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Journal of Pediatric and Adolescent... Oct 2017The congenital adrenal hyperplasias comprise a family of autosomal recessive disorders that disrupt adrenal steroidogenesis. The most common form is due to... (Review)
Review
The congenital adrenal hyperplasias comprise a family of autosomal recessive disorders that disrupt adrenal steroidogenesis. The most common form is due to 21-hydroxylase deficiency associated with mutations in the 21-hydroxylase gene, which is located at chromosome 6p21. The clinical features associated with each disorder of adrenal steroidogenesis represent a clinical spectrum that reflect the consequences of the specific mutations. Treatment goals include normal linear growth velocity and "on-time" puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and preservation of fertility. For adolescent and adult men, prevention and early treatment of testicular adrenal rest tumors is beneficial. In this article key aspects regarding pathophysiology, diagnosis, and treatment of congenital adrenal hyperplasia are reviewed.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Adult; Child; Female; Fertility; Hirsutism; Humans; Male; Mutation; Sexual Maturation; Steroid 21-Hydroxylase
PubMed: 28450075
DOI: 10.1016/j.jpag.2017.04.001 -
The Journal of Clinical Endocrinology... Feb 1992
Review
Topics: Adrenal Cortex; Adrenal Cortex Hormones; Child; Female; Humans; Male; Puberty, Precocious
PubMed: 1730802
DOI: 10.1210/jcem.74.2.1730802 -
Annals of the New York Academy of... Dec 2006Premature adrenarche is characterized by an early increase in adrenal androgen production that results in the development of pubic hair before the age of 8 years in... (Review)
Review
Premature adrenarche is characterized by an early increase in adrenal androgen production that results in the development of pubic hair before the age of 8 years in girls and 9 years in boys, with or without axillary hair, and with no other signs of sexual development. Premature adrenarche has no adverse effects on the onset and progression of gonadarche and final height. However, it can no longer be considered a benign condition as it has been associated with hyperinsulinemia, dyslipidemia, and obesity already in the prepubertal period and polycystic ovary syndrome (PCOS) at adolescence. Furthermore, a possible association between premature adrenarche and metabolic and endocrine abnormalities with low birth weight has been postulated. PCOS, as recently redefined, is the most common endocrine disorder to affect women of reproductive age and has been associated with increased risk for type 2 diabetes and increased prevalence of cardiovascular risk factors at an earlier age than expected. Premature adrenarche and PCOS share similar metabolic disturbances. It may be that metabolic abnormalities start very early in life during the prenatal or prepubertal period and premature adrenarche may be a forerunner of PCOS and the metabolic syndrome in some girls. Large long-term epidemiological studies are needed to allow clear association of the two conditions and assessment of the risk of disease in later life.
Topics: Female; Humans; Polycystic Ovary Syndrome; Puberty, Precocious
PubMed: 17308141
DOI: 10.1196/annals.1365.013 -
Current Opinion in Pediatrics Aug 2020Adrenarche is the pubertal maturation of the innermost zone of the adrenal cortex, the zona reticularis. The onset of adrenarche occurs between 6 and 8 years of age when... (Review)
Review
PURPOSE OF REVIEW
Adrenarche is the pubertal maturation of the innermost zone of the adrenal cortex, the zona reticularis. The onset of adrenarche occurs between 6 and 8 years of age when dehydroepiandrosterone sulfate (DHEAS) concentrations increase. This review provides an update on adrenal steroidogenesis and the differential diagnosis of premature development of pubic hair.
RECENT FINDINGS
The complexity of adrenal steroidogenesis has increased with recognition of the alternative 'backdoor pathway' and the 11-oxo-androgens pathways. Traditionally, sulfated steroids such as DHEAS have been considered to be inactive metabolites. Recent data suggest that intracellular sulfated steroids may function as tissue-specific intracrine hormones particularly in the tissues expressing steroid sulfatases such as ovaries, testes, and placenta.
SUMMARY
The physiologic mechanisms governing the onset of adrenarche remain unclear. To date, no validated regulatory feedback mechanism has been identified for adrenal C19 steroid secretion. Available data indicate that for most children, premature adrenarche is a benign variation of development and a diagnosis of exclusion. Patients with premature adrenarche tend to have higher BMI values. Yet, despite greater knowledge about C19 steroids and zona reticularis function, much remains to be learned about adrenarche.
Topics: Adrenal Glands; Adrenarche; Androgens; Child; Child Development; Dehydroepiandrosterone Sulfate; Female; Humans; Pregnancy; Puberty; Puberty, Precocious; Steroids; Zona Reticularis
PubMed: 32692055
DOI: 10.1097/MOP.0000000000000928 -
European Journal of Endocrinology Aug 2011Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS.... (Review)
Review
Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.
Topics: Adrenarche; Adult; Age of Onset; Androgens; Animals; Female; Humans; Male; Models, Biological; Osmolar Concentration; Puberty, Precocious; Time Factors
PubMed: 21622478
DOI: 10.1530/EJE-11-0223 -
Nature Reviews. Endocrinology Feb 2017This Consensus Statement summarizes recommendations for clinical diagnosis, investigation and management of patients with Silver-Russell syndrome (SRS), an imprinting...
This Consensus Statement summarizes recommendations for clinical diagnosis, investigation and management of patients with Silver-Russell syndrome (SRS), an imprinting disorder that causes prenatal and postnatal growth retardation. Considerable overlap exists between the care of individuals born small for gestational age and those with SRS. However, many specific management issues exist and evidence from controlled trials remains limited. SRS is primarily a clinical diagnosis; however, molecular testing enables confirmation of the clinical diagnosis and defines the subtype. A 'normal' result from a molecular test does not exclude the diagnosis of SRS. The management of children with SRS requires an experienced, multidisciplinary approach. Specific issues include growth failure, severe feeding difficulties, gastrointestinal problems, hypoglycaemia, body asymmetry, scoliosis, motor and speech delay and psychosocial challenges. An early emphasis on adequate nutritional status is important, with awareness that rapid postnatal weight gain might lead to subsequent increased risk of metabolic disorders. The benefits of treating patients with SRS with growth hormone include improved body composition, motor development and appetite, reduced risk of hypoglycaemia and increased height. Clinicians should be aware of possible premature adrenarche, fairly early and rapid central puberty and insulin resistance. Treatment with gonadotropin-releasing hormone analogues can delay progression of central puberty and preserve adult height potential. Long-term follow up is essential to determine the natural history and optimal management in adulthood.
Topics: Disease Management; Gonadotropin-Releasing Hormone; Human Growth Hormone; Humans; Internationality; Silver-Russell Syndrome
PubMed: 27585961
DOI: 10.1038/nrendo.2016.138 -
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 -
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 -
The Journal of Clinical Endocrinology... Dec 2020Girls with premature adrenarche (PA) may have a higher risk of developing polycystic ovary syndrome (PCOS) and metabolic syndrome. The biological purpose of adrenarche... (Observational Study)
Observational Study
CONTEXT
Girls with premature adrenarche (PA) may have a higher risk of developing polycystic ovary syndrome (PCOS) and metabolic syndrome. The biological purpose of adrenarche is unknown and the role of novel biosynthetic pathways remains unclear.
OBJECTIVE
To compare the urinary steroid metabolome and enzyme activities of girls with PA to age-matched control girls and to published steroid values of girls with normal adrenarche and of women with PCOS and their newborn daughters.
DESIGN
Prospective observational study from 2009 to 2014.
SETTING
Academic pediatric endocrinology referral center.
PARTICIPANTS
Twenty-three girls with PA and 22 healthy, age-matched girls.
MAIN OUTCOME MEASURES
Steroid metabolites in 24-hour urine samples, including 4 progesterones, 5 corticosterones, aldosterone, 13 androgens, 2 estrogens, 14 glucocorticoids, and enzyme activities represented by metabolite ratios.
RESULTS
Girls with PA had a higher body mass index (mean standard deviation scores 0.9 vs -0.3, P = 0.013). Androgen excretion was higher in PA girls than in control girls (median 3257 nmol/24 hours vs 1627 nmol/24 hours, P < 0.001), in particular metabolites from alternate androgen pathways. The amount of progesterone, corticosterone, aldosterone, estrogen, and cortisol metabolites were similar between groups. Activities of 17β-hydroxysteroid-dehydrogenase and of 17,20-lyase were higher in girls with PA. Activities of 3β-hydroxysteroid-dehydrogenase, 21-hydroxylase, and 5α-reductase activity were not different between groups, in contrast to published results on girls with normal adrenarche or PCOS females.
CONCLUSIONS
Metabolites and enzymes involved in alternate androgen pathways appear to be markers of PA. Prospective studies should assess whether steroid production in PA also differs from adrenarche at normal timing and persists into adulthood.
Topics: 17-Hydroxysteroid Dehydrogenases; Adrenarche; Androgens; Case-Control Studies; Child; Child, Preschool; Corticosterone; Estrogens; Female; Humans; Hydrocortisone; Metabolome; Puberty, Precocious; Steroid 17-alpha-Hydroxylase; Switzerland; Up-Regulation
PubMed: 32865200
DOI: 10.1210/clinem/dgaa598