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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 11.3

March 2014

 

Is Priming with Sex Steroids Useful for Defining Patients who will Benefit from GH Treatment?

Vincenzo De Sanctis MD1, Ashraf T Soliman MD, PhD, FRCP2, Mohamed Yassin, MBBS, CABM, MSc, FACP3, Salvatore Di Maio MD4

Abstract

Classic criteria for diagnosing GHD include: short stature (height below the third percentile), slow growth velocity, delayed bone age and failure to produce growth hormone in response to two provocative tests. While provocation tests can diagnose complete GHD, debate still exists about of what constitutes a normal or a subnormal GH response in subjects with “idiopathic” short stature or constitutional delay of growth and puberty. It has been suggested that in children with intermediate GH responses to pharmacologic stimuli, a pre-treatment with sex steroids priming may be of value in enhancing the GH response and in helping to clarify the diagnosis, particularly in children with delayed onset of puberty. Nevertheless, the use of priming with sex steroids prior to GH stimulation test in the peripubertal period is still controversial because it is considered an “unphysiologic method” and may mask children with transient GHD. Further studies and uniform guidelines are needed before solving this intriguing puzzle.

Ref: Ped Endocrinol. Rev. 2014:11.3: 284-289

Keywords: Growth hormone (GH) ,short stature, constitutional delay of growth and puberty (CDGP), sex steroids priming test

 

Polythelia: Simple Atavistic Remnant or a Suspicious Clinical Sign for Investigation?

Assimina Galli-Tsinopoulou, Dorothea Stergidou

Abstract

Supernumerary nipples (or polythelia) usually appear along the embryonic milk lines or in other sites including the back, thigh, vulva, neck etc. The frequency of polythelia ranges from 0.2% to 5.6%. Despite the plethora of published cases concerning its association with other congenital malformations or syndromes with different patterns of inheritance, polythelia still remains a controversial and theoretical issue. Although most reports describe a link between supernumerary nipples and kidney/urinary tract anomalies, a potential relationship with other congenital anomalies or malignancies has also been speculated. Additionally, polythelia has been associated with genodermatoses, thus being related with an increased malignant potential, as well as with an increased risk for solid tumors such as renal adenocarcinoma, testicular cancer, prostate cancer, and urinary bladder carcinoma. The fact that the Scaramanga (ska) mutant mice presented with ectopic breast tissue imply that misregulation of the neuregulin-3 signaling pathway may be critical in the occurrence of polythelia. This is an attempt to review existing literature in order to (a) draw reliable conclusions whether polythelia is a manifestation of simple atavism or may be associated with concomitant severe conditions needing further investigation and/or management, (b) elucidate its aetiology and (c) establish appropriate clinical and laboratory approach.

Ref: Ped Endocrinol. Rev. 2014:11.3: 290-297

Keywords: polythelia, supernumerary nipples,aberrant nipple

Abbrev iat ions: SNN=supernumerar y n ipple, S N B = s u p e r n u m e r a r y b r e a s t, T G Fα = t r a n s fo r m i n g growth factor α, TGFβ=transforming growth factor β, EGFR=epidermal growth factor receptor, FGF10=fibroblast growth factor 10, Tbx3=T-box transcription factor 3, wnt=wingless (Drosophila melanogaster segment polarity gene) and Integrase-1 (the vertebrate homologue), Gli3=glioma-associated oncogene family zinc finger 3

 

Aromatase Excess Syndrome: A Rare Autosomal Dominant Disorder Leading to Pre- or Peri-pubertal Onset Gynecomastia

Maki Fukami1 MD, Mami Miyado1 PhD, Keisuke Nagasaki1,2 MD, Makio Shozu3 MD, Tsutomu Ogata1,4 MD

Abstract

Overexpression of CYP19A1 encoding aromatase results in a rare genetic disorder referred to as aromatase excess syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, gonadotropin deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an aromatase inhibitor appears to benefit patients with AEXS, although longterm safety of this class of drugs remains unknown.

Ref: Ped Endocrinol. Rev. 2014:11.3: 298-305

Keywords: aromatase, CYP19A1, estrogen, genomic rearrangement, gynecomastia

 

Review of Outcomes After Cessation of Gonadotropin-releasing Hormone Agonist Treatment of Girls with Precocious Puberty

Paul Thornton MB, BCh, MRCPI1; Lawrence A. Silverman MD2; Mitchell E. Geffner MD3; E. Kirk Neely MD4; Errol Gould PhD5; Theodore M. Danoff MD, PhD6

Abstract

Although gonadotropin-releasing hormone agonists (GnRHa) have been the standard of care of central precocious puberty (CPP) management for many years, there are still questions about the long-term consequences of treatment. With increased utilization of GnRHa treatment, it is now possible to assess posttreatment outcomes in the immediate posttreatment period and into adulthood. This literature review reports on the long-term effects of GnRHa therapy in girls with CPP after therapy has been discontinued. Published reports confirm the reversibility of hypothalamic-pituitary-ovarian axis suppression in females after cessation of GnRHa therapy, with the majority of patients achieving ovulatory menstrual cycles of normal timing and duration. GnRHa therapy does not appear to induce polycystic ovary syndrome or have long-term negative repercussions on either bone mineral density or body composition. Evidence is currently insufficient to identify agent-specific differences in outcomes, reproductive function, and health of offspring.

Ref: Ped Endocrinol. Rev. 2014:11.3: 306-317

Keywords: Fertility, gonadotropin-dependent, gonadotropin-releasing hormone agonist, menarche, polycystic ovary syndrome, precocious puberty, reproductive function

 

Glycogen Storage Disease Type III in Israel: Presentation and Long Term Outcome

Eli Hershkovitz1 MD, Itay Forschner1 MD, Hanna Mandel2 MD, Ronen Spiegel3 MD, Tally Lerman-Sagie4 MD, Yair Anikster5 MD, Zeharia A6 MD, Shimon Moses1 MD

Abstract

Glycogen storage disease type III (GSD III) was found in the past with an unusual frequency among North African Jews in Israel. The aim of this study was to review the long term clinical course of GSD III’s patients in Israel. Relevant pediatric and adult clinical units of all Israeli hospitals were approached to report on their GSD III patients. 21 (14 M/7F) live patients were located. The average age of the patients was nearly twenty years. Eleven patients were older than 18 years of age. 76% of the patients were of Jewish North African origin, 14% of Jewish European origin, and 10% were Arab Muslims. The symptoms at presentation were fasting, hypoglycemia, hepatomegaly slight hypotonia in infancy and delayed growth. Although in most of the patients their signs and symptoms ameliorated after childhood, significant complications were observed in some 20% of the patients. Consequently, a life long follow up of GSDIII patients is required

Ref: Ped Endocrinol. Rev. 2014:11.3: 318-323

Keywords: GSD III, metabolism, glycogen, debranching

 

Can GLP-1 Preparations be Used in Children and Adolescents with Diabetes Mellitus?

Naim Shehadeh MD, Elena Daich MD, Nehama Zuckerman-Levin MD

Abstract

The number of young diabetics is increasing and therapeutic options for these patients are limited. Glucagon-like peptide-1 (GLP-1) is secreted from the gut after meals and enhances glucose-induced insulin secretion, inhibits glucagon secretion, suppresses appetite, and delays the gastric-emptying rate. GLP-1 analogs are already widely used in the adult population to improve glycemic control and induce weight loss in overweight subjects with type 2 diabetes. The glucoselowering effects resulting from the inhibition of glucagon secretion and the gastric-emptying rate could be of clinical importance in type 1 diabetes. In this article we review clinical data regarding the use of GLP-1 receptor agonists in youth and address the potential benefits and safety aspects of these compounds. Large scale clinical trials are still needed in the pediatric population.

Ref: Ped Endocrinol. Rev. 2014:11.3: 324-327

Keywords: GLP-1preparations, children, diabetes mellitus, type 1, type 2, obesity

 

2013 Lwpes/Espe 9th Joint Meeting, Milan, Italy, Selected Highlights

Sukran Poyrazoglu MD¹, Thomas M.K. Völkl MD², Maria Karantza MD³

Ref: Ped Endocrinol. Rev. 2014:11.3: 328-337

Keywords: idiopathic short stature, growth hormone, IGF-I-based dosing, SPRY2, ATG7, neonatal diabetes, prematurity, gonadotropins, testosterone, puberty, polymorphisms, phthalates, GWAS, TAC3, TACR3, MKRN3 menarche

 

The Many Faces of Rare Diseases (RD): Meeting Report on Rare Disease in South-Eastern Europe, 15–16 November 2013, Skopje, Republic of Macedonia

Gucev Z¹, Tasic V¹, Polenakovic M²

Abstract

The Second meeting on Rare Diseases in South Eastern Europe (SEE) was held in Skopje, Macedonia on November 15-16, 2013. Objective and main data: Rare diseases (RD) are a major problem in developed and especially in countries without affluence. 6-8% of every population suffers from RD. The cumulative effect of RDs on the health system of a country is increasing. Diagnosis often remains a challenge and requires international collaboration. Treatment in diseases for which medication exist is often inaccessible to patients because of the high costs. All countries of SEE need screening programs that address more diseases. Patient organizations play a major role in increasing awareness and providing the needed pressure on society to treat treatable RDs. On the other hand, RDs are frequently a source of valuable new molecular insights not only on mechanisms of their etiology and pathology, but sometimes provide an insight on mechanisms of frequent diseases in man. Further efforts are needed in improving all the RD aspects mentioned.

Ref: Ped Endocrinol. Rev. 2014:11.3: 338-339

Keywords: Rare diseases, Orphan diseases, South Eastern Europe.

 

The 47th Annual Meeting of the Japanese Society for Pediatric Endocrinology (JSPE)

Tatsuhiko Urakami MD

Ref: Ped Endocrinol. Rev. 2014:11.3: 340-341

Keywords: idiopathic short stature, growth hormone, IGF-I-based dosing, SPRY2, ATG7, neonatal diabetes, prematurity, gonadotropins, testosterone, puberty, polymorphisms, phthalates, GWAS, TAC3, TACR3, MKRN3 menarche

 

Adolescent Growth: Genes, Hormones and the Peer Group. Proceedings of the 20th Aschauer Soiree, held at Glücksburg castle, Germany, 15th to 17th November 2013.

Hermanussen M1, Meitinger T2, Veldhuis JD3, Low MJ4, Pfäffle R5, Staub K6, Panczak R6, Groth D7, Brabec M8, von Salisch M9, Loh CPA10, Tassenaar V11, Scheffler C12, Mumm R12, Godina E13, Lehmann A12, Tutkuviene J14, Gervickaite S14, Nierop AFM15,16, Holmgren A15, Aßmann C17, van Buuren S18, Koziel S19, Żądzińska E20, Varela-Silva I21, Vignerová J22, Salama E23, El-Shabrawi M24, Huijic A25, Satake T26, Bogin B21

Abstract

The association between poverty, malnutrition, illness and poor socioeconomic conditions on the one side, and poor growth and short adult stature on the other side, is well recognized. Yet, the simple assumption by implication that poor growth and short stature result from poor living conditions, should be questioned. Recent evidence on the impact of the social network on adolescent growth and adult height further challenges the traditional concept of growth being a mirror of health. Twenty-nine scientists met at Glücksburg castle, Northern Germany, November 15th - 17th 2013, to discuss genetic, endocrine, mathematical and psychological aspects and related issues, of child and adolescent growth and final height.

Ref: Ped Endocrinol. Rev. 2014:11.3: 342-355

Keywords: Adolescent growth, peer group, growth hormone, community effect, body height