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Journal of Chromatography. B,... Apr 2023The measurement of dehydroepiandrosterone-sulphate (DHEAs) is an important second-line test to aid in the diagnosis of premature adrenarche, peripubertal gynaecomastia...
A liquid chromatography-tandem mass spectrometry method for the analysis of dehydroepiandrosterone sulphate (DHEAs) in serum and plasma with comparison to an immunoassay method in a neonatal population.
The measurement of dehydroepiandrosterone-sulphate (DHEAs) is an important second-line test to aid in the diagnosis of premature adrenarche, peripubertal gynaecomastia in males and in identifying the source of elevated androgens in females. Historically, DHEAs has been measured by immunoassay platforms which are prone to poor sensitivity and more importantly poor specificity. The aim was to develop an LC-MSMS method for the measurement of DHEAs in human plasma and serum, develop an in-house paediatric (<6 year old) reference limit and compare the performance against the Abbott Alinity DHEAs immunoassay method. Following pre-treatment with an internal standard, samples were loaded onto EVOLUTE® EXPRESS ABN plate. Analytes were separated with reverse-phase chromatography using ACQUITY® UPLC® HSS T3 2.1 mm × 50 mm, 1.8 μm column. Mass spectrometry detection was performed using a Waters® Xevo TQ-XS in electrospray negative mode. For the paediatric reference range, samples were collected from an inpatient setting (age ≤ 6 years old) with no evidence of adrenal dysfunction or history of/current steroid use. The method comparison was performed using samples from this cohort aged between 0 and 52 weeks. The assay demonstrated linearity up to 15 µmol/L (r > 0.99) with a functional sensitivity of 0.1 µmol/L. Accuracy results revealed a mean bias of 0.7% (-14% to 15%) when compared against the NEQAS EQA LC-MSMS consensus mean (n = 48). The paediatric reference limit was calculated as ≤ 2.3 µmol/L (95% C.I. 1.4 to 3.8 µmol/L) for ≤ 6 year olds (n = 38). Comparison of neonatal (<52 weeks) DHEAs with the Abbott Alinity revealed that the immunoassay ran at a 166% positive bias (n = 24) which appeared to lessen with increasing age. Described is a robust LC-MSMS method for the measurement of plasma or serum DHEAs validated against internationally recognised protocols. Comparison of paediatric samples of <52 weeks against an immunoassay platform demonstrated that in the immediate new-born period results generated from the LC-MSMS method offer superior specificity than an immunoassay platform.
Topics: Male; Infant, Newborn; Female; Humans; Child; Infant; Dehydroepiandrosterone Sulfate; Tandem Mass Spectrometry; Chromatography, Liquid; Plasma; Immunoassay
PubMed: 36906955
DOI: 10.1016/j.jchromb.2023.123615 -
Problemy Endokrinologii Nov 2022Adrenocortical adenomas are often followed with steroid hormones hyperproduction, and therefore determination of their concentration plays an important role in the...
BACKGROUND
Adrenocortical adenomas are often followed with steroid hormones hyperproduction, and therefore determination of their concentration plays an important role in the differential diagnosis of adrenal diseases. Steroid profiling by tandem mass spectrometry is one of the main diagnostic methods in steroidogenesis characterization. Currently plasma and urinary steroid profiling is of particular interest in differential diagnosis and subtyping patients with adrenocortical adenomas.
AIM
Steroid profiling of pediatric patients with adrenal diseases (incidentalomas, ACTH-secreting pituitary adenoma, ACTH-independent Cushing syndrome, premature adrenarche).
MATERIALS AND METHODS
We conducted a retrospective analysis of steroid profile of 41 pediatric patients with adrenal diseases who were observed between 2005 and 2020 at the Endocrinology Research Centre.
RESULTS
All patients were divided into groups due to diagnosis: with ACTH-secreting pituitary adenoma [n=7], ACTH-independent Cushing syndrome (autonomous cortisol secretion by an adrenal adenoma) [n=4], with incidentaloma [n=7] and premature adrenarche [n=23]. In group of patients with ACTH-independent Cushing syndrome identified statistically significant higher levels of 11-deoxycortisol (р=0, 0035) and significant lower levels of 17-hydroxypregnenolone (р=0, 0026) and DHEA (р=0, 0047) compared to other groups. Statistically significant differences in steroid profiles between other groups were not identified.
CONCLUSION
Results of our study steroid profiling can be used as additional differential diagnosis method in patients with adrenocortical adenomas with or without hormonal hyperproduction (ACTH-independent Cushing syndrome and incidentaloma). Further studies are needed to identify steroid markers for subtyping pediatric adrenal diseases.
Topics: Humans; Child; Adrenocortical Adenoma; ACTH-Secreting Pituitary Adenoma; Hydrocortisone; Retrospective Studies; Adenoma
PubMed: 36689716
DOI: 10.14341/probl13166 -
Journal of Pediatric Endocrinology &... Feb 2023Prader-Willi syndrome (PWS) is characterized by obesity, growth hormone deficiency, hypogonadism, and a high prevalence of premature adrenarche despite reported...
OBJECTIVES
Prader-Willi syndrome (PWS) is characterized by obesity, growth hormone deficiency, hypogonadism, and a high prevalence of premature adrenarche despite reported hypothalamic-pituitary-adrenal axis dysfunction. While idiopathic premature adrenarche is associated with accelerated pre-pubertal growth and advanced bone age, the consequences of elevated adrenal androgens on growth and bone maturation in PWS remain unknown. This study therefore sought to describe age-related changes in dehydroepiandrosterone sulfate (DHEAS) and their effects on growth and bone maturation in PWS.
METHODS
This retrospective observational study included 62 children with PWS. Simple and multiple regression models were constructed to relate age and BMI-SDS with DHEAS levels. Height velocity was compared to age and sex-based norms with t-tests and two-way ANOVA. Patterns in bone age Z-score were examined with two-way ANOVA, and the contributions of age, BMI-SDS, and DHEAS to bone age Z-score were analyzed with multiple regression.
RESULTS
DHEAS levels rose earlier and were less strongly correlated with age in males and females with PWS (R=0.12 and 0.30) compared to healthy controls (R=0.89 and 0.88) in a pattern unrelated to BMI-SDS (adjusted R=0.076, p=0.10 for age, and 0.29 for BMI-SDS). Mid-childhood height velocity was increased in males and preserved in females with PWS before declining at the age of expected puberty (p<0.0001). Peri-adrenarchal bone age was advanced in a manner associated with DHEAS but not BMI-SDS (p<0.0001; adjusted R=0.48, p=0.0014 for DHEAS, and 0.78 for BMI-SDS).
CONCLUSIONS
An obesity-independent increase in adrenal androgens is associated with accelerated mid-childhood growth and bone maturation in PWS.
Topics: Child; Female; Humans; Male; Adrenarche; Androgens; Hypothalamo-Hypophyseal System; Obesity; Pituitary-Adrenal System; Prader-Willi Syndrome; Puberty, Precocious
PubMed: 36458449
DOI: 10.1515/jpem-2022-0468 -
Hormone Research in Paediatrics 2022Descriptions of probable PCOS can be found in ancient Roman writings and in Renaissance art. Attention to domesticated animal reproduction led ancient observers to... (Review)
Review
Descriptions of probable PCOS can be found in ancient Roman writings and in Renaissance art. Attention to domesticated animal reproduction led ancient observers to understand the role of the testes in male phenotypes, proven experimentally by testicular transplantation (in chickens) in 1849. Testosterone was isolated and its structure determined in the 1930s, but the multiple pathways of androgen synthesis have only been delineated recently. Adrenarche as an event separate from puberty was described in 1937, but the mechanism(s) triggering its onset remains unclear, although most work points to intraadrenal events. The identification of 11-ketotestosterone as the principal adrenal androgen is very recent (2018). Definitions of PCOS have evolved with the elucidation of its complex biology. PCOS is now recognized as a complex disorder characterized by irregular menses and hyperandrogenism often associated with infertility; its prevalence may be as high as 20% of reproductive age women. Work in the 1980s associated premature exaggerated adrenarche with PCOS, linking the adrenal to an "ovarian" syndrome. Obesity has long been noted in many patients with PCOS, and associated insulin resistance was noted in the 1980s, possibly associated with fetal developmental events such as low birth weight, but the mechanistic link between carbohydrate metabolism and hyperandrogenism remains unclear, despite intensive investigation. Genome-wide association studies have identified apparently associated genes, but mechanistic links are apparent for only some of these. Adrenarche, PCOS, and adrenal and ovarian hyperandrogenism remain very active areas of clinical and basic research.
Topics: Animals; Female; Male; Humans; Hyperandrogenism; Polycystic Ovary Syndrome; Adrenarche; Androgens; Genome-Wide Association Study; Chickens; Sexual Maturation
PubMed: 36446329
DOI: 10.1159/000526722 -
Journal of Clinical Research in... Feb 2023Premature adrenarche (PA) has been associated with an increase in adrenal androgens, and the hyperandrogenic hormonal environment is known to lead to increased platelet...
OBJECTIVE
Premature adrenarche (PA) has been associated with an increase in adrenal androgens, and the hyperandrogenic hormonal environment is known to lead to increased platelet (PLT) aggregation. Here, we evaluated the effects of PA on PLT aggregation in PLT-rich plasma samples from female patients.
METHODS
The study included 40 female patients diagnosed with PA between February, 2014 and June, 2018 and 30 healthy female individuals as a control group. Adenosine diphosphate (ADP) and collagen-induced PLT aggregation were studied via the photometric aggregometry method.
RESULTS
There were no significant differences in the PLT count or volume values between those participants with PA and the control group. Additionally, the ADP-induced maximum aggregation time, value, and slope values did not significantly differ between the patient and control groups (p>0.05). However, the collagen-induced maximum aggregation time, value, and slope values were significantly higher in the studygroup (p<0.001).
CONCLUSION
Increased collagen-induced PLT aggregation was detected in female patients with PA. As PA is associated with a higher risk of cardiovascular events later in life, close follow-up of PA in this respect may be beneficial.
Topics: Humans; Female; Platelet Aggregation; Adrenarche; Androgens; Puberty, Precocious; Adenosine Diphosphate; Collagen
PubMed: 36264033
DOI: 10.4274/jcrpe.galenos.2022.2022-6-13 -
Frontiers in Endocrinology 2022Wiedemann-Steiner Syndrome (WSS) is a genetic disorder associated with an array of clinical phenotypes, including advanced bone age and short stature....
CONTEXT
Wiedemann-Steiner Syndrome (WSS) is a genetic disorder associated with an array of clinical phenotypes, including advanced bone age and short stature. 11-ketotestosterone (11KT) is a member of the group known as 11-oxygenated C19 androgens that are implicated in premature adrenarche.
CASE DESCRIPTION
Case 1: The patient is a 3 year and 11-month-old female diagnosed with WSS due to deletion of detected on CGH microarray. At two years and 11 months, imaging revealed an advanced bone age. We obtained an 11KT level on this patient. 11KT in case 1 was elevated at 26.3 ng/dL, while the normal reference range is 7.3-10.9 ng/dL and the reference interval for premature adrenarche is 12.3-22.9 ng/dL, The repeat 11KT at follow up (chronological age 4 years and 6 months) was still elevated at 33.8 ng/dL Case 2: A second child with WSS and a 5kb intragenic deletion was evaluated at 11 months of age; his 11KT was 4.5 ng/dL.
CONCLUSIONS
The elevated 11KT may indicate maturational changes related to increasing adrenal gland androgenic activation and may explain the advanced bone age seen in some patients with WSS. To our knowledge, this is the first case report that describes 11KT as a bioactive androgen potentially causing bone age advancement in WSS. Lack of elevation of 11KT in the second child who is an infant suggests increasing androgenic precursors and metabolites related to premature adrenarche may need to be longitudinally followed.
Topics: Female; Humans; Androgens; Abnormalities, Multiple; Intellectual Disability
PubMed: 36263329
DOI: 10.3389/fendo.2022.1004114 -
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 -
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 -
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