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You are looking at 121 - 130 of 255 items for
- Abstract: adrenarche x
- Abstract: amenorrhoea x
- Abstract: fertility x
- Abstract: Gender x
- Abstract: Hypogonadism x
- Abstract: infertility x
- Abstract: Kallmann x
- Abstract: Klinefelter x
- Abstract: menarche x
- Abstract: menopause x
- Abstract: puberty x
- Abstract: transsexual x
- Abstract: sperm* x
- Abstract: ovary x
- Abstract: follicles x
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INSERM Unité 1203 (DEFE), Université de Montpellier, Montpellier, France
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Département d'Endocrinologie et de Gynécologie Pédiatrique, Hôpital Arnaud de Villeneuve, Université de Montpellier, Montpellier, France
INSERM Unité 1203 (DEFE), Université de Montpellier, Montpellier, France
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Although hyperandrogenism is a frequent cause of consultation in adolescent girls, more severe forms with virilization must lead to suspicion of an adrenal or ovarian tumor. However, they may also reveal a 46,XY disorder of sexual development (DSD). Here, we describe four adolescent girls referred for pubertal virilization and in whom we diagnosed a 46,XY DSD. We performed gene mutation screening by Sanger sequencing (all patients) and by next-generation sequencing (NGS) in patient #4. We identified new heterozygous NR5A1 gene variants in patients #1 and #2 and a homozygous SRD5A2 gene deletion in patient #3. Patient #4 received a diagnosis of complete androgen insensitivity in childhood; however, due the unusual pubertal virilization, we completed the gene analysis by NGS that revealed two heterozygous HSD17B3 variants. This work underlines the importance of considering the hypothesis of 46,XY DSD in adolescent girls with unexplained virilization at puberty.
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St.Anna Kinderspital, Medical University of Vienna, Vienna, Austria
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Objective
Treatment of classic congenital adrenal hyperplasia (CAH) is necessary to compensate for glucocorticoid/mineralocorticoid deficiencies and to suppress androgen excess. Hydrocortisone (HC) is preferred in growing children with classic CAH but recommendations regarding dosage/administration are inconsistent. The aim of this study was to evaluate HC dosing in children with CAH in relation to chronological age, sex, and phenotype based on a multicenter CAH registry.
Design
The CAH registry was initiated in 1997 by the AQUAPE in Germany. On December 31st 2018, data from 1571 patients were included.
Methods
A custom-made electronic health record software is used at the participating centers. Pseudonymized data are transferred for central analysis. Parameters were selected based on current guidelines. Descriptive analyses and linear regression models were implemented with SAS 9.4.
Results
We identified 1288 patients on exclusive treatment with hydrocortisone three times daily (604 boys; median age 7.2 years; 817 salt-wasting phenotype, 471 simple-virilizing phenotype). The mean (lower-upper quartiles) daily HC dose (mg/m² body surface area) was 19.4 (18.9–19.8) for patients <3 months (n = 329), 15.0 (14.6–15.3) for age ≥3–12 months (n = 463), 14.0 (13.7–14.3) for age 1–5.9 years (n = 745), 14.2 (14.0–14.5) for age 6 years to puberty entry (n = 669), and 14.9 (14.6–15.2) during puberty to 18 years (n = 801). Fludrocortisone was administered in 74.1% of patients with a median daily dosage of 88.8 µg.
Conclusion
Our analyses showed that still a high proportion of children are treated with HC doses higher than recommended. This evaluation provides comprehensive information on nationwide hydrocortisone substitution dosages in children with CAH underlining the benefit of systematic data within a registry to assess daily practice.
Division of Endocrinology and Metabolism, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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NIHR Health Protection Research Unit on Chemical Radiation Threats and Hazards, Imperial College London, London, UK
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NIHR Health Protection Research Unit on Chemical Radiation Threats and Hazards, Imperial College London, London, UK
National Institute for Health Research (NIHR) Health Protection Research Unit in Environmental Exposures and Health, Imperial College London, London, UK
Mohn Centre for Children’s Health and Wellbeing, Imperial College London, London, UK
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NIHR Health Protection Research Unit on Chemical Radiation Threats and Hazards, Imperial College London, London, UK
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NIHR Health Protection Research Unit on Chemical Radiation Threats and Hazards, Imperial College London, London, UK
National Institute for Health Research (NIHR) Health Protection Research Unit in Environmental Exposures and Health, Imperial College London, London, UK
Mohn Centre for Children’s Health and Wellbeing, Imperial College London, London, UK
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Context
Salivary androgens represent non-invasive biomarkers of puberty that may have utility in clinical and population studies.
Objective
To understand normal age-related variation in salivary sex steroids and demonstrate their correlation to pubertal development in young adolescents.
Design, setting and participants
School-based cohort study of 1495 adolescents at two time points for collecting saliva samples approximately 2 years apart.
Outcome measures
The saliva samples were analyzed for five androgens (testosterone, androstenedione (A4), 17-hydroxyprogesterone, 11-ketotestosterone and 11β-hydroxyandrostenedione) using liquid chromatography-mass spectrometry; in addition, salivary dehydroepiandrosterone (DHEA) and oestradiol (OE2) were analysed by ELISA. The pubertal staging was self-reported using the Pubertal Development Scale (PDS).
Results
In 1236 saliva samples from 903 boys aged between 11 and 16 years, salivary androgens except DHEA exhibited an increasing trend with an advancing age (ANOVA, P < 0.001), with salivary testosterone and A4 concentration showing the strongest correlation (r = 0.55, P < 0.001 and r = 0.48, P < 0.001, respectively). In a subgroup analysis of 155 and 63 saliva samples in boys and girls, respectively, morning salivary testosterone concentrations showed the highest correlation with composite PDS scores and voice-breaking category from PDS self-report in boys (r = 0.75, r = 0.67, respectively). In girls, salivary DHEA and OE2 had negligible correlations with age or composite PDS scores.
Conclusion
In boys aged 11–16 years, an increase in salivary testosterone and A4 is associated with self-reported pubertal progress and represents valid non-invasive biomarkers of puberty in boys.
Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, USA
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA
Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, Oregon, USA
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Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, USA
Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon, USA
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Like women, old female rhesus macaques undergo menopause and show many of the same age-associated changes, including perturbed activity/rest cycles and altered circulating levels of many hormones. Previous studies showed that administration of an estrogen agonist increased activity in female monkeys, that hormone therapy (HT) increased activity in postmenopausal women and that obesity decreased activity in women. The present study sought to determine if postmenopausal activity and circulating hormone levels also respond to HT when monkeys are fed a high-fat, high-sugar Western style diet (WSD). Old female rhesus macaques were ovo-hysterectomized (OvH) to induce surgical menopause and fed a WSD for 2 years. Half of the animals received estradiol-17β (E), beginning immediately after OvH, while the other half received placebo. Animals in both groups showed an increase in body weight and a decrease in overall activity levels. These changes were associated with a rise in both daytime and nocturnal serum leptin concentrations, but there was no change in serum concentrations of either cortisol or dehydroepiandrosterone sulfate (DHEAS). These data suggest that 2 years of HT has little or no effect on locomotor activity or circadian hormone patterns in menopausal macaques fed an obesogenic diet.
Department of Pediatrics, Navarra Hospital Complex, Pamplona, Spain
Navarra Institute for Health Research (IdisNA), Pamplona, Spain
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Navarra Institute for Health Research (IdisNA), Pamplona, Spain
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Navarra Institute for Health Research (IdisNA), Pamplona, Spain
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Objective
The objective of this study was to analyze whether some auxological characteristics or a single basal gonadotropin measurement will be sufficient to distinguish the prepubertal from pubertal status.
Methods
Auxologycal characteristics were recorded and serum LH and FSH were measured by immunochemiluminescence assays before and after GnRH stimulation test in a sample of 241 Caucasian girls with breast budding between 6- and 8-years old. Peak LH levels higher than 5 IU/L were considered a pubertal response. Area under the curve, cut-off points, sensitivity, and specificity for auxologycal variables and basal gonadotropins levels were determined by receiver operating curves.
Results
There were no significant differences in age at onset, weight, height, BMI and height velocity between both groups. Bone age was significantly higher in pubertal girls (P < 0.05), although with limited discriminatory capacity. The sensitivity and specificity for the basal LH levels were 89 and 82%, respectively, for a cut off point of 0.1 IU/L. All girls in the pubertal group had a basal LH higher than 1.0 IU/L (positive predictive value of 100%). There was a wide overlap of basal FSH and LH/FSH ratio between prepubertal and pubertal girls.
Conclusions
Auxologycal characteristics should not be used only in the differential diagnosis between prepubertal from pubertal status in 6- to 8-year-old girls. We found a high specificity of a single basal LH sample and it would be useful for establishing the diagnosis of puberty in this age group, reducing the need for GnRH stimulation testing.
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Objective
To evaluate the safety and efficacy of letrozole in girls with progressive precocious puberty (PP) associated with McCune–Albright syndrome (MAS).
Design
Monocentric retrospective cross-sectional and longitudinal study of consecutive patients.
Patients
Ten MAS patients treated at Peking Union Medical College Hospital between September 1999 and December 2017 were retrospectively reviewed; those with complications due to PP were followed.
Results
The mean age at letrozole initiation was 4.5 ± 2.6 years, while the mean duration of treatment was 3.3 ± 2.4 years. Letrozole was highly effective at decreasing the rate of skeletal maturation, with a significant decrease in the bone age-to-chronological age (BA/CA) ratio from 1.9 ± 1.1 pre-treatment to 1.5 ± 1.2 on letrozole treatment (P = 0.016). Moreover, growth velocity Z-scores declined from 0.41 ± 0.5 to −0.2 ± 0.31 with treatment (P < 0.001). Predicted adult height Z-scores increased significantly from −2.03 ± 2.33 at baseline to 1.13 ± 0.84 following treatment initiation (P = 0.029). Moreover, vaginal bleeding declined significantly on letrozole.
Conclusions
Our findings suggest that letrozole may be an effective therapy in some girls with MAS, as treatment results in improved BA/CA ratio, growth velocity and predicted adult height. Possible adverse effects include nettle rash.
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The sexually dimorphic expression of cytochromes P450 (CYP) drug metabolizing enzymes has been reported in all species examined. These sex differences are initially expressed during puberty and are solely regulated by sex differences in the circulating growth hormone (GH) profiles. Once established, however, the different male- and female-dependent CYP isoforms are permanent and immutable, suggesting that adult CYP expression requires imprinting. Since the hormone that regulates an adult function is likely the same hormone that imprints the function, we selectively blocked GH secretion in some newborn male rats while others also received a concurrent physiologic replacement of rat GH. Rats were subsequently challenged, peripubertally, with either a masculine-like episodic GH regimen or the GH vehicle alone. The results demonstrate that episodic GH regulation of male-specific CYP2C11 and CYP3A2, as well as female-predominant CYP2C6, are dependent on developmental GH imprinting. Moreover, the induction and/or activation of major components in the signal transduction pathway regulating the expression of the principal CYP2C11 isoform is obligatorily dependent on perinatal GH imprinting without which CYP2C11 and drug metabolism would be permanently and profoundly suppressed. Since there are additional adult metabolic functions also regulated by GH, pediatric drug therapy that is known to disrupt GH secretion could unintentionally impair adult health.
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Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Robert-Debré, Department of Pediatric Endocrinology and Diabetology, and Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Paris, France
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Objective
There is a scarcity of data from randomised controlled trials on the association of growth hormone (GH) with gonadotrophin-releasing hormone agonists in idiopathic short stature (ISS), although this off-label use is common. We aimed to test whether delaying pubertal progression could increase near-adult height (NAH) in GH-treated patients with ISS.
Methods
Patients with ISS at puberty onset were randomised to GH with leuprorelin (combination, n = 46) or GH alone (n = 45). NAH standard deviation score (SDS) was the primary outcome measure. The French regulatory authority requested premature discontinuation of study treatments after approximately 2.4 years; patients from France were followed for safety.
Results
Mean (s.d.) baseline height SDS was −2.5 (0.5) in both groups, increasing at 2 years to −2.3 (0.6) with combination and −1.8 (0.7) with GH alone. NAH SDS was −1.8 (0.5) with combination (n = 19) and −1.9 (0.8) with GH alone (n = 16). Treatment-emergent adverse events and bone fractures occurred more frequently with combination than GH alone.
Conclusion
Due to premature discontinuation of treatments, statistical comparison of NAH SDS between the two cohorts was not possible. During the first 2–3 years of treatment, patients treated with the combination grew more slowly than those receiving GH alone. However, mean NAH SDS was similar in the two groups. No new GH-related safety concerns were revealed. A potentially deleterious effect of combined treatment on bone fracture incidence was identified.
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Precision medicine employs digital tools and knowledge of a patient’s genetic makeup, environment and lifestyle to improve diagnostic accuracy and to develop individualised treatment and prevention strategies. Precision medicine has improved management in a number of disease areas, most notably in oncology, and it has the potential to positively impact others, including endocrine disorders. The accuracy of diagnosis in young patients with growth disorders can be improved by using biomarkers. Insulin-like growth factor I (IGF-I) is the most widely accepted biomarker of growth hormone secretion, but its predictive value for recombinant human growth hormone treatment response is modest and various factors can affect the accuracy of IGF-I measurements. These factors need to be taken into account when considering IGF-I as a component of precision medicine in the management of growth hormone deficiency. The use of genetic analyses can assist with diagnosis by confirming the aetiology, facilitate treatment decisions, guide counselling and allow prompt intervention in children with pubertal disorders, such as central precocious puberty and testotoxicosis. Precision medicine has also proven useful during the transition of young people with endocrine disorders from paediatric to adult services when patients are at heightened risk of dropping out from medical care. An understanding of the likelihood of ongoing GH deficiency, using tools such as MRI, detailed patient history and IGF-I levels, can assist in determining the need for continued recombinant human growth hormone treatment during the process of transitional care.
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark
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The 3rd International Workshop on Klinefelter Syndrome, Trisomy X, and 47,XYY syndrome was held in Leiden, the Netherlands, on September 12–14, 2022.
Here, we review new data presented at the workshop and discuss scientific and clinical trajectories. We focus on shortcomings in knowledge and therefore point out future areas for research.
We focus on the genetics and genomics of supernumerary sex chromosome syndromes with new data being presented. Most knowledge centre specifically on Klinefelter syndrome, where aspects on testosterone deficiency and the relation to bone, muscle and fat were discussed, as was infertility and the treatment thereof. Both trisomy X and 47,XYY syndrome are frequently affected by infertility.
Transitioning of males with Klinefelter syndrome was addressed, as this seemingly simple process in practise is often difficult.
It is now realized that neurocognitive changes are pervasive in all supernumerary sex chromosome syndromes, which were extensively discussed. New intervention projects were also described, and exciting new data concerning these were presented.
Advocacy organizations were present, describing the enormous burden carried by parents when having to explain their child’s specific syndrome to most professionals whenever in contact with health care and education systems. It was also pointed out that most countries do not have health care systems that diagnose patients with supernumerary sex chromosome syndromes, thus pinpointing a clear deficiency in the current genetic testing and care models.
At the end of the workshop, a roadmap towards the development of new international clinical care guidelines for Klinefelter syndrome was decided.
