Histiocytosis Presenting as Bilateral Adrenal Masses: A Case Report.

Introduction: Adrenal masses are a rare diagnosis in children, with bilateral masses even less common. At present, appearance of the mass on imaging and histology can give important clues to the diagnosis; however, there is significant overlap in 10-30% of cases and it can be difficult to distinguish benign from malignant adrenal masses. As a result, the clinical presentation remains a large part of the diagnostic process, as well as thorough endocrinology evaluation to determine if the tumor is functional versus nonfunctional. Case Presentation: We present a recent case of bilateral adrenal masses in a pediatric patient at our institution, with an unusual diagnosis of histiocytosis. Conclusion: In this case, the diagnosis was unclear, until genetic testing and pathology allowed for expedient diagnosis and targeted therapy for this patient. We hope that presenting this case will increase physician awareness of this condition and expedite diagnosis and treatment in other patients with this rare presentation.

Description of a novel SLC34A3.c.671delT mutation causing hereditary hypophosphatemic rickets with hypercalciuria in two adolescent boys and response to recombinant human growth hormone.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is an autosomal recessive disorder characterized by hypophosphatemia, rickets, hyperphosphaturia, elevated 1,25(OH)2D, and hypercalciuria. Mutations in SLC34A3, the gene encoding the sodium-dependent cotransporter NPT2c, have previously been described as a cause of HHRH. Here, we describe two male siblings with rickets and hypercalciuric nephrolithiasis born to unrelated parents, and their response to oral phosphate supplementation and growth hormone therapy. Whole exome sequencing of the oldest brother, and polymerase chain reaction and Sanger sequence analysis of the identified SLC34A3 mutations, was performed for confirmation and to evaluate his siblings and parents. Serum and urine biochemical parameters of mineral homeostasis before and after therapy were evaluated. Whole exome sequencing analysis identified a previously reported heterozygous deletion SLC34A3.g.2259-2359del101bp on the maternal allele, and a novel heterozygous single nucleotide deletion SLC34A3.c.671delT on the paternal allele of the two affected brothers. The parents and the unaffected brother are heterozygous carriers. Recombinant human growth hormone (rHGH) plus oral phosphate in one affected brother improved the renal phosphate leak and resulted in accelerated linear growth superior to that seen with oral phosphate supplementation alone in the other affected brother. Our case study is the first to demonstrate that rHGH can be considered in addition to oral supplementation with phosphorus to improve linear growth in patients with this disorder, and suggests that renal phosphate reabsorption in response to rHGH is NPT2c-independent.

Case Studies in Pediatric Endocrinology: An Interactive Learning Module.

INTRODUCTION: Pediatrics is an exciting field because it requires having a background in physiology that evolves as the patient ages. As a subspecialty, pediatric endocrinology encompasses a wide range of disease processes both acute and chronic. This module was created to provide a review of endocrine physiology, promote understanding of the biopsychosocial model of children diagnosed with an endocrine disorder, and utilize simulated case studies to become familiar with patient management. METHODS: The material and case studies presented are based on firsthand experiences in a pediatric clinic and diabetes camp, as well as an extensive literature review. The information in this resource teaches interview questions and problem-solving techniques and ensures that the learner understands the basic equipment used by the patients. Implementation of this module will advance students' and residents' efficacy in caring for this pediatric population. The approximate time to complete this module is 3 to 5 hours. To evaluate the effectiveness of this module, pre- and postmodule surveys were administered to medical students. Factors analyzed included overall user satisfaction, utility of the module, comfort in approaching pediatric endocrine patients, and suggestions for improvement. RESULTS: A cohort of medical students (N = 26) completed both surveys and the module, with an equal distribution of first- and second-year students to third- and fourth-year students. The surveys showed a general trend of improvement in self-reported comfort with both basic science and clinical skills components. DISCUSSION: This module would be most beneficial to a medical student who may rotate with a pediatric endocrinologist during the clinical years. The target audience can be broadened to include not only medical students but also physician assistant students, nursing/nurse practitioner students, pediatric residents, and pediatric endocrinology fellows.

Type 2 diabetes mellitus in children and adolescents.

Type 2 diabetes mellitus (T2DM) is a chronic progressive disease with high morbidity and mortality rates. Previously an adult onset disease, it is now being diagnosed more and more in childhood and adolescence. Lately, Asia has become the epicenter of this epidemic. Childhood T2DM is a new challenge for the pediatrician. Due to similarities in presentation, children may initially be misdiagnosed with Type 1 diabetes mellitus (T1DM). Most oral anti-diabetic agents have not been approved for use in adolescents, and there is a concern for safety of their use. Lifestyle intervention is difficult to conduct, and adherence to recommendations is lower in adolescents than in adults with T2DM. Higher incidence and early onset of co-morbidities, with lack of long term outcomes data make the management problematic. In many communities, due to a shortage of specialists, general practitioners will treat children with T2DM. Guidelines cited in this review are designed to help with the diagnostic process and management.

Hereditary vitamin D resistant rickets: identification of a novel splice site mutation in the vitamin D receptor gene and successful treatment with oral calcium therapy.

OBJECTIVE: To study the vitamin D receptor (VDR) gene in a young girl with severe rickets and clinical features of hereditary vitamin D resistant rickets, including hypocalcemia, hypophosphatemia, partial alopecia, and elevated serum levels of 1,25-dihydroxyvitamin D. STUDY DESIGN: We amplified and sequenced DNA samples from blood from the patient, her mother, and the patient's two siblings. We also amplified and sequenced the VDR cDNA from RNA isolated from the patient's blood. RESULTS: DNA sequence analyses of the VDR gene showed that the patient was homozygous for a novel guanine to thymine substitution in the 5'-splice site in the exon 8-intron J junction. Analysis of the VDR cDNA using reverse transcriptase-polymerase chain reaction showed that exons 7 and 9 were fused, and that exon 8 was skipped. The mother was heterozygous for the mutation and the two siblings were unaffected. CONCLUSIONS: A novel splice site mutation was identified in the VDR gene that caused exon 8 to be skipped. The mutation deleted amino acids 303-341 in the VDR ligand-binding domain, which is expected to render the VDR non-functional. Nevertheless, successful outpatient treatment was achieved with frequent high doses of oral calcium.

Obstructive sleep apnea in children.

Daina Dreimane, MD, discusses the epidemiology, pathophysiology, diagnosis, and surgical and medical treatment of obstructive sleep apnea in children.

Feasibility of a hospital-based, family-centered intervention to reduce weight gain in overweight children and adolescents.

OBJECTIVE: To evaluate the effects of a hospital-based, family-centered lifestyle program (Kids N Fitness) on weight and health in overweight 7-17-year-old children. DESIGN: The Kids N Fitness program consisting of up to twelve 90-min sessions was conducted in an outpatient setting. The program comprised interactive nutrition and exercise sessions with behavior modification. Subjects completed a logbook and child's health questionnaire. Measures and surveys were taken before, during, and after the program. PARTICIPANTS: Two hundred and sixty-four overweight children (137 female, 73% Hispanic), mean age 11.5+/-2.1 years, with body mass index (BMI)=85th percentile, no physical limitations, and attendance of >or=50% of sessions. A subgroup of 115 children was observed for up to 6 months prior to program. INTERVENTION RESULTS: Weight and BMI velocity, and BMI, and BMI z-score were lower during the program than during the pre-program observation period. Compared, subjects in the 12-week program had significantly reduced gains in weight and greater losses in body mass index, than in 8 weeks. Improvements in emotional well-being and behavior correlated positively with weight loss (p=0.005). CONCLUSIONS: Positive health outcomes suggest that family-centered programs, stressing healthy eating strategies, participation in team-oriented physical activities, and behavior modification, are effective in improving weight dynamics and psychological functioning.

Improvement in risk factors for metabolic syndrome and insulin resistance in overweight youth who are treated with lifestyle intervention.

OBJECTIVE: To evaluate the prevalence of risk factors that are associated with the metabolic syndrome and insulin resistance in overweight youth and to determine the effect of a short-term, family-centered, lifestyle intervention on various associated anthropometric and metabolic measures. METHODS: Overweight youth who were between 8 and 16 years of age participated in a 12-week, family-centered, lifestyle intervention program. Anthropometric and metabolic measures were assessed before the program in all participants (n = 109) and after the program in a subset of the participants (n = 43). RESULTS: At baseline, 49.5% of youth had multiple risk factors associated with the metabolic syndrome, based on a modified definition of the National Cholesterol Education Program, and 10% had impaired fasting glucose and/or impaired glucose tolerance. Measures of insulin resistance correlated significantly with the risk factors of the metabolic syndrome. Forty-three youth had pre- and postintervention evaluations that showed statistically significant improvements in body mass index, systolic blood pressure, lipids (total, low-density lipoprotein cholesterol, and triglycerides), postprandial glucose, and leptin levels. CONCLUSION: Overweight youth have multiple risk factors associated with the metabolic syndrome. A 12-week lifestyle program may have a positive effect on reducing risk factors for the metabolic syndrome and insulin resistance in overweight youth.

A retrospective study of growth hormone use in adolescents with cystic fibrosis.

OBJECTIVES: Studies of growth hormone (GH) effectiveness in prepubertal children with cystic fibrosis (CF) have been published previously. We present a retrospective study of GH treatment in adolescents with CF. STUDY DESIGN: We performed a retrospective evaluation of data from 25 pubertal adolescents (ages 13 years 4 months to 16 years 11 months, Tanner stage III or IV). Thirteen (4 F) were followed for 1 year, then received 1 year of treatment with GH (GHTX). We compared the results with a 'control' group of 12 (4 F) whose growth was followed for 1 year (NonTX) but who were not treated with GH at the time of this review. Anthropometric data included: height, weight, lean tissue mass (LTM) and bone mineral content (BMC). Pulmonary function, number of hospitalizations, glycosylated haemoglobin (HbA1c), random blood glucose levels, IGF-I, oestradiol and testosterone levels are also reported. RESULTS: There was no difference between the groups at baseline. After 1 year, GHTX had significantly greater height and weight velocity, height and weight Z-scores, body mass index (BMI), LTM and BMC. Absolute pulmonary function was better and hospitalizations were fewer in the GHTX. No subject developed glucose intolerance or had any other side-effects. CONCLUSION: These results suggest that GH use in pubertal adolescents with CF safely improves height, body weight, bone mineralization and clinical status.