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Hormone Research in Paediatrics 2018We propose that the normal adrenarche-related rise in dehydroepiandrosterone (DHEA) secretion is ultimately caused by the rise in cortisol production occurring during... (Review)
Review
We propose that the normal adrenarche-related rise in dehydroepiandrosterone (DHEA) secretion is ultimately caused by the rise in cortisol production occurring during childhood and adolescent growth, by the following mechanisms. (1) The onset of childhood growth leads to a slight fall in serum cortisol concentration due to growth-induced dilution and a decrease in the negative feedback of cortisol upon ACTH secretion. (2) In response, ACTH rises and stimulates increased cortisol synthesis and secretion in the growing body to restore the serum cortisol concentration to normal. (3) The cortisol concentration produced within and taken up by adrenocortical steroidogenic cells may rise during this time. (4) Cortisol competitively inhibits 3β-hydroxysteroid dehydrogenase type 2 (3βHSD2)-mediated conversion of 17αOH-pregnenolone to cortisol, causing a further fall in serum cortisol, a further decrease in the negative feedback of cortisol upon ACTH, a further rise in ACTH, and further stimulation of adrenal steroidogenesis. (5) The cortisol-mediated inhibition of 3βHSD2 also blocks the conversion of DHEA to androstenedione, causing a rise in adrenal DHEA and DHEA sulfate relative to androstenedione secretion. Thus, the combination of normal body growth plus inhibition of 3βHSD2 by intra-adrenal cortisol may cause normal adrenarche. Childhood obesity may hasten this process by causing a pathologic increase in body size that triggers these same processes at an earlier age, resulting in the premature onset of adrenarche.
Topics: 3-Hydroxysteroid Dehydrogenases; Adolescent; Adrenal Cortex; Adrenarche; Adrenocorticotropic Hormone; Animals; Child; Child, Preschool; Female; Humans; Hydrocortisone; Male; Models, Biological; Obesity
PubMed: 29847819
DOI: 10.1159/000488777 -
The Journal of Clinical Endocrinology... Aug 2021Premature adrenarche (PA) may increase the risk for polycystic ovary syndrome (PCOS).
CONTEXT
Premature adrenarche (PA) may increase the risk for polycystic ovary syndrome (PCOS).
OBJECTIVE
To study features of PCOS in young adult women with a history of PA.
METHODS
Thirty PA and 42 control females were followed from prepuberty to young adulthood (median age 18.1 years). The main outcome measures were ovarian function, the use of contraceptives, and clinical and biochemical indicators of hyperandrogenism.
RESULTS
We found no differences in the use of hormonal contraceptives (50 vs 50%, PA vs controls, respectively; P > .999), indication for using contraceptives (P = .193), or in the history of oligo- (17 vs 26%, P = .392) and amenorrhea (0 vs 0%, P > .999). Among women not using hormonal contraceptives, those with a history of PA had a higher prevalence of hirsutism (27 vs 0%, P = .023) but not acne (87 vs 67%, P = .252). Steroid profiles were broadly comparable between the groups, but PA women had lower sex hormone-binding globulin (SHBG) concentrations (30.1 vs 62.4 nmol/L, P < .001) resulting in higher free androgen index (3.94 vs 2.14, P < .001). The difference in SHBG levels persisted through body mass index adjustment. SHBG correlated negatively with the homeostasis model assessment for insulin resistance (r -0.498, P = .003). Anti-Müllerian hormone concentrations were comparable between the groups (39.3 vs 32.1 pmol/L, P = .619).
CONCLUSION
PA was not associated with evident ovarian dysfunction in young adult women. However, women with a history of PA had decreased SHBG levels and thus, increased bioavailability of circulating androgens.
Topics: Acne Vulgaris; Adolescent; Adrenarche; Amenorrhea; Androgens; Anti-Mullerian Hormone; Body Mass Index; Case-Control Studies; Contraceptives, Oral, Hormonal; Female; Follow-Up Studies; Hirsutism; Humans; Hyperandrogenism; Insulin Resistance; Ovarian Function Tests; Polycystic Ovary Syndrome; Prevalence; Sex Hormone-Binding Globulin; Steroids; Young Adult
PubMed: 34060603
DOI: 10.1210/clinem/dgab385 -
Acta Paediatrica Scandinavica Sep 198318 girls with premature adrenarche were evaluated both clinically and by serum steroid measurements. Age at first appearance of the symptoms ranged from 3.0 to 7.8...
18 girls with premature adrenarche were evaluated both clinically and by serum steroid measurements. Age at first appearance of the symptoms ranged from 3.0 to 7.8 years. Clinical findings included pubic or axillary hair, acne, accelerated growth, adult-type perspiration and oily skin or hair. Bone age was 0.3-3.2 years ahead of chronological age. 15 of these 18 girls had accelerated growth and most of these already before the appearance of pubic hair. Five girls had severe acne requiring topical treatment. Serum dehydroepiandrosterone was elevated for age in all patients. Androstenedione and testosterone correlated positively with the dehydroepiandrosterone values. Dihydrotestosterone was also elevated in many girls. Administration of dexamethasone brought about a rapid normalization of the elevated steroid levels.
Topics: 17-alpha-Hydroxyprogesterone; Acne Vulgaris; Adrenal Glands; Androgens; Androstenedione; Child; Child, Preschool; Dehydroepiandrosterone; Dihydrotestosterone; Female; Humans; Hydroxyprogesterones; Pregnenolone; Progesterone; Testosterone
PubMed: 6227200
DOI: 10.1111/j.1651-2227.1983.tb09798.x -
The Journal of Clinical Endocrinology... Jan 2013Premature adrenarche (PA) is characterized by an earlier than normal increase in adrenocortical androgen production, and it is associated with increased serum IGF-I...
CONTEXT
Premature adrenarche (PA) is characterized by an earlier than normal increase in adrenocortical androgen production, and it is associated with increased serum IGF-I concentrations. Both the GH-IGF system and androgens, particularly testosterone, are known to enhance erythropoiesis.
OBJECTIVE
Our objective was to test the hypothesis that blood erythrocyte count and blood hemoglobin (B-Hb) concentration are increased in PA.
DESIGN, PARTICIPANTS, AND SETTING
Sixty-four prepubertal children (10 boys) with clinically and biochemically defined PA and 62 healthy prepubertal controls (10 boys) participating in our Premature Adrenarche study were examined, and a fasting blood sample was drawn at a university hospital.
MAIN OUTCOME MEASURES
We evaluated B-Hb and erythrocyte, thrombocyte, and leukocyte counts and their association with serum dehydroepiandrosterone sulfate (DHEAS), testosterone and IGF-I concentrations.
RESULTS
Children with PA had higher mean blood erythrocyte count (4.74 vs. 4.64 × 10(12)/liter, P = 0.04; significant difference in girls but not in boys) and a tendency toward higher B-Hb (130 vs. 128 g/liter, P = 0.06) than their controls. No difference was observed in leukocyte or thrombocyte counts between the study groups. In linear regression models including age, sex, body mass index SD score, IGF-I, and DHEAS or testosterone, B-Hb was associated with serum DHEAS (P = 0.04), testosterone (P = 0.01), and IGF-I (P ≤ 0.003) concentrations in the entire study cohort and with IGF-I separately in girls (P ≤ 0.02). Similar models showed a significant association of blood erythrocyte count with serum IGF-I concentration (P = 0.003-0.049) but not with DHEAS or testosterone.
CONCLUSIONS
Increased erythrocyte count in PA girls suggests that relatively small increases in serum androgen or IGF-I concentrations during adrenarche may associate with enhanced erythropoiesis.
Topics: Adrenarche; Age Factors; Case-Control Studies; Child; Child, Preschool; Dehydroepiandrosterone Sulfate; Erythrocyte Count; Erythrocytes; Female; Hemoglobins; Humans; Insulin-Like Growth Factor I; Male; Osmolar Concentration; Puberty, Precocious
PubMed: 23162102
DOI: 10.1210/jc.2012-2783 -
Frontiers in Endocrinology 2017Premature adrenarche (PA) has been linked to early thelarche and menarche, but longitudinal data on growth and pubertal development after PA are insufficient.
BACKGROUND
Premature adrenarche (PA) has been linked to early thelarche and menarche, but longitudinal data on growth and pubertal development after PA are insufficient.
METHODS
Growth and pubertal development of mostly full-term and appropriate for gestational age-born 43 PA (36 girls) and 63 control children (52 girls) were analyzed prospectively. Children examined first at the mean age of 7.6 years were reexamined at the mean age of 12.0 years.
RESULTS
The PA girls but not the boys were taller and had higher body mass index (BMI) than the controls. A higher proportion of the PA than control girls had reached menarche, while the same percentage of the PA and control boys were at Tanner genital stage ≥2. The PA girls with premature pubarche (PP) were taller but not heavier and had more often reached menarche by the age of 12 years than the PA girls without PP. The PA girls with menarche had lower birth length (BL) and higher prepubertal insulin-like growth factor 1 (IGF-1) concentrations compared with non-menarcheal PA girls. In logistic regression analyses for all girls, lower BL standard deviation score, earlier maternal menarche, and higher prepubertal IGF-1 were independently associated with menarche.
CONCLUSION
At 12 years of age, the PA girls had higher BMI, advanced linear growth, and accelerated pubertal development with earlier menarche than the control girls. The PA girls with PP were taller and had earlier menarche than the PA girls without PP. Lower BL and higher prepubertal IGF-1 concentration were predictive factors for menarche by the age of 12 years.
PubMed: 29163361
DOI: 10.3389/fendo.2017.00291 -
Acta Paediatrica (Oslo, Norway : 1992).... Dec 1999Adrenarche is characterized by a prepubertal rise in adrenal secretion of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) that is independent of the gonads or...
Adrenarche is characterized by a prepubertal rise in adrenal secretion of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) that is independent of the gonads or gonadotropins. Adrenopause is the corresponding diminution in DHEA and DHEAS concentrations in later life. The mechanisms by which adrenarche and adrenopause are induced and regulated are unknown. Early work focused on identifying hypothetical adrenal androgen regulatory hormones that would induce DHEA in much the same way that adrenocorticotropin induces cortisol, but no such factors have been found. Current studies of adrenarche focus on intra-adrenal events, particularly those concerning 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17alpha-hydroxylase/17,20-lyase (P450c17). Molecular data implicate a decrease in 3beta-HSD specifically in the adrenal zona reticularis. However, a decrease in 3beta-HSD is insufficient to explain why the reticularis catalyzes 17,20-lyase activity and hence makes DHEA, rather than catalyzing only 17alpha-hydroxylase activity, as does the zona fasciculata. P450c17 appears to catalyze 17,20-lyase activity only if P450c17 has undergone serine phosphorylation and has access to cytochrome b5 as an allosteric cofactor. Although these two factors have not yet been investigated in adrenarche, it appears that both a zone-specific diminution in 3beta-HSD and a zone-specific induction of 17,20-lyase activity are required to account for the physiological data. Exaggerated premature adrenarche appears to be an early sign of polycystic ovary syndrome (PCOS). Mechanistic considerations of PCOS suggest a key role for serine phosphorylation of P450c17 in both adrenarche and some forms of heritable PCOS.
Topics: Adrenal Glands; Child; Cytochrome P-450 Enzyme System; Dehydroepiandrosterone; Female; Humans; Phosphorylation; Polycystic Ovary Syndrome; Puberty; Puberty, Precocious
PubMed: 10626547
DOI: 10.1111/j.1651-2227.1999.tb14405.x -
Journal of Pediatric Endocrinology &... May 2008Girls with premature adrenarche (PA) are at risk for multiple problems related to exaggerated androgen synthesis. Whether PA carries a risk of psychopathology remains...
Girls with premature adrenarche (PA) are at risk for multiple problems related to exaggerated androgen synthesis. Whether PA carries a risk of psychopathology remains unknown. This study examined group differences in: (a) anthropometric and endocrine parameters, and (b) mood and behavior problems, in 6-8 year-old girls with PA (n = 40) compared to on-time adrenarche girls (n = 36). PA girls were taller (p < or =0.05) and heavier (p < or =0.01) than the on-time adrenarche girls but body mass index showed no difference. PA girls had significantly (p <0.05) higher adrenal androgen and testosterone concentrations but not cortisol or leptin. PA girls also had significantly more oppositional defiant disorder, and higher symptom counts reflecting anxiety, mood or disruptive behavior disorders. PA girls may be more vulnerable to psychopathology than on-time adrenarche girls. The challenge of future studies is to determine which PA girls are at risk for psychopathology and which are more resilient.
Topics: Adrenarche; Affect; Androgens; Anxiety; Body Height; Body Weight; Case-Control Studies; Child; Female; Humans; Hydrocortisone; Leptin; Puberty, Precocious; Testosterone
PubMed: 18655525
DOI: 10.1515/jpem.2008.21.5.439 -
Hormone Research in Paediatrics 2018Children with premature adrenarche (PA) are taller and more overweight than their healthy peers, and PA girls have a slightly accelerated pubertal development. There is...
BACKGROUND/AIM
Children with premature adrenarche (PA) are taller and more overweight than their healthy peers, and PA girls have a slightly accelerated pubertal development. There is some evidence that early exposure to androgens may have an influence on psychosocial development. The aim of this cross-sectional case-control study was to evaluate health-related quality of life (HRQoL) in PA children at the age of 12 years.
METHODS
The HRQoL was assessed for 43 PA (36 girls) and 63 control children (52 girls) at the median age of 12.0 years using the standardized 16D instrument, and the scores of the PA children were compared to those of the control children and reference population.
RESULTS
The mean overall HRQoL scores did not differ between PA and control girls, PA and control boys, or all PA and control children or the reference population. Independently of PA, overweight girls had a lower mean overall HRQoL score than lean girls, and both overweight girls and boys were on average worse off on the dimension of appearance than their lean peers.
CONCLUSIONS
PA children have as good self-rated HRQoL as their peers at the age of 12 years. Overweight is associated with a worse HRQoL profile independently of PA.
Topics: Adrenarche; Case-Control Studies; Child; Cross-Sectional Studies; Female; Humans; Male; Quality of Life
PubMed: 29502117
DOI: 10.1159/000487134 -
Clinics (Sao Paulo, Brazil) 2019Follow-up studies of girls with premature adrenarche have reported the development of polycystic ovary syndrome, insulin resistance, and dyslipidemia and a propensity to...
OBJECTIVE
Follow-up studies of girls with premature adrenarche have reported the development of polycystic ovary syndrome, insulin resistance, and dyslipidemia and a propensity to cardiovascular disease. The aim of this study was to analyze the presence of these conditions in patients previously treated at the Universidade Federal do Triângulo Mineiro.
METHODS
A total of 130 medical records reported premature adrenarche. One hundred and twenty-two patients were invited to participate, of whom 54 accepted; 34 patients were selected, as they had reached their final height. Anthropometric, blood glucose, insulin, and lipid and hormonal profile (LH, FSH, estradiol, 17α-OH-progesterone, androstenedione, dehydroepiandrosterone sulfate, testosterone) data were obtained, the HOMA-IR index was calculated, and pelvic ultrasonography was performed. To characterize polycystic ovary syndrome and metabolic syndrome, the Rotterdam and International Diabetes Federation criteria, respectively, were used. Data were analyzed according to measures of dispersion, frequency and correlations of interest.
RESULTS
The age of the participants ranged from 15.2 to 28.2 years/months; 23.5% of the patients were overweight, 11.8% were obese, 29.4% had a large waist circumference, and 8.8% were hypertensive. None of the patients had altered glucose levels, and insulin levels and HOMA-IR were elevated in 29.4% and 38.2% of the participants, respectively; 14.7% of the patients exhibited acanthosis nigricans. The lipid profiles of the participants were variable, and one patient (2.9%) had metabolic syndrome. Polycystic ovary syndrome was found in 41.2% of patients.
CONCLUSION
The percentage of patients with polycystic ovary syndrome who also had overweight, obesity and insulin resistance corroborates the literature data about the need for follow-up aiming at interventions, especially for conditions associated with cardiometabolic risk.
Topics: Adolescent; Adrenarche; Adult; Body Mass Index; Cardiovascular Diseases; Cholesterol; Dyslipidemias; Female; Hormones; Humans; Insulin Resistance; Metabolic Syndrome; Overweight; Polycystic Ovary Syndrome; Puberty, Precocious; Reference Values; Retrospective Studies; Risk Factors; Triglycerides; Young Adult
PubMed: 31241662
DOI: 10.6061/clinics/2019/e836 -
Endocrinology and Metabolism Clinics of... Mar 1991Current concepts of normal and pathologic puberty have been reviewed. The key event in normal puberty is the commencement of pulsatile secretion of GnRH during sleep,... (Review)
Review
Current concepts of normal and pathologic puberty have been reviewed. The key event in normal puberty is the commencement of pulsatile secretion of GnRH during sleep, which leads to augmentation of LH levels with the onset of sleep. Schemata are presented for the initial evaluation of patients with primary amenorrhea and secondary amenorrhea based on whether they are hypoestrogenic or estrogenized. Menstrual abnormalities are also discussed from a diagnosis-based perspective. The role of the bone age in differential diagnosis of pubertal disorders is emphasized. The variable presentations of Turner syndrome, hyperprolactinemia, and PCOS are reviewed. Current understanding of the role of undernutrition and stress in anorexia nervosa, psychogenic amenorrhea, and athletic amenorrhea is presented, and management guidelines are reviewed. The evidence that premature pubarche is usually due to premature adrenarche is discussed. The concept that premature thelarche lies on a spectrum between normal and early puberty is discussed. The reader is also reminded that many girls with idiopathic true sexual precocity do not require treatment to preserve height potential.
Topics: Adolescent; Female; Hormones; Humans; Menarche; Menstruation Disturbances; Puberty; Puberty, Delayed; Puberty, Precocious; Reproduction
PubMed: 2029884
DOI: No ID Found