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The Journal of Clinical Endocrinology... Aug 2023Accelerated early growth and early timing of puberty or pubertal variant have been noticed as risk factors for metabolic syndrome, more frequently observed in children... (Review)
Review
Accelerated early growth and early timing of puberty or pubertal variant have been noticed as risk factors for metabolic syndrome, more frequently observed in children born small for gestational age (SGA) or children with premature adrenarche (PA). Children with SGA, especially if they make an accelerated catch-up growth in early life, carry a higher risk for long-term metabolic consequences, such as type 2 diabetes, insulin resistance, and cardiovascular diseases. Furthermore, multiple studies support that these children, either born SGA or with a history of PA, may have earlier pubertal timing, which is also associated with various metabolic risks. This review aims to summarize the recent studies investigating the association between early infantile growth, the timing of puberty, and metabolic risks to expand our knowledge and gain more insight into the underlying pathophysiology.
Topics: Infant, Newborn; Female; Humans; Child; Diabetes Mellitus, Type 2; Puberty; Infant, Small for Gestational Age; Fetal Growth Retardation; Metabolic Syndrome
PubMed: 37029976
DOI: 10.1210/clinem/dgad202 -
Hormone Research in Paediatrics 2017The aim of this study was to investigate the cardiovascular risk of children with premature adrenarche (PA). (Clinical Trial)
Clinical Trial
AIM
The aim of this study was to investigate the cardiovascular risk of children with premature adrenarche (PA).
METHODS
A total of 75 children (44 with PA and 31 control subjects) aged 6-10 years were included in the study. Their metabolic, anthropometric, and echocardiographic parameters were recorded and compared.
RESULTS
Triglyceride, DHEA-SO4, and 17-hydroxyprogesterone levels were significantly higher in the PA group (p = 0.04, p = 0.002, and p = 0.01, respectively). The echocardiographic assessments revealed that the left ventricular end-diastolic diameter (LVEDD) (p < 0.001), left ventricle (LV) and right ventricle (RV) ejection times (p = 0.031 and p = 0.035, respectively), and LV and RV Tei index measurements (p = 0.033 and p = 0.006, respectively) were significantly higher in the PA group than in the control group, whereas the E/e' ratio of the mitral lateral annulus was significantly lower in the PA group (p = 0.006). Additionally, carotid intima-media thickness and epicardial adipose tissue measurements were significantly increased in the PA group compared to the control group (p < 0.001).
CONCLUSION
Early atherosclerotic changes and subclinical impairment of cardiac function were observed in children with PA. It is possible that these children are on a course for early cardiovascular disease.
Topics: Adipose Tissue; Adrenarche; Atherosclerosis; Carotid Intima-Media Thickness; Child; Dehydroepiandrosterone Sulfate; Echocardiography; Female; Humans; Male; Pericardium; Stroke Volume; Triglycerides
PubMed: 27871080
DOI: 10.1159/000452445 -
Metabolomics : Official Journal of the... Oct 2022Premature adrenarche (PA) for long time was considered a benign condition but later has been connected to various diseases in childhood and adulthood which remains...
INTRODUCTION
Premature adrenarche (PA) for long time was considered a benign condition but later has been connected to various diseases in childhood and adulthood which remains controversial.
OBJECTIVE
To investigate the effect of premature adrenarche on the metabolic phenotype, and correlate the clinical and biochemical data with the metabolic profile of children with PA.
METHODS
Nuclear magnetic resonance (NMR)-based untargeted and targeted metabolomic approach in combination with multivariate and univariate statistical analysis applied to study the metabolic profiles of children with PA. Plasma, serum, and urine samples were collected from fifty-two children with Idiopathic PA and forty-eight age-matched controls from the division of Pediatric Endocrinology of the University Hospital of Patras were enrolled.
RESULTS
Metabolomic results showed that plasma and serum glucose, myo-inositol, amino acids, a population of unsaturated lipids, and esterified cholesterol were higher and significantly different in PA children. In the metabolic profiles of children with PA and age-matched control group a gradual increase of glucose and myo-inositol levels was observed in serum and plasma, which was positively correlated their body mass index standard deviation score (BMI SDS) values respectively. Urine H NMR metabolic fingerprint of PA children showed positive correlation and a clustering-dependent relationship with their BMI and bone age (BA) respectively.
CONCLUSION
This study provides evidence that PA driven metabolic changes begin during the childhood and PA may has an inductive role in a BMI-driven increase of specific metabolites. Finally, urine may be considered as the best biofluid for identification of the PA metabolism as it reflects more clearly the PA metabolic fingerprint.
Topics: Adrenarche; Amino Acids; Cholesterol; Glucose; Inositol; Lipids; Magnetic Resonance Spectroscopy; Metabolomics
PubMed: 36239863
DOI: 10.1007/s11306-022-01941-4 -
Journal of Pediatric Endocrinology &... Aug 2021Premature adrenarche may be associated with an intrauterine programmed metabolic syndrome which should be considered as a warning sign for coronary heart disease due to...
OBJECTIVES
Premature adrenarche may be associated with an intrauterine programmed metabolic syndrome which should be considered as a warning sign for coronary heart disease due to accelerated atherosclerosis, hypertension, type 2 diabetes mellitus (DM), and polycystic ovary syndrome.
METHODS
Seventy-three patients with premature adrenarche were evaluated for metabolic parameters and aortic elasticity to evaluate the susceptibility to atherosclerosis and compared with a control group. The patients were examined in two groups as overweight and nonoverweight, and metabolic and cardiac parameters were also compared among these groups. Strain, distensibility, and stiffness index parameters were used to evaluate aortic elasticity.
RESULTS
Biochemical parameters and cardiac measurements were not statistically different between patients and controls. They also did not differ between patients with normal weight and overweight groups. Atherogenic index and insulin resistance were closely related and a positive correlation between cholesterol and triglyceride, and ascending aortic stiffness was found.
CONCLUSIONS
The results may suggest that cholesterol and triglyceride-related arterial involvement is more involved in the pathogenesis of arterial stiffness. It can be considered that 'being overweight' or 'having metabolic profile characterized by insulin resistance and dyslipidemia' are the major coexisting factors influencing the vascular structure, rather than increased androgens and premature adrenarche itself.
Topics: Adrenal Gland Diseases; Adrenarche; Atherosclerosis; Case-Control Studies; Child; Female; Follow-Up Studies; Humans; Insulin Resistance; Male; Metabolic Syndrome; Overweight; Prognosis; Risk Factors; Vascular Stiffness
PubMed: 34167179
DOI: 10.1515/jpem-2021-0160 -
Current Pharmaceutical Design 2020Early activation of the adrenal zona reticularis, leading to adrenal androgen secretion, mainly dehydroepiandrosterone sulfate (DHEAS), is called premature adrenarche...
Early activation of the adrenal zona reticularis, leading to adrenal androgen secretion, mainly dehydroepiandrosterone sulfate (DHEAS), is called premature adrenarche (PA). The fact that adrenal hyperandrogenism in females has been linked to a cluster of cardiovascular (CV) risk factors, even in prepubertal children, warrants investigation. Controversial results have been obtained in this field, probably due to genetic, constitutional, and environmental factors or differences in the characteristics of participants. In an attempt to understand, in depth, the impact of PA as a potential activator of CV risk, we critically present available data stratified according to pubertal status. It seems that prepubertally, CV risk is increased in these girls, but is somewhat attenuated during their second decade of life. Furthermore, different entities associated with PA, such as polycystic ovary syndrome, non-classical congenital adrenal hyperplasia, heterozygosity of CYP21A2 mutations, and the impact of DHEAS on CV risk, are reviewed. At present, firm and definitive conclusions cannot be drawn. However, it may be speculated that girls with a history of PA display a hyperandrogenic hormonal milieu that may lead to increased CV risk. Accordingly, appropriate long-term follow-up and early intervention employing a patient-oriented approach are recommended.
Topics: Adrenarche; Cardiovascular Diseases; Child; Female; Heart Disease Risk Factors; Humans; Puberty, Precocious; Risk Factors; Steroid 21-Hydroxylase
PubMed: 33045962
DOI: 10.2174/1381612826666201012164726 -
The Journal of Clinical Endocrinology... Apr 2021Virilization is the medical term for describing a female who develops characteristics associated with male hormones (androgens) at any age, or when a newborn girl shows... (Review)
Review
UNLABELLED
Virilization is the medical term for describing a female who develops characteristics associated with male hormones (androgens) at any age, or when a newborn girl shows signs of prenatal male hormone exposure at birth. In girls, androgen levels are low during pregnancy and childhood. A first physiologic rise of adrenal androgens is observed at the age of 6 to 8 years and reflects functional activation of the zona reticularis of the adrenal cortex at adrenarche, manifesting clinically with first pubic and axillary hairs. Early adrenarche is known as "premature adrenarche." It is mostly idiopathic and of uncertain pathologic relevance but requires the exclusion of other causes of androgen excess (eg, nonclassic congenital adrenal hyperplasia) that might exacerbate clinically into virilization. The second modest physiologic increase of circulating androgens occurs then during pubertal development, which reflects the activation of ovarian steroidogenesis contributing to the peripheral androgen pool. However, at puberty initiation (and beyond), ovarian steroidogenesis is normally devoted to estrogen production for the development of secondary female bodily characteristics (eg, breast development). Serum total testosterone in a young adult woman is therefore about 10- to 20-fold lower than in a young man, whereas midcycle estradiol is about 10- to 20-fold higher. But if androgen production starts too early, progresses rapidly, and in marked excess (usually more than 3 to 5 times above normal), females will manifest with signs of virilization such as masculine habitus, deepening of the voice, severe acne, excessive facial and (male typical) body hair, clitoromegaly, and increased muscle development. Several medical conditions may cause virilization in girls and women, including androgen-producing tumors of the ovaries or adrenal cortex, (non)classical congenital adrenal hyperplasia and, more rarely, other disorders (also referred to as differences) of sex development (DSD). The purpose of this article is to describe the clinical approach to the girl with virilization at puberty, focusing on diagnostic challenges. The review is written from the perspective of the case of an 11.5-year-old girl who was referred to our clinic for progressive, rapid onset clitoromegaly, and was then diagnosed with a complex genetic form of DSD that led to abnormal testosterone production from a dysgenetic gonad at onset of puberty. Her genetic workup revealed a unique translocation of an abnormal duplicated Y-chromosome to a deleted chromosome 9, including the Doublesex and Mab-3 Related Transcription factor 1 (DMRT1) gene.
LEARNING OBJECTIVES
Identify the precise pathophysiologic mechanisms leading to virilization in girls at puberty considering that virilization at puberty may be the first manifestation of an endocrine active tumor or a disorder/difference of sex development (DSD) that remained undiagnosed before and may be life-threatening. Of the DSDs, nonclassical congenital adrenal hyperplasia occurs most often.Provide a step-by-step diagnostic workup plan including repeated and expanded biochemical and genetic tests to solve complex cases.Manage clinical care of a girl virilizing at puberty using an interdisciplinary team approach.Care for complex cases of DSD manifesting at puberty, such as the presented girl with a Turner syndrome-like phenotype and virilization resulting from a complex genetic variation.
Topics: Adrenal Hyperplasia, Congenital; Adrenarche; Androgens; Child; Female; Humans; Puberty; Virilism
PubMed: 33367768
DOI: 10.1210/clinem/dgaa948 -
The Journal of Clinical Endocrinology... Nov 2017Premature adrenarche has been reported to be frequent in Silver-Russell syndrome (SRS), but systematic studies are lacking. Here, we studied the prevalence of early...
OBJECTIVES
Premature adrenarche has been reported to be frequent in Silver-Russell syndrome (SRS), but systematic studies are lacking. Here, we studied the prevalence of early adrenarche in SRS, potential predictors, and consequences based on cases with long-term follow-up.
DESIGN AND SETTING
This retrospective longitudinal single-center study included 62 patients with SRS (34 boys) with documented age at adrenarche and positive Netchine-Harbison clinical score who were seen during the past 20 years with a median follow-up of 12.8 years. Clinical and biochemical characteristics were collected from patient records. Adrenarche was defined by reaching a serum dehydroepiandrosterone concentration >500 ng/mL.
RESULTS
Boys reached adrenarche at a median age of 9.2 years (quartiles: 7.6, 10.9 years) and pubarche at a median age of 11.7 years (quartiles: 10.7, 12.8 years). Girls reached adrenarche at a median age of 8.1 years (quartiles: 6.6, 10.1 years) and pubarche at a median age of 9.8 years (quartiles: 8.3, 10.8). Premature adrenarche occurred in 13% of the patients. Multiple linear regression analysis revealed that early adrenarche was associated with early initiation of recombinant human growth hormone (rhGH) treatment (P = 0.0024 in boys; P = 0.0195 in girls), but not with the Netchine-Harbison clinical score (P > 0.25). Response to rhGH treatment (median dose, 50 µg/kg/d) and adult height (n = 43) were not compromised by early adrenarche.
CONCLUSIONS
Early or premature adrenarche was more frequent in SRS than in the general population and was associated with early age at initiation of rhGH treatment. Response to rhGH treatment and adult height were not compromised by early adrenarche.
Topics: Adolescent; Adrenarche; Age Factors; Child; Dehydroepiandrosterone; Female; Follow-Up Studies; Hormone Replacement Therapy; Human Growth Hormone; Humans; Longitudinal Studies; Male; Puberty, Precocious; Retrospective Studies; Silver-Russell Syndrome; Time Factors
PubMed: 28945864
DOI: 10.1210/jc.2017-00874 -
European Journal of Endocrinology Nov 2015The normal function of the female reproductive system is closely linked to energy homeostasis with the ultimate scope of fertility and human race perpetuation through... (Review)
Review
The normal function of the female reproductive system is closely linked to energy homeostasis with the ultimate scope of fertility and human race perpetuation through the centuries. During a woman's lifetime there are normal events such as puberty, pregnancy and menopause which are related to alterations in energy homeostasis and gonadal steroids levels followed by increase of body fat and insulin resistance, important components of metabolic syndrome (MetS). Pathological conditions such as premature adrenarche, polycystic ovary syndrome and gestational diabetes also present with shifts in gonadal steroid levels and reduced insulin sensitivity. The aim of this review is to discuss these conditions, both normal and pathological, analyzing the changes or abnormalities in ovarian function that coexist with metabolic abnormalities which resemble MetS in relationship with environmental, genetic and epigenetic factors.
Topics: Female; Humans; Menopause; Metabolic Syndrome; Polycystic Ovary Syndrome; Pregnancy; Puberty; Puberty, Precocious
PubMed: 26034072
DOI: 10.1530/EJE-15-0275 -
Clinical Endocrinology Mar 2022An association between premature adrenarche and metabolic syndrome at presentation has been described. Our aim was to assess whether the presence of high... (Observational Study)
Observational Study
CONTEXT
An association between premature adrenarche and metabolic syndrome at presentation has been described. Our aim was to assess whether the presence of high dehydroepiandrosterone sulphate (DHEAS [HD]) at the adrenarche determines the risk of metabolic syndrome during puberty, taking into account body mass index (BMI) and birth weight.
DESIGN
Prospective observational.
PATIENTS
Five hundred four girls from the Growth and Obesity Chilean Cohort Study were followed from birth through puberty. At age ~7, subjects were classified by DHEAS concentrations into the HD (>75th percentile) or normal DHEAS (ND, ≤75th percentile) subgroups.
MEASUREMENTS
Anthropometrics, semiannual clinical pubertal staging and hormonal and metabolic levels. The relationships among DHEAS at age ~7, metabolic syndrome, and each of its components independently, were analyzed by linear and logistic regression models during puberty and 1-year postmenarche, adjusted by confounders.
RESULTS
Girls with HD at 7 years exhibited higher BMI, more central fat and higher serum androgen and insulin like growth factor (IGF)-I levels throughout puberty. Also, girls with HD had a greater prevalence of hyperglycemia at B2 and B4 breast stages, and of low HDL at B4. At 1 year after menarche, HD girls had a higher prevalence of metabolic syndrome, and those with BMI > 1 SD score had a higher metabolic score and insulin levels than ND girls with similar BMI.
CONCLUSIONS
Our observations suggest that girls with HD at the age of adrenarche may be at greater risk for metabolic syndrome at adolescence, especially in those who are overweight or obese. Our results emphasize the importance of lifestyle interventions for childhood overweight and obesity among girls with HD.
Topics: Adolescent; Adrenarche; Body Mass Index; Child; Cohort Studies; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Male; Metabolic Syndrome; Obesity; Puberty
PubMed: 34904249
DOI: 10.1111/cen.14654