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Pediatric Endocrinology Reviews (PER) is the most respected international peer reviewed journal in Pediatric Diabetes, Nutrition Metabolism and Genetics. Hypothyriodism, Hyperthyriodism, Glycemic Management for Children with Diabetes Glucose Monitoring Adrenal Insufficiency Turner Syndrome Late Adolescence Klinefelter Syndrome Children with Short Stature and Growth Failure: Heightism Type 1 Diabetes in Children Growth Hormone Treatment for GHD Insulin-like Growth Factor-I Growth Hormone Deficiency SGA Children with Short Stature Receiving GH Treatment Hypothalamic Obesity Adolescent Gynecomastia Hematospermia in Adolescents Gain-of-Function CDKN1C Mutations Craniopharyngioma Succinate-Dehydrogenase Deficient Paragangliomas/Pheochromocytomas Adrenal Steroidogenesis: Impact on Gonadal Function Focal Congenital Hyperinsulinism (CHI)  Longevity Hormone Klotho Pediatric Congenital Hypothyroid Lysosomal Storage Diseases Juvenile NCL (CLN3 Disease) GM1 and GM2 Gangliosidoses Types A and B Niemann-Pick Disease CLN2 Disease (Classic Late Infantile Neuronal Ceroid Lipofuscinosis) Krabbe Disease Fucosidosis Nuclear Factor Kappa B (NF-κB) in Growth Plate Chondrogenesis Persistent Müllerian Duct Syndrome LHX4 Gene Alterations Stunted Growth 45,X/46,XY Gonadal Dysgenesis Thyroid Hemiagenesis Nutrimetabolomics and Adipocitokines Chromosomal Microarray Analysis (CMA) Chromosomal microarray, Copy Number Variant (CNV), Prenatal, Amniocentesis, Comparative genomic hybridization, SNP array, Diagnosis, Clinical Abreviations: aCGH – array-based comparative genomic hybridization, ASD – autism spectrum disorder, BAC – bacterial artificial chromosome, CHD – congenital heart disease, CMA – chromosomal microarray analysis, CNV – copy number variant, CVS – chorionic villus sampling, DD – developmental delay, DNA – deoxyribonucleic acid, FISH – fluorescent in situ hybridization, GABA - gammaaminobutyric acid, ID – intellectual disability, LOH – loss of heterozygosity, NGS – next generation sequencing, NIPT – noninvasive prenatal testing, NOS – not otherwise specified, PGD - preimplantation genetic diagnosis, SNP – single nucleotide polymorphism, VUS – variant of unclear clinical significance Central precocious puberty, Traumatic brain injury, Pathophysiology Nephrolithiasis, Nephrocalcinosis, Hypercalciuria, Hyperoxaluria, Hypouricemia, Cystinuria, Genetics 

Vol. 10.4

June 2013

 

Pituitary Adenomas in Childhood and Adolescence

Suzanne Jackman MD and Frank Diamond MD, Pediatric Endocrinology, All Children’s Hospital, St Petersburg, Florida

Abstract

Scientific advances are revealing the complexity of pituitary development, which i s cont r o l led by multiple trans c r i p t i o n factors and signaling molecules. Unregulated pituitary cell growth, resul t ing in pituitary adenoma, is usually sporadic and results from monoclonal expansion of a single mutated cell. However, some adenomas develop as part of a genetic syndrome. Prolactinoma is the most common hormonally active pituitary adenoma in children. The non-functioning (non-secreting) pituitary adenoma is the second most common and often stains positive for GH, PRL, and/or TSH. While Cushing disease, resulting from an ACTH-secreting adenoma, commonly manifests as weight gain with growth deceleration i n children, GH excess causes gigantism with rapid, accelerated growth inappropriate for the height of the family. TSH secreting pituitary adenomas are rare, and biochemical analysis will show an elevated thyroxine level with a non-suppressed o r high TSH. Though the natural h i s t o r y o f pituitary incidentalomas in children is unknown, adult practice guidelines are established.

Ref: Ped. Endocrinol. Rev. 2013;10(4): 450-459

Key Words: pituitary, adenoma, tumor, children, adolescents, pituitary development, prolactinoma, nonfunctioning adenoma

 

IGF-I Deficiency and Hearing Loss: Molecular Clues and Clinical Implications

Isabel Varela-Nieto1,2,3 PhD, Silvia Murillo-Cuesta1,2,3 PhD, Lourdes Rodríguezde la Rosa1,2,3 PhD, Luis Lassaletta1,2,3,4 PhD MD, Julio Contreras1,2,3,5 PhD

Abstract

Sensorineural hearing loss is a clinical heterogeneous disorder and a significant health-care problem wit h tremendous soc io-economic impact. According to WHO, “Over 5% of the world’s population has disabling hearing loss -328 million adults and 32 million children-”. In children, early hearing loss affects language acquisition. Hearing deficits are generally associated with the loss of the sensory “hair” cells and/or neurons caused by primary genetic defects or secondary to environmental factors including infections, noise and ototoxic drugs. Hearing loss cannot be reversed and currently the available treatment is limited to hearing aids and cochlear implants. Studies are being conducted to develop alternative treatments combining both preventive and reparative strategies. Human insulin like growth factor (IGF) I deficiency is a rare disease associated with hearing loss, poor growth rates and mental retardation (ORPHA73272, OMIM608747). Similarly, Igf1−/− mice are dwarfs with poor survival rates and congenital profound sensorineural deafness. IGF-I is known to be a neuroprotective agent that maintains cellular metabolism, activates growth, proliferation and differentiation, and limits cell death. Here we will discuss the basic mechanisms underlying IGF-I actions in the auditory system and their clinical implications to pursue novel treatments to ameliorate hearing loss.

Ref: Ped. Endocrinol. Rev. 2013;10(4): 460-472

Keywords: auditory neurons, deafness, IGF1R, IGF system, sensory impairment.

 

Novel Mechanisms of Regulation of IGF-1R Action: Functional and Therapeutic Implications

Claire Worrall1, PhD, Daniela Nedelcu1, 2 ,MSc, Julianna Serly1 ,PhD, Naida Suleymanova1 M.D., Iulian Oprea1 MD, PhD, Ada Girnita1,3 ,MD, PhD, Leonard Girnita1 MD, PhD

Abstract

The IGF-1R pathway is essential for the initiation and progression of many cancers. In contrast to other receptor tyrosine kinases involved in cancer, it is not frequently mutated or amplified. The classical model of signaling through the IGF-1R centers on ligand initiated kinase activation, allowing binding of adaptor molecules and downstream activation of the MAPK and PI3K pathways. The signaling is terminated through receptor ubiquitination and subsequent degradation. To date, therapies targeting IGF-1R have been designed solely aiming to block phosphorylation mediated signaling by preventing receptor-ligand interaction or by limiting kinase activation. Yet, the classical model is insufficient to explain receptor behavior induced by some IGF-1R inhibitors. This review advocates an updated model of IGF-1R signaling, accommodating the “classical” kinase signaling and the IGF-1R-kinase independent signaling thus providing the theoretical background for receptor downregulation induced by IGF-1R inhibitors. This model should be considered for future design of effective therapies targeting the IGF-1R pathway.

Ref: Ped. Endocrinol. Rev. 2013;10(4): 473-484

Key Words: IGF-1R, beta-arrestins, ubiquitination, cancer, GRK, biased agonism

 

Vitamin D in Childhood Cancer: A Promising Anticancer Agent?

D Bahar Genc1 MD, M Alp Ozkan2 MD, Atilla Buyukgebiz3 MD

Abstract

Children diagnosed and treated for cancer are vulnerable to Vitamin D defic iency depending on many factors. The Vitamin D status in children with cancer has been mostly regarded as a contributory factor for skeletal pathologies so far. However, the calcitriol was found to promote cell differentiation, inhibit malignant prol i f e r a t ion , a n d e x h i b i t a n t i - inflammatory, proapoptotic and antiangiogenic p rop e r t ies . I n a d d i t ion to t h i s , n ume rous epidemiological studies link Vitamin D and cancer and indicate to possible role of Vitamin D in cancer pathogenesis and progression. This article aims to provide an overview of the possible role of Vitamin D deficiency in childhood cancer in terms of prevention and treatment.

Ref: Ped. Endocrinol. Rev. 2013;10(4): 485-493

Key words: Vitamin D, childhood cancer, prevention, treatment

Pediatric Endocrinology Reviews (PER) ● Volume 10 ● No 4 ● July 2013 485

 

Determination of C-Peptide in Children: When is it Useful?

REJ Besser BSc MBBS (Hons) BSc MBBS (Hons) MRCPCH PhD, Peninsula NIHR Clinical Research Facility, Peninsula Medical School, University of Exeter, UK

Abstract

Diabetes resul ts f rom insul in defic iency b ut d e s p i t e t h i s e n d o g e n ous i n sul i n s e c r e t i o n i s i n f re q ue n t l y measur e d . C-peptide is not present in synthetic insulin so it’s presence indicates endogenous secretion. One of the key roles for measuring C-peptide in childhood is to assist in the diagnosis of diabetes subtypes, which in turn determines appropriate management. It is also useful in Type 1 diabetes to monitor d isease course, bot h i n c l i n i c a l practice and in trials following intervention with disease modifying agents. Measuring C-peptide routinely in Type 1 diabetes provides valuable information to the patient and clinician about glucose variability, risk of hypoglycemia and ketoacidosis. Newer more practical methods of C-peptide determination are now avai lable to allow assessment of endogenous insulin secretion i n routine c l i n i c a l prac t i c e . We review t he physiology of insul in secretion, the essential roles and methods for C-peptide determination in blood and in urine.

Ref: Ped. Endocrinol. Rev. 2013;10(4): 494-502

Key Words: C-peptide, type 1, type 2, diabetes, MODY, honeymoon, partial remission