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Ying Sun, Jiao Fang, Yuhui Wan, Puyu Su, and Fangbiao Tao


Previous finding suggests that children growing up under chronic stress tend to experience earlier sexual maturity. The present study aims to examine polygenic risk by experience interaction in predicting pubertal timing, as well as provide insight regarding the relevance of two G × E paradigms.

Design and methods

Data were analyzed from a 3-year prospective puberty cohort in Anhui Province, China. Breast Tanner stage and testicular volume (TV) of 997 children were annually assessed. The polygenic risk score (PRS) was computed based on 17 SNPs for early pubertal timing. Hair cortisol concentrations (HCC) were assessed in the first 3 cm hair segment as a biological marker of chronic stress.


Comparing with participants under moderate levels of stress as measured by HCC, the puberty-accelerating effects of chronic stress were only observed among girls with moderate (1.7 months earlier, P = 0.007) and low genetic susceptibility (2.2 months earlier, P < 0.001) and among boys with high genetic susceptibility (2.0 months earlier, P = 0.005). Polygenic differences (PRSs) in age at thelarche was most prominent in those with low levels of stress by HCC (9.06, 9.36 and 9.53 years for high, moderate and low PRS, respectively; F = 105.06, P < 0.0001), while polygenic differences in age at TV ≥4 mL was strongest in those under chronic stress (10.91, 11.06 and 11.17 years for high, moderate and low PRS, respectively; F = 100.48, P < 0.0001).


Chronic stress predicts earlier age at pubertal onset in a sex-specific and genetic background-dependent manner. The bioecological G × E model for girls and diathesis stress model for boys in pubertal timing warrants further investigation.

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Robin Michelet, Johanna Melin, Zinnia P. Parra-Guillen, Uta Neumann, J Martin Whitaker, Viktoria Stachanow, Wilhelm Huisinga, John Porter, Oliver Blankenstein, Richard J. Ross, and Charlotte Kloft


Accurate hydrocortisone dosing in children with adrenal insufficiency is important to avoid the risks of over and under treatment including iatrogenic Cushing’s syndrome and adrenal crisis.


To establish a population pharmacokinetic model of hydrocortisone in children and use this to refine hydrocortisone replacement regimens.

Design and methods:

Pharmacokinetic study of hydrocortisone granules, available in 0.5, 1, 2 and 5 mg dose strengths, in 24 children with adrenal insufficiency aged 2 weeks to 6 years. Cortisol concentrations quantified by LC-MS/MS were used to refine an adult pharmacokinetic model to a paediatric population model which was then used to simulate seven different hydrocortisone treatment regimens.


Pre-dose cortisol levels were undetectable in 54% of the 24 children. The developed pharmacokinetic model had good predictive performance. Simulations for the seven treatment regimens using either three- or four-times daily dosing showed treatment regimens delivered an AUC0- 24h within the 90% reference range for healthy children except in neonates where two regimens had an AUC below the 5th percentile. Cortisol concentrations at individual time points in the 24 h were outside the 90% reference range for healthy individuals in 50%, 55–65% and 70–75% for children, infants and neonates, respectively, with low cortisol levels being most prevalent.


Current paediatric hydrocortisone treatment regimens based on either three- or four-times daily administration replicate cortisol exposure based on AUC0- 24h, but the majority of cortisol levels are above or below physiological cortisol levels with low levels very common before the next dose.

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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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S.-I. Björklund and C. C. Jensen

During the neonatal period infants of diabetic mothers often have attacks of cyanosis, temporary cardiac murmurs and arrhythmia. Electrocardiographic changes have been observed both in the presence and in the absence of such disturbances, but in none of the children with any of these disturbances was the electrocardiogram normal (Björklund, 1953 b). The hypothesis has been advanced that the clinical symptoms and electrocardiographic changes are caused by hypokalaemia, secondary to hyperinsulinism with concomitant hyperfunction or dysfunction of the adrenal cortex (Björklund, 1953 a, b).

Venning et al. (1949) found in 2 premature infants of diabetic mothers, delivered by Caesarean section, increased glucocorticoid excretion during the first few days of life. Normalization of the excretion occurred on about the fifth day. Since these 2 infants had atelectasis and cyanosis, Venning et al. considered that the stress to which these babies were exposed was the cause of the increased function of the

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C. Friderichsen

Adrenal failure in the infant or in the child – in contrast to the adult – is more frequently acute than chronic. This may possibly be due to the anatomical peculiarity that the adrenal glands at birth are comparatively large, constituting 0.2 per cent. of the body weight, as against 0.1 per cent in adults.

In childhood adrenal hemorrhages appear as two widely different syndromes.

The one is observed in the newborn: neonatal suprarenal hemorrhage, shortly after birth. This syndrome has nothing to do with infection; it was previously considered a traumatic sequela, but since this syndrome has virtually disappeared with the introduction of prophylactic vitamin K treatment during pregnancy, there is every probability that the great proportion of cases suffered from K avitaminosis, as in melena of the newborn.

The clinical picture of adrenal hemorrhage in the newborn is dominated by three symptoms: 1. Asphyxia – 2. severe cyanosis

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E. Thamdrup

The term premature pubarche is given to conditions in which there is precocious growth of sexual hair (pubes and axillary hair) without any other symptoms of precocious puberty, i. e. without development of the genitals and, in girls, without growth of the breasts. Girls do not become virilized as in the case of the adrenogenital syndrome.

The series of cases comprises 17 patients, 12 girls and 5 boys. The symptoms in the former were observed before the age of 8, and in the latter before the age of 9 years. The patients were from the Dronning Louises Børnehospital (children's hospital, Copenhagen), the Paediatric Department of the University Hospital, Copenhagen, and 5 homes for the mentally defective: Andersvænge, Brejning, Ebberødgård, Ribe and Rødbygård.

Twelve of the patients had severe cerebral disorder, they were all mentally retarded, seven had epilepsy and seven spastic pareses. Four were blind, two had a coloboma of

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Margaret Cristina da Silva Boguszewski and Adriane de Andre Cardoso-Demartini

Approximately 15 million babies are born preterm across the world every year, with less than 37 completed weeks of gestation. Survival rates increased during the last decades with the improvement of neonatal care. With premature birth, babies are deprived of the intense intrauterine growth phase, and postnatal growth failure might occur. Some children born prematurely will remain short at later ages and adult life. The risk of short stature increases if the child is also born small for gestational age. In this review, the effects of being born preterm on childhood growth and adult height and the hormonal abnormalities possibly associated with growth restriction are discussed, followed by a review of current information on growth hormone treatment for those who remain with short stature during infancy and childhood.

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Juliane Léger

Congenital hypothyroidism (CH) is the most common congenital endocrine disorder. The early treatment of CH patients has successfully improved the prognosis and management of this disorder. Optimal treatment and management throughout the patient's life, beginning in the neonatal period, are required to ensure long-term health. Affected patients should be offered assessments of associated medical conditions and provided with accurate information about their condition throughout their lives, but particularly during the transition from pediatric to adult services. This review provides a summary of current knowledge about the long-term outcomes of these patients and appropriate management into early adulthood. We carried out a systematic search of the Medline database to identify relevant articles. Despite major improvements in prognosis, the impact of CH is clearly not uniform, and management should take into account a broader range of relevant indicators, including CH severity, associated comorbid conditions and the adequacy of treatment during childhood and adulthood. The early diagnosis and management of associated medical conditions, and better educational strategies to improve compliance with treatment, should improve the long-term prognosis. Further studies are required to explore changes with aging.

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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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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.