PER Volume 12. 1
Sotos Syndrome 1 and 2
Juan F. Sotos MD
Sotos syndrome, described in 1964, was characterized by overgrowth, a distinctive craniofacial configuration, and a non-progressive neurological disorder with mental retardation. There have been many developments since then and an update should be informative.
The syndrome is associated with a number of abnormalities: brain, cardiac, urogenital, musculoskeletal (scoliosis), ophthalmologic, dental and neoplastic.
It is a genetic disorder due to haploinsufficiency of the NSD1 gene (Nuclear receptor-binding SET Domain protein 1) on chromosome 5q35.2-35.3 in 90% of the patients: Sotos syndrome 1.
Recently, heterozygous mutations in the NFIX gene (Nuclear Factor I, X type) on chromosome 19p13.3 were identified in a few children with the Sotos syndrome phenotype: Sotos syndrome 2.
Genotype-phenotype correlations have been obtained. Many studies have been conducted to find out the functional pathway and the manner that the mutated genes altered transcription of other genes and the interaction with other proteins to generate the phenotype, but the functional pathway is largely unknown.
Ref: Ped Endocrinol. Rev. 2014:12(1):2-16
Keywords: Sotos syndrome, Cerebral gigantism, Overgrowth, NSD1, Tall stature Sotos syndrome 2
Globesity: The Root Causes of the Obesity Epidemic in the USA and Now Worldwide
Fima Lifshitz MD,1,2 Jere Ziffer Lifshitz RN, MS1
T he epidemic of obesity is a well-known phenomenon affecting the world population. This pandemic has occurred since the 1980’s with increasing frequency, despite multiple attempts and recommendations to mitigate the prevalence of obesity and its co-morbidities. The causes of obesity have been recognized and are largely related to a genetic predisposition and an environmental susceptibility to gain weight due to increased energy intake and reduced energy expenditures. Furthermore, various structural environmental changes that have occurred since the 1980’s have created an obesogenic environment with abundance of high-caloric density, low-quality food and under activity. All of this leads to increased body weight gain and a global public health problem – not only a distinct patient’s disease that generally fails to respond to diets and/or increased activity. The structural environmental changes resulted from the unintended consequences of laws that created unregulated marketing and advertisements, food subsidies to a “food industrial complex” which manufactures obesogenic foods that foster addiction to its foodstuffs. Additionally, the economic policies implemented over the last 3 to 4 decades have produced a stagnation of income and wages for the preponderance of the population with major wealth disparities between the majority of people versus the top of the socioeconomic group. The current economic realities have resulted in altered family dynamics, eating habits, and food availability compared to previous generations. The root causes of the epidemic of obesity are governmental policies and the food industry which make obesity difficult to escape in the US and now worldwide.
Ref: Ped Endocrinol. Rev. 2014:12(1):17-34
Key Words: Obesity, overweight, pandemic, governmental policies and laws, deregulation, subsidies, food industry, obesogenic foods, energy intake and expenditures, economic disparities, family dynamics, eating behaviors, refined carbohydrates, sweetened beverages, food addiction, sociocultural accommodations, smoking and cardiovascular disease.
Body Mass Index and Waist Circumference to Define Thinness, Overweight and Obesity in Portuguese Adolescents: Comparison Between CDC, IOTF, WHO References
Beatriz Minghelli1 Msc, Carla Nunes2 PhD, Raul Oliveira3 PhD
Objectives: This study compared the criteria for classification of Body Mass Index (BMI) by Centers for Disease Control and Prevention (CDC), International Obesity Task Force (IOTF) and World Health Organization (WHO) references and by waist circumference (WC).
Methods: The sample involved 966 students aged 10 to 16 years. The evaluation of weight status was verified according to CDC, IOTF, WHO criteria and WC curves for Portuguese adolescents.
Results: For classification of overweight and obesity, the agreement between the criteria of CDC and IOTF was the
highest (K=0.82) and the lowest was between the IOTF and WC (K=0.34). In regard to evaluation of thinness, the agreement between all criteria of BMI was considered moderated to fair (K=0.33-0.51) and a poor level of agreement between the BMI and WC (K=0.14-0.16).
Conclusion: The highest level of agreement for thinness, overweight and obesity classification in adolescents was obtained with the IOTF and CDC criteria.
Ref: Ped Endocrinol. Rev. 2014:12(1):35-41
Keywords: adolescents, body mass index, obesity, thinness, waist circumference
Human Chorionic Gonadotrophin (HCG) Stimulation Test and Testosterone Response in Children with Micropenis
Jaja Tamunopriye,1 Oduwole Abiola O2
Background: Human chorionic gonadotropin (HCG) stimulation test is a reliable dynamic test for the evaluation of testicular function during childhood. A single dose of HCG injection at dose of 100 iu/kg is able to produce a progressive but modest rise in testosterone level for 72 to 120 hours in presence of a viable testicular leydig cells.
Objective: To describe pattern of testicular response to HCG stimulation in prepubertal children with micropenis seen at a paediatric endocrinology training centre
Methodology: A retrospective review of all children seen over a fifteen months period and evaluated for micropenis using single dose HCG stimulation protocol. Information was retrieved from the clinic register and case notes of patients. Information retrieved includes age, anthropometry, associated clinical finding and results of stimulation test. Interpretation of test was as sited by Knorr and colleagues.
Results: Six children with micropenis had HCG stimulation test. Mean age of children was 49.9months age range 2months to 84 months. Base line testosterone level ranged from 0 ng/ml to 0.35ng/ml with a mean of 0.3ng/ml. The mean testosterone level after HCG stimulation was 1.26ng/ml and range between 0.35 and 3.2ng/ml. Three subjects had normal increase in testosterone level post stimulation. There was no significant increase in mean stretched penile length of 0.4cm.
Conclusion: HCG stimulation is an important test to determine leydig cell function and testosterone
secretion in children with micropenis. 3(50%) including a cryptochid child showed normal rise in testosterone level post HCG stimulation. The normal response indicates a normal leydig cell function and possible presence of viable testicular tissues in the cryptochid.
Ref: Ped Endocrinol. Rev. 2014:12(1):42-45
Key Words: HCG, Stimulation, Children, Micropenis
State of the Art Review in Hypospadias: Challenges in Diagnosis and Medical Management
Min-Jye Chen MD1, Lefkothea P. Karaviti MD PhD1, Charles G. Macias MD MPH2,
David R. Roth MD3, Sheila Gunn MD1, V. Reid Sutton MD4, Bruce Schlomer MD3
H ypospadias is a common congenital malformation in males, the cause of which may be genetic, hormonal, or environmental, although it usually is idiopathic or possibly multifactorial. Determining the optimal diagnostic testing and management remains a challenge. Hypospadias is corrected with surgery, and androgen therapy often is used preoperatively as an adjunctive therapy, although its use, timing, and effectiveness are unclear. No standardized approach has been established for the diagnostic testing for hypospadias or for preoperative androgen therapy. We reviewed current literature and used the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence and provide recommendations for a diagnostic testing algorithm from an endocrine and genetic perspective and for the optimal use of preoperative androgen therapy. These recommendations are an important step towards standardizing the use of diagnostic testing and the management of patients with hypospadias.
Ref: Ped Endocrinol. Rev. 2014:12(1):46-54
Key Words: hypospadias, diagnosis, karyotype, endocrine, androgen therapy, testosterone, dihydrotestosterone, human chorionic gonadotropin
Abbreviations used: FSH: follicle stimulating hormone; LH: luteinizing hormone; HCG: human chorionic gonadotropin; ACTH: adrenocorticotrophic hormone; AMH: Antimullerian hormone; MIS: Mullerian inhibiting substance; FISH: fluorescence in situ hybridization; CMA: chromosomal microarray; DHT: dihydrotestosterone; GRADE: Grading of Recommendation, Assessment, Development and Evaluation; HSD: hydroxysteroid dehydrogenase
2014 Pediatric Endocrine Society Meeting, Vancouver Canada, Selected Highlights
Monica Serrano Gonzalez, MD1, Evan Graber, MD2, Lindsey Waldman, MD2, Cedric Ng, MD1
Ref: Ped Endocrinol. Rev. 2014:12(1):55-64
Key Words: islet cell transplantation, ß-cell regeneration, macro-encapsulation, premature adrenarche, PCOS, intra-adrenal cortisol, oxandrolone, testosterone, gonadotropin-releasing hormone (GnRH) agonists, aromatase inhibitors, glucocorticoids, hypothalamic-pituitary-adrenal (HPA) axis, ACTH stimulaton test