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Acta Bio-medica : Atenei Parmensis Dec 2023Children born small for gestational age (SGA), defined by a birth weight and/or length standard deviation score (SDS) of < -2 based on an appropriate reference...
Children born small for gestational age (SGA), defined by a birth weight and/or length standard deviation score (SDS) of < -2 based on an appropriate reference population, represent a diverse group due to multiple underlying causes of reduced growth. This classification results in a heterogeneous patient cohort. SGA children are prone to endocrinological and metabolic issues not only in childhood but also extending into adolescence and adulthood. This population faces elevated health risks, including persistent short stature, premature adrenarche, pubertal development alterations, neurocognitive problems, and metabolic syndrome. Insulin resistance emerges as a pivotal factor c nht6j7ikontributing to these metabolic complications, prominently featuring obesity, insulin resistance, hypertension, and an increased risk of type 2 diabetes mellitus in adulthood. These medium- to long-term complications significantly impact their quality of life. Growth hormone (GH) therapy for short children born SGA facilitates height normalization throughout childhood, adolescence, and into adulthood. Catch-up growth, however, correlates with heightened risks of obesity, insulin resistance, and metabolic syndrome. Conversely, those without catch-up growth tend to exhibit pronounced short stature and cognitive dysfunction. Given these determinants, comprehensive management and clinical monitoring of SGA children should commence in the neonatal period and extend into adulthood. Recognizing and addressing these challenges early in life can mitigate the long-term impact on health and well-being, emphasizing the importance of a lifelong approach to their care.
Topics: Infant, Newborn; Child; Humans; Adolescent; Adult; Insulin Resistance; Diabetes Mellitus, Type 2; Metabolic Syndrome; Gestational Age; Quality of Life; Infant, Small for Gestational Age; Obesity
PubMed: 38054664
DOI: 10.23750/abm.v94i6.15428 -
Life (Basel, Switzerland) Oct 2020Puberty in children with Prader-Willi syndrome (PWS) is usually delayed and/or incomplete but in some patients premature/early adrenarche is observed. We assessed the...
Premature Adrenarche in Children with Prader-Willi Syndrome Treated with Recombinant Human Growth Hormone Seems to Not Influence the Course of Central Puberty and the Efficacy and Safety of the Therapy.
Puberty in children with Prader-Willi syndrome (PWS) is usually delayed and/or incomplete but in some patients premature/early adrenarche is observed. We assessed the premature adrenarche (PA) in PWS patients during the recombinant human growth hormone (rhGH) therapy and influence of PA on the course of central puberty (CP), rhGH efficacy and safety, and patients' metabolic state. Forty-nine PWS patients were treated with rhGH, 11 presented with PA (group 1) and 14 had normal course of adrenarche (group 2). PA was observed in 22.5% of the PWS children treated with rhGH. The mean time between the rhGH start and the adrenarche, the rhGH dose, the growth velocity and the insulin-like growth factor 1 SD (IGF1 SD) during the treatment, as well as the time of CP, final height SD and BMI SD were similar in both groups. There were also no significant differences in the metabolic assessment-the oral glucose tolerance test (OGTT) and lipid profile results. PA may be a part of the clinical picture of PWS, apart from hypogonadotrophic hypogonadism and it seems to have no influence on CP in PWS patients. The rhGH efficacy and safety were comparable in the patients with PA and the normal course of adrenarche.
PubMed: 33050529
DOI: 10.3390/life10100237 -
Molecular and Cellular Endocrinology Jun 2024Adrenarche is a normal developmental event in mid-childhood characterized by increasing adrenal androgen secretion. The role of the classic androgen pathway has been...
CONTEXT
Adrenarche is a normal developmental event in mid-childhood characterized by increasing adrenal androgen secretion. The role of the classic androgen pathway has been well described in adrenarche, but the role of newer active androgens and additional androgen pathways is less clear.
OBJECTIVE
To study the contribution of novel androgens and related steroid biosynthesis pathways to the development of adrenarche, and to identify additional steroid biomarkers of adrenarche.
DESIGN
A longitudinal study of children aged 6-8 years at baseline, followed up at ages 8-10 and 14-16 years. A total of 34 children (20 girls) with clinical and/or biochemical signs of adrenarche (cases) and 24 children (11 girls) without these signs (controls) at age 8-10 years were included. Serum steroid profiling was performed by liquid chromatography high-resolution mass spectrometry.
MAIN OUTCOME MEASURES
Thirty-two steroids compartmentalized in progestagens, gluco- and mineralocorticoid pathways, and four androgen related pathways, including the classic, backdoor, 11-oxy, and 11-oxy backdoor pathways.
RESULTS
The classic and 11-oxy androgen pathways were more active, and serum concentrations of main androgens in the classic (dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione and androsterone) and 11-oxy (11β-hydroxyandrostenedione, 11β-hydroxytestosterone, 11-ketoandrostenedione, and 11-ketotestosterone) pathways were higher in cases at ages 6-8 and 8-10 years. Pregnenolone concentrations at adrenarchal age (8-10 years) and cortisol concentrations at adolescence (14-16 years) were higher in cases. 11β-hydroxyandrosterone and 11-ketoandrosterone tended to be higher in cases with clinical signs compared to cases who had only biochemical evidence of adrenarche, albeit they were detected at low levels. In biomarker analyses, calculated steroid ratios with cortisol, cortisone, or 11-deoxycortisone as dividers were better classifiers for adrenarche than single steroids. Among these ratios, androstenedione/cortisone was the best.
CONCLUSIONS
The classic and 11-oxy androgen pathways are active in adrenarche. Children with earlier timing of adrenarche have higher serum cortisol levels at late pubertal age, suggesting that early adrenarche might have long-term effects on adrenal steroidogenesis by increasing the activity of the glucocorticoid pathway. Future studies should employ comprehensive steroid profiling to define novel classifiers and biomarkers for adrenarche and premature adrenarche.
PubMed: 38838762
DOI: 10.1016/j.mce.2024.112293 -
Frontiers in Endocrinology 2022Idiopathic premature adrenarche (IPA) is considered a normal variant of puberty, presenting more commonly in female patients. There are concerns as to whether IPA alters...
INTRODUCTION
Idiopathic premature adrenarche (IPA) is considered a normal variant of puberty, presenting more commonly in female patients. There are concerns as to whether IPA alters the final height of these girls. Our main objectives were to (a) compare the adult height of girls with IPA against their target height and (b) design a mathematical model to predict adult height at diagnosis in female patients with IPA.
MATERIALS AND METHODS
A cohort study of girls with IPA was conducted from the time of IPA diagnosis until adult height. The following data were collected: target height, perinatal history, anthropometric and biochemical variables and bone age at diagnosis, age at Tanner stage 2 and menarcheal age, and adult height. First, we performed a univariate statistical analysis after which we carried out a multiple linear regression analysis using adult height as the dependent variable.
RESULTS
We obtained data from 79 female patients diagnosed with IPA with a mean adult height of 164.6 cm (95% CI: 163.36-165.85 cm). The mean follow-up time was 6.60 years. Average age at Tanner stage 2 was 9.71 years. Mean menarcheal age was 11.64 years. There were no significant differences between target height and adult height. Of the several predictive models designed for these patients, one of them, which included bone age, obtained an value of 71%.
CONCLUSIONS
Although slightly advanced puberty was observed among the girls with IPA, their adult height was preserved. The use of predictive models of adult height on diagnosis of IPA could facilitate closer follow-up of girls at risk of reduced adult height.
Topics: Adrenarche; Body Height; Child; Cohort Studies; Female; Humans; Male; Puberty; Puberty, Precocious
PubMed: 35311244
DOI: 10.3389/fendo.2022.852422 -
Reproductive Sciences (Thousand Oaks,... Mar 2022Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disease affecting about 20-25% of women in reproductive age. Different mechanisms could contribute to the... (Review)
Review
Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disease affecting about 20-25% of women in reproductive age. Different mechanisms could contribute to the development of its typical clinical features (i.e. hirsutism, acne, oligo-amenorrhea, alopecia). Some genetic and epigenetic aspects and lifestyle changes seem to be involved in PCOS development. In this review, we shall summarize data from principal studies evaluating the impact of major genetic, epigenetic and environmental factors on the appearance of this female disorder. Literature review and analysis of the most relevant data until May 2020. Current data suggest the importance of genetics and epigenetics in the appearance of PCOS. Several genes, including those related to adrenal and ovarian steroidogenesis as well as those associated with hormonal response to gonadotrophins, androgens and insulin, have been demonstrated to be associated with PCOS. Besides, the phenomenon of methylation of genes and the presence of specific microRNA (miRNA) could take part in PCOS aetiology. Intrauterine exposure to androgens, glucocorticoids and/or some stressful conditions for foetus could contribute to the development of PCOS and other disorders observed in adolescence and later (e.g. premature adrenarche, atypical puberty, metabolic syndrome). Emerging studies report a theoretical role of endocrine disruptors, intestinal dysbiosis and Advanced Glycation End products (AGEs) in PCOS. PCOS is a polygenic and multifactorial hormonal and metabolic dysfunction. An appropriate knowledge of personal and/or family history, lifestyle and nutritional habits of PCOS patients has a great importance to early identify and manage this syndrome.
Topics: Epigenomics; Female; Humans; Life Style; Polycystic Ovary Syndrome
PubMed: 33709373
DOI: 10.1007/s43032-021-00515-4 -
Thyroid : Official Journal of the... Apr 2022The human adrenal cortex undergoes several rapid remodeling steps during its lifetime. In rodents, similar remodeling occurs postnatally in the "X-zone" layer through...
The human adrenal cortex undergoes several rapid remodeling steps during its lifetime. In rodents, similar remodeling occurs postnatally in the "X-zone" layer through unknown mechanisms. Furthermore, little is known regarding the impact of thyroid hormone (TH) on adrenal glands in humans. To investigate the impact of TH on adrenal pathophysiology, we created two genetic murine models mimicking human nonautoimmune hypothyroidism and hyperthyroidism. Moreover, we analyzed serum thyrotropin (TSH) and steroid hormone concentrations in patients diagnosed with congenital hypothyroidism and premature adrenarche (PA). We found that TH receptor beta-mediated hypertrophy of the X-zone significantly elevated the adrenal weights of hyperthyroid women. In the hypothyroid model, the X-zone was poorly developed in both sexes. Moreover, large reciprocal changes in the expression levels of genes that regulate adrenal cortical function were observed with both models. Unexpectedly, up- and downregulation of several genes involved in catecholamine synthesis were detected in the adrenal glands of the hypothyroid and hyperthyroid models, respectively. Furthermore, TSH and adrenal steroid concentrations correlated positively in pediatric patients with congenital hypothyroidism and PA. Our results revealed that congenital hypothyroidism and hyperthyroidism functionally affect adrenal gland development and related steroidogenic activity, as well as the adrenal medulla.
Topics: Animals; Child; Congenital Hypothyroidism; Female; Gene Expression; Humans; Hyperthyroidism; Male; Mice; Thyroid Hormones; Thyrotropin
PubMed: 35044245
DOI: 10.1089/thy.2021.0535 -
Frontiers in Pediatrics 2023The purpose of this study was to investigate the frequency of autoimmune thyroiditis (AT) among euthyroid prepubertal girls presenting with premature adrenarche (PA). We...
OBJECTIVE
The purpose of this study was to investigate the frequency of autoimmune thyroiditis (AT) among euthyroid prepubertal girls presenting with premature adrenarche (PA). We also aimed to identify the clinical, metabolic, and endocrine profile of girls with AT and concurrent PA and compare them to girls with AT without PA, PA alone and healthy controls.
METHODS
Ninety-one prepubertal girls aged 5-10 years, who attended our department for AT, PA and normal variants of growth and puberty were recruited for the study: 73 girls had PA, 6 AT without PA and 12 were referred for investigation of growth. All girls underwent clinical examination, detailed biochemical and hormonal screen. Standard dose Synachten stimulation test (SDSST) and oral glucose tolerance test (OGTT) were performed in all girls with PA. The whole study population was divided in 4 groups: Group PA-/AT+ included 6 girls with AT without PA; Group PA+/AT- PA subjects without AT; Group PA+/AT+ girls with PA and concomitant AT; Group PA-/AT- twelve healthy girls without PA nor AT (controls).
RESULTS
Among 73 girls presenting with PA 19 had AT (26%). BMI, systolic blood pressure (SBP) and the presence of goiter significantly differed between the four groups ( = 0.016, = 0.022 and < 0.001, respectively). When comparing hormonal parameters among the four groups significant differences were found in leptin ( = 0.007), TSH ( = 0.044), anti-TPO ( = 0.002), anti-TG ( = 0.044), IGF-BP1 ( = 0.006), 4- ( = 0.01), DHEA-S (= <0.001), IGF-1 ( = 0.012) and IGF-BP3 ( = 0.049) levels. TSH levels were significantly higher in Group PA+/AT+ compared to PA+/AT- and PA-/AT- ( = 0.043 and = 0.016, respectively). Moreover, girls with AT (Groups PA-/AT+ and PA+/AT+) had higher TSH levels than those in Group PA+/AT- ( = 0.025). Girls in Group PA+/AT + showed higher cortisol response at 60 min post-SDSST than girls in Group PA+/AT- ( = 0.035). During the OGTT, insulin concentrations at 60 min were significantly higher in Group PA+/AT + compared to Group PA+/AT- ( = 0.042).
CONCLUSION
A high frequency of AT among euthyroid prepubertal girls with PA was observed. The combination of PA with AT even in euthyroid state may be associated with a greater degree of insulin resistance, than PA alone.
PubMed: 37009276
DOI: 10.3389/fped.2023.1064177 -
The Tohoku Journal of Experimental... Apr 2021The human adrenal cortex is a complex endocrine organ that produces mineralocorticoids, glucocorticoids and androgens. These steroids are produced in distinct cell types... (Review)
Review
The human adrenal cortex is a complex endocrine organ that produces mineralocorticoids, glucocorticoids and androgens. These steroids are produced in distinct cell types located within the glomerulosa, fasciculata and reticularis of the adrenal cortex. Abnormal adrenal steroidogenesis leads to a variety of diseases that can cause hypertension, metabolic syndrome, infertility and premature adrenarche. The adrenal cortex can also develop steroid-producing adenomas and rarely adrenocortical carcinomas. In vitro cell culture models provide important tools to study molecular and cellular mechanisms controlling both the physiologic and pathologic conditions of the adrenal cortex. In addition, the presence of multiple steroid-metabolizing enzymes within adrenal cells makes it a model for defining possible endocrine disruptors that might block these enzymes. The regulation and dysregulation of human adrenal steroid production and cell division/tumor growth can be studied using freshly isolated cells but this requires access to human adrenal glands, which are not available to most investigators. Immortalized human adrenocortical cell lines have proven to be of considerable value in studying the molecular and biochemical mechanisms controlling adrenal steroidogenesis and tumorigenesis. Current human adrenal cell lines include the original NCI-H295 and its substrains: H295A, H295R, HAC13, HAC15, HAC50 and H295RA as well as the recently established MUC-1, CU-ACC1 and CU-ACC2. The current review will discuss the use of primary cultures of fetal and adult adrenal cells as well as adrenocortical cell lines as in vitro models for the study of human adrenal physiology and pathophysiology.
Topics: Adrenal Cortex; Cell Line, Tumor; Cells, Cultured; Humans; Models, Biological
PubMed: 33840647
DOI: 10.1620/tjem.253.217 -
Clinical Endocrinology Feb 2020Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities... (Review)
Review
Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities can be caused by direct effects of adrenal hormones, particularly glucocorticoids and sex steroids, or be mediated by indirect mechanisms such as the disturbance of the growth hormone-insulin-like growth factor-1 axis and aromatization of androgens to oestrogens. The early diagnosis and optimal treatment of adrenal disorders can prevent or minimize growth disturbance and facilitate improved height gain. Mechanisms of growth disturbance in the following abnormal states will be discussed; hypercortisolaemia, hyperandrogenaemia and obesity. Prevalence and features of growth disturbance will be discussed in ACTH-dependent and ACTH-independent Cushing's syndrome, adrenocortical tumours, premature adrenarche, congenital adrenal hyperplasia and adrenal insufficiency disorders. Recommendations for management have been included.
Topics: Adrenal Gland Diseases; Age of Onset; Body Height; Child; Child Development; Endocrinology; Growth Disorders; Humans; Pediatrics; Practice Guidelines as Topic; Prevalence
PubMed: 31747461
DOI: 10.1111/cen.14131 -
Journal of the Endocrine Society Jan 2021The conclusion of Panayiotopoulos that glucocorticoid resistance accounted for 57% to 67% of their premature adrenarche and polycystic ovary syndrome cases cannot be...
The conclusion of Panayiotopoulos that glucocorticoid resistance accounted for 57% to 67% of their premature adrenarche and polycystic ovary syndrome cases cannot be accepted from the data presented. This is because proper validation of their method for determining glucocorticoid sensitivity is not presented. Furthermore, the method seems insensitive to physiologic glucocorticoid concentrations.
PubMed: 33367193
DOI: 10.1210/jendso/bvaa163