Deep Vein Thrombosis as the Presenting Sign in an Adolescent With New-Onset Type 2 Diabetes.

Prothrombin G20210A mutation occurs in only 2% to 3% of the population, but usually does not become apparent unless the individual exhibits another risk factor for clotting. A risk factor such as hyperglycemia in the setting of diabetes mellitus may accelerate this clotting process, even at a very young age. In this case report, we discuss a 15-year-old boy presenting with left calf swelling and pain, found to have extensive deep vein thrombosis in the setting of hyperglycemia and a newly discovered prothrombin G20210A mutation. Venous thromboembolism in the setting of type 2 diabetes mellitus has not been described in children.

Thyrotoxicosis and Impending Thyroid Storm: A Rare Paraneoplastic Syndrome in an Infant With Hepatoblastoma.

Graves' disease is the most common cause of pediatric hyperthyroidism and thyrotoxicosis. Thyroid storm is a rare initial manifestation of Graves' disease and represents an endocrine emergency. We report a case of transient hyperthyroidism, possibly a paraneoplastic syndrome presenting as impending thyroid storm in a patient with undiagnosed hepatoblastoma. To our knowledge, this is the first case of this association reported in children. A previously healthy 21-month-old male presented with abdominal pain and unremitting tachycardia. He was managed for thyrotoxicosis and impending thyroid storm. He subsequently was found to have hepatomegaly leading to a diagnosis of hepatoblastoma. Autoimmune markers for Graves' disease were negative, along with a negative human chorionic gonadotropin. After initiation of neoadjuvant chemotherapy, he had complete resolution of thyrotoxicosis. Paraneoplastic syndromes may occur with any tumor. We present a unique case of a patient developing human chorionic gonadotropin-negative hyperthyroidism, possibly as a paraneoplastic syndrome from hepatoblastoma.

Telehealth and Type 1 Diabetes Care During COVID-19: Perceptions From Youth of Color, Caregivers, and Health Care Providers.

Objective: At the outset of the coronavirus disease 2019 (COVID-19) pandemic, health care systems rapidly implemented telehealth services to maintain continuity of type 1 diabetes care. Youth of color are more likely to have suboptimal glycemic control and may benefit most from efforts to ensure continuity of care. However, research examining the perspectives of families of youth of color regarding telehealth for pediatric type 1 diabetes care is limited. We gathered perspectives from youth of color, their caregivers, and health care providers (HCPs) on telehealth for type 1 diabetes care during COVID-19. Methods: Fifty participants (22 caregivers, 19 youth, and nine HCPs) completed semi-structured interviews conducted in English (n = 44) or Spanish (n = 6). Transcripts containing mentions of telehealth (n = 33) were included for qualitative analysis to extract themes pertaining to perceptions of type 1 diabetes care and telehealth use during COVID-19. Results: Themes related to perceptions, feasibility, and quality of telehealth diabetes care were obtained. Most families had positive perceptions of telehealth. Families and HCPs described logistical and technical challenges and noted the potential for disparities in telehealth access and use. Furthermore, caregivers and HCPs felt that the lack of in-person interaction and limited access to clinical data affected the quality of care. Conclusion: Families of youth of color with type 1 diabetes mostly had positive perceptions of telehealth but also identified issues with feasibility and quality of care. Our findings highlight a need for interventions promoting equal access to telehealth and quality care for all youth with type 1 diabetes to minimize disruptions in care.

Two Unusual Cases of Pituitary Tumors Presenting with Pediatric Acromegaly.

Gigantism and acromegaly are most commonly caused by a growth hormone (GH)-secreting pituitary adenoma. Pediatric cases are diagnostically and therapeutically challenging due to their insidious nature. This article presents two adolescent females who were referred to the endocrinology clinic primarily for the evaluation of menstrual disorders rather than for concerns about GH excess. Patient one was a 16-year-old who presented with primary amenorrhea and tall stature, and patient two, a 15-year-old, presented with a history of irregular menstruation. Both patients were noted to have acromegalic features, and an extensive work-up confirmed GH-secreting pituitary adenomas. In addition, patient two had significant hyperprolactinemia. Transsphenoidal tumor resection was performed on both patients; patient one had a successful complete resection and achieved endocrine remission, while patient two underwent partial resection followed by a short clinical trial of pegvisomant without significant success. Improved clinical knowledge through case reports can assist with the early diagnosis and management of such rare pediatric conditions.

Treatment Burden of Weekly Somatrogon vs Daily Somatropin in Children With Growth Hormone Deficiency: A Randomized Study.

Context: Somatrogon is a long-acting recombinant human growth hormone treatment developed as a once-weekly treatment for pediatric patients with growth hormone deficiency (GHD). Objective: Evaluate patient and caregiver perceptions of the treatment burden associated with the once-weekly somatrogon injection regimen vs a once-daily Somatropin injection regimen. Methods: Pediatric patients (≥3 to <18 years) with GHD receiving once-daily somatropin at enrollment were randomized 1:1 to Sequence 1 (12 weeks of once-daily Somatropin, then 12 weeks of once-weekly somatrogon) or Sequence 2 (12 weeks of once-weekly somatrogon, then 12 weeks of once-daily Somatropin). Treatment burden was assessed using validated questionnaires completed by patients and caregivers. The primary endpoint was the difference in mean overall life interference (LI) total scores after each 12-week treatment period (somatrogon vs Somatropin), as assessed by questionnaires. Results: Of 87 patients randomized to Sequence 1 (n = 43) or 2 (n = 44), 85 completed the study. Once-weekly somatrogon had a significantly lower treatment burden than once-daily Somatropin, based on mean overall LI total scores after somatrogon (8.63) vs Somatropin (24.13) treatment (mean difference -15.49; 2-sided 95% CI -19.71, -11.27; P < .0001). Once-weekly somatrogon was associated with greater convenience, higher satisfaction with treatment experience, and less LI. The incidence of treatment-emergent adverse events (TEAEs) for Somatropin and somatrogon was 44.2% and 54.0%, respectively. No severe or serious AEs were reported. Conclusion: In pediatric patients with GHD, once-weekly somatrogon had a lower treatment burden and was associated with a more favorable treatment experience than once-daily Somatropin.

Erratum: Feasibility of Implementing a Pediatric Diabetes Clinic via Telehealth. Diabetes Spectrum 2021;34:190-197 (https://doi.org/10.2337/ds20-0060).

[This corrects the article on p. 190 in vol. 34, PMID: 34149260.].

Feasibility of Implementing a Pediatric Diabetes Clinic via Telehealth.

OBJECTIVE: In response to the coronavirus disease 2019 (COVID-19) pandemic and social distancing guidelines, our pediatric diabetes team rapidly changed the format of conducting diabetes clinic from in person to telehealth. We compared the actual number and rate of completed, canceled, and no-show visits between an 8-week period in 2019, when we exclusively conducted visits in person and the same 8-week period in 2020, during the COVID-19 quarantine, when we exclusively conducted visits via telehealth. METHODS: We used electronic health record data for all patients, as well as Dexcom continuous glucose monitoring data collected for a subset of youths during the COVID-19 quarantine and the immediate pre-COVID-19 period. RESULTS: Although there was a difference in the absolute number of in-person versus telehealth visits canceled during these two time periods, there was no difference in the rates of completed, canceled, and no-show visits completed in person or via telehealth. This finding suggests that, despite a rapid shift to a completely new health care delivery model, our providers completed a similar rate of patient care via telehealth during the COVID-19 quarantine and that telehealth may be a feasible method for providing diabetes care. However, our results also suggested that youths' glucose management was less optimal during the quarantine period. CONCLUSION: COVID-19 presented an opportunity to adopt and test the feasibility of using a telehealth delivery model for routine diabetes care. Yet, to make telehealth a viable treatment delivery alternative will likely involve the uptake of new clinic procedures, investment in institutional infrastructure, and team-based flexibility.

A Case of Familial Male-limited Precocious Puberty with a Novel Mutation

Familial male-limited precocious puberty (FMPP), also known as testotoxicosis, is a rare cause of precocious puberty in males. It is caused by a mutation in the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) gene, resulting in the receptor being constitutively activated. This causes excessive production of testosterone, leading to precocious puberty in males. Generally, boys present with signs of puberty, such as pubic hair growth, acne, and increased height velocity around the age of 2-4 years old. Like any other cause of precocious puberty, the goal of treatment is to prevent virilization and also delay closure of the epiphyseal plates to maintain adult height potential. Treatment, therefore, is aimed at decreasing the effects of testosterone, as well as stopping the conversion of testosterone to estrogen. Little is known about the long-term effects of treatment because the disorder is so rare. However, studies using bicalutamide and anastrozole have been promising. In this report, we present a boy with FMPP with a novel mutation in the LHCGR gene, who has been responding well to therapy using both drugs.

Severe Hypercalcemia in an Adolescent with New-Onset Diabetes Mellitus and Diabetic Ketoacidosis.

Severe hypercalcemia in diabetic ketoacidosis (DKA) among children is rare and can be life-threatening. Its exact etiology is not clear and several mechanisms related to dehydration and metabolic acidosis have been proposed. Rigorous hydration with the correct fluid choice usually corrects the hypercalcemia in those without other underlying causes of hypercalcemia such as hyperparathyroidism. Specific medications to treat the hypercalcemia may be avoided. We present a 13-year-old girl with new type 1 onset diabetes mellitus in DKA with unusually severe and persistent hypercalcemia and severe hypernatremia that gradually responded to rigorous intravenous hydration with Plasmalyte A (Baxter International Inc., Deerfield, Illinois).

Prevalence of Vitamin D Deficiency in Children with Type 1 Diabetes Mellitus.

Background In the recent years, controversy has emerged regarding the relationship between vitamin D deficiency and the potential effects it could have on glycemic control in patients with type 1 diabetes mellitus (T1D). This study investigates the prevalence of vitamin D insufficiency/deficiency in pediatric patients with T1D from a single, large volume practice. Methods This was a retrospective chart review that collected clinical/demographic data as well as serum 25(OH) D levels from medical records of 395 children between the ages of 3 and 18 years with T1D followed at Nemours Children's Hospital. This data was compared to the National Health and Nutrition Examination Survey (NHANES) database. A Pearson's Chi-square test was used between group associations. All statistical tests were two-sided and p < 0.05 was used for statistical significance. Results Of the 395 children included in these analyses, 4% were vitamin D deficient and 60% were vitamin D insufficient. There were no significant associations of vitamin D deficiency based on sex and age. Vitamin D deficiency was more common among White children when compared to Hispanic children and African American children (42% vs 29%; p < 0.001). Of those that were vitamin D insufficient (n = 235), most were Hispanic (51%), 36% White and 13% African American. There was a significant association between vitamin D deficiency and body mass index (BMI) (p = 0.035). In the summer, children were less likely to be vitamin D deficient (3% vs 6% in winter) and less likely to be vitamin D insufficient (55% vs 71% in winter) (p = 0.007). Conclusions Vitamin D insufficiency is highly prevalent among pediatric type 1 diabetics of Central Florida and statistically significant correlation was found between vitamin D status and ethnicity, BMI as well as seasonal variation.

Electronically Verified Use of Internet-Based, Multimedia Decision Aids by Adolescents With Type 1 Diabetes and Their Caregivers.

Decision aids (DAs) are central to shared decision making (SDM) interventions, yet little is known about patients' actual DA use. Adequate utilization of DAs could optimize SDM effectiveness. Electronic DAs enable more objective tracking and analysis of actual DA utilization than do paper DAs. This report is part of an ongoing randomized controlled SDM trial enrolling adolescents with type 1 diabetes and their caregivers (n = 153) who were considering use of an insulin pump or continuous glucose monitor. Extensive stakeholder engagement guided creation of two online DAs. After completing baseline measures, 133 dyads were randomized to SDM (access to the pertinent DA) or Usual Care (clinic routines for preparing candidates for adopting these devices). Utilization data showed that 80% of caregivers and 66% of youths logged into a DA at least once; youths and caregivers, respectively, dedicated a mean of 44.7 and 55.0 minutes to website use and viewed 72.2% and 77.4% of the DA content. Median total duration from enrollment to last DA logout was 48.2 days for adolescents and 45.6 days for caregivers. Bivariate comparisons showed that non-Hispanic, Caucasian females from households with higher socioeconomic status were significantly more likely to login to the assigned DA at least once. Hierarchical multiple regression showed that adolescent males with lower levels of health literacy demonstrated fewer DA logins (F = 2.59; P < 0.009), but identified no significant predictors of adolescents' or caregiver' duration of DA use or proportion of DA content viewed. Future SDM trials should seek to promote DA use, especially by non-White adolescents, perhaps with direct assistance with the initial DA login. Trials employing electronic DAs should routinely report and analyze utilization data.

Consideration of Insulin Pumps or Continuous Glucose Monitors by Adolescents With Type 1 Diabetes and Their Parents: Stakeholder Engagement in the Design of Web-Based Decision Aids.

PURPOSE: This article describes the stakeholder-driven design, development, and testing of web-based, multimedia decision aids for youth with type 1 diabetes who are considering the insulin pump or continuous glucose monitoring and their parents. This is the initial phase of work designed to develop and evaluate the efficacy of these decision aids in promoting improved decision-making engagement with use of a selected device. METHODS: Qualitative interviews of 36 parents and adolescents who had previously faced these decisions and 12 health care providers defined the content, format and structure of the decision aids. Experts in children's health media helped the research team to plan, create, and refine multimedia content and its presentation. A web development firm helped organize the content into a user-friendly interface and enabled tracking of decision aid utilization. Throughout, members of the research team, adolescents, parents, and 3 expert consultants offered perspectives about the website content, structure, and function until the design was complete. RESULTS: With the decision aid websites completed, the next phase of the project is a randomized controlled trial of usual clinical practice alone or augmented by use of the decision aid websites. CONCLUSIONS: Stakeholder-driven development of multimedia, web-based decision aids requires meticulous attention to detail but can yield exceptional resources for adolescents and parents contemplating major changes to their diabetes regimens.

A 4-Year, Open-Label, Multicenter, Randomized Trial of Genotropin® Growth Hormone in Patients with Idiopathic Short Stature: Analysis of 4-Year Data Comparing Efficacy, Efficiency, and Safety between an Individualized, Target-Driven Regimen and Standard Dosing.

BACKGROUND/AIMS: Growth hormone (GH) treatment regimens for children with non-GH-deficient, idiopathic short stature (ISS) have not been optimized. To compare the efficacy, efficiency, and safety of an individualized, target-driven GH regimen with standard weight-based dosing after 4 years of treatment. METHODS: This is a 4-year, open-label, multicenter, randomized trial comparing individualized, formula-based dosing of Genotropin® versus a widely used ISS dose of Genotropin®. Subjects were prepubertal, had a bone age of 3-10 years for males and 3-9 years for females, were naive to GH treatment, and had a height standard deviation score (Ht SDS) of -3 to -2.25, a height velocity <25th percentile for their bone age, and peak stimulated GH >10 ng/ml. After the first 2 years, the individualized-dosing group was further randomized to either 0.18 or 0.24 mg/kg/week. RESULTS: At 4 years, subjects in all treatment regimens achieved similar average height gains of +1.3 SDS; however, the individualized dosing regimen utilized less GH to achieve an equivalent height gain. CONCLUSION: Individualized, formula-based GH dosing, followed by a dose reduction after 2 years, provides a more cost-effective growth improvement in patients with ISS than currently employed weight-based regimens.

A new missense mutation in the growth hormone-releasing hormone receptor gene in familial isolated GH deficiency.

OBJECTIVE: Mutations in the GH-releasing hormone (GHRH) receptor (GHRHR) gene (GHRHR) cause autosomal recessive familial isolated GH deficiency (IGHD). We searched for GHRHR mutations in two siblings with IGHD type IB and a history of parental consanguinity. DESIGN: We analyzed peripheral genomic DNA of an index patient. After identifying a novel mutation in the GHRHR, we performed functional studies in order to confirm that the mutation causes receptor malfunction. METHODS: The entire GHRHR was analyzed in the index case by denaturing gradient gel electrophoresis. Abnormally migrating bands were isolated and sequenced. The mutated area was then sequenced in all family members whose DNA was available. The newly found mutation was inserted into a GHRHR cDNA. Wild-type and mutant cDNAs were expressed into CHO cells and the cyclic AMP (cAMP) response to GHRH was measured. In order to determine whether the mutant receptor was properly expressed on the cell membrane surface, CHO cells were transfected with wild-type or mutant GHRHR cDNA containing a FLAG epitope tag in the extracellular N-terminus. RESULTS: Both patients were homozygous for a new missense mutation in codon 176, corresponding to the second transmembrane domain of the receptor protein that replaces alanine with valine (A176V). The mother and three unaffected siblings were heterozygous for the mutation; DNA from the father was not available. Cells expressing the A176V receptor had a significantly reduced cAMP response to GHRH, despite appropriate expression on the cell surface. CONCLUSIONS: We describe two siblings with IGHD due to a new mutation in the GHRHR that disrupts GHRH signaling and leads to GHRH resistance.

Neonatal hypocalcemic seizures: case report and literature review.

Seizures during the neonatal period have a broad differential diagnosis, many with a specific treatment and prognosis. In the case reported, a combination of dietary and endocrinologic abnormalities resulted in hypocalcemic seizures, which continued despite aggressive correction of serum ionized calcium levels. Serial electroencephalograms (EEG) performed during the hospitalization were markedly abnormal, and treatment with anticonvulsant drugs was considered given the persistence of seizures despite normalization of serum calcium levels. After 4 days of intravenous calcium administration, the seizure activity resolved, and the patient returned to his normal baseline level of functioning. This case highlights the clinical course of neonatal hypocalcemic seizures, EEG findings in several cases, and possible mechanisms for both hypocalcemic precipitation of seizures and anticonvulsant ineffectiveness.