Vol. 10.3

March 2013


If One Daily Injection of IGF-I Has the Same Growth-Promoting Effect As 2 Injections Per Day, Why Continue To Give Two Injections?

Zvi Laron, MD, PhD (h.c.)


Comparison of the growth velocity of 1 vs. 2 IGF-I injections per day in patients with Laron Syndrome (primary GH insensitivity) revealed similar effects.

Ref: Ped. Endocrinol. Rev. 2013;10(3): 277-279

Keywords: IGF-I treatment, Laron Syndrome, primary GH insensitivity

William H. Daughaday and the Foundations of Modern Research into Growth Hormone and the Insulin-like Growth Factors

Peter Rotwein, MD


This vignette summarizes some of the scientific accomplishments of Dr. William H. Daughaday, a founder of modern research into the biological effects of growth hormone and the insulin-like growth factors, and formulator of the somatomedin hypothesis of GH actions on growth.

Ref: Ped. Endocrinol. Rev. 2013;10(3): 280-283

Key words: GH, GH receptor, human growth disorders, IGF-I, IGF-II, somatomedin, tumor hypoglycemia


Reproductive Health in Young Male Adults with Chronic Diseases in Childhood

Vincenzo De Sanctis1, MD, Ashraf Soliman2, MD PhD FRCP, Mohamed Yassin3, MBBS, CABM, M Sc, FACP


The Centres for Disease Control and Prevention have defined a chronic diseases as an "illnesses that are prolonged, do not resolve spontaneously, and are rarely cured completely". Approximately 20% of all children have a chronic illness and 65% of them the illness is severe enough to interfere with daily activities .Failure of pubertal growth, delay or absence of sexual development, infertility and sexual dysfunction due to hypogonadism and defective spermatogenesis are well recognized disturbances among adolescents and young male adult patients with chronic diseases. The causes are multifactorial and can be due to disease itself, associated complications or drugs. Haemoglobinopathies, endocrine disorders, gastrointestinal and renal diseases are some examples that frequently cause some degree of disability. Infertility affects the future quality of life of these patients and is a predictor of stress in current and future relationships. Health care providers often neglect the reproductive health of chronically ill adolescents and young adults, although many studies indicate that they are sexually active and interested in knowing about their future fertility. This review article provides an overview of the literature concerning the impact of some chronic diseases in adolescents and young adults on reproductive health but will not address patients with cancer because it has been tackled adequately in the literature.MEDLINE database search of English-language medical journal articles published between 1975 and 2012 for papers related to reproductive health in adolescents and young adults with chronic diseases since childhood was done. Several Authors, recommend that all young adult patients with severe/prolonged chronic disease in childhood should be offered reproductive health care in a specialized center with appropriate expertise, involving a multidisciplinary team, including endocrinologists, andrologists, geneticists, psychologists, urologists and specialist nurses. Adequate information must be provided to these patients about adolescent reproductive health, including types of contraception, pregnancy, sexually transmitted infections and fertility. The importance of transitional care between pediatric and adult medical care should not be ignored. In the development of this process the adolescent must be involved in decision-making regarding treatment or referral. Reproductive health medicine should take a wider view to create a physical, psychological and genetic wellbeing of these patients.

Ref: Ped. Endocrinol. Rev. 2013;10(3): 284-296

Key words: Adolescents, young adults, reproductive health, chronic diseases, diagnosis


Metabolic Syndrome and Endothelial Dysfunction in a Population Born Small for Gestational Age Relationship to Growth and Gh Therapy

Antonio de Arriba1,2, MD, PhD, Mercedes Domínguez3, MD, José I Labarta4, MD, PhD, Manuel Domínguez4, MD, Beatriz Puga1, PhD, Esteban Mayayo4, MD, PhD, Ángel Ferrández Longás1, MD, PhD.


Being born small for gestational age (SGA) and a rapid increase in weight during early childhood and infancy have been strongly linked to metabolic syndrome. A transversal study was conducted on 167 pre-pubertal and 102 pubertal subjects; auxological parameters, systolic and diastolic blood pressure, laboratory data, and carotid-wall thickness (CA-IMT) were measured. Results: Patients born SGA with spontaneous catch-up growth have higher values of BMI, blood pressure, HOMA index, and CA-IMT than those treated with GH and the appropriate-forgestational age (AGA) group. In conclusion, subjects born SGA are at high risk of developing chronic diseases, including obesity, hypertension, insulin resistance, and endothelial dysfunction, at an early age, mainly those with good catch-up growth compared with those receiving GH because of negative catch-up growth. Our data is compared with published results.

Ref: Ped. Endocrinol. Rev. 2013;10(3): 297-307

Key words: small for gestational age, metabolic syndrome, carotid intima-media thickness, GH treatment.


Antipsychotic Drugs and Breastfeeding

Gil Klinger1-3, MD, Bracha Stahl2, MSc Pharm, Paolo Fusar-Poli4, MD, Paul Merlob1-3, MD


Objective: The incidence of psychotic disorders during the postpartum period is higher than at any other time during a women's life and coincides with the time when breastfeeding is most recommended. As a result, safety data on use of antipsychotic drugs during lactation is essential. Our aim was to analyze the medical literature for information on antipsychotic drug use during breastfeeding and to determine the safety of their use for the exposed infant. Data Sources: Medline (U.S. National Library of Medicine), LactMed (U.S. National Library of Medicine) and Reprotox (Reproductive Toxicology Center) databases were searched to identify all relevant medical literature on antipsychotic medications and lactation. The database search, updated to March, 2012, used the generic name of each antipsychotic drug in combination with the terms breastfeeding or lactation or breast-milk. Study selection: 4 prospective studies, 12 case series, 28 case reports and 1 pharmaceutical registry were included. Data extraction: Infant outcomes focusing on longterm outcome were summarized from all reports of breastfeeding mothers taking antipsychotic medications. Recommendations for drug use during breastfeeding were based on safety data and on pharmacokinetic drug properties. Recommendations were categorized as acceptable, possible under medical supervision, or, not recommended.

Results: Among 21 antipsychotic drugs used in clinical practice, for 7 there are no data at all regarding breastfeeding and for 6 others the data are based only on few infant exposures. Only few prospective studies assessing use of haloperidol, chlorpromazine and olanzapine during breastfeeding were identified. Olanzapine and quetiapine were categorized as acceptable for breastfeeding. Chlorpromazine, haloperidol, risperidone and zuclopenthixol were categorized as possible for breastfeeding under medical supervision. Breastfeeding cannot be currently recommended for the following medications: aripiprazole, asenapine, chlorprothixene, clozapine, droperidol, fluphenazine, flupenthixol, iloperidone, lurasidone, paliperidone, perphenazine, pimozide, trifluoperazine, thiothixene and ziprasidone.

Conclusions: With a limited number of infants exposed to antipsychotic drugs during breastfeeding, for most drugs a firm and evidence-based conclusion cannot be reached. Counseling of breastfeeding mothers should be carefully assessed. Pharmacokinetic drug characteristics, disease severity, behavioral or psychosocial alternatives, preventative interventions and possible impact of discontinuing breastfeeding on the maternal-infant relationship should all be considered.

Ref: Ped. Endocrinol. Rev. 2013;10(3): 308-317

Key words: adverse drug effects, anti-psychotic drugs, breastfeeding, infant, outcome


Bone Health in Children and Adolescents: Risk Factors for Low Bone Density

Pisit Pitukcheewanont1, MD, Juliana Austin2, MD, Paul Chen1, BS Natavut Punyasavatsut3, MD


Osteoporosis is a common disease that is characterized by low bone mineral density (BMD). Decreased BMD is associated with increased fracture risk. In adults, normal BMD results from the balance between accrual of peak bone mass (PBM) at the end of adolescence, and subsequent bone loss with age. Although environmental factors play a role, hereditary factors are the major contributors (up to 80%) to the variability in PBM. This review examines the effects of genetics, physical activity and immobilization, smoking, chronic diseases and medications, vitamin D, calcium, and various other dietary factors on bone integrity in children, adolescents, and adults.

Ref: Ped. Endocrinol. Rev. 2013;10(3): 318-335

Keywords: Abbreviations: bone mineral density (BMD), peak bone mass (PBM), computerized tomography (CT), bone mineral content (BMC), dual-energy, x-ray absorptiometry (DXA), vitamin D receptor (VDR), collagen type Iα1 (COLIA1), genome-wide association studies (GWAS), single nucleotide polymorphisms (SNPs), ultraviolet B (UVB), low nutrient density (LND), and carbonated soft drinks (CSD), World Health Organization (WHO)


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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