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The Journal of Pediatrics Jun 2009
Topics: Adrenarche; Age of Onset; Child; Female; Growth; Humans; Male; Puberty, Precocious
PubMed: 19446090
DOI: 10.1016/j.jpeds.2009.04.025 -
Journal of Pediatric Endocrinology &... 2000The complications of hyperinsulinism and insulin resistance are becoming more common in pediatrics (including type 2 diabetes mellitus, dyslipidemia and polycystic ovary... (Review)
Review
The complications of hyperinsulinism and insulin resistance are becoming more common in pediatrics (including type 2 diabetes mellitus, dyslipidemia and polycystic ovary syndrome) because of the increased occurrence of obesity in children. We report the occurrence of insulin resistance and marked hyperandrogenism in prepubertal minority group girls (African-American and Caribbean Hispanic) with premature adrenarche. Approximately one-third of our prepubertal patients with premature adrenarche evaluated have been noted to have marked hyperandrogenism with ACTH stimulated levels of 17-hydroxypregnenolone and the ratio of 17-hydroxypregnenolone/17-hydroxyprogesterone more than two standard deviations above the mean of normal early pubertal girls (Tanner II-III). Furthermore, those girls with the more marked hyperandrogenism have been noted to have insulin resistance as assessed by the frequently sampled intravenous glucose tolerance test. A preliminary evaluation of adolescent girls previously evaluated for premature adrenarche has revealed that those girls with hyperandrogenism and insulin resistance when evaluated in the prepubertal period continue to have obesity, insulin resistance, hyperandrogenism and symptoms of hyperandrogenism (irregular menses, hirsutism and acne). Hence, the early identification of children at risk for insulin resistance should permit early intervention in order to avoid complications.
Topics: Acanthosis Nigricans; Black People; Caribbean Region; Hispanic or Latino; Humans; Insulin Resistance; Puberty, Precocious
PubMed: 11117667
DOI: No ID Found -
Nature Reviews. Endocrinology May 2020The adrenal gland is a source of sex steroid precursors, and its activity is particularly relevant during fetal development and adrenarche. Following puberty, the... (Review)
Review
The adrenal gland is a source of sex steroid precursors, and its activity is particularly relevant during fetal development and adrenarche. Following puberty, the synthesis of androgens by the adrenal gland has been considered of little physiologic importance. Dehydroepiandrosterone (DHEA) and its sulfate, DHEAS, are the major adrenal androgen precursors, but they are biologically inactive. The second most abundant unconjugated androgen produced by the human adrenals is 11β-hydroxyandrostenedione (11OHA4). 11-Ketotestosterone, a downstream metabolite of 11OHA4 (which is mostly produced in peripheral tissues), and its 5α-reduced product, 11-ketodihydrotestosterone, are bioactive androgens, with potencies equivalent to those of testosterone and dihydrotestosterone. These adrenal-derived androgens all share an oxygen atom on carbon 11, so we have collectively termed them 11-oxyandrogens. Over the past decade, these androgens have emerged as major components of several disorders of androgen excess, such as congenital adrenal hyperplasia, premature adrenarche and polycystic ovary syndrome, as well as in androgen-dependent tumours, such as castration-resistant prostate cancer. Moreover, in contrast to the more extensively studied, traditional androgens, circulating concentrations of 11-oxyandrogens do not demonstrate an age-dependent decline. This Review focuses on the rapidly expanding knowledge regarding the implications of 11-oxyandrogens in human physiology and disease.
Topics: Adrenal Glands; Adrenal Hyperplasia, Congenital; Androgens; Endocrine System Diseases; Female; Humans; Male; Oxygen; Polycystic Ovary Syndrome; Prostatic Neoplasms; Puberty, Precocious
PubMed: 32203405
DOI: 10.1038/s41574-020-0336-x -
Pediatrics International : Official... Oct 2018Vitamin D, an important factor in calcium-phosphate homeostasis, has recently been suggested to play an important role in the pathogenesis of numerous chronic conditions...
BACKGROUND
Vitamin D, an important factor in calcium-phosphate homeostasis, has recently been suggested to play an important role in the pathogenesis of numerous chronic conditions such as hyperandrogenism. The aim of this study was to investigate the relationship between vitamin D status and premature adrenarche (PA).
METHODS
A total of 71 girls with PA and 52 healthy girls, as the control group, were recruited. Axillary and/or pubic hair development before the age of 8 years was defined as PA. Bone age and anthropometric measures including height, weight, and body mass index (BMI) were obtained. 25-Hydroxyvitamin D (25(OH)D), fasting plasma glucose and insulin were measured. Vitamin D insufficiency was defined as <20 ng/mL.
RESULTS
The PA patients had older bone age, higher BMI standard deviation score, homeostasis model of assessment-insulin resistance (HOMA-IR), and androgen but lower 25(OH)D than the control group. HOMA-IR and dehydroepiandrosterone sulfate were also higher in PA patients with vitamin D insufficiency compared with those with normal vitamin D. There was a negative correlation between 25(OH)D and HOMA-IR.
CONCLUSION
Low vitamin D is associated with PA; and insulin resistance may be a factor in this association.
Topics: Adrenarche; Case-Control Studies; Child; Cross-Sectional Studies; Female; Humans; Hyperandrogenism; Insulin Resistance; Logistic Models; Puberty, Precocious; Risk Factors; Vitamin D Deficiency
PubMed: 30129969
DOI: 10.1111/ped.13682 -
Acta Paediatrica (Oslo, Norway : 1992).... Dec 1999Premature adrenarche was previously thought to be a benign condition. However, the authors and several other research groups have noted hyperinsulinism and insulin...
Premature adrenarche was previously thought to be a benign condition. However, the authors and several other research groups have noted hyperinsulinism and insulin resistance in many girls with premature adrenarche. African-American and Caribbean-Hispanic girls with premature adrenarche are frequently obese with marked hyperandrogenism, signs which correlate with the degree of insulin resistance (i.e., those girls who are obese and insulin resistant tend to have higher levels of adrenocorticotropic hormone-stimulated androgens). Also, girls with premature adrenarche and reduced insulin sensitivity can have subtle decreases in their high-density lipoprotein (HDL) profile. Many of these girls have a strong family history of type 2 diabetes mellitus. Preliminary data regarding long-term follow-up of girls with premature adrenarche indicate that those girls who remain obese are at risk of developing polycystic ovary syndrome (PCOS). The term 'syndrome X' refers to the constellation of laboratory and clinical findings associated with hyperinsulinism stemming from insulin resistance. These findings include obesity, acanthosis nigricans, glucose intolerance, type 2 diabetes mellitus, dyslipidaemia with reduced HDL and elevated low-density lipoprotein, cardiovascular disease and PCOS. Hence, for certain girls, premature adrenarche may be a part of the clinical spectrum of syndrome X.
Topics: Acanthosis Nigricans; Adrenal Glands; Black People; Caribbean Region; Child; Female; Humans; Insulin-Like Growth Factor I; Microvascular Angina; Ovary; Puberty, Precocious; White People
PubMed: 10626548
DOI: 10.1111/j.1651-2227.1999.tb14406.x -
Journal of the Endocrine Society Sep 2020We hypothesize that impaired glucocorticoid sensitivity (GC sensitivity) plays a role in the development of premature adrenarche (PA) and polycystic ovarian syndrome...
CONTEXT
We hypothesize that impaired glucocorticoid sensitivity (GC sensitivity) plays a role in the development of premature adrenarche (PA) and polycystic ovarian syndrome (PCOS) by increasing androgen synthesis.
OBJECTIVE
To study glucocorticoid sensitivity in vitro in subjects with PA and PCOS.
PATIENTS AND METHODS
Fourteen subjects (10 girls, 4 boys, 6.9 ± 0.6 years) with PA; 27 subjects with PCOS (17 ± 2.5 years) and 31 healthy controls were enrolled in the study. All subjects and controls underwent GC sensitivity analysis in vitro using a fluorescein labeled-dexamethasone (F-DEX) assay. A GC sensitivity index (GCSI) was calculated as area under the curve of the F-DEX assay results. Subjects were classified as GC resistant if the GCSI ≤ 264 and GC sensitive if the GCSI ≥ 386.
RESULTS
In the PA group, 8 of 14 subjects were resistant with GCSI of 179.7 ± 39.9, 4 were within the normal range with GCSI of 299.6 ± 27.9, and 2 had increased GC sensitivity with GCSI of 423.5 ± 47.9. In the PCOS group, 18 of 27 subjects were GC-resistant with GCSI of 180.9 ± 58.2, 8 were within the normal range with GCSI of 310.7 ± 26.4, and 1 had increased GCSI of 395.4. In the PCOS GC-resistant subgroup, cortisol was higher compared with PCOS with normal GCSI ( < 0.05). In the combined PCOS plus female control group, GCSI correlated negatively with cortisol and testosterone ( < 0.05).
CONCLUSION
GC resistance was found in more than 50% of patients with PCOS and PA. The findings strongly suggest that GC resistance is associated with states of PA and PCOS.
PubMed: 32904537
DOI: 10.1210/jendso/bvaa111 -
The Journal of Pediatrics Jul 2017To examine differences in the growth pattern and the age at adiposity rebound (AR) between children with premature adrenarche (PA) and their healthy peers (controls).
OBJECTIVES
To examine differences in the growth pattern and the age at adiposity rebound (AR) between children with premature adrenarche (PA) and their healthy peers (controls).
STUDY DESIGN
In this cross-sectional study of 82 prepubertal children with PA and 63 controls, the main outcome measures were height and body mass index SDS progression, from birth to presentation at the clinic, baseline biochemical and hormonal evaluation, bone age determination, and age at AR.
RESULTS
Children with PA were significantly taller and more adipose than controls from the first years of life. 33% of children with PA presented the growth pattern of constitutional advancement of growth (ie, early growth acceleration) vs 19% of controls (P = .045). Children with PA had an earlier AR compared with controls; mean age at AR in girls with PA was 3.73 (1.03) years vs 4.93 (1.36) years for control girls (P = .001) and in boys with PA was 3.45 (0.73) vs 5.10 (1.50) years in control boys (P = .048). Both obese and nonobese girls with PA were taller and had earlier age at AR compared with nonobese controls.
CONCLUSIONS
Early AR and constitutional advancement of growth may be triggering factors for adrenal androgen production and PA.
Topics: Adiposity; Adrenarche; Age Determination by Skeleton; Age Factors; Body Height; Body Mass Index; Case-Control Studies; Child; Child Development; Cross-Sectional Studies; Female; Humans; Male; Puberty, Precocious
PubMed: 28457524
DOI: 10.1016/j.jpeds.2017.03.058 -
The Journal of Endocrinology Aug 2012The human adrenal cortex comprises three distinct zones with unique steroid products, namely the zona glomerulosa, which secretes the mineralocorticoids, the zona...
The human adrenal cortex comprises three distinct zones with unique steroid products, namely the zona glomerulosa, which secretes the mineralocorticoids, the zona fasciculate, which secretes the glucocorticoids and the zona reticularis (ZR), which at adrenarche, begins to produce the so-called adrenal androgens. Of all the adrenal zones, we still understand control of ZR emergence the least, and yet the consequences of such dysregulation can be devastating. Premature adrenarche is a growing problem and the correspondingly inappropriate emergence of ZR function can negatively influence puberty and lead to adult infertility. Our understanding is limited and more needs to be done. The purpose of these three reviews is to provide a survey of where we are in our current understanding of what adrenarche is, and indeed if it is unique to humans at all. Furthermore, these reviews describe what is also known of how the functional ZR emerges during adrenarche and what steroids of physiologic relevance result beyond the widely known DHEA and DHEAS elevated at this time. Such advances in human, primate and indeed stem-cell biology are clearly laying the foundation for new directions in the hunt for the factors involved in the regulation and functional emergence of a ZR at the appropriate time, as well as insight into how they may fail. Given support for these new directions, considerable progress can clearly be made.
Topics: Adolescent; Adrenal Cortex; Adrenal Glands; Adrenarche; Adult; Animals; Child; Child Development; Comprehension; Humans; Mice; Models, Biological; Rats; Zona Reticularis
PubMed: 22700191
DOI: 10.1530/JOE-12-0246 -
Primary Care Jun 2020Evaluation of the child with abnormal pubertal development can be challenging for the primary care provider. Understanding the factors associated with timing of pubertal... (Review)
Review
Evaluation of the child with abnormal pubertal development can be challenging for the primary care provider. Understanding the factors associated with timing of pubertal onset and the normal sequence of pubertal changes is useful in evaluation of children with puberty disorders. A thorough workup includes assessment of growth rate, Tanner staging, and rate of pubertal progression, in addition to an extensive history and physical examination to identify signs and symptoms of disorders associated with abnormal pubertal timing. Initial diagnostic studies will most often include a bone age, levels of gonadotropins, and levels of estradiol (for girls) or testosterone (for boys).
Topics: Child; Female; Gonadal Disorders; Gonadal Steroid Hormones; Humans; Hypogonadism; Male; Primary Health Care; Puberty, Delayed; Puberty, Precocious
PubMed: 32423709
DOI: 10.1016/j.pop.2020.02.001 -
Clinical Pediatrics Jan 1986Premature adrenarche (PA) or isolated growth of sexual hair in young children, is a benign condition that may initially be confused with true precocious puberty or...
Premature adrenarche (PA) or isolated growth of sexual hair in young children, is a benign condition that may initially be confused with true precocious puberty or pathologic virilizing disorders. The clinical findings, family history, and serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) were compared in 24 children with PA (79% black females) seen in a 2-year period and in an age-matched control group of 17 black females. Twenty three of 24 patients, but none of the controls, had an adult-type axillary odor. There was a positive family history of PA in only three of 24 children with PA, and in one of 17 controls. The mean serum DHEA-S was significantly higher in the PA children than in the controls, but there was a broad range of concentrations (10-143 micrograms/dl), with values in 10 of 24 cases falling within the control range for age. We conclude that: (1) PA is a relatively common finding in black females between ages 3 and 8, (2) an axillary odor is almost always present in children with PA, and (3) determination of serum DHEA-S may be of some help in confirming the clinical impression of a modest increase in adrenal androgen secretion and in ruling out a more serious disorder. In most cases, however, the diagnosis of PA can be made on the basis of the history, physical examination, and lack of rapid progression over time; the use of laboratory tests to rule out a pathologic virilizing process may best be reserved for those children with very early onset, increased linear growth, or other signs of virilization.
Topics: Adrenal Glands; Age Factors; Black People; Child; Child, Preschool; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Hair; Humans; Male; Puberty, Precocious
PubMed: 2935348
DOI: 10.1177/000992288602500105