Aвтоимун тироидит по долга употреба на агонист на гонадотропин- ослободувачки хормон како третман за предвремен централен пубертет – приказ на случај

There is a small number of studies that have reported abnormalities in endocrine function after a long-term gonadotropin-releasing hormone agonist (GnRHa) treatment in girls. This treatment is considered as safe and effective by most authors. We report our second case of unusual outcome of long-term GnRHa therapy in a girl with central precocious puberty (CPP) of idiopathic or familial etiology. She has received monthly depot of injections of triptorelin for a time period of 4 years. We have examined thyroid function by measuring serum levels of thyrotropin (TSH), thyroxine (T4), thyroid antibodies and ultrasound of thyroid gland. At the age of 11 years she developed a mild goiter and presented with autoimmune thyroiditis, having elevated thyroid antibodies and ultrasound of thyroid gland typical for Hashimoto thyroiditis. Having in mind these two cases, we suggest a closer monitoring of thyroid function in girls with CPP, before and during therapy with GnRH agonist.Постојат мал број студии кои пријавиле нарушувања на ендокрината функција по долга употреба на агонист на гонадотропин – ослободувачки хормон (ГнРХа) кај девојчиња. Овој третман е опишан како безбеден и ефикасен од повеќе автори. Прикажуваме случај на невообичаен исход по долготрајна терапија со ГнРХа кај девојче со централен предвремен пубертет (ЦПП) од идиопатска или фамилијарна етиологија. Во период од 4 години, девојчето примало еднаш месечно трипторелин депо. Ние ја испитавме функцијата на тироидната жлезда со мерење на серумските нивоа на тиротропин (ТСХ), тироксин (Т4), тироидни антитела и ултразвук на тироидната жлезда. На 11 години таа развила блага гушавост презентирана како автоимун тироидит, со покачени тироидни антитела и тироидна жлезда типична за Хашимото тироидит. Затоа, предлагаме редовно следење на функцијата на тироидната жлезда кај девојчиња со ЦПП пред и за време на терапија со агонист на ГнРХ

Поврзаност на Poland-oв синдром и хипертиреоза кај женско дете во пубертет – Приказ на случај

Poland syndrome (PS) is a rare congenital malformation, most commonly characterized by absence of chest wall muscles on one side of the body. It may be accompanied with other deformities of the extremities. We present the case of a 10-year-old girl with Poland syndrome and hypertrichosis of the back of the trunk and extremities. The clinical examination did not reveal the etiology of the syndrome, such as familial predisposition or some event that led to interrupted blood flow during the early embionic growth. The pregnancy was concieved with in vitro fertilization (IVF); triplets were born and our patient is one of these three girls. The hypertrychosis appeared at 8 years of life, without evidence of previous familial occurance, medications or hormonal disbalance. Other malformations that were found were: a mild form of kyphoscoliosis and mitral valve prolapse. The child was evaluated using a multidisciplinary approach, with further follow-up planned with surgical correction of the chest wall and breast augmentation.Поландовиот синдром е ретка конгенитална малформација, која најчесто се карактеризира со отсуство на мускули на градниот кош на една страна на телото. Може да биде придружена и со други деформитети на екстремитетите. Нашиот приказ на случај е женско дете старо 10 години со Поландов синдром, здружен со појава на хипертрихоза на грбот и екстремитетите. Направените иследувања кај детето не ја открија етиологијата на синдромот, како генетска предиспозиција или настан за време на бременоста на мајката кој довел до намалена циркулација за време на раниот ембрионален раст на плодот. Кај мајката е спроведена in vitro фертилизација (IVF) и ова е едно од трите женски деца кои се родени. Хипертрихозата се појавила на 8-годишна возраст, без податок за претходна фамилијарна појава, медикаментозна терапија или хормонален дисбаланс. Додатни малформации кои се најдени беа: лесна форма на кифосколиоза и пролапс на митрална валвула. Детето е водено мултидисциплинарно со план за понатамошна хируршка корекција на градниот кош и неразвиената града

Конечна висина кај момче со ахондроплазија третирано со хормон за раст – приказ на случај

Achondroplasia is the most common genetic form of skeletal dysplasia in humans. It is characterized by short stature and skeletal disproportion. Patients with this condition have comorbidities, such as cardiovascular problems, spinal cord problems, hearing and dental problems as well as psychological issues. We report final height of 147 cm in a 17-year-old boy treated with growth hormone, however without improvement in body proportions. Surgical therapy for limb lengthening had been proposed, which the patient refused. At this age he developed hypertension and was referred to a cardiologist, nephrologist, as well as to an orthopedic surgeon and psychologist. Recently, a new treatment with vosoritide has been introduced, promising better height outcome, but uncertain phenotype improvement. Multidisciplinary approach is recommended for these patients and close monitoring during childhood, adolescence and adulthood. Genetic counseling is also advised.    Ахондроплазијата е најчеста генетска форма на скелетна дисплазија кај луѓето. Се карактеризира со низок раст и скелетна диспропорција. Пациентите со оваа состојба имаат коморбидитети, како што се кардиоваскуларни, проблеми со 'рбетниот мозок,  со слухот и забите, како и психолошки проблеми. Утврдивме конечна висина од 147 cm кај 17-годишно момче третирано со хормон за раст, но без подобрување во пропорциите на телото. Предложена е хируршка терапија за издолжување на екстремитетите, која беше одбиена од страна на пациентот. На истата  возраст кај пациентот се појавила хипертензија и бил упатен на кардиолог, нефролог, како и на ортопед и психолог. Неодамна, воведен е нов третман со восоритид, кој ветува подобри резултати во однос на висината, но со ограничени резултати за фенотипска презентација. За овие пациенти се препорачува мултидисциплинарен пристап и внимателно следење во периодот на  детството, адолесценцијата и зрелоста. Кај нив се предлага и генетско советување

Два случаја на несиндромска конгенитална унилатерална хипоплазија во една фамилија

Micromastia or breast hypoplasia is described as underdevelopment of a woman's mammary tissue. We present the case of a 15-year-old girl with unilateral micromastia, with familial predisposition. Ultrasound, hormonal, dysmorphic, cardiologic, genetic examinations and testing were performed. No mutation in the whole- exome sequencing was found, nor novel mutation. Some of these cases have been reported to be related to breаst cancer so further follow-up is mandatory. Therapy consists of surgical reconstruction of the affected breast. This is a rare condition and it requires a multidisciplinary approach.Микромастија или хипоплазија на дојки е опишана како недоразвиеност на ткивото на дојката кај жените. Опишавме случај на 15-годишно девојче со унилатерална микромастија со фамилијарна предиспозиција. Беа направени ехосонографски, хормонални, дисморфични, кардиолошки и генетски испитувања и тестови. Не беше пронајдена мутација на целокупниот секвенциониран ексом, ниту пак нова мутација. Некои од овие случаи се прикажани како да се поврзани со канцер на дојката и затоа се потребни понатамошни задолжителни следења. Терапијата се состои од хируршка реконструкција на афектираната дојка. Ова претставува ретка состојба, но бара мултидисциплинарен пристап

Централна дебелина: oбем на половина, однос обем на половина и колкови, однос обем на половина и висина кај 13-годишни деца

Obesity in children is a growing worldwide health problem, with a tenfold increase over just four decades. The aim of this study was to determine the prevalence of obesity and to identify central obesity in children aged 13 years from southwestern part of North Macedonia. Materials and methods: This cross-sectional study included a total of 178 healthy children of both sexes (boys 98, girls 80) aged 13 years living in Tetovo, North Macedonia. Results: The prevalence of categorized BMI according to CDC in all 13-year old children (n=178) was 4.5% underweight, 20.2% overweight and 16.3% obese. Among boys, the total prevalence of underweight, overweight and obese was consistently 4.1% vs. 19.4 %vs. 15.3%, while girls had statistically insignificant higher prevalence of underweight, overweight and obese 5% vs. 21.2% vs. 17.5%. At a comparison of the central obesity parameters like WC,WHR, WHtR showed statistically significant differences between sexes (p<0.003, p<0.0001, p<0.011).In the entire sample, the prevalence of high risk for waist-to-hip ratio (WHR) was 34.3% and the prevalence of high risk for waist-to-height ratio (WHtR) was 31.5%. In boys, the prevalence of high risk for WHR was 51% and for WHtR was 35.7% while in girls for WHR was 13.8 % and for WHtR 26.2%. A significant association of male gender with high risk for WHR (X2=27.161; df=1; p=0.0001) was found while for WHtR (X2 =1.830; p=0.176) there was no statistically significant sssociation. It is important to underline that in boys the risk of central obesity was 6.53 times higher compared to girls of the same age [OR=6.53 (3.08–13.83) 95% CI. Conclusions: In our study girls had a higher BMI prevalence of general overweight and obesity vs. boys, and a significant association of male gender with high risk for WHR was detected. Additionally, healthcare professionals should always consider assessing the measurements and risk of central obesity in obese or overweight children, and seek for the unique risk factors associated with each type of obesity and tailor interventions accordingly.Дебелината во детска возраст е сè поголем јавноздравствен проблем глобално, со десеткратно зголемување во текот на последниве четири децении. Целта на оваа студија беше да се процени преваленцијата на дебелината и да се идентификува централната дебелина кај децата на возраст од 13 години во северозападниот дел на Р.С. Македонија. Материјали и методи: Во оваа студија на пресек беа вклучени вкупно 178 здрави деца од двата пола (момчиња 98, девојчиња 80) на 13-годишна возрастод Тетово, Северна Македонија. Резултати: Преваленцијата на катагоризираниот БМИ според CDC кај сите 13-годишни деца (n=178) беше 4,5% потхранети, 20,2% натхранети и 16,3% дебели. Кај момчињата вкупната преваленција на потхранети, натхранети и дебели беше 4,1%; 19,4%; 15,3%,  додека кај девојчињата имаше статистички незначителна поголема преваленција на потхранети, натхранети, и дебели 5%; 21,2%; 17,5%. При споредбата на параметрите за централна дебелина како WC, WHR, WHtR истите покажаа статистички значајни разлики помеѓу половите (p<0,003, p<0,0001, p<0,011). Кај целиот примерок, преваленцијата на висок ризик за WHR беше 34,3%, додека преваленцијата на висок ризик за WHtR беше 31,5%. Кај момчињата, преваленцијата на висок ризик за WHR беше 51%, а заWHtR беше 35,7% додека кај девојчињата за WHR беше 13,8%,а за WHtR 26,2%. Утврдивме статистички сигнификантна поврзаност на машкиот пол со висок ризик за WHR (X2=27.161; df=1; p=0,0001), додека за WHtR (X2 =1.830; p=0.176) не постои статистички значајна поврзаност. Важно е да се нагласи дека кај момчињата ризикот од централна дебелина беше 6,53 пати поголем во споредба со оној кај девојчињата на истата возраст [OR=6,53 (3,08-13,83) 95% CI]. Заклучок: Оваа студија покажа дека девојчињата во споредба со момчињата имаа повисока преваленција на БМИ, потхранетост и дебелина, а беше регистрирана значајна поврзаност на машкиот пол со висок ризик за WHR. Здравствените работници треба секогаш да размислуваат за проценка и на ризикот од централна дебелина кај дебели и натхранети деца, како и идентификување  на факторите на ризик поврзани со секој тип на дебелина и соодветно приспособување на понатамошните интервенции

Timing of Menarche in Girls Adopted from China: a Cohort Study

Background: Girls adopted internationally from some states have been found to have high rates of early puberty, including early menarche. Explanations for the link between international adoption and early puberty include post-adoption catch-up growth triggering puberty, and under-recorded age. Methods: We compared menarcheal age in a cohort of 814 girls adopted from China into North America against menarcheal ages in girls in China. Adoptive parents provided survey data on their daughters’ weight in 2005 and on menarcheal status and age at menarche in 2011. Results: Estimated median age at menarche for adopted Chinese girls is 12.37y (95% CI: 11.84-13.00y). Estimated prevalence of menarcheal age ≤10.00y for adopted girls is 3%. These findings are similar to published findings on non-adopted Chinese girls. The distribution of menarche of adopted girls and non-adopted girls at the estimated incidence rates P3-P97 are also similar. Among the 609 girls whose parents reported on their weight shortly after adoption, 148 (24.3%) were –2SD or more below the median weight in the WHO weight-for-age tables. The proportion of these girls who had attained menarche was not statistically different from other girls. Conclusions: For girls adopted from China, the age of menarche, the percentage of girls attaining menarche <10y and the distribution of menarcheal age are all similar to Chinese girls growing up in China

IGF1R Gene Alterations in Children Born Small for Gestitional Age (SGA)

BACKGROUND: Small for gestational age (SGA)-born children are a heterogeneous group with few genetic causes reported. Genetic alterations in the IGF1 receptor (IGF1R) are found in some SGA children. AIM: To investigate whether alterations in IGF1R gene are present in SGA born children. PATIENTS AND METHODS: We analysed 64 children born SGA who stayed short (mean -3.25 ± 0.9 SDS) within the first 4 years of age, and 36 SGA children who caught up growth (0.20 ± 1.1 SDS). PCR products of all coding IGF1R exons were screened by dHPLC followed by direct sequencing of conspicuous fragments to identify small nucleotide variants. The presence of IGF1R gene copy number alterations was determined by Multiplex Ligation-dependent Probe Amplification (MLPA). RESULTS: The cohort of short SGA born children revealed a heterozygous, synonymous variant c.3453C &gt; T in one patient and a novel heterozygous 3 bp in-frame deletion (c.3234_3236delCAT) resulting in one amino acid deletion (p.Ile1078del) in another patient. The first patient had normal serum levels of IGF1. The second patient had unusually low IGF1 serum concentrations (-1.57 SD), which contrasts previously published data where IGF1 levels rarely are found below the age-adjusted mean. CONCLUSIONS: IGF1R gene alterations were present in 2 of 64 short SGA children. The patients did not have any dysmorphic features or developmental delay. It is remarkable that one of them had significantly decreased serum concentrations of IGF1. Growth response to GH treatment in one of the patients was favourable, while the second one discontinued the treatment, but with catch-up growth

Is Early Puberty Triggered by Catch-Up Growth Following Undernutrition?

Undernutrition during fetal and postnatal life is still a major problem in many low- and middle-income countries. Even in high-income countries malnutrition may exist in cases of intrauterine growth retardation, as well as in chronic conditions such as anorexia nervosa and inflammatory bowel disease. Children adopted from developing countries are often chronically malnourished. Nutritional rehabilitation, resulting in catch-up growth, is often complicated by influences originating in fetal life as well as during postnatal growth. This may result in hormonal and metabolic changes as well as alterations in pubertal development. The present review focuses on fetal, postnatal and fetal-postnatal undernutrition and subsequent catch-up growth as well as catch-up growth in relation to pubertal development. Catch-up growth in children can be associated with early puberty following fetal or combined fetal-postnatal undernutrition. However, early puberty does not seem to occur following catch-up growth after isolated postnatal undernutrition. Gonadotropins have been reported to be elevated in prepubertal adopted girls as well as during catch-up growth in animals. Even if other factors may contribute, linear catch-up growth seems to be associated with the timing of pubertal development. The mechanisms behind this are still unknown. Future research may elucidate how to carry out nutritional rehabilitation without risk for early pubertal development

Effects of early prepubertal exposure to bisphenol A on the onset of puberty, ovarian weights, and estrous cycle in female mice

Objective: Bisphenol A (BPA) is a chemical used extensively to manufacture plastics and epoxy resin liners for food and beverage cans. BPA, with properties similar to estrogen, has endocrine-disrupting effects. In the present study, we examined the effects of early prepubertal BPA exposure on the onset of puberty and reproductive parameters such as estrous cycle and reproductive organ weights in female mice. Methods: Female mice were injected subcutaneously at postnatal day (PND) 8 with BPA (0.1, 1, 10, 100 mg/kg) in sesame oil or with sesame oil alone. Body weight was measured from PND 10 to 70. Vaginal opening and estrous cycle were monitored from PND 20 to 29. Animals were sacrificed at PND 25, 30, and 70, and the ovary and uterus weights were measured. Results: Early prepubertal exposure to BPA (10 and 100 mg/kg) significantly decreased body weight from PND 18 to 30. BPA treated mice at testing dose levels showed early opening of the vagina compared to the control group. The number of estrous cycle and days of estrus were significantly decreased in high dose (100 mg/kg) BPA treated mice. The ovary weight at PND 25 and 30 was significantly decreased in all BPA treatment groups. Conclusion: Early prepubertal exposure to BPA accelerated the onset of puberty but decreased reproductive parameters in female mice

Evo-devo of human adolescence: beyond disease models of early puberty

Despite substantial heritability in pubertal development, much variation remains to be explained, leaving room for the influence of environmental factors to adjust its phenotypic trajectory in the service of fitness goals. Utilizing evolutionary development biology (evo-devo), we examine adolescence as an evolutionary life-history stage in its developmental context. We show that the transition from the preceding stage of juvenility entails adaptive plasticity in response to energy resources, other environmental cues, social needs of adolescence and maturation toward youth and adulthood. Using the evolutionary theory of socialization, we show that familial psychosocial stress fosters a fast life history and reproductive strategy rather than early maturation being just a risk factor for aggression and delinquency. Here we explore implications of an evolutionary-developmental-endocrinological-anthropological framework for theory building, while illuminating new directions for research