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Effects of high dose oestrogen and testosterone treatment in adolescents upon trabecular and compact bone measured by 125I computed tomography. A preliminary study

Gerhard Ulrich Exner, Andrea Prader, Urs Elsasser, and Max Anliker

Abstract.

125I Computed Tomography (CT) allows for the selective determination of trabecular and compact bone mineral parameters in the radius. Using this technique the effects of high dose oestrogen treatment in 11 tall girls, and of high dose testosterone treatment in 5 tall boys were monitored. In both groups trabecular bone density (TBD) increased steadily during treatment at a rate of about 1% per month. Also in both groups the compact bone mineral increased steadily. These results are compared with those from a cross sectional study on 49 normal children and 36 normal adults, in whom TBD was found to be independent of age and sex, so that the increases in TBD in both treatment groups can be attributed directly to the influence of the sex hormones. Since the compact bone mineral is higher in adults than in children it cannot yet be decided whether the increases seen in the treated patients are related to the sex hormone treatment, or reflect only the normal development of the bone during adolescence.

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COMPARATIVE STUDY OF ENDEMIC GOITRE IN MAN AND CATTLE IN ISRAEL

Naphtali Brand, Ruwen A. Kathein, and Gideon Hasis

ABSTRACT

A parallelism in the incidence of human and bovine goitre in the northern part of Israel is described.

Among 1475 children and adolescents from 8–18 years of age of both sexes and examined from Upper Galilee an average incidence of goitre of more than 10% was found.

A three years follow up study showed an increase in percentage of goitre to 30% among girls. No cretins or deaf or dumb subjects were found.

Thyroid weights of 385 heads of cattle slaughtered at the slaughter-houses or on the farms were determined. While the mean weight of thyroids of cattle from a non-endemic control area was 17.7 g the mean weight for the goitrous area attained 23.4 g. The mean relative thyroid weights for the control and goitrous areas were 3.75 and 6.98 g/100 kg respectively. The histopathological examination of several excised non selected thyroids from Upper Galilee showed pathological findings: hyperplasia, fibrosis, nodular goitre.

These data are the first evidence of the incidence of endemic goitre of cattle in Israel and suggest most strongly that here the unfavourable environment plays a decisive role among the factors which influence the weight of bovine thyroids.

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Distribution of the homeostasis model assessment of insulin resistance in Mexican children and adolescents

Celia Aradillas-García, Martha Rodríguez-Morán, María Eugenia Garay-Sevilla, Juan Manuel Malacara, Ramón Alberto Rascon-Pacheco, and Fernando Guerrero-Romero

Objective

Several cutoff points of the homeostasis model assessment of insulin resistance (HOMA-IR; varying from 2.5 to 4.0) have been suggested for diagnosing IR in youth. In this study, we determined the distribution of the HOMA-IR in Mexican children and adolescents.

Design and methods

A total of 6132 children and adolescents from San Luis Potosi, León, Queretaro, and Durango, which are cities in central and northern Mexico, were enrolled in a population-based cross-sectional study. Eligible participants were apparently healthy children and adolescents aged 6–18 years. Pregnancy and the presence of chronic illnesses were exclusion criteria.

Results

A total of 3701 (60.3%) girls and 2431 (39.7%) boys were included in this study. In the overall population, the mean body mass index, insulin levels, and fasting glucose levels were 21.8±1.3 kg/m2, 7.1±3.2 μU/ml, and 86.2±10.0 mg/dl respectively. The concentrations of insulin and fasting glucose gradually increased from 6 to 12 years of age, whereas the concentrations tended to plateau in the 13- to 18-year-old population. The absolute mean of the HOMA-IR was 2.89±0.7. The HOMA-IR gradually increased with age and reached a plateau at 13 years of age.

Conclusions

Because the insulin concentrations, glucose levels, and HOMA-IR exhibited a gradual increase with age that was not related to obesity, our results suggested that the evaluation of IR in children should be based on percentiles of the HOMA-IR rather than a dichotomous value derived from a single cutoff point.

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BMI percentile-for-age overestimates adiposity in early compared with late maturing pubertal children

Kaspar Sørensen and Anders Juul

Objective

Early pubertal timing is consistently associated with increased BMI percentile-for-age in pubertal girls, while data in boys are more ambiguous. However, higher BMI percentile-for-age may be a result of the earlier puberty per se rather than vice versa. The aim was to evaluate markers of adiposity in relation to pubertal timing and reproductive hormone levels in healthy pubertal boys and girls.

Study design

Population-based cross-sectional study (The Copenhagen Puberty Study). Eight-hundred and two healthy Caucasian children and adolescents (486 girls) aged 8.5–16.5 years participated. BMI and bioelectric impedance analyses (BIA) were used to estimate adiposity. Clinical pubertal markers (Tanner stages and testicular volume) were evaluated. LH, FSH, estradiol, testosterone, SHBG and IGF1 levels were determined by immunoassays.

Results

In all age groups, higher BMI (all 1 year age-groups, P≤0.041) was found with early compared with late maturation, despite similar BIA–estimated body fat percentage (BIA–BF%). Neither BMI nor BIA–BF% differed for a given stage of maturation. BMI percentile-for-age and prevalence of overweight/obesity were higher in the early compared with late matured pubertal children (all P≤0.038), despite similar BIA–BF%. Pubertal girls with BIA–BF >29% had significantly lower LH and FSH levels compared with normal-weight girls (P≤0.041).

Conclusions

Early maturational timing was not associated with higher adiposity for a given stage of puberty. Using BMI percentile-for-age overestimated the degree of adiposity in early pubertal compared with late pubertal children.

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Ovarian function after allogeneic hematopoietic stem cell transplantation in childhood and adolescence

A Vatanen, M Wilhelmsson, B Borgström, B Gustafsson, M Taskinen, U M Saarinen-Pihkala, J Winiarski, and K Jahnukainen

Objective

The aim of the study was to evaluate long-term ovarian function after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood and adolescence.

Subjects and methods

Predictive factors for ovarian function were evaluated among 92 adult or pubertal female survivors transplanted at Huddinge and Helsinki University Hospital during 1978–2000, at a mean age of 9±4.3 years (range 1–19). At the time of the study a mean±s.d. of 13±5.5 years (range 6–27) had elapsed since the HSCT and the mean age of the participants was 22±6.3 years (range 9–41).

Results

Spontaneous puberty based on breast development occurred in 40 and menarche in 30 of the 70 girls who were prepubertal at transplantation. Six out of 20 girls who received HSCT after initiation of pubertal development recovered their ovarian function. Younger age at HSCT, conditioning without total body irradiation (TBI), and a non-leukemia diagnosis predicted the spontaneous menarche. The incidence of menarche was higher after fractioned vs single fraction TBI (P<0.05), cyclophosphamide (Cy) vs busulfan (Bu)-based conditioning (P<0.05), and among leukemia patients transplanted at first remission vs later remissions (P<0.01) and with no cranial irradiation (cranial radiotherapy, CRT) vs given CRT (14–24 Gy) (P<0.01). The majority of recipients conditioned with only Cy vs TBI (P<0.001) or vs Bu-based regimens (P<0.01) showed preserved ovarian function and required no estrogen replacement at their latest follow-up visit at a mean age of 23±6.3 years (range 15–41). Ten women became pregnant.

Conclusions

Patients conditioned with TBI or Bu-based regimes are at high risk of ovarian failure. Intensive anti-leukemia therapy before HSCT including CRT especially among relapsed patients may further decrease the possibility of spontaneous menarche.

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Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting

Claus H Gravholt, Niels H Andersen, Gerard S Conway, Olaf M Dekkers, Mitchell E Geffner, Karen O Klein, Angela E Lin, Nelly Mauras, Charmian A Quigley, Karen Rubin, David E Sandberg, Theo C J Sas, Michael Silberbach, Viveca Söderström-Anttila, Kirstine Stochholm, Janielle A van Alfen-van derVelden, Joachim Woelfle, Philippe F Backeljauw, and On behalf of the International Turner Syndrome Consensus Group

Turner syndrome affects 25–50 per 100,000 females and can involve multiple organs through all stages of life, necessitating multidisciplinary approach to care. Previous guidelines have highlighted this, but numerous important advances have been noted recently. These advances cover all specialty fields involved in the care of girls and women with TS. This paper is based on an international effort that started with exploratory meetings in 2014 in both Europe and the USA, and culminated with a Consensus Meeting held in Cincinnati, Ohio, USA in July 2016. Prior to this meeting, five groups each addressed important areas in TS care: 1) diagnostic and genetic issues, 2) growth and development during childhood and adolescence, 3) congenital and acquired cardiovascular disease, 4) transition and adult care, and 5) other comorbidities and neurocognitive issues. These groups produced proposals for the present guidelines. Additionally, four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with a separate systematic review of the literature. These four questions related to the efficacy and most optimal treatment of short stature, infertility, hypertension, and hormonal replacement therapy. The guidelines project was initiated by the European Society of Endocrinology and the Pediatric Endocrine Society, in collaboration with the European Society for Paediatric Endocrinology, the Endocrine Society, the European Society of Human Reproduction and Embryology, the American Heart Association, the Society for Endocrinology, and the European Society of Cardiology. The guideline has been formally endorsed by the European Society of Endocrinology, the Pediatric Endocrine Society, the European Society for Paediatric Endocrinology, the European Society of Human Reproduction and Embryology and the Endocrine Society. Advocacy groups appointed representatives who participated in pre-meeting discussions and in the consensus meeting.

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MANAGEMENT OF ENDOCRINE DISEASE: Transition of care for young adult patients with Turner syndrome

Valérie Bernard, Bruno Donadille, Tiphaine Le Poulennec, Mariana Nedelcu, Laetitia Martinerie, and Sophie Christin-Maitre

Turner syndrome (TS), affecting 1/2000 to 1/2500 live born girls, is a chromosomal aberration with a total or partial loss of one of the X chromosomes. The diagnosis can be established from the intra-uterine life to adulthood. TS is a chronic disease with particular morbidity and mortality. The loss to follow-up rate, during transition, between children and adult units, remains a crucial issue. This review focusses on the adolescent and young adult patients with TS. The different goals of TS transition are presented as well as some of the tools available in order to improve this transition. The involvement of the patient’s family, advocacy groups and therapeutic educational programs are discussed. A specificity concerning TS transition, as compared to other chronic diseases, relies on the fact that patients with TS may present a peculiar neurocognitive profile. They are in general more anxious than the general population. Therefore, psychological support should be offered to optimize transition. Data illustrating the beneficial impact of an organised transition of TS, from paediatric units to multidisciplinary adult care systems, within the same reference centre are presented. Further studies are required to evaluate the mid-to-long-term transition of paediatric patients with TS referred to adult units.

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Detection of late-onset adrenal hyperplasia in girls with peripubertal virilization

J. Sólyom, G. Gács, K. Keszei, K. Láng, J. Örley, I. Petheö, and L. Ságodi

Abstract. We investigated the value of serum levels of adrenal steroids (dehydroepiandrosterone sulphate, testosterone, 17-hydroxyprogesterone, cortisol) in the identification in peripubertal females with late-onset congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Among 68 females (age 3–18 years) with virilization in childhood, peripubertally or postpubertally, we selected 21 girls for an ACTH test by measurement of basal blood-spot or serum 17-hydroxyprogesterone (17-OHP) levels. Eight of 21 patients had supranormal post-ACTH serum 17-OHP concentration (57–153 nmol/l) with low normal cortisol concentration. All of them had supranormal basal and post-ACTH 17-OHP to cortisol ratios. These data show a relatively high incidence (about 12%) of mild 21-hydroxylase deficiency among prepubertal and adolescent girls with virilization. It is concluded that the first step in the investigation of peripubertally virilized girls should be the determination of serum 17-OHP and cortisol. Patients with basal morning 17-OHP concentration and 17-OHP to cortisol ratio above reference range should be given an ACTH test.

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Idiopathic precocious puberty in girls: Long-term effects on adolescent behavior

ANKE A. EHRHARDT and HEINO F.L. MEYER-BAHLBURG

ABSTRACT

Precocious puberty in girls has endocrinological as well as behavioral implications. We present data from a first systematic controlled follow-up study of 16 adolescent girls with a history of idiopathic precocious puberty (IPP) compared to closely pairmatched adolescent control subjects of comparable pubertal status and normal pubertal history. Findings in four areas of behavior are reported: (1) Psychiatric sequelae: the IPP sample showed an increase in minor psychopathological symptoms. (2) Psychosexual development: The IPP sample was advanced in sociosexual milestones, albeit mostly within the normal range for adolescents. (3) Intelligence: IQ was not different from controls. However, school achievement was accelerated during childhood. (4) Cognitive pattern: The IPP sample had lower spatial perception scores than controls.

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Circadian fluctuation of plasma melatonin in Prader-Willi's syndrome and obesity

R.P. WILLIG, W. BRAUN, J.C. COMMENTZ, and N. STAHNKE

Abstract

In 3 groups of 8 children and adolescents each 1) with Prader-Willi-Labhart's Syndrome (PW-S), 2) obese patients matched for body weight (control I), and 3) normal weight subjects matched for pubertal stage (control II) plasma concentrations of melatonin, cortisol, growth hormone (hGH), insulin, gonadal hormones, and gonadotropins were measured every 1 to 4 hours in 24-hour-profiles. All hormones were determined by radioimmunoassay. The specific melatonin antibody was raised in rabbits. Criteria of the melatonin assay were as follows: detection limit for plasma concentrations of 13 pg/ml, intraassay and interassay variations: 8.4 and 11.2 %, respectively.

PW-S-patients showed cortisol fluctuations within normal limits. hGH was lower than 5 μg/l even during sleep, insulin ranged between 5 and 17o mU/l, and no excessively high glucose levels were found. Estradiol and testosterone were low for age and for pubertal development in all patients except in two girls. Basal LH and FSH levels were in the low normal range and showed sluggish response to LHRH. Plasma melatonin was low during the day, increased at mid-night and peaked at 3 a.m. Melatonin levels in PW-S were not significantly different from those in both control groups. We concluded that the impairment of gonadotropin secretion in patients with PW-S is not due to elevated levels of plasma melatonin.