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PER Volume 12. 2

December 2014


For Debate: Are the New Automated Methods for Bone Age Estimation Advantageous over the Manual Approaches?

Vincenzo De Sanctis, MD, Ashraf T Soliman, MD, PhD, FRCP, Salvatore Di Maio, MD, Said Bedair, MD, MBBS, MSc



Bone Age Assessment (BAA) is performed worldwide for the evaluation of endocrine, genetic and chronic diseases, to monitor response to medical therapy and to determine the growth potential of children and adolescents. It is also used for consultation in planning orthopedic procedures, for determination of chronological age for adopted children, youth sports participation and in forensic settings. The main clinical methods for skeletal bone age estimation are the Greulich and Pyle (GP) and the Tanner and Whitehouse (TW) methods. Seventy six per cent (76%) of radiologists or pediatricians usually use the method of GP, 20% that of TW and 4% other methods. The advantages of using the TW method, as opposed to the GP method, are that it overcomes the subjectivity problem and results are more reproducible. However, it is complex and time consuming; for this reason its usage is just about 20% on a world-wide scale. Moreover, there are some evidences that bone age assignments by different physicians can differ significantly. Computerized and Quantitative Ultrasound Technologies (QUS) for assessing skeletal maturity have been developed with the aim of reducing many of the inconsistencies associated with radiographic investigations. In spite of the fact that the volume of automated methods for BAA has increased, the majotity of them are still in an early phase of development. QUS is comparable to the GP based method, but there is not enough established data yet for the healthy population. The Authors wish to stimulate the attention on the accuracy, reliability and consistency of BAA and to initiate a debate on manual versus automated approaches to enhance our assessment for skeletal maturation in children and adolescents.


Ref: Ped. Endocrinol. Rev. 2014;12(2):200-205

Key words: Bone age, Greulich and Pyle method,Tanner and Whitehouse method, Automated bone age, Quantitative ultrasound technology, Growth and development



Novel Long-Acting GH Preparations

Mirjana Doknic, MD, PhD, Marko Stojanovic, MD, Vera Popovic, MD, PhD, FRCP



Background: Growth hormone (GH) treatment currently requires years of treatment. Maintaining full compliance with daily injections has been difficult. Teens have the highest rate of non-concordance (missing injections 1-2 per week). In adults the rate of low concordance (low IGF1) rises with each year of treatment. Improving compliance to GH therapy by less burdensome means of GH replacement can be achieved either by changing GH delivery frequency (weekly, monthly) or by changing injection device characteristics (minimal preparation, easy setting, minimal pain, automatic needle insertion, needle free devices). Long acting formulations: Long-acting forms of GH have been developed either as sustained-release preparations of GH (Nutropin-depot, which has been withdrawn in 2004 and LB 03002 once weekly GH, which has received a positive opinion by CHMP of EMA in early 2013) or as the conjugated analogues which prolong the half life of GH. Currently a variety of modified GH molecules which delay GH clearance (CTP modified GH, recombinant polypeptide XTEN, GH conjugated with albumin, GH linked to immunoglobulin) are studied and the ongoing studies are in different phases (from I-III).Each of these preparations has been tested in experimental animal models. Efficacy and safety: Although different long-acting GH and we still need to improve our knowledge about these formulations of GH. Long-term studies are needed to confirm the value and safety (greater exposure to GH) of these agents.


Ref: Ped Endocrinol. Rev. 2014:12(2):206-212

Key words: Growth Hormone Deficiency, Long- Acting GH Preparations


Prevalence of Dyslipidemia and Metabolic Syndrome Risk Factor in Overweight and Obese Children

Patricia L. Casavalle1,2, MD, Fima Lifshitz3, MD, Laura S. Romano4, RD, Marcela Pandolfo5, BS, Anabella Caamaño5, BS, Patricia M. Boyer6, PhD, Patricia N. Rodríguez1, PhD, Silvia M. Friedman1, PhD



Objective: To study the prevalence of dyslipidemia and metabolic syndrome risk factors in overweight/ obese children and adolescents. Methodology: The study included 139 healthy white Argentinean children/adolescents (aged 8-14 years) who were overweight (n=30) or obese (n=109), based on BMI z score according to WHO, 2007. Children were referred to the Nutrition Clinic, San Martin University Hospital, Buenos Aires, Argentina for evaluation and treatment. Dyslipidemia was considered when one or more serum lipids (mg/dL) were out of range: total cholesterol ≥200, high-density lipoprotein (HDL-C) ≤40, triglycerides (TG) ≥110, low-density lipoprotein (LDL-C) ≥130 or non-HDL-C >145 and fasting blood glucose (FBG) > 110. Additional metabolic syndrome risk factors included: increased waist circumference (WC, ≥90th percentile) and high blood pressure (>90th percentile). A history of low birth weight (<2.5 kg) and a family history of: dyslipidemia (FHDL), premature acute myocardial infarction (FHPAMI) and/or type 2 diabetes mellitus (FHT2DM) were also assessed. Results: The prevalence of dyslipidemia among overweight and obese children was 50.4% and its pattern was: hypertriglyceridemia 31.9%, low HDL-C 29.7%, high non- HDL-C 15.8%, hypercholesterolemia 11.9%, and elevated LDL-C 10.7%. The dyslipidemia was more often detected among those with increased WC (55.4%), FHDL (51.1%), and FHT2DM (48%); prevalence was lower in those with FHPAMI (18.7%) and low birth weight (4.3%). Most children presented a variety of metabolic syndrome risk factors; only 25.8% did not have any such alterations identified.

BMI z score showed a positive association with TG andnegative with HDL-C. Overweight  and obesity increased the odds ratios of metabolic syndrome risk factors, hypertriglyceridemia and low HDL-C. Conclusions: Overweight/obese children were prone to have dyslipidemia and metabolic syndrome. Excess body weight is an important harbinger of health that requires the assessment of multiple parameters to discern further health concerns that may be amenable to specific treatment.


Ref: Ped Endocrinol. Rev. 2014:12(2):213-223

Key words: Obesity, Overweight, Metabolic syndrome, Hyperlipidemia, Dyslipidemia, Hypertriglyceridemia, Hypercholesterolemia, Hypertension, Cardio vascular disease, Type 2 Diabetes Mellitus, Children, Adolescents


Nonclassical Congenital Adrenal Hyperplasia: Targets of Treatment and Transition

Bonnie McCann-Crosby1, MD, Min-Jye Chen1, MD, Sarah K. Lyons1, MD, Yuezhen Lin1, MD, Marni Axelrad2, PhD, Jennifer E. Dietrich3, MD, V. Reid Sutton4, MD, Charles G. Macias5, MD, MPH, Sheila Gunn1, MD, Lefkothea Karaviti1, MD, PhD



Nonclassical congenital adrenal hyperplasia (NCCAH) caused by 21-hydroxylase deficiency is a common autosomal recessive condition that can present with a wide range of hyperandrogenemic signs in childhood or adulthood. The management of children with NCCAH can be challenging, as no universally accepted guidelines have been established. Our goal was to evaluate the literature and develop an evidence-based guideline for the medical management of children and adolescents with NCCAH. We reviewed the published literature and used the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system when appropriate to grade the evidence and provide recommendations for the medical management of children and adolescents with NCCAH, appropriate transition practices from pediatric to adult endocrine care, and psychological issues that should be addressed in parents and patients with NCCAH. We offer recommendations, based on the available evidence, for the management of NCCAH at the different developmental stages from diagnosis through transition to adulthood.


Ref: Ped Endocrinol. Rev. 2014:12(2):224-238

Key words: Nonclassical Congenital Adrenal Hyperplasia,Children, Adolescents, Treatment, Transition


Meeting Report: Endocrine Society, 96th Annual Meeting & EXPO, Chicago, IL USA (June 20-24, 2014) Selected Highlights

Isabel Hsu, MD, PhD, Anna Ryabets-Lienhard, DO, Brian Miyazaki, MD


Ref: Ped Endocrinol. Rev. 2014:12(2):239-255

Key words: Pituitary tumor, Acromegaly, Cushing disease, Non-functioning pituitary adenoma, Endocrinedisrupting chemicals, Obesity, Brown adipose tissue, White adipose tissue, Adipocytes, Central precocious puberty, KISS1R, MKRN3, Gonadotropin-releasing

hormone analogs




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