scholarly journals Continuum of phenotypes and sympathoadrenal function in premature adrenarche

2009 ◽  
Vol 160 (4) ◽  
pp. 657-665 ◽  
Author(s):  
Pauliina Utriainen ◽  
Raimo Voutilainen ◽  
Jarmo Jääskeläinen
Keyword(s):  
Clinical Signs ◽  
Dehydroepiandrosterone Sulfate ◽  
Pubic Hair ◽  
Adrenal Androgen ◽  
Pronounced Increase ◽  
Adrenal Steroid ◽  
Premature Adrenarche ◽  
Adrenal Hyperandrogenism ◽  
Early Rise ◽  
Design And Methods

ObjectivesPremature adrenarche (PA), the early rise in adrenal androgen (AA) production, can manifest with different clinical signs of androgen effect. Premature pubarche defined as appearance of pubic hair before the age of 8/9 years in girls/boys, is the most prominent clinical sign of PA and often erroneously described as a synonym of PA. Our aim was to determine the association of circulating AA concentrations with different prepubertal signs of androgen action (SAA). Secondly, we tested whether adrenomedullary function is altered in children with SAA, as it is in congenital adrenal hyperplasia (CAH) also causing adrenal hyperandrogenism.Design and methodsWe examined 73 Finnish prepubertal children with any hyperandrogenic sign(s) having appeared before the age of 8/9 years (girls/boys) (35 with pubic and/or axillary hair=PAH; 38 without=nonPAH), and 98 age- and sex-matched controls. Circulating adrenal steroid and catecholamine concentrations were measured and correlated with clinical parameters.ResultsNone of the children with SAA had CAH or virilizing tumor. Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione concentrations overlapped between the SAA and control children, and they were lower in the nonPAH than PAH group (P<0.01). SAA children had similar plasma epinephrine but higher norepinephrine (NE) concentrations than their controls (mean (95% confidence interval) 1.61 (1.44, 1.77) versus 1.39 (1.30, 1.49) nmol/l, P=0.03).ConclusionsPA forms a continuum with more pronounced increase in circulating androgens in children with PAH than in those without. Some children show SAA with fairly low androgen concentrations. The clinical significance of elevated NE concentrations associated with SAA needs to be confirmed in further studies.

Premature Adrenarche and its Association with Cardiovascular Risk in Females

2020 ◽  
Vol 26 (43) ◽  
pp. 5609-5616
Author(s):  
Sarantis Livadas ◽  
Christina Bothou ◽  
Djuro Macut
Keyword(s):  
Polycystic Ovary ◽  
Dehydroepiandrosterone Sulfate ◽  
Adrenal Androgen ◽  
Premature Adrenarche ◽  
Adrenal Hyperandrogenism ◽  
Long Term Follow Up ◽  
History Of ◽  
Hormonal Milieu ◽  
The Impact

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.

scholarly journals Normal and Premature Adrenarche

2021 ◽  
Author(s):  
Robert L Rosenfield
Keyword(s):  
Polycystic Ovary ◽  
Molecular Genetic ◽  
Bone Age ◽  
Dehydroepiandrosterone Sulfate ◽  
Hydroxysteroid Dehydrogenase ◽  
Pubic Hair ◽  
Growth Potential ◽  
Adrenal Androgen ◽  
Premature Adrenarche ◽  
Premature Pubarche

Abstract Adrenarche is the maturational increase in adrenal androgen production that normally begins in early childhood. It results from changes in the secretory response to 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. 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. Five-10% of premature pubarche 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 premature pubarche.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.

scholarly journals Familial Hyperinsulinism due to HNF4A Deficiency and Benign Premature Adrenarche: A Case Report

2021 ◽  
Author(s):  
Edward Compton ◽  
David Geller ◽  
Alaina Vidmar
Keyword(s):  
Fasting Blood Glucose ◽  
Tanner Stage ◽  
Bone Age ◽  
Free Testosterone ◽  
Dehydroepiandrosterone Sulfate ◽  
Pubic Hair ◽  
Hyperinsulinemic Hypoglycemia ◽  
Premature Adrenarche ◽  
Synergistic Mechanism ◽  
Work Up

Background: Familial Hyperinsulinism due to HNF4A deficiency (FHI-HNF4A) is a form of diazoxide-sensitive, diffuse hyperinsulinism, characterized by transient or persistent hyperinsulinemic hypoglycemia, and a propensity to develop Maturity-Onset Diabetes of the Young type 1 (MODY1). The association between FHI-HNF4A deficiency and benign premature adrenarche (BPA) is unknown. The Case: We report the case of a 5-year-old girl with FHI-HNF4A, controlled on diazoxide, who presented with BPA and Tanner stage III pubic hair associated with body odor and acne. Work-up revealed elevated dehydroepiandrosterone sulfate (DHEAS), elevated free testosterone, and advanced bone age. Insulin levels were elevated in the setting of normal fasting blood glucose. We discuss the possible hormonal underpinnings of hyperandrogenism. Conclusion: Though the underlying pathophysiology of this phenotype is unclear, a possible synergistic mechanism exists between insulin-induced hyperandrogenism and HNF4A deficiency leading to a transient decrease of SHBG and thus increased free testosterone levels. Further investigation is required to determine the association between HNF4A dysfunction and BPA.

scholarly journals Premature Adrenarche—Normal Variant or Forerunner of Adult Disease?*

2000 ◽  
Vol 21 (6) ◽  
pp. 671-696 ◽  
Author(s):  
Lourdes Ibáñez ◽  
Joan DiMartino-Nardi ◽  
Neus Potau ◽  
Paul Saenger
Keyword(s):  
Final Height ◽  
Later Life ◽  
Pubic Hair ◽  
Adrenal Androgen ◽  
Positive Role ◽  
Adult Disease ◽  
Premature Adrenarche ◽  
Functional Ovarian Hyperandrogenism ◽  
Ovarian Hyperandrogenism ◽  
Ovarian Syndrome

Abstract 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.

Dissociation of cortisol and adrenal androgen secretion in poorly controlled insulin-dependent diabetes mellitus

1992 ◽  
Vol 127 (2) ◽  
pp. 115-117 ◽  
Author(s):  
RM Couch
Keyword(s):  
Diabetes Mellitus ◽  
Good Control ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dehydroepiandrosterone Sulfate ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Poor Control ◽  
Adrenal Androgen ◽  
Insulin Dependent ◽  
Androgen Secretion

In acute illness, cortisol secretion increases whereas that of the adrenal androgens, dehydroepiandrosterone and dehydroepiandrosterone sulfate declines. The present study examined if a similar dissociation of cortisol and adrenal androgen secretion occurs in poorly controlled diabetes mellitus. Serum concentrations of cortisol, dehydroepiandrosterone and dehydroepiandrosterone sulfate obtained at 08.00 were compared in 13 post-pubertal diabetics (mean age 18.0 years) in good control (HbA1C<8.0%) and 10 post-pubertal diabetics (mean age 17.0 years) in poor control (HbA1C> 10.0%). Those in poor control had significantly higher serum cortisol (597±94 nmol/l vs 479±208, p < 0.05), lower dehydroepiandrosterone (13.1±5.5 nmol/l vs 25.3±16.9, p<0.025) and lower dehydroepiandrosterone sulfate (4.5±2.4 μmol/l vs 7.0±3.7, p<0.025). The ratios of dehydroepiandrosterone and dehydroepiandrosterone sulfate to cortisol were also significantly lower in those with poor control. It is concluded that poor control of insulin-dependent diabetes mellitus results in a dissociation of cortisol and adrenal androgen secretion.

Comparing adolescent self staging of pubertal development with hormone biomarkers

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Nana-Hawa Yayah Jones ◽  
Jane C. Khoury ◽  
Yingying Xu ◽  
Nicholas Newman ◽  
Heidi J. Kalkwarf ◽  
...  
Keyword(s):  
Least Squares ◽  
Pubertal Development ◽  
Dehydroepiandrosterone Sulfate ◽  
Pubic Hair ◽  
Birth Cohort Study ◽  
Physical Examinations ◽  
Environment Study ◽  
Hair Development ◽  
Stage 1 ◽  
Self Examination

Abstract Objectives Physical examinations to characterize pubertal maturation may be unacceptable for children enrolled in research studies. Studies confirm the utility of pubertal self staging for research, but there has been limited comparison of self examination with hormone biomarkers. Our objective was to assess concordance of pubertal self staging with hormone biomarkers of puberty. Methods Participants were enrolled in the Health Outcomes and Measures of the Environment Study, a longitudinal pregnancy and birth cohort study. At age 12 years, 139 females and 112 males completed pubertal self staging including breast and pubic hair development in females and pubic hair development in males. No clinical physical examination was performed. Hormone concentrations were measured in 102 females and 96 males including serum dehydroepiandrosterone sulfate, luteinizing hormone, and follicle-stimulating hormone in all; estradiol in females; and testosterone in males. Results Estradiol was significantly associated with female breast stage, even when adjusted for BMI, with geometric least squares means (95%CI) of 13.2 (8.7, 20.2), 38.3 (29.9, 49.1), 59.4 (39.8, 88.6), and 81.2 (45.6, 144) pg/mL for breast stage 1–2, 3, 4, and 5, respectively. Testosterone was significantly associated with male pubic hair stage, with adjusted geometric least squares means (95%CI) of 37.6 (19.9, 71.1), 43.4 (27.7, 68.3), 126 (78.4, 203), 275 (146, 521), and 559 (237, 1319) ng/dL for pubic hair stage 1, 2, 3, 4, and 5, respectively. Conclusions Self assessed pubertal development was positively associated with hormonal biomarkers of puberty.

REPLACEMENT ORAL ETHINYLOESTRADIOL THERAPY FOR GONADAL DYSGENESIS: GROWTH AND ADRENAL ANDROGEN STUDIES

1979 ◽  
Vol 91 (3) ◽  
pp. 519-528 ◽  
Author(s):  
Anne W. Lucky ◽  
Samuel P. Marynick ◽  
Robert W. Rebar ◽  
Gordon B. Cutler ◽  
Michael Glen ◽  
...  
Keyword(s):  
Gonadal Dysgenesis ◽  
Bone Age ◽  
Pubic Hair ◽  
Height Velocity ◽  
First Year ◽  
Adrenal Androgen ◽  
Secondary Sexual Characteristics ◽  
Sexual Characteristics ◽  
Second Year ◽  
Pre Treatment

ABSTRACT We have studied growth and adrenal dehydroepiandrosterone (DHA) responses to iv synthetic adrenocorticotrophic hormone (ACTH, Cortrosyn) in 6 girls with gonadal dysgenesis before and during treatment with lowdose ethinyloestradiol (EOe2). In all patients there was a statisfactory induction of secondary sexual characteristics including increase in breasts and pubic hair and onset of withdrawal bleeding within 6 months of therapy. Height velocity increased from 2.8 ± 0.9 cm/year pre-treatment to 5.3 ± 1.5 cm/year (P < 0.02) in the first year. There was deceleration to 1.9 ± 1.1 cm/year in the second year. There was no disproportionate advancement in bone age and thus, presumably, no loss of ultimate height. We could demonstrate no change in basal or ACTH-stimulated levels of DHA, a specific adrenal androgen, to account for the increased pubic hair and growth in these patients.

scholarly journals Hormonal function of sexual glands and adrenals in monkeys of different age

1996 ◽  
Vol 42 (2) ◽  
pp. 37-41
Author(s):  
N. D. Goncharova ◽  
L. A. Mkhitarova
Keyword(s):  
Dehydroepiandrosterone Sulfate ◽  
Papio Hamadryas ◽  
Adrenal Androgens ◽  
Adrenal Steroid ◽  
Hormonal Function ◽  
Group 3 ◽  
Sexual Glands ◽  
Group 2 ◽  
Lh Releasing Hormone ◽  
Group 1

The levels of bioactive LH, major sex and adrenal steroid hormones and their precursors in the system of biosynthesis were measured in the peripheral blood of 37 male Papio hamadryas of different age under baseline conditions and after injection of ACTH, LH releasing hormone, and human chorionic gonadotropin. The measurements were carried out in adult animals with the optimal reproductive characteristics (group 1, aged 6 to 9, and group 2, aged 10 to 15 years) and in aging males (group 3, aged 20 to 26 years). The levels of hydrocortisone and its immediate precursor in the biosynthesis chain of 11-deoxyhydrocortisone virtually did not change with age, whereas the concentrations of ∆5-precursors (pregnenolone and 17-hydroxypregnenolone) gradually reduced with aging. The levels of the major adrenal androgens dehydroepiandrosterone and dehydroepiandrosterone sulfate also appreciably decreased with age. The levels of sex hormones did not change between 6 and 15 years of age; but in animals aged 20 to 26 the concentration of testosterone showed a trend to reduction, and that of LH to increase. In group 3 the peaks of LH and testosterone secretion in response to LH releasing factor were delayed. On the other hand, the amplitude and duration of the increment of both LH and testosterone in response to LH releasing factor was virtually unchanged at all ages and was largely determined by the basal level of LH. The detected age-specific changes in the hormonal function of adrenals and sex glands of Papio hamadryas are much similar to those in humans.

scholarly journals Non-Classic Disorder of Adrenal Steroidogenesis and Clinical Dilemmas in 21-Hydroxylase Deficiency Combined with Backdoor Androgen Pathway. Mini-Review and Case Report

2020 ◽  
Vol 21 (13) ◽  
pp. 4622
Author(s):  
Marta Sumińska ◽  
Klaudia Bogusz-Górna ◽  
Dominika Wegner ◽  
Marta Fichna
Keyword(s):  
Dehydroepiandrosterone Sulfate ◽  
Childhood And Adolescence ◽  
Adrenal Androgen ◽  
Hydroxylase Deficiency ◽  
Cyp21a2 Gene ◽  
Peripheral Tissues ◽  
Biochemical Alterations ◽  
Genes Encoding ◽  
Classic Form ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) is the most common cause of primary adrenal insufficiency in children and adolescents. It comprises several clinical entities associated with mutations in genes, encoding enzymes involved in cortisol biosynthesis. The mutations lead to considerable (non-classic form) to almost complete (classic form) inhibition of enzymatic activity, reflected by different phenotypes and relevant biochemical alterations. Up to 95% cases of CAH are due to mutations in CYP21A2 gene and subsequent 21α-hydroxylase deficiency, characterized by impaired cortisol synthesis and adrenal androgen excess. In the past two decades an alternative (“backdoor”) pathway of androgens’ synthesis in which 5α-androstanediol, a precursor of the 5α-dihydrotestosterone, is produced from 17α-hydroxyprogesterone, with intermediate products 3α,5α-17OHP and androsterone, in the sequence and with roundabout of testosterone as an intermediate, was reported in some studies. This pathway is not always considered in the clinical assessment of patients with hyperandrogenism. The article describes the case of a 17-year-old female patient with menstrual disorders and androgenization (persistent acne, advanced hirsutism). Her serum dehydroepiandrosterone sulfate and testosterone were only slightly elevated, along with particularly high values for 5α-dihydrotestosterone. In 24 h urine collection, an increased excretion of 16α-OHDHEA—a dehydroepiandrosterone metabolite—and pregnanetriolone—a 17α-hydroxyprogesterone metabolite—were observed. The investigations that we undertook provided evidence that the girl suffered from non-classic 21α-hydroxylase deficiency with consequent enhancement of the androgen “backdoor” pathway in adrenals, peripheral tissues or both, using adrenal origin precursors. The paper presents diagnostic dilemmas and strategies to differentiate between various reasons for female hyperandrogenism, especially in childhood and adolescence.

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