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The Journal of Pediatrics Feb 2019To assess whether the serum levels of anti-Müllerian hormone (AMH) are increased in girls with premature adrenarche because they are at a higher risk of developing...
OBJECTIVES
To assess whether the serum levels of anti-Müllerian hormone (AMH) are increased in girls with premature adrenarche because they are at a higher risk of developing polycystic ovary syndrome (PCOS) later in life.
STUDY DESIGN
We measured serum levels of AMH, dehydroepiandrosterone sulfate (DHEAS), testosterone, sex hormone binding globulin, androstenedione, and 17-hyroxyprogesterone in 89 girls with premature adrenarche aged 6.98 ± 1.60 years, and in 55 prepubertal normal girls aged 6.78 ± 1.60 years.
RESULTS
AMH was significantly higher in girls with premature adrenarche (2.95 ± 1.20 ng/mL) compared with normal prepubertal girls (2.00 ± 0.95 ng/mL; P < .001), whereas their body mass index SD score was similar (P > .05). DHEAS, testosterone, and androstenedione were increased in premature adrenarche, whereas sex hormone binding globulin was decreased in girls with premature adrenarche. Among the 89 girls with premature adrenarche, 33 were daughters of mothers with a positive history of PCOS, whereas the mothers of the remaining 56 girls with premature adrenarche had a negative history of PCOS. The girls with a mother with a positive history of PCOS had significantly higher AMH serum levels compared with girls with a mother with a negative history of PCOS (3.37 ± 1.72 ng/mL vs 2.70 ± 1.25 ng/mL; P < .05) with no differences in testosterone, DHEAS, androstenedione, and sex hormone binding globulin. The serum concentration of AMH was only positively related to androstenedione (r = 0.538; P < .0001).
CONCLUSIONS
Girls with premature adrenarche, especially those from mothers with a history of PCOS, could have a higher risk of developing PCOS later in life because they have increased serum AMH.
Topics: Adrenarche; Anti-Mullerian Hormone; Biomarkers; Body Mass Index; Child; Female; Genetic Predisposition to Disease; Humans; Mothers; Nuclear Family; Polycystic Ovary Syndrome; Puberty; Radioimmunoassay
PubMed: 30529136
DOI: 10.1016/j.jpeds.2018.09.064 -
EClinicalMedicine Dec 2021Extremely tall children (defined as height SDS (HSDS) ≥+3) are frequently referred to specialized healthcare for diagnostic work-up. However, no systematic studies...
BACKGROUND
Extremely tall children (defined as height SDS (HSDS) ≥+3) are frequently referred to specialized healthcare for diagnostic work-up. However, no systematic studies focusing on such children currently exist. We investigated the aetiology, clinical features, and auxological clues indicative of syndromic tall stature in extremely tall children subject to population-wide growth monitoring and screening rules.
METHODS
Subjects with HSDS ≥+3 after three years of age born between 1990 and 2010 were identified from the Helsinki University Hospital district growth database. We comprehensively reviewed their medical records up to December 2020 and recorded underlying diagnoses, auxological data, and clinical features.
FINDINGS
We identified 424 subjects (214 girls and 210 boys) who fulfilled the inclusion criteria. Underlying growth disorder was diagnosed in 61 (14%) patients, in 36 (17%) girls and 25 (12%) boys, respectively (P=0•15). Secondary causes were diagnosed in 42 (10%) patients and the two most frequent secondary diagnoses, premature adrenarche, and central precocious puberty were more frequent in girls. Primary disorder, mainly Marfan or Sotos syndrome, was diagnosed in 19 (4%) patients. Molecular genetic studies were used as a part of diagnostic work-up in 120 subjects. However, array CGH or next-generation sequencing studies were seldom used. Idiopathic tall stature (ITS) was diagnosed in 363 (86%) subjects, and it was considered familial in two-thirds. Dysmorphic features or a neurodevelopmental disorder were recorded in 104 (29%) children with ITS. The probability of a monogenic primary growth disorder increased with the degree of tall stature and deviation from target height.
INTERPRETATION
A considerable proportion of extremely tall children have an underlying primary or secondary growth disorder, and their risk is associated with auxological parameters. Clinical features related to syndromic tall stature were surprisingly frequent in subjects with ITS, supporting the view that syndromic growth disorders with mild phenotypes may be underdiagnosed in extremely tall children. Our results lend support to comprehensive diagnostic work-up of extremely tall children.
FUNDING
Päivikki and Sakari Sohlberg Foundation, Foundation for Pediatric Research, and Helsinki University Hospital research grants.
PubMed: 34849478
DOI: 10.1016/j.eclinm.2021.101208 -
Journal of the Endocrine Society Mar 2023Premature adrenarche (PA) may predispose to some adverse long-term health outcomes. Cardiorespiratory fitness (CRF) is one of the strongest factors known to predict...
CONTEXT
Premature adrenarche (PA) may predispose to some adverse long-term health outcomes. Cardiorespiratory fitness (CRF) is one of the strongest factors known to predict overall health, but no data exist on the CRF of women with a history of PA.
OBJECTIVE
To study if hyperandrogenism in childhood resulting from PA leads to a measurable difference in CRF between young adult PA and control women.
METHODS
A total of 25 women with PA and 36 age-matched controls were followed from prepubertal age until adulthood. Anthropometric measurements, body composition, biochemical, and lifestyle factors were assessed. The main outcome measure was maximal cycle ergometer test result at the mean age of 18.5 years. We also assessed prepubertal predicting factors for CRF with different linear regression models.
RESULTS
Though prepubertal children with PA were taller and heavier than their non-PA peers, there were no significant differences in height, body mass index, body composition, or physical activity in young adulthood. We observed no significant differences in any of the parameters of the maximal cycle ergometer test, including maximal load ( = .194) or peak oxygen consumption ( = .340). Hemodynamic responses of the groups were similar. None of the examined models or prepubertal factors significantly predicted CRF at adult age.
CONCLUSION
This study suggests that hyperandrogenism in childhood/adolescence resulting from PA does not have a significant impact on adulthood CRF.
PubMed: 37077523
DOI: 10.1210/jendso/bvad041 -
Congenital adrenal hyperplasia caused by compound heterozygosity of two novel CYP11B1 gene variants.Hormones (Athens, Greece) Mar 2022Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by pathogenic variants in seven genes involved in the cortisol and aldosterone... (Review)
Review
BACKGROUND
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by pathogenic variants in seven genes involved in the cortisol and aldosterone biosynthetic pathway. The second most common cause, 11β-hydroxylase deficiency (11βOHD), is attributed to pathogenic variants in the CYP11B1 gene encoding for the enzyme 11β-hydroxylase (11βOH).
CASE PRESENTATION
A 13-year-old girl was referred to the pediatric endocrinologist due to a syncopal episode. She is the third child of non-consanguineous parents. She presented with premature adrenarche at the age of 6 years and menarche at the age of 12 years. On physical examination, her height was 154.5 cm and weight 50 kg, while she presented with acne, hirsutism, clitoromegaly, and normal blood pressure. Laboratory investigation revealed increased androgen levels and poor cortisol response to the ACTH stimulation test. From the family history, the mother was diagnosed with CAH at the age of 10 years and was under treatment with methylprednisolone. Previous molecular investigation of the CYP21A2 gene was negative. Due to the increased androstenedione levels in the index patient, the suspicion of 11βOH was raised, and she was investigated for 11-deoxycortisol, 11-deoxycorticosterone, and CYP11B1 gene pathogenic variants. The patient and her mother were found to be compound heterozygous for two novel variants of the CYP11B1 gene.
CONCLUSION
We present a case of CAH due to compound heterozygosity of two novel pathogenic variants of the CYP11B1 gene, emphasizing the importance of molecular investigation in order to confirm clinical diagnosis and allow proper genetic counseling of the family.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Aldosterone; Child; Female; Humans; Hydrocortisone; Mutation; Steroid 11-beta-Hydroxylase; Steroid 21-Hydroxylase
PubMed: 34697763
DOI: 10.1007/s42000-021-00322-1 -
Journal of Ovarian Research Nov 2023Existing studies have investigated the relationship between the levels of serum inhibin B (INHB), anti-müllerian hormone (AMH) and precocious puberty in girls, but the... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS
Existing studies have investigated the relationship between the levels of serum inhibin B (INHB), anti-müllerian hormone (AMH) and precocious puberty in girls, but the results are inconsistent.
OBJECTIVE
The aim of this meta-analysis was to assess whether the INHB and AMH levels changed in girls with precocious puberty relative to healthy controls.
METHODS
PubMed, Embase, Cochrane Library and Web of Science were searched through June 2022. We included observational clinical studies reporting the serum levels INHB and AMH in girls with precocious puberty. Conference articles and observational study abstracts were included if they contained enough information regarding study design and outcome data. Case series and reports were excluded. An overall standard mean difference (SMD) between precocious puberty and healthy controls was estimated using a DerSimonian-Laird random-effects model.
RESULTS
A total of 11 studies featuring 552 girls with precocious puberty and 405 healthy girls were selected for analysis. The meta-analysis showed that the INHB level of precocious puberty [including central precocious puberty (CPP) and premature the larche (PT)] were significantly increased. While there was no significant association between precocious puberty [including CPP, PT, premature pubarche (PP) and premature adrenarche (PA)] and the level of serum AMH.
CONCLUSION
Scientific evidence suggested that the INHB level, but not the AMH level, altered in girls with precocious puberty compared with healthy controls. Through our results we think that INHB level might be a marker for the auxiliary diagnosis of precocious puberty (especially CPP and PT). Therefore, it is important to evaluate and thoroughly investigate the clinical indicators (e.g., INHB) in order to ensure early diagnosis and medical intervention, and the risk of physical, psychological and social disorders in immature girls with precocious puberty is minimized.
Topics: Female; Humans; Anti-Mullerian Hormone; Follicle Stimulating Hormone; Inhibins; Observational Studies as Topic; Puberty, Precocious
PubMed: 37996919
DOI: 10.1186/s13048-023-01302-2 -
Practical Laboratory Medicine Aug 2022Androstenedione (ASD) is a biomarker used in the diagnostic workup of hyperandrogenism, congenital adrenal hyperplasia, premature adrenarche, and polycystic ovary...
UNLABELLED
Androstenedione (ASD) is a biomarker used in the diagnostic workup of hyperandrogenism, congenital adrenal hyperplasia, premature adrenarche, and polycystic ovary syndrome (PCOS). The Elecsys ASD competitive electrochemiluminescence immunoassay (Roche Diagnostics, Indianapolis, IN) is a new assay recently available in the US.
OBJECTIVE
This study evaluated the analytical and clinical performance of the Elecsys ASD assay.
DESIGN & METHODS
We evaluated the linearity/analytical measuring range (AMR), precision, and accuracy of the Elecsys ASD assay on the cobas e601 analyzer. ASD was measured in serum/plasma in the Elecsys ASD, Immulite (Siemens Medical Solutions USA, Inc. Malvern, PA), and LC-MS/MS assays. Reference intervals (RI) were evaluated across genders, menopausal status, and in children. Statistical analysis was performed using EP evaluator and R program.
RESULTS
The Elecsys ASD assay had a linear response across the AMR. The intra- and inter-assay coefficients of variation at various concentrations were ≤4.5%. The Elecsys ASD assay had a mean difference of -0.04 ng/mL (-1.7%) with the LC-MS/MS assay, whereas the Immulite assay had a mean difference of 1.17 ng/mL (66%) and -1.22 ng/mL (-38%) compared to the LC-MS/MS and Elecsys ASD assays, respectively. The Roche recommended RIs for healthy men (0.280-1.52 ng/mL) and postmenopausal women (0.187-1.07 ng/mL) were successfully verified. The RIs for children were adopted from published data. For pre-menopausal women, a RI of <1.60 ng/mL was established. The ASD concentrations in women with and without PCOS overlapped.
CONCLUSIONS
The Elecsys ASD assay has superior comparability to the LC-MS/MS assay than the Immulite assay.
PubMed: 35620064
DOI: 10.1016/j.plabm.2022.e00279 -
Hormone Research in Paediatrics 2018Children with premature adrenarche (PA) are taller and more overweight than their healthy peers, and PA girls have a slightly accelerated pubertal development. There is...
BACKGROUND/AIM
Children with premature adrenarche (PA) are taller and more overweight than their healthy peers, and PA girls have a slightly accelerated pubertal development. There is some evidence that early exposure to androgens may have an influence on psychosocial development. The aim of this cross-sectional case-control study was to evaluate health-related quality of life (HRQoL) in PA children at the age of 12 years.
METHODS
The HRQoL was assessed for 43 PA (36 girls) and 63 control children (52 girls) at the median age of 12.0 years using the standardized 16D instrument, and the scores of the PA children were compared to those of the control children and reference population.
RESULTS
The mean overall HRQoL scores did not differ between PA and control girls, PA and control boys, or all PA and control children or the reference population. Independently of PA, overweight girls had a lower mean overall HRQoL score than lean girls, and both overweight girls and boys were on average worse off on the dimension of appearance than their lean peers.
CONCLUSIONS
PA children have as good self-rated HRQoL as their peers at the age of 12 years. Overweight is associated with a worse HRQoL profile independently of PA.
Topics: Adrenarche; Case-Control Studies; Child; Cross-Sectional Studies; Female; Humans; Male; Quality of Life
PubMed: 29502117
DOI: 10.1159/000487134 -
BMC Pediatrics Nov 2019Obesity is associated with many chronic diseases including cortisol rhythm disorder and low testosterone. Furthermore, studies on obese children are quite limited and no...
BACKGROUND
Obesity is associated with many chronic diseases including cortisol rhythm disorder and low testosterone. Furthermore, studies on obese children are quite limited and no concordance results have been obtained, especially for boys in puberty. Moreover, the sample sizes of previous studies were small, and were not representative.
METHODS
We conducted a cross-sectional survey including 1148 boys aged 6-14 years, they were divided into overweight/obesity (OW/OB) group and normal weight (NW) group. Puberty status was assessed according to Tanner scale and testicular volume. Serum levels of pregnenolone, 17-OH progesterone, corticosterone, dehydroepiandrosterone (DHEA), and androstenedione were detected by LC-MS. Serum free testosterone and sex hormone-binding globulin (SHBG) levels were measured by chemiluminescence immunoassay.
RESULTS
The 17-OH progesterone, DHEA, androstenedione and free testosterone levels of OW/OB boys at prepubertal stage or at the age 6 = < 10 years group were higher than those of the NW boys (all the P values were < 0.01). Furthermore, androstenedione and free testosterone levels were lower in OW/OB boys at late puberty, and the trend continued at the post pubertal stage for FT (P < 0.01-0.05). DHEA, androstenedione, and FT levels persisted to be higher at the 10~ < 12 years in OW/OB boys but not for 17-OH progesterone. FT level was lower in the OW/OB group at the 12~ < 15 years group. The SHBG levels in the OW/OB boys were lower than those in the NW ones at the 6~12 years group, and prepubertal to early pubertal stage.
CONCLUSIONS
Premature adrenarche is more likely in OW/OB boys. More attention should be given to the lower androgen levels of OW/OB boys at late pubertal and post pubertal stages.
Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Cortex Hormones; Age Factors; Androstenedione; Child; Corticosterone; Cross-Sectional Studies; Dehydroepiandrosterone; Humans; Male; Organ Size; Overweight; Pediatric Obesity; Pregnenolone; Puberty; Puberty, Precocious; Sex Hormone-Binding Globulin; Testis; Testosterone
PubMed: 31690265
DOI: 10.1186/s12887-019-1755-5 -
Hormone Research in Paediatrics 2015Studies that evaluate both body composition and metabolic syndrome (MeS) risk in prepubertal children with premature adrenarche (PA) are limited.
BACKGROUND
Studies that evaluate both body composition and metabolic syndrome (MeS) risk in prepubertal children with premature adrenarche (PA) are limited.
METHODS
Fifty-eight prepubertal children (aged 5-9 years, 33 female and 25 male), 30 with PA and 28 controls, were evaluated for the presence of MeS as defined by age-modified National Cholesterol Education Program Adult Treatment Panel III criteria. A subset had dual-energy X-ray absorptiometry and bone markers (n = 23/58) to evaluate the effect of hyperandrogenism on metabolic abnormalities and body composition.
RESULTS
There was no difference in the prevalence of MeS between PA and controls (p = 0.138). Children with MeS were obese with an increased waist circumference (WC) and decreased high-density lipoprotein levels. Androgens were not associated with having more than one criterion for MeS (p = 0.08) but were associated with triglycerides and WC (p = 0.029 and p = 0.041, respectively). Lean mass was greater in PA subjects (p = 0.039), and androgens correlated with bone mineral density (p = 0.029) and total body fat (p = 0.008). Subjects with a higher percent of body fat were more likely to have more than one MeS risk factor (p = 0.005).
CONCLUSIONS
MeS was seen only in obese subjects whether or not they had PA. Thus, it appears that obesity drives metabolic risk in the prepubertal population rather than PA. Our findings are important in determining how the prepubertal patient with PA should be evaluated for metabolic risk.
Topics: Adipose Tissue; Adrenarche; Age Factors; Body Composition; Child; Child, Preschool; Cholesterol; Female; Humans; Male; Metabolic Syndrome; Obesity; Puberty, Precocious; Triglycerides; Waist Circumference
PubMed: 26513727
DOI: 10.1159/000441498 -
The Journal of Adolescent Health :... May 2020This project investigated internal consistency and test-retest reliability of the frequently used Pubertal Development Scale (PDS) and compared parent and child reports...
PURPOSE
This project investigated internal consistency and test-retest reliability of the frequently used Pubertal Development Scale (PDS) and compared parent and child reports with clinician-rated Tanner staging.
METHODS
Using a repository of data collected from 1995 to 2016, 252 participants (aged 7.8-17.7 years) provided self- and parent-reported PDS and received Tanner staging by a certified health care professional within 30 days. Internal consistency and test-retest reliability statistics were evaluated for 56 children across two assessments occurring within 6 months. Comparisons with Tanner staging involved examining concurrent validity and calibration analysis using data from 233 child and 252 parental ratings.
RESULTS
Self- and parent-reported PDS demonstrated good internal consistency, with Cronbach's alpha .91-.96; high test-retest reliability was confirmed with intraclass correlation coefficient .81-.92. The association of Tanner stage with self- and parent-reported PDS was moderate to high; Kendall's Tau ranged from .67 to .76, and intraclass correlation coefficient ranged from .73 to 83. The absolute agreement of Tanner stage with self- and parent-reported PDS was low; Cohen's Kappa ranged from .20 to .37. However, combining pubertal scores into three stages of development (pre/early-, mid-, and late/post-pubertal) improved interrater agreement across measures (κ = .65, 95% confidence interval = .57-.73).
CONCLUSIONS
The present study shows that the PDS is reliable and generally tracks with Tanner staging (for both self and parent report). Low absolute agreement indicates that PDS categories do not map directly to specific Tanner stages, partly because a premature adrenarche is often misinterpreted by parents and pediatricians alike. However, three broad categories showed better agreement and are generally adequate for most applications in child and adolescent research.
Topics: Adolescent; Child; Family; Humans; Puberty; Reproducibility of Results; Surveys and Questionnaires
PubMed: 31974011
DOI: 10.1016/j.jadohealth.2019.11.308