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Endocrine Reviews Nov 2021Adrenarche is the maturational increase in adrenal androgen production that normally begins in early childhood. It results from changes in the secretory response to... (Review)
Review
Adrenarche is the maturational increase in adrenal androgen production that normally begins in early childhood. It results from changes in the secretory response to adrenocorticotropin (ACTH) that are best indexed by dehydroepiandrosterone sulfate (DHEAS) rise. These changes are related to the development of the zona reticularis (ZR) and its unique gene/enzyme expression pattern of low 3ß-hydroxysteroid dehydrogenase type 2 with high cytochrome b5A, sulfotransferase 2A1, and 17ß-hydroxysteroid dehydrogenase type 5. Recently 11-ketotestosterone was identified as an important bioactive adrenarchal androgen. Birth weight, body growth, obesity, and prolactin are related to ZR development. Adrenarchal androgens normally contribute to the onset of sexual pubic hair (pubarche) and sebaceous and apocrine gland development. Premature adrenarche causes ≥90% of premature pubarche (PP). Its cause is unknown. Affected children have a significantly increased growth rate with proportionate bone age advancement that typically does not compromise growth potential. Serum DHEAS and testosterone levels increase to levels normal for early female puberty. It is associated with mildly increased risks for obesity, insulin resistance, and possibly mood disorder and polycystic ovary syndrome. Between 5% and 10% of PP is due to virilizing disorders, which are usually characterized by more rapid advancement of pubarche and compromise of adult height potential than premature adrenarche. Most cases are due to nonclassic congenital adrenal hyperplasia. Algorithms are presented for the differential diagnosis of PP. This review highlights recent advances in molecular genetic and developmental biologic understanding of ZR development and insights into adrenarche emanating from mass spectrometric steroid assays.
Topics: Adrenal Hyperplasia, Congenital; Adrenarche; Androgens; Child; Child, Preschool; Female; Humans; Polycystic Ovary Syndrome; Puberty, Precocious
PubMed: 33788946
DOI: 10.1210/endrev/bnab009 -
Pediatric Annals Jan 2018Adrenarche is when a child's adrenal cortex starts to secrete adrenal androgen precursors. Dehydroepiandrosterone (DHEA) is the most abundant product of the adrenal... (Review)
Review
Adrenarche is when a child's adrenal cortex starts to secrete adrenal androgen precursors. Dehydroepiandrosterone (DHEA) is the most abundant product of the adrenal cortex, and is a weak androgen agonist thought to be responsible for the clinical signs of pubarche by conversion to more potent androgens, testosterone, and dihydrotestosterone. DHEA's extra-adrenal sulfation product, dehydroepiandrosterone sulfate, is a stable marker for adrenal androgenic activity. Pubarche is the physical manifestation of androgenic hormone production, and includes the development of pubic and axillary hair, adult body odor, and acne. This stage is usually considered premature if it commences before age 8 years in girls or age 9 years in boys. Premature adrenarche is a diagnosis of exclusion, as true centrally mediated precocious puberty, congenital adrenal hyperplasia, exogenous androgen exposure, and androgen-secreting tumors must be ruled out. Premature adrenarche may be associated with a history of an infant who was small for gestational age at birth who then gained weight rapidly thereafter or became obese. In some instances, premature adrenarche may predict functional ovarian hyperandrogenism in adolescence. Management of premature adrenarche is largely aimed at observation, lifestyle adjustments for weight concerns, and monitoring for future possible persistent androgen excess and insulin resistance. [Pediatr Ann. 2018;47(1):e7-e11.].
Topics: Adrenarche; Child; Diagnosis, Differential; Female; Humans; Male; Prognosis; Puberty, Precocious
PubMed: 29323690
DOI: 10.3928/19382359-20171214-04 -
Archives of Disease in Childhood Mar 2012Premature adrenarche refers to the presence of secondary sexual hair in girls younger than 8 years old and boys younger than 9 years old. It is a relatively common... (Review)
Review
Premature adrenarche refers to the presence of secondary sexual hair in girls younger than 8 years old and boys younger than 9 years old. It is a relatively common presentation to paediatricians and is more frequent in girls than boys. It is a benign diagnosis, but other causes of androgen excess such as congenital adrenal hyperplasia or adrenal tumours should be excluded first. In conjunction with history and clinical examination, first line investigations should include determination of serum androgen concentrations, along with bone age, proceeding to synacthen stimulation test (for 17OHP levels) and adrenal ultrasound if indicated. The phenotype of premature adrenarche varies considerably between populations but may be associated with low birth weight, insulin resistance, adverse cardio-metabolic risk and progression to polycystic ovarian syndrome in some populations. In the majority of cases, no specific treatment is recommended, but where there is a history of low birth weight, with associated insulin resistance, intervention with the insulin sensitising agent metformin may be considered on a case by case basis.
Topics: Adrenarche; Algorithms; Birth Weight; Child; Female; Genetic Predisposition to Disease; Humans; Infant, Newborn; Male; Physical Examination; Polycystic Ovary Syndrome; Puberty, Precocious
PubMed: 21835833
DOI: 10.1136/archdischild-2011-300011 -
Journal of Endocrinological... Oct 2001Adrenarche is the puberty of the adrenal gland. The descriptive term "pubarche" indicates the appearance of pubic hair, which may be accompanied by axillary hair. This... (Review)
Review
Adrenarche is the puberty of the adrenal gland. The descriptive term "pubarche" indicates the appearance of pubic hair, which may be accompanied by axillary hair. This process is considered premature if it occurs before age 8 yr in girls and 9 yr in boys. The chief hormonal products of adrenarche are DHEA and DHEAS. The well-documented evolution of adrenarche in primates and men is incompatible with either a neutral or harmful role for DHEA and implies most likely a positive role for some aspects of young adult pubertal maturation and developmental maturation. Premature adrenarche has no adverse effects on the onset and progression of gonadarche and/or final height. Mechanisms for initiation of adrenal androgen secretion at adrenarche are still not well understood. Maturational increases in 17-hydroxylase and 17,20-lyase are seen together with a lower activity of 3beta-hydroxysteroid dehydrogenase (3beta-HSD). There is good evidence that the zona reticularis is the source of adrenal androgens. Adrenarche and gonadarche are regulated differently. Although premature adrenarche has been thought to be a benign, normal variant of puberty, our findings indicate that, for certain girls, premature adrenarche represents an early clinical feature of syndrome X (obesity, hypertension, dyslipidemia, insulin resistance). Perhaps the early identification of these patients will permit early therapy, such as lifestyle changes, including dietary and activity level intervention. As insulin resistance is an underlying feature of premature adrenarche, it seems rational to assess the efficacy and safety of using insulin-sensitizing agents to treat these individuals. In the absence of controlled longitudinal studies, the cross-sectional data available from our studies suggest that premature pubarche driven by premature adrenarche and hyperinsulinemia may precede the development of ovarian hyperandrogenism, and this sequence may have an early origin with low birth weight serving as a marker. Premature adrenarche may thus be a forerunner of syndrome X in some girls.
Topics: Adrenal Glands; Androgens; Blood Glucose; Child; Dehydroepiandrosterone; Female; Humans; Hyperandrogenism; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Male; Microvascular Angina; Puberty; Steroid 17-alpha-Hydroxylase
PubMed: 11716159
DOI: 10.1007/BF03343917 -
The Journal of Steroid Biochemistry and... Jan 2015Adrenarche means the morphological and functional change of the adrenal cortex leading to increasing production of adrenal androgen precursors (AAPs) in mid childhood,... (Review)
Review
Adrenarche means the morphological and functional change of the adrenal cortex leading to increasing production of adrenal androgen precursors (AAPs) in mid childhood, typically at around 5-8 years of age in humans. The AAPs dehydroepiandrosterone (DHEA) and its sulfate conjugate (DHEAS) are the best serum markers of adrenal androgen (AA) secretion and adrenarche. Normal ACTH secretion and action are needed for adrenarche, but additional inherent and exogenous factors regulate AA secretion. Inter-individual variation in the timing of adrenarche and serum concentrations of DHEA(S) in adolescence and adulthood are remarkable. Premature adrenarche (PA) is defined as the appearance of clinical signs of androgen action (pubic/axillary hair, adult type body odor, oily skin or hair, comedones, acne, accelerated statural growth) before the age of 8 years in girls or 9 years in boys associated with AAP concentrations high for the prepubertal chronological age. To accept the diagnosis of PA, central puberty, adrenocortical and gonadal sex hormone secreting tumors, congenital adrenal hyperplasia, and exogenous source of androgens need to be excluded. The individually variable peripheral conversion of circulating AAPs to biologically more active androgens (testosterone, dihydrotestosterone) and the androgen receptor activity in the target tissues are as important as the circulating AAP concentrations as determinants of androgen action. PA has gained much attention during the last decades, as it has been associated with small birth size, the metabolic and polycystic ovarian syndrome (PCOS), and thus with an increased risk for type 2 diabetes and cardiovascular diseases in later life. The aim of this review is to describe the known hormonal changes and their possible regulators in on-time and premature adrenarche, and the clinical features and possible later health problems associating with PA.
Topics: Adrenal Cortex; Adrenarche; Body Weight; Child; Female; Hair; Humans; Hyperandrogenism; Hyperinsulinism; Male; Odorants; Overweight; Phosphorylation; Puberty, Precocious; Steroid 17-alpha-Hydroxylase; Steroids
PubMed: 24923732
DOI: 10.1016/j.jsbmb.2014.06.004 -
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 -
Hormone Research in Paediatrics 2015Adrenarche refers to a maturational increase in the secretion of adrenal androgen precursors, mainly dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). In premature... (Review)
Review
Adrenarche refers to a maturational increase in the secretion of adrenal androgen precursors, mainly dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). In premature adrenarche (PA), clinical signs of androgen action appear before the age of 8/9 years in girls/boys, concurrently with the circulating DHEA(S) concentrations above the usually low prepubertal level. The most pronounced sign of PA is the appearance of pubic/axillary hair, but also other signs of androgen effect (adult type body odor, acne/comedones, greasy hair, accelerated statural growth) are important to recognize. PA children are often overweight and taller than their peers, and the higher prevalence of PA in girls than in boys is probably explained by higher female adiposity and peripheral DHEA(S) conversion to active androgens. PA diagnosis requires exclusion of other causes of androgen excess: congenital adrenal hyperplasia, androgen-producing tumors, precocious puberty, and exogenous source of androgens. PA has been linked with unfavorable metabolic features including hyperinsulinism, dyslipidemia, and later-appearing ovarian hyperandrogenism. Although this common condition is usually benign, PA children with additional risk factors including obesity should be followed up, with the focus on weight and lifestyle. Long-term follow-up studies are warranted to clarify if the metabolic changes detected in PA children persist until adulthood.
Topics: Adrenal Glands; Adrenarche; Female; Humans; Hyperandrogenism; Male
PubMed: 25676474
DOI: 10.1159/000369458 -
Journal of Pediatric Health Care :... 2008Premature adrenarche refers to the precocious secretion of adrenal androgens, which results in the isolated development of pubic hair (pubarche) before the age of eight...
Premature adrenarche refers to the precocious secretion of adrenal androgens, which results in the isolated development of pubic hair (pubarche) before the age of eight years in girls and nine years in boys. The female to male ratio is approximately 10:1. Dark, coarse and curly hair is limited initially to the labia majora in girls and to the root of the penis in boys. The hair extends gradually into the pubic region. Axillary hair, increased body odor, and acne can also be present. Hirsutism, deepening of the voice, clitoral enlargement, breast development, and phallic or testicular enlargement are characteristically absent. A transient acceleration of growth is common but final height is usually not affected. The onset of puberty usually occurs at the normal age. Premature adrenarche can be a forerunner of polycystic ovary syndrome and/or syndrome X. Continued observation and periodic re-evaluation is necessary.
Topics: Adrenarche; Cross-Sectional Studies; Diagnosis, Differential; Female; Humans; Male
PubMed: 18590867
DOI: 10.1016/j.pedhc.2007.07.002 -
Hormone Research in Paediatrics 2020
Topics: Adrenarche; Breast; Female; Humans; Male; Puberty, Precocious; Unnecessary Procedures; Watchful Waiting
PubMed: 33352558
DOI: 10.1159/000512764 -
Endocrine Reviews Dec 2000Adrenarche is the puberty of the adrenal gland. The descriptive term pubarche indicates the appearance of pubic hair, which may be accompanied by axillary hair. This... (Review)
Review
Adrenarche is the puberty of the adrenal gland. The descriptive term pubarche indicates the appearance of pubic hair, which may be accompanied by axillary hair. This process is considered premature if it occurs before age 8 yr in girls and 9 yr in boys. The chief hormonal product of adrenarche is dehydroepiandrosterone (DHEA) and its sulfated product DHEA-S. The well documented evolution of adrenarche in primates and man is incompatible with either a neutral or harmful role for DHEA and implies most likely a positive role for some aspect of young adult pubertal maturation and developmental maturation. Premature adrenarche has no adverse effects on the onset and progression of gonadarche in final height. Both extra- and intraadrenal factors regulate adrenal androgen secretion. Recent studies have shown that premature adrenarche in childhood may have consequences such as functional ovarian hyperandrogenism, polycystic ovarian syndrome, and insulin resistance in later life, sometimes already recognizable in childhood or adolescence. Premature adrenarche may thus be a forerunner of syndrome X in some children. The association of these endocrine-metabolic abnormalities with reduced fetal growth and their genetic basis remain to be elucidated.
Topics: Adrenal Glands; Female; Genetic Variation; Humans; Hyperandrogenism; Insulin Resistance; Male; Microvascular Angina; Polycystic Ovary Syndrome; Puberty, Precocious
PubMed: 11133068
DOI: 10.1210/edrv.21.6.0416