Ovarian tumors in the pediatric population: An update.

Research reveals that 1% of neoplasms in females under 17 years of age are ovarian neoplasms and though usually benign, malignant tumors may occur in the pediatric age group. This review considers various current concepts of these tumors including the epidemiology, risk factors, clinical presentations, diagnosis, differential diagnosis, and treatment options including the need to provide fertility-sparing surgery as well as their potential impacts on the psychological well-being of children and adolescents. We gathered data from the published articles ranging from studies, meta-analyses, retrospective studies, and reviews. We focused on the articles published in English between January 1, 2000, and August 31, 2023. Only a few articles published prior to 2000 were included for historical perspective.

Type 1 Diabetes in a Pediatric Patient With Beckwith-Wiedemann Syndrome.

Beckwith-Wiedemann syndrome (BWS) is a genetic overgrowth syndrome with multiple clinical manifestations, including hypoglycemia. Various genetic alterations leading to BWS have been described. Literature has also described the association between BWS and congenital diabetes, but little is known about the association with type 1 diabetes (T1D). We report a 4-year-old female patient with co-occurring BWS and T1D. The patient presented with 2.4-kilogram weight loss in 3 months accompanied by headache, polyuria, and polydipsia. Initial workup showed blood glucose of 681 mg/dL (37.8 mmol/L). Additional workup revealed marked elevation of the glutamic acid decarboxylase 65 and insulin antibodies, confirming the diagnosis of T1D. The patient's initial genetic test results revealed BWS caused by hypomethylation of the imprinting center 2 (IC2) found on maternal chromosome 11. Concurrence of BWS and T1D is rare and there are cases previously described where BWS has co-occurred with congenital diabetes but not T1D. Although the etiology of acquired autoimmunity is unclear, the answer may lie in genetic analysis or autoimmunity secondary to preceding viral illness. Regardless of the etiology, this case emphasizes further exploration of the association between BWS and T1D.

Health equity in pediatrics: Current concepts for the care of children in the 21st century (Dis Mon).

This is an analysis of important aspects of health equity in caring for children and adolescents written by a multidisciplinary team from different medical centers. In this discussion for clinicians, we look at definitions of pediatric health equity and the enormous impact of social determinants of health in this area. Factors involved with pediatric healthcare disparities that are considered include race, ethnicity, gender, age, poverty, socioeconomic status, LGBT status, living in rural communities, housing instability, food insecurity, access to transportation, availability of healthcare professionals, the status of education, and employment as well as immigration. Additional issues involved with health equity in pediatrics that are reviewed will include the impact of the COVID-19 pandemic, behavioral health concepts, and the negative health effects of climate change. Recommendations that are presented include reflection of one's own attitudes on as well as an understanding of these topics, consideration of the role of various healthcare providers (i.e., community health workers, peer health navigators, others), the impact of behavioral health integration, and the need for well-conceived curricula as well as multi-faceted training programs in pediatric health equity at the undergraduate and postgraduate medical education levels. Furthermore, ongoing research in pediatric health equity is needed to scrutinize current concepts and stimulate the development of ideas with an ever-greater positive influence on the health of our beloved children. Clinicians caring for children can serve as champions for the optimal health of children and their families; in addition, these healthcare professionals are uniquely positioned in their daily work to understand the drivers of health inequities and to be advocates for optimal health equity in the 21st century for all children and adolescents.

Ergogenic Aids and Testing in Pediatric Athletes.

In the quest for winning the game, some athletes take various chemicals (ie, drugs, herbs, or supplements) in attempts to develop greater strength, endurance, or other elements that bring a competitive advantage. There are more than 30,000 chemicals sold throughout the world with unrestrained and unproven claims; however, some athletes consume them with hopes of increasing their athletic abilities, often without knowledge of the potential adverse effects and with limited evidence of efficacy. Complicating this picture is that research on ergogenic chemicals is typically conducted with elite adult male athletes and not with athletes who are in high school. A few of these ergogenic aids include creatine, anabolic androgenic steroids, selective androgen receptor modulators, clenbuterol, androstenedione, dehydroepiandrosterone, human growth hormone, ephedrine, gamma hydroxybutyrate, caffeine, stimulants (amphetamines or methylphenidate), and blood doping. In this article, we describe the purpose of ergogenic aids as well as the potential side effects. [Pediatr Ann. 2023;52(6):e207-e212.].

Psychosocial aspects of sports medicine in pediatric athletes: Current concepts in the 21st century.

Behavioral aspects of organized sports activity for pediatric athletes are considered in a world consumed with winning at all costs. In the first part of this treatise, we deal with a number of themes faced by our children in their sports play. These concepts include the lure of sports, sports attrition, the mental health of pediatric athletes (i.e., effects of stress, anxiety, depression, suicide in athletes, ADHD and stimulants, coping with injuries, drug use, and eating disorders), violence in sports (i.e., concepts of the abused athlete including sexual abuse), dealing with supervisors (i.e., coaches, parents), peers, the talented athlete, early sports specialization and sports clubs. In the second part of this discussion, we cover ergolytic agents consumed by young athletes in attempts to win at all costs. Sports doping agents covered include anabolic steroids (anabolic-androgenic steroids or AAS), androstenedione, dehydroepiandrostenedione (DHEA), human growth hormone (hGH; also its human recombinant homologue: rhGH), clenbuterol, creatine, gamma hydroxybutyrate (GHB), amphetamines, caffeine and ephedrine. Also considered are blood doping that includes erythropoietin (EPO) and concepts of gene doping. In the last section of this discussion, we look at disabled pediatric athletes that include such concepts as athletes with spinal cord injuries (SCIs), myelomeningocele, cerebral palsy, wheelchair athletes, and amputee athletes; also covered are pediatric athletes with visual impairment, deafness, and those with intellectual disability including Down syndrome. In addition, concepts of autonomic dysreflexia, boosting and atlantoaxial instability are emphasized. We conclude that clinicians and society should protect our precious pediatric athletes who face many challenges in their involvement with organized sports in a world obsessed with winning. There is much we can do to help our young athletes find benefit from sports play while avoiding or blunting negative consequences of organized sport activities.

Electrical status epilepticus during sleep in a child with Prader-Willi syndrome: a case report.

Prader-Willi syndrome (PWS) is a rare and complex genomic imprinting disorder caused by an absence of expression of paternal genes from chromosome 15q11.2-q13. Clinical manifestations of PWS depends on age. In early infancy, PWS patients is characterized by hypotonia and failure to thrive. Later in life, they can also exhibit hyperphagia, obesity, short stature, hypogonadism, behavioral issues and cognitive disability. Multiple sleep abnormalities including obstructive and/or central sleep apnea, daytime hypersomnolence, and impaired responses to hypercapnia and hypoxia have been described in patients with PWS. Recent studies also demonstrated an increased risk of seizures in PWS patients. Electrical status epilepticus in sleep (ESES) is an age-limited epilepsy with various seizure types, neurophysiological and motor impairment. The classic electroencephalogram (EEG) pattern of ESES involves continuous epileptic activity at 2-3 Hz occupying greater than 85% of non-rapid eye movement (REM) sleep. Treatment of the ESES syndrome consists of anti-epileptic drugs in routine cases, and corticosteroids, gamma globulins, the ketogenic diet, and surgery in refractory cases. In this project, we describe ESES during polysomnography in a 5-year-old female with PWS and no history of seizure disorder. To the best of our knowledge, this is the first case report on ESES in a PWS patient.

An adolescent female with a testosterone-secreting ovarian teratoma: a case report.

Ovarian neoplasms constitute 1% of childhood tumors. The majority of them are teratomas and usually are asymptomatic or present with paraneoplastic syndromes. Our case is a 16-year-old female who presented with chronic abdominal pain, virilization and oligomenorrhea and found to have a complex cystic mass of the left ovary, more likely cystic teratoma on abdomen and pelvis CT. Further work-up revealed significantly elevated serum total and free testosterone. The patient subsequently underwent left salpingo-oophorectomy confirming the radiological findings. Within two week after surgery, serum testosterone normalized and the patient started having regular menstrual cycles. In summary, ovarian teratomas should be include in the differential diagnosis of abdominal pain and menstrual abnormalities in female adolescents. Further studies are needed to determine the role of ovarian-sparing surgery in this patient population.

Intractable Vomiting in an 11-Month-Old Boy With Trisomy 21: A Case Report on Abnormal Calcium/Calcinosis/Creatinine in Down Syndrome.

Abnormal calcium/calcinosis/creatinine in Down syndrome (ABCD syndrome) is a very rare condition with no clear etiology. In this paper, we describe our clinical encounter with this disease. We report the case of an 11-month-old male infant with Down syndrome (DS) who presented to the hospital with intractable vomiting and decreased oral intake and urine output. The evaluation revealed an acute kidney injury (AKI) and hypercalcemia. Although his AKI improved with intravenous hydration, his hypercalcemia persisted. Extensive studies were notable for an elevated urinary excretion of calcium and bilateral medullary nephrocalcinosis seen on renal ultrasound (US). As a result, he was diagnosed with ABCD syndrome. Dietary calcium restriction was implemented. During his follow-up visit with a pediatric endocrinologist, his serum calcium was found to be normalized. To our knowledge, this is only the seventh case report on ABCD syndrome in the literature.

Diabetes education in pediatrics: How to survive diabetes.

Diabetes mellitus is the most common abnormal carbohydrate metabolism disorder affecting millions of people worldwide. It is characterized by hyperglycemia as a result of ß-cell destruction or dysfunction by both genetic and environmental factors. Over time chronic hyperglycemia leads to microvascular (i.e., retinopathy, nephropathy and neuropathy) and macrovascular (i.e., ischemic heart disease, peripheral vascular disease, and cerebrovascular disease) complications of diabetes. Diabetes complication trials showed the importance of achieving near-normal glycemic control to prevent and/or reduce diabetes-related morbidity and mortality. There is a staggering rate of increased incidence of diabetes in youth, raising concerns for future generations' health, quality of life and its enormous economic burden. Despite advancements in the technology, diabetes management remains cumbersome. Training individuals with diabetes to gain life-long survival skills requires a comprehensive and ongoing diabetes education by a multidisciplinary team. Diabetes education and training start at the time of diagnosis of diabetes and should be continuous throughout the course of disease. The goal is to empower the individuals and families to gain diabetes self-management skills. Diabetes education must be individualized depending on the individual's age, education, family dynamics, and support. In this article, we review the history of diabetes, etiopathogenesis and clinical presentation of both type 1 and type 2 diabetes in children as well as adolescents. We then focus on diabetes management with education methods and materials.

Interferon autoantibodies associated with AIRE deficiency decrease the expression of IFN-stimulated genes.

Neutralizing autoantibodies to type I, but not type II, interferons (IFNs) are found at high titers in almost every patient with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), a disease caused by AIRE gene mutations that lead to defects in thymic T-cell selection. Combining genome-wide expression array with real time RT-PCR assays, we here demonstrate that antibodies against IFN-alpha cause highly significant down-regulation of interferon-stimulated gene expression in cells from APECED patients' blood by blocking their highly dilute endogenous IFNs. This down-regulation was lost progressively as these APECED cells matured in cultures without neutralizing autoantibodies. Most interestingly, a rare APECED patient with autoantibodies to IFN-omega but not IFN-alpha showed a marked increase in expression of the same interferon-stimulated genes. We also report unexpected increases in serum CXCL10 levels in APECED. Our results argue that the breakdown of tolerance to IFNs in AIRE deficiency is associated with impaired responses to them in thymus, and highlight APECED as another autoimmune disease with associated dysregulation of IFN activity.

Prevalence, clinical characteristics and long-term outcomes of classical 11 ß-hydroxylase deficiency (11BOHD) in Turkish population and novel mutations in CYP11B1 gene.

Congenital adrenal hyperplasia (CAH) due to 11ß-hydroxylase deficiency (11BOHD) is a rare autosomal recessive disorder and the second most common form of CAH. AIM: To investigate genotype-phenotype correlation and to evaluate clinical characteristics and long-term outcomes of patients with 11BOHD. METHODS: A total of 28 patients (n = 14, 46,XX; n = 14, 46,XY) with classical 11BOHD from 25 unrelated families were included in this study. Screening of CYP11B1 is performed by Sanger sequencing. Pathogenic features of novel variants are investigated by the use of multiple in silico prediction tools and with family based co-segregation studies. Protein simulations were investigated for two novel coding region alterations. RESULTS: The age at diagnosis ranged from 6 days to 12.5 years. Male patients received diagnose at older ages than female patients. The rate of consanguinity was high (71.4%). Five out of nine 46,XX patients were diagnosed late (age 2-8.7 years) and were assigned as male due to severe masculinization. Twenty one patients have reached adult height and sixteen were ultimately short due to delayed diagnosis. Two male patients had testicular microlithiasis and 5 (35.7%) patients had testicular adrenal rest tumor during follow up. Four patients (28.6%) had gynecomastia. Mutation analyses in 25 index patients revealed thirteen different mutations in CYP11B1 gene, 4 of which were novel (c.393 + 3A > G, c.428G > C, c.1398 + 2T > A, c.1449_1451delGGT). The most frequent mutations were c.896T > C with 32%, c.954G > A with 16% and c.1179_1180dupGA with 12% in frequency. There was not a good correlation between genotype and phenotype; phenotypic variability was observed among the patients with same mutation. CONCLUSION: This study presents the high allelic heterogeneity of CYP11B1 mutations in CAH patients from Turkey. Three dimensional protein simulations may provide additional support for the pathogenicity of the genetic alterations. Our results provide reliable information for genetic counseling, preventive and therapeutic strategies for the families.

Two novel mutations found in a patient with 17alpha-hydroxylase enzyme deficiency.

CONTEXT: Congenital adrenal hyperplasia resulting from 17alpha-hydroxylase deficiency (17OHD) is a rare disorder associated with hypertension. SUBJECT AND METHODS: We describe a phenotypically and hormonally affected female patient with 17OHD. DNA sequencing of her CYP17 gene revealed a maternal heterozygous mutation in exon 2 (R125Q) and a paternal heterozygous mutation in exon 8 (R416H). These are novel mutations in the CYP17 gene that completely eliminate enzyme activity. CONCLUSION: Identification of novel mutations in the CYP17 gene is vital in understanding the molecular mechanisms of its deficiency and in providing additional information about the structure and enzymatic functions of P450c17.

Growth hormone treatment and risk of second neoplasms in the childhood cancer survivor.

CONTEXT: GH deficiency is common in childhood cancer survivors. In a previous report, although we did not find an increase in the risk of disease recurrence in survivors treated with GH, GH-treated survivors did have an increased risk of developing a second neoplasm (SN) (rate ratio, 3.21). OBJECTIVE: In this analysis, we have reassessed the risk of GH-treated survivors developing an SN after an additional 32 months of follow-up. DESIGN AND SETTING: We conducted a retrospective cohort multicenter study. PATIENTS: Among a total of 14,108 survivors who were enrolled in the Childhood Cancer Survivor Study, a retrospective cohort of 5-yr survivors of childhood cancer, we identified 361 who were treated with GH. MAIN OUTCOME: We assessed the risk of developing an SN. RESULTS: During the extended follow-up, five new SN developed in survivors treated with GH, for a total of 20 SN, all solid tumors. Using a time-dependent Cox model, the rate ratio of GH-treated survivors developing an SN, compared with non-GH-treated survivors, was 2.15 (95% confidence interval, 1.3-3.5; P < 0.002). Meningiomas were the most common SN (n = 9) among the GH-treated group. CONCLUSION: Although cancer survivors treated with GH appear to have an increased risk of developing SN compared with survivors not so treated, the elevation of risk due to GH use appears to diminish with increasing length of follow-up. Continued surveillance is essential.

Clinical, hormonal and cytogenetic evaluation of 46,XX males and review of the literature.

The main factor influencing the sex determination of an embryo is the genetic sex determined by the presence or absence of the Y chromosome. However, some individuals carry a Y chromosome but are phenotypically female (46,XY females) or have a female karyotype but are phenotypically male (46,XX males). 46,XX maleness is a rare sex reversal syndrome affecting 1 in 20,000 newborn males. Molecular analysis of sex-reversed patients led to the discovery of the SRY gene (sex-determining region on Y). The presence of SRY causes the bipotential gonad to develop into a testis. The majority of 46, SRY-positive XX males have normal genitalia; in contrast SRY-negative XX males usually have genital ambiguity. A small number of SRY-positive XX males also present with ambiguous genitalia. Phenotypic variability observed in 46,XX sex reversed patients cannot be explained only by the presence or absence of SRY despite the fact that SRY is considered to be the major regulatory factor for testis determination. There must be some other genes either in the Y or other autosomal chromosomes involved in the definition of phenotype. In this article, we evaluate four patients with 46,XX male syndrome with various phenotypes. Two of these cases are among the first reported to be diagnosed prenatally.

Oral insulin therapy to prevent progression of immune-mediated (type 1) diabetes.

Repeated ingestion of insulin has been suggested as an immune tolerization therapy to prevent immune-mediated (type 1) diabetes. We performed a placebo-controlled, two-dose, oral insulin tolerance trial in newly diagnosed (< 2 years) diabetic patients who had required insulin replacement for less than 4 weeks and were found to have cytoplasmic islet cell autoantibodies (ICAs). No oral hypoglycemic agents were permitted during the trial. Endogenous insulin reserves were estimated at six-month intervals by plasma C-peptide responses to a mixed meal. Positive ICAs were found in 262 (31%) of the 846 patients screened. Of the 197 who agreed to participate, 187 could be followed for 6 to 36 months. Endogenous insulin retention was dependent upon initial stimulated C-peptide response, age at diabetes onset, and numbers of specific islet cell autoantibodies found. Oral insulin improved plasma C-peptide responses in patients diagnosed at ages greater than 20 years, best seen at the low (1 mg/day) over the high (10 mg/day) insulin dose (P = .003 and P = .01, respectively). In patients diagnosed before age 20 years, the 1 mg dose was ineffective, whereas the 10 mg dose actually accelerated C-peptide loss (P = .003). There were no adverse effects. If confirmed, these findings suggest that diabetic patients over age 20 years with ICA evidence of late-onset immune-mediated diabetes should be considered for oral insulin at 1 mg/day to better retain endogenous insulin secretion.

Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines.

Chronic mucocutaneous candidiasis (CMC) is frequently associated with T cell immunodeficiencies. Specifically, the proinflammatory IL-17A-producing Th17 subset is implicated in protection against fungi at epithelial surfaces. In autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED, or autoimmune polyendocrine syndrome 1), CMC is often the first sign, but the underlying immunodeficiency is a long-standing puzzle. In contrast, the subsequent endocrine features are clearly autoimmune, resulting from defects in thymic self-tolerance induction caused by mutations in the autoimmune regulator (AIRE). We report severely reduced IL-17F and IL-22 responses to both Candida albicans antigens and polyclonal stimulation in APECED patients with CMC. Surprisingly, these reductions are strongly associated with neutralizing autoantibodies to IL-17F and IL-22, whereas responses were normal and autoantibodies infrequent in APECED patients without CMC. Our multicenter survey revealed neutralizing autoantibodies against IL-17A (41%), IL-17F (75%), and/ or IL-22 (91%) in >150 APECED patients, especially those with CMC. We independently found autoantibodies against these Th17-produced cytokines in rare thymoma patients with CMC. The autoantibodies preceded the CMC in all informative cases. We conclude that IL-22 and IL-17F are key natural defenders against CMC and that the immunodeficiency underlying CMC in both patient groups has an autoimmune basis.

Effects of protease inhibitors on glucose tolerance, lipid metabolism, and body composition in children and adolescents infected with human immunodeficiency virus.

OBJECTIVE: To evaluate the effects of protease inhibitors (PIs) as antiretroviral therapy in comparison with other antiretroviral (non-PI) medications on glucose tolerance, lipid metabolism, and body fat distribution in human immunodeficiency virus (HIV)-infected young patients. METHODS: We conducted a cross-sectional clinical study in an outpatient HIV clinic. The study population consisted of 21 patients (15 female and 6 male) who had had at least 6 months of antiretroviral treatment. The mean age of the patients was 11.9 years (range, 6 to 16.5). RESULTS: Fifteen patients treated with PIs and 6 patients treated with non-PIs were enrolled in the study. We found no significant differences in the lipid panel and insulin resistance, as determined by using the Quantitative Insulin Sensitivity Check Index formula, in the PI group in comparison with the non-PI group. Lipodystrophy was observed in 47% (7 of 15) of the PI group and 33% (2 of 6) of the non-PI group (P = 0.66). In the presence of lipodystrophy, serum triglyceride levels were higher in the PI group than in the non-PI group (P = 0.046). No such difference was found between the treatment groups when no lipodystrophy was present. There was no significant difference in insulin resistance between the treatment groups in the presence or absence of lipodystrophy. CONCLUSION: Our study found the presence of lipodystrophy in HIV-infected young patients regardless of whether they were taking PIs or not. In the patients who had lipodystrophy, those treated with PIs had higher serum triglyceride levels than those not treated with PIs.