of a didactic lecture followed by an insulin pump (IP) device demonstration of three commonly available brands. Knowledge score (KS) was calculated for each RES based on the total correct responses. Attitudes were assessed via 5-point Likert scale. Frequencies, t-test and McNemar tests were used to analyse data. RESULTS: Thirty four completed surveys were analysed out of 49 RES (69.3%) who attended the workshop. Among them, there were 19 first-year, 8 second-year and 7 third-year residents. Following the intervention, KS increased significantly (p<0.001) with progression in residents' attitudes. Overall, more RES reported being comfortable with handling the IP, including looking up and changing the settings (p<0.001). CONCLUSION: There is scope for improvement in the knowledge and perceptions of RES regarding IPs. Educational interventions like ours are needed to familiarise our future physicians with IPs to allow hospitals to provide their systematic and safe inpatient use.

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.

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.

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.

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.

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.

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.

Presence of 21-Hydroxylase Antibodies in a Boy with X-Linked Adrenal Hypoplasia Congenita.

BACKGROUND: X-linked adrenal hypoplasia congenita is a rare cause of primary adrenal insufficiency (PAI) in children due to mutations in NR0B1/DAX1 (nuclear receptor subfamily 0, group B, member 1/dosage-sensitive sex reversal-adrenal hypoplasia congenita at the critical region of the X chromosome, gene 1). Another rare cause of PAI in children is autoimmune adrenal disease (AAD) which could be either isolated or as part of autoimmune polyglandular syndrome. Antibody to major auto-antigen, 21-hydroxylase, is highly specific for AAD. METHODS: We report a now 19-month-old male with PAI due to NR0B1 gene mutation and positive adrenal antibodies. Initially, he presented at 15 days of life with isolated hypoaldosteronism which later unfolded into complete PAI. Data analysis was done via retrospective chart review. RESULTS: Genetic analysis of the NR0B1 gene revealed a known hemizygous mutation in c.1069C>T; p.Gln357X. Simultaneously, he was noted to have positive 21-hydroxylase antibodies. CONCLUSION: According to our knowledge, this is the first case in the literature with NR0B1 mutation causing adrenal insufficiency with coexistent positive adrenal antibodies. In addition to his already compromised adrenal function due to NR0B1 mutation, he is now at risk for the development of associated autoimmune conditions requiring close follow-up.