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Volume 16.4

June 2019

Worth Remembering:

Henning Jesper Andersen, MD (1916-1978) 

Knud W. Kastrup, MD



For Debate: Testicular Volume Development along Ages: Evaluation by Different Methods

Vincenzo De Sanctis, MD, Ashraf T. Soliman, MD, PhD, FRCP, Salvatore Di Maio, MD, Giuseppe Millimaggi, MD, Christos Kattamis, MD



In the last five decades an increasing number of studies and clinical reports demonstrated the importance

of testicular volume assessment in pediatric and adolescent population. Reliable and accurate determination of testicular volume (TV) through infancy and adolescence is of great importance for assessing normal pubertal development to diagnose disturbances in

development and to suspect certain genetic and endocrine diseases. Various approaches are available for the

assessment of TV, including orchidometry, rulers, callipers, and ultrasonography (USG). Our report focuses on the

importance of the evolution of TV from birth to adulthood and debates the main factors influencing the accuracy of

different TV measurements. We endorse that any method for the evaluation of TV must satisfy certain criteria: a.

be applicable to persons of all ages from pre-adolescence, through the pubertal spurt to full maturity, b. be simple

to use, c. be free from observer error as possible, and d. have a high degree of correlation with other observable

developmental characteristics.


Ref: Ped. Endocrinol. Rev. 2019;16(4):421-430

doi: 10.17458/per.vol16.2019.dsm.fd.testicularvolume

Key words: Testicular volume, Testicular function, Methods for assessment, Age, Pros and cons



For Karyotype - Phenotype Associations in Patients with Turner Syndrome

Iris D. Noordman, Bsc, Janiëlle AEM van der Velden, MD, PhD, Henri JLM Timmers, MD, PhD, Catherine Pienkowski, MD, Birgit Köhler, MD, PhD, Marlies Kempers, MD, PhD, Nicole Reisch, MD, PhD, Annette Richter-Unruh, MD, PhD, Wiebke Arlt, MD, PhD, Anna Nordenström, MD, PhD, Emma A. Webb, MD, PhD, Nel Roeleveld, PhD, Hedi L. Claahsen-van der Grinten, MD, PhD



Variation in karyotype may be associated with the phenotype of patients with Turner syndrome (TS).

Our objective was to identify these associations between karyotype and phenotype in TS patients. This

study was part of the European multicentre dsd-LIFE study. We evaluated the associations between different

karyotypes of TS patients and age at diagnosis, Turner stigmata, cardiac/renal involvement and gonadal function.

Information was available for 328 TS patients. Participants had a monosomy 45,X (46%), mosaicism 45,X/46,XX (10%),

karyotype with isochromosome (18%), or other karyotype (26%). The clinical signs of TS were the most severe

in patients with monosomy 45,X and the least severe in patients with mosaicism 45,X/46,XX. Patients with

isochromosome and y-material showed an intermediate phenotype. Despite the more severe features in patients

with monosomy 45,X, the median age at diagnosis was only slightly lower compared to patients with other

karyotypes, which suggests opportunities for improvement of knowledge and diagnostics.


Ref: Ped. Endocrinol. Rev. 2019;16(4):431-440

doi: 10.17458/per.vol16.2019.nvt.karyotypeturnersyndrome

Key words: Karyotype, Phenotype, Turner syndrome



Sleep Disorders and Obesity in Childhood: A New Component in Solving Obesity

Muge Atar M, MD, Pirgon O, MD, Atilla Buyukgebiz A, MD



Sleep disorders have been widely reported in obese individuals. Previous studies have shown that together

with an increase in obesity prevalence, so does sleep duration in children and adolescents decrease. By

contributing to energy imbalances, hormonal changes occurring with reduced sleep quality may cause weight

gain and obesity. Current evidence shows that short sleep duration has effects on body weight and weight gain.

Compared to individuals sleeping for a normal duration, insulin sensitivity is lower in those who sleep less. Lack

of sleep increases the desire for food and has a direct effect on physical activity. Further studies are required to

determine the contribution of sufficient sleep to obesity treatment.


Ref: Ped. Endocrinol. Rev. 2019;16(4):441-451

doi: 10.17458/per.vol16.2019.apb.sleepdisordersobesitychildhood

Key words: Obesity, Adolescent, Sleep quality, Restless legs syndrome, Children


Hormones and their Structural and Functional Effects on the Brain: How Can We Change our Practice Moving


Bonnie McCann-Crosby, MD, Laurel Hyle JD, MPH, David Mann,MD, MA, Sheila Gunn, MD, Katherine Flynn, Jennifer Bercaw-Pratt, MD, Oluyemisi Adeyemi, MD, Jennifer Dietrich, MD, Duong Tu, MD, Paul F Austin, MD, V. Reid Sutton, MD, Marni Axelrad, PhD, Lefkothea Karaviti, MD, PhD



Is hormone treatment an invasive procedure? In this paper, we discuss aspects related to the choice of

treating disorders of sex development (DSD) using hormones. Specifically, we focus on some of the challenging

issues related to this treatment and the need to establish a standard of care for the use of hormone therapy in this

patient population. The objectives of this paper are to: 1. Enhance understanding of the uncertainties in

the decision-making process regarding hormonal interventions to treat patients with DSD.

2. Recognize that the effects of hormonal interventions might require a consent process similar to that applied

for surgical procedures. 3. Emphasize the need to establish treatment algorithms

that could form the basis of a standard of care for this

patient population.


Ref: Ped. Endocrinol. Rev. 2019;16(4):452-456

doi: 10.17458/per.vol16.2019.chm.hormonestructuraleffects



Height SDS Changes (ΔhSDS) in Healthy Children from Birth to 18 Years, with Correction Factors for Measurement

Intervals of Less than One Year

Michael Hermanussen, MD, PhD, Rebekka Mumm, MEd, Aileen Rintisch, BEd, Janina Tutkuviene, MD, PhD, Andrej Suchomlinov, PhD, Kálmán Joubert, PhD, Angel Ferrandez Longas, MD, PhD, Christiane Scheffler, PhD



Background: Growth is volatile and non-linear. Assessing the instantaneous speed of growth (momentary height velocity) depends on the

precision and the number of measurements and the duration of the observation period. Measurements at

short intervals reflect both the non-linearity of growth and the technical error of measurements (TEM). Material:

We reanalyzed longitudinal measurements of body length at age 0, 3 months, 6 months, 9 months, 12 months, 18

months, and 24 months, from 1879 healthy infants (956 girls, 923 boys) from France (180 girls, 173 boys), Vilnius,

Lithuania (507 girls, 507 boys), Lublin, Poland (67 girls, 56 boys), Zürich, Switzerland (94 girls, 102 boys) and

Spain (108 girls, 95 boys); and longitudinal measurements of annual body height from age 2 to 18 years from 1528

healthy children and adolescents (774 girls, 754 boys) from France (41 girls, 47 boys), Vilnius, Lithuania (23

girls, 27 boys), Lublin, Poland (70 girls, 58 boys), Zürich, Switzerland (111 girls, 120 boys), Spain (94 girls, 74 boys),

the Czech Republic (65 girls, 69 boys), Hungary (316 girls, 320 boys), and Berkeley, USA (54 girls, 39 boys). Results:

We calculated age - and sex-specific mean values for height and SD for height separately for each country. In addition,

we defined the instantaneous speed of growth by the difference of two measures of hSDS , or in the case of multiple measurements, by the slope of the linear regression (βhSDS(t)). Based on the longitudinal measurements of body length, we present reference values

for annual growth velocity given in the form of SD of annual hSDS changes (ΔhSDS), from birth to maturity.

Correction factors are added for validating measurements obtained at intervals of less than one year. The correction

factors depend on number of measurements, and duration of the observation period.


Ref: Ped. Endocrinol. Rev. 2019;16(4):457-467

doi: 10.17458/per.vol16.2019.hmr.heightsdschanges

Key words: Height SDS changes, Height, Reference, Short term growth


Meeting Report:

2019 Annual Meeting of the Endocrine Society

New Orleans, LA (March 23-26, 2019) Selected Highlights

Swashti Agarwal, MD, Amy Seagroves, MD, Marwan Bakhach, MD, Ishita Jindal, MD


Ref: Ped. Endocrinol. Rev. 2019;16(4):468-477

doi: 10.17458/

Key words: Congenital adrenal hyperplasia, 21-Hydroxylase deficiency, Thyroid nodules, Insulin analogs, Continuous

glucose monitors, Closed loop systems, Youth-onset type 2 diabetes

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