Faculty Bibliography

Objective/UNASSIGNED:Neutropenia can occur from untreated autoimmune hyperthyroidism (AIH) or methimazole (MMI); starting MMI in children and adolescents with AIH and neutropenia could thus be worrisome. We aimed to describe the prevalence of neutropenia in children and adolescents with AIH prior to treatment with antithyroid drugs and to assess the effect of antithyroid drugs on the neutrophil count. Methods/UNASSIGNED:This was a retrospective study of patients with AIH seen at a Pediatric Endocrinology clinic. ANC data at presentation and during anti-thyroid treatment for up to 24 weeks was collected. AIH was defined as elevated fT4 or fT3, suppressed TSH, and positive thyroid autoantibodies. Neutropenia was defined as ANC <1500 cells/μl. Results/UNASSIGNED:31 patients were included: 71% females, 29% males, median age 14.71 years (IQR 11.89-17.10). Neither fT4 nor fT3 levels significantly correlated with ANC at presentation (rs = 0.22, p = 0.24 and rs = 0.13, p = 0.54, respectively). 26/31 (84%) had normal baseline ANC; none developed neutropenia with thionamides. 5/31 (16%) had baseline neutropenia (median 1,200/μl; IQR 874-1200); 4/5 patients started MMI at diagnosis; 1/5 started propranolol only then added MMI 1 week later; all normalized ANC within 24 weeks. Conclusion/UNASSIGNED:A small percentage of AIH patients may have neutropenia at presentation, but it resolves in the short term and does not worsen with thionamides. Thionamides may be used with caution in these patients with close monitoring of blood counts.

BACKGROUND:Diabetes is a risk factor for poor COVID-19 outcomes, but pediatric patients with type 1 diabetes are poorly represented in current studies. METHODS:T1D Exchange coordinated a US type 1 diabetes COVID-19 registry. Forty-six diabetes centers submitted pediatric cases for patients with laboratory confirmed COVID-19. Associations between clinical factors and hospitalization were tested with Fisher's Exact Test. Logistic regression was used to calculate odds ratios for hospitalization. RESULTS:Data from 266 patients with previously established type 1 diabetes aged <19 years with COVID-19 were reported. Diabetic ketoacidosis (DKA) was the most common adverse outcome (n = 44, 72% of hospitalized patients). There were four hospitalizations for severe hypoglycemia, three hospitalizations requiring respiratory support (one of whom was intubated and mechanically ventilated), one case of multisystem inflammatory syndrome in children, and 10 patients who were hospitalized for reasons unrelated to COVID-19 or diabetes. Hospitalized patients (n = 61) were more likely than nonhospitalized patients (n = 205) to have minority race/ethnicity (67% vs 39%, P < 0.001), public insurance (64% vs 41%, P < 0.001), higher A1c (11% [97 mmol/mol] vs 8.2% [66 mmol/mol], P < 0.001), and lower insulin pump and lower continuous glucose monitoring use (26% vs 54%, P < 0.001; 39% vs 75%, P < 0.001). Age and gender were not associated with risk of hospitalization. Higher A1c was significantly associated with hospitalization, with an odds ratio of 1.56 (1.34-1.84) after adjusting for age, gender, insurance, and race/ethnicity. CONCLUSIONS:Higher A1c remained the only predictor for hospitalization with COVID-19. Diabetic ketoacidosis is the primary concern among this group.

Background:Coronavirus-19 (COVID-19) is a disease caused by the SARS-CoV-2 virus, the seventh coronavirus identified as causing disease in humans. The SARS-CoV-2 virus has multiple potential pathophysiologic interconnections with endocrine systems, potentially causing disturbances in glucose metabolism, hypothalamic and pituitary function, adrenal function and mineral metabolism. A growing body of data is revealing both the effects of underlying endocrine disorders on COVID-19 disease outcome and the effects of the SARS-CoV-2 virus on endocrine systems. However, comprehensive assessment of the relationship to endocrine disorders in children has been lacking. Content:In this review, we present the effects of SARS-CoV-2 infection on endocrine systems and review the current literature on complications of COVID-19 disease in underlying paediatric endocrine disorders. We provide recommendations on management of endocrinopathies related to SARS-CoV-2 infection in this population. Summary and outlook:With the surge in COVID-19 cases worldwide, it is important for paediatric endocrinologists to be aware of the interaction of SARS-CoV-2 with the endocrine system and management considerations for patients with underlying disorders who develop COVID-19 disease. While children and adults share some risk factors that influence risk of complications in SARS-CoV-2 infection, it is becoming clear that responses in the paediatric population are distinct and outcomes from adult studies cannot be extrapolated. Evidence emerging from paediatric studies provides some guidance but highlights the need for more research in this area.

Summary/UNASSIGNED:We describe a case of an infant who presented with clinical features of hyperthyroidism. The child was found to be tachycardic, hypertensive and diaphoretic, she was noted to have poor weight gain and difficulty in sleeping. The child was admitted to the pediatric intensive care unit for care. She was found to have biochemical evidence of hyperthyroidism with positive thyroid stimulating immunoglobulin. She responded well to methimazole and propranolol and had a remarkable recovery. She is the youngest patient to be diagnosed with Graves disease in the English literature, at 12 months of life. Learning points/UNASSIGNED:Hyperthyroidism must always be considered even at very young age, for patient presenting with poor weight gain and hyperdynamic state. Autoimmune diseases are becoming more common in infancy. Craniosynostosis and increased height for age are well-documented consequences of untreated hyperthyroidism in developing children.

OBJECTIVES/OBJECTIVE:There have been few large-scale studies utilizing exome sequencing for genetically undiagnosed maturity onset diabetes of the young (MODY), a monogenic form of diabetes that is under-recognized. We describe a cohort of 160 individuals with suspected monogenic diabetes who were genetically assessed for mutations in genes known to cause MODY. METHODS:. The average age of onset of hyperglycemia or diabetes diagnosis was 19 years (median 14 years) with an average HbA1C of 7.1%. RESULTS:. For those probands with available family members, 100% of the variants segregated with diabetes in the family. Cascade genetic testing in families identified 75 additional family members with a familial MODY mutation. CONCLUSIONS:Our study is one of the largest and most ethnically diverse studies using exome sequencing to assess MODY genes. Tiered testing is an effective strategy to genetically diagnose atypical diabetes, and familial cascade genetic testing identified on average one additional family member with monogenic diabetes for each mutation identified in a proband.

OBJECTIVE:We examined whether diabetic ketoacidosis (DKA), a serious complication of type 1 diabetes (T1D) was more prevalent among Non-Hispanic (NH) Black and Hispanic patients with T1D and laboratory-confirmed coronavirus disease 2019 (COVID-19) compared with NH Whites. METHOD:This is a cross-sectional study of patients with T1D and laboratory-confirmed COVID-19 from 52 clinical sites in the United States, data were collected from April to August 2020. We examined the distribution of patient factors and DKA events across NH White, NH Black, and Hispanic race/ethnicity groups. Multivariable logistic regression analysis was performed to examine the odds of DKA among NH Black and Hispanic patients with T1D as compared with NH White patients, adjusting for potential confounders, such as age, sex, insurance, and last glycated hemoglobin A1c (HbA1c) level. RESULTS:We included 180 patients with T1D and laboratory-confirmed COVID-19 in the analysis. Forty-four percent (n = 79) were NH White, 31% (n = 55) NH Black, 26% (n = 46) Hispanic. NH Blacks and Hispanics had higher median HbA1c than Whites (%-points [IQR]: 11.7 [4.7], P < 0.001, and 9.7 [3.1] vs 8.3 [2.4], P = 0.01, respectively). We found that more NH Black and Hispanic presented with DKA compared to Whites (55% and 33% vs 13%, P < 0.001 and P = 0.008, respectively). After adjusting for potential confounders, NH Black patients continued to have greater odds of presenting with DKA compared with NH Whites (OR [95% CI]: 3.7 [1.4, 10.6]). CONCLUSION:We found that among T1D patients with COVID-19 infection, NH Black patients were more likely to present in DKA compared with NH White patients. Our findings demonstrate additional risk among NH Black patients with T1D and COVID-19.

BACKGROUND:The diagnosis of hypoglycemia and the use of diazoxide have risen in the last decade. Diazoxide is the only Food and Drug Agency-approved pharmacologic treatment for neonatal hypoglycemia caused by hyperinsulinism (HI). Recent publications have highlighted that diazoxide has serious adverse effects (AEs) such as pulmonary hypertension (2-3%) and neutropenia (15%). Despite its increasing use, there is little information regarding dosing of diazoxide and/or monitoring for AEs. METHODS:We convened a working group of pediatric endocrinologists who were members of the Drug and Therapeutics Committee of the Pediatric Endocrine Society (PES) to review the available literature. Our committee sent a survey to its PES members regarding the use of diazoxide in their endocrine practices. Our review of the results concluded that there was substantial heterogeneity in usage and monitoring for AEs for diazoxide among pediatric endocrinologists. CONCLUSIONS:Based on our extensive literature review and on the lack of consensus regarding use of diazoxide noted in our PES survey, our group graded the evidence using the framework of the Grading of Recommendations, Assessment, Development and Evaluation Working Group, and has proposed expert consensus practice guidelines for the appropriate use of diazoxide in infants and children with HI. We summarized the information on AEs reported to date and have provided practical ideas for dosing and monitoring for AEs in infants treated with diazoxide.

OBJECTIVE:s rates of childhood obesity and pediatric type 2 diabetes (T2D) increase, a better understanding is needed of how these two conditions relate, and which subgroups of children are more likely to develop diabetes with and without obesity. METHODS:To compare hotspots of childhood obesity and pediatric T2D in New York City, we performed geospatial clustering analyses on obesity estimates obtained from surveys of school-aged children and diabetes estimates obtained from healthcare claims data, from 2009-2013. Analyses were performed at the Census tract level. We then used multivariable regression analysis to identify sociodemographic and environmental factors associated with these hotspots. RESULTS:We identified obesity hotspots in Census tracts with a higher proportion of Black or Hispanic residents, with low median household income, or located in a food swamp. 51.1% of pediatric T2D hotspots overlapped with obesity hotspots. For pediatric T2D, hotspots were identified in Census tracts with a higher proportion of Black residents and a lower proportion of Hispanic residents. CONCLUSIONS:Non-Hispanic Black neighborhoods had a higher probability of being hotspots of both childhood obesity and pediatric type 2 diabetes. However, we identified a discordance between hotspots of childhood obesity and pediatric diabetes in Hispanic neighborhoods, suggesting either under-detection or under-diagnosis of diabetes, or that obesity may influence diabetes risk differently in these two populations. These findings warrant further investigation of the relationship between childhood obesity and pediatric diabetes among different racial and ethnic groups, and may help guide pediatric public health interventions to specific neighborhoods.