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Clinical Endocrinology Mar 2022Premature adrenarche (PA) has been suggested as a risk factor for future health problems, such as metabolic syndrome and early menarche. However, not all girls with PA...
OBJECTIVE
Premature adrenarche (PA) has been suggested as a risk factor for future health problems, such as metabolic syndrome and early menarche. However, not all girls with PA have these features and it is not certain who will develop them. We propose that these abnormalities might be identified earlier, even before they are visible.
DESIGN
Case-control study.
SETTING
Tertiary care hospital.
PARTICIPANTS
Forty-eight girls with premature pubarche due to PA and age (mean age 7.6 ± 1.0 years), weight, body mass index (BMI), birth weight and gestational age-matched 49 girls with no palpable breast tissue.
MEASUREMENTS
Early pubertal pelvic and breast ultrasonographic changes and their associations with obesity and metabolic parameters were evaluated. Blood samples were collected, breast and pelvic ultrasound examinations were performed and bone ages were assessed.
RESULTS
Girls with PA were taller and their bone ages were higher (p = .049 and p = .005). Fasting blood glucose, insulin, triglycerides, high-density lipoprotein and low-density lipoprotein cholesterol were not different between the groups. Luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol were not different either. Ultrasonography revealed breast gland tissue in 30% of girls with PA and 5% of controls (p = .006). Uterine volume and endometrial thickness were higher in girls with PA (p = .03 and p = .04). Endometrial thickness was positively associated with serum insulin levels in the whole study group and after adjusting for age, diagnosis, BMI, mean ovarian volume and LH, FSH, estradiol levels, this association remained with a borderline p-value (R = 0.486, p = .050).
CONCLUSIONS
We found early changes in uterus and breast glands of girls with PA and endometrial thickness was positively associated with insulin levels.
Topics: Adrenarche; Case-Control Studies; Child; Estradiol; Female; Follicle Stimulating Hormone; Humans; Insulin; Luteinizing Hormone; Male; Puberty, Precocious; Ultrasonography
PubMed: 34918373
DOI: 10.1111/cen.14662 -
The Journal of Pediatrics Feb 2019To assess whether the serum levels of anti-Müllerian hormone (AMH) are increased in girls with premature adrenarche because they are at a higher risk of developing...
OBJECTIVES
To assess whether the serum levels of anti-Müllerian hormone (AMH) are increased in girls with premature adrenarche because they are at a higher risk of developing polycystic ovary syndrome (PCOS) later in life.
STUDY DESIGN
We measured serum levels of AMH, dehydroepiandrosterone sulfate (DHEAS), testosterone, sex hormone binding globulin, androstenedione, and 17-hyroxyprogesterone in 89 girls with premature adrenarche aged 6.98 ± 1.60 years, and in 55 prepubertal normal girls aged 6.78 ± 1.60 years.
RESULTS
AMH was significantly higher in girls with premature adrenarche (2.95 ± 1.20 ng/mL) compared with normal prepubertal girls (2.00 ± 0.95 ng/mL; P < .001), whereas their body mass index SD score was similar (P > .05). DHEAS, testosterone, and androstenedione were increased in premature adrenarche, whereas sex hormone binding globulin was decreased in girls with premature adrenarche. Among the 89 girls with premature adrenarche, 33 were daughters of mothers with a positive history of PCOS, whereas the mothers of the remaining 56 girls with premature adrenarche had a negative history of PCOS. The girls with a mother with a positive history of PCOS had significantly higher AMH serum levels compared with girls with a mother with a negative history of PCOS (3.37 ± 1.72 ng/mL vs 2.70 ± 1.25 ng/mL; P < .05) with no differences in testosterone, DHEAS, androstenedione, and sex hormone binding globulin. The serum concentration of AMH was only positively related to androstenedione (r = 0.538; P < .0001).
CONCLUSIONS
Girls with premature adrenarche, especially those from mothers with a history of PCOS, could have a higher risk of developing PCOS later in life because they have increased serum AMH.
Topics: Adrenarche; Anti-Mullerian Hormone; Biomarkers; Body Mass Index; Child; Female; Genetic Predisposition to Disease; Humans; Mothers; Nuclear Family; Polycystic Ovary Syndrome; Puberty; Radioimmunoassay
PubMed: 30529136
DOI: 10.1016/j.jpeds.2018.09.064 -
Pediatrics International : Official... Feb 2005The aim of this study was to evaluate serum lipids and atherosclerosis risk in children with premature adrenarche (PA) in comparison with age-matched controls.
BACKGROUND
The aim of this study was to evaluate serum lipids and atherosclerosis risk in children with premature adrenarche (PA) in comparison with age-matched controls.
METHODS
Lipid profile, glucose, insulin, and insulin-like growth factor binding protein-1 (IGFBP-1) levels were studied in 24 girls with premature adrenarche and 13 healthy age-matched controls after overnight fasting.
RESULTS
The bone age, weight and body mass index were higher in the premature adrenarche group than the control group. Systolic, diastolic and mean arterial blood pressure of patients were higher than controls. The mean total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C), TC/high-density lipoprotein-cholesterol (HDL-C) and LDL-C/HDL-C ratio, and atherogenic index were significantly higher in the premature adrenarche group compared to the control group. There was no significant difference in the levels of apolipoprotein A1, apolipoprotein B and lipoprotein (a) in both groups. In the premature adrenarche group there were inverse correlations between the levels of IGFBP-1 and TC/HDL-C (rho, -0.54; P, 0.011), and LDL-C/HDL-C (rho, -0.50; P < 0.05) and atherogenic index (AI; rho, -0.54; P < 0.05). Dehydroepiandrosterone sulfate levels of the patients was negatively correlated with AI and TC/HDL-C (rho, -0.0503, P < 0.05).
CONCLUSIONS
Girls with premature adrenarche should be investigated for serum lipids, and atherogenic risk criteria should be assessed periodically in the follow up of patients with PA, as PA seems to be a risk factor for future atherosclerosis.
Topics: Adrenal Glands; Arteriosclerosis; Body Size; Case-Control Studies; Child; Female; Humans; Lipids; Puberty, Precocious; Risk Factors
PubMed: 15693861
DOI: 10.1111/j.1442-200x.2004.02006.x -
Frontiers in Pediatrics 2023The purpose of this study was to investigate the frequency of autoimmune thyroiditis (AT) among euthyroid prepubertal girls presenting with premature adrenarche (PA). We...
OBJECTIVE
The purpose of this study was to investigate the frequency of autoimmune thyroiditis (AT) among euthyroid prepubertal girls presenting with premature adrenarche (PA). We also aimed to identify the clinical, metabolic, and endocrine profile of girls with AT and concurrent PA and compare them to girls with AT without PA, PA alone and healthy controls.
METHODS
Ninety-one prepubertal girls aged 5-10 years, who attended our department for AT, PA and normal variants of growth and puberty were recruited for the study: 73 girls had PA, 6 AT without PA and 12 were referred for investigation of growth. All girls underwent clinical examination, detailed biochemical and hormonal screen. Standard dose Synachten stimulation test (SDSST) and oral glucose tolerance test (OGTT) were performed in all girls with PA. The whole study population was divided in 4 groups: Group PA-/AT+ included 6 girls with AT without PA; Group PA+/AT- PA subjects without AT; Group PA+/AT+ girls with PA and concomitant AT; Group PA-/AT- twelve healthy girls without PA nor AT (controls).
RESULTS
Among 73 girls presenting with PA 19 had AT (26%). BMI, systolic blood pressure (SBP) and the presence of goiter significantly differed between the four groups ( = 0.016, = 0.022 and < 0.001, respectively). When comparing hormonal parameters among the four groups significant differences were found in leptin ( = 0.007), TSH ( = 0.044), anti-TPO ( = 0.002), anti-TG ( = 0.044), IGF-BP1 ( = 0.006), 4- ( = 0.01), DHEA-S (= <0.001), IGF-1 ( = 0.012) and IGF-BP3 ( = 0.049) levels. TSH levels were significantly higher in Group PA+/AT+ compared to PA+/AT- and PA-/AT- ( = 0.043 and = 0.016, respectively). Moreover, girls with AT (Groups PA-/AT+ and PA+/AT+) had higher TSH levels than those in Group PA+/AT- ( = 0.025). Girls in Group PA+/AT + showed higher cortisol response at 60 min post-SDSST than girls in Group PA+/AT- ( = 0.035). During the OGTT, insulin concentrations at 60 min were significantly higher in Group PA+/AT + compared to Group PA+/AT- ( = 0.042).
CONCLUSION
A high frequency of AT among euthyroid prepubertal girls with PA was observed. The combination of PA with AT even in euthyroid state may be associated with a greater degree of insulin resistance, than PA alone.
PubMed: 37009276
DOI: 10.3389/fped.2023.1064177 -
The Journal of Clinical Endocrinology... Nov 2017Premature adrenarche has been reported to be frequent in Silver-Russell syndrome (SRS), but systematic studies are lacking. Here, we studied the prevalence of early...
OBJECTIVES
Premature adrenarche has been reported to be frequent in Silver-Russell syndrome (SRS), but systematic studies are lacking. Here, we studied the prevalence of early adrenarche in SRS, potential predictors, and consequences based on cases with long-term follow-up.
DESIGN AND SETTING
This retrospective longitudinal single-center study included 62 patients with SRS (34 boys) with documented age at adrenarche and positive Netchine-Harbison clinical score who were seen during the past 20 years with a median follow-up of 12.8 years. Clinical and biochemical characteristics were collected from patient records. Adrenarche was defined by reaching a serum dehydroepiandrosterone concentration >500 ng/mL.
RESULTS
Boys reached adrenarche at a median age of 9.2 years (quartiles: 7.6, 10.9 years) and pubarche at a median age of 11.7 years (quartiles: 10.7, 12.8 years). Girls reached adrenarche at a median age of 8.1 years (quartiles: 6.6, 10.1 years) and pubarche at a median age of 9.8 years (quartiles: 8.3, 10.8). Premature adrenarche occurred in 13% of the patients. Multiple linear regression analysis revealed that early adrenarche was associated with early initiation of recombinant human growth hormone (rhGH) treatment (P = 0.0024 in boys; P = 0.0195 in girls), but not with the Netchine-Harbison clinical score (P > 0.25). Response to rhGH treatment (median dose, 50 µg/kg/d) and adult height (n = 43) were not compromised by early adrenarche.
CONCLUSIONS
Early or premature adrenarche was more frequent in SRS than in the general population and was associated with early age at initiation of rhGH treatment. Response to rhGH treatment and adult height were not compromised by early adrenarche.
Topics: Adolescent; Adrenarche; Age Factors; Child; Dehydroepiandrosterone; Female; Follow-Up Studies; Hormone Replacement Therapy; Human Growth Hormone; Humans; Longitudinal Studies; Male; Puberty, Precocious; Retrospective Studies; Silver-Russell Syndrome; Time Factors
PubMed: 28945864
DOI: 10.1210/jc.2017-00874 -
Endocrinology and Metabolism Clinics of... Mar 2021The pathophysiology of symptomatic polycystic ovary syndrome (PCOS) often unfolds across puberty, but the ontogeny of PCOS is difficult to study because, in general, its... (Review)
Review
The pathophysiology of symptomatic polycystic ovary syndrome (PCOS) often unfolds across puberty, but the ontogeny of PCOS is difficult to study because, in general, its pathophysiology is well entrenched before the diagnosis can be confirmed. However, the study of high-risk groups (daughters of women with PCOS, girls with premature pubarche, and girls with obesity) can offer insight in this regard. Available data support the hypothesis that the pubertal development of PCOS involves various combinations of genetic predisposition, intrauterine programming, hyperinsulinism, and numerous other abnormalities that provoke reproductive symptoms (eg, hyperandrogenism, ovulatory dysfunction) in response to the pubertal increase in gonadotropin secretion.
Topics: Adolescent; Female; Humans; Hyperandrogenism; Obesity; Polycystic Ovary Syndrome; Puberty; Puberty, Precocious
PubMed: 33518184
DOI: 10.1016/j.ecl.2020.10.003 -
Journal of the Endocrine Society Mar 2023Premature adrenarche (PA) may predispose to some adverse long-term health outcomes. Cardiorespiratory fitness (CRF) is one of the strongest factors known to predict...
CONTEXT
Premature adrenarche (PA) may predispose to some adverse long-term health outcomes. Cardiorespiratory fitness (CRF) is one of the strongest factors known to predict overall health, but no data exist on the CRF of women with a history of PA.
OBJECTIVE
To study if hyperandrogenism in childhood resulting from PA leads to a measurable difference in CRF between young adult PA and control women.
METHODS
A total of 25 women with PA and 36 age-matched controls were followed from prepubertal age until adulthood. Anthropometric measurements, body composition, biochemical, and lifestyle factors were assessed. The main outcome measure was maximal cycle ergometer test result at the mean age of 18.5 years. We also assessed prepubertal predicting factors for CRF with different linear regression models.
RESULTS
Though prepubertal children with PA were taller and heavier than their non-PA peers, there were no significant differences in height, body mass index, body composition, or physical activity in young adulthood. We observed no significant differences in any of the parameters of the maximal cycle ergometer test, including maximal load ( = .194) or peak oxygen consumption ( = .340). Hemodynamic responses of the groups were similar. None of the examined models or prepubertal factors significantly predicted CRF at adult age.
CONCLUSION
This study suggests that hyperandrogenism in childhood/adolescence resulting from PA does not have a significant impact on adulthood CRF.
PubMed: 37077523
DOI: 10.1210/jendso/bvad041 -
Clinical Endocrinology Mar 2004Adrenarche refers to the onset of dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) production from the adrenal zona reticularis that can be detected at around 6... (Review)
Review
Adrenarche refers to the onset of dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) production from the adrenal zona reticularis that can be detected at around 6 years of age. The phenotypic result of adrenarche is pubarche or the development of axillary and pubic hair that occurs in both girls and boys at about age 8. The phenomenon of adrenarche is unique to human beings and to some Old World primates, and a reversal of adrenarche appears to occur in the ageing process. Premature and exaggerated adrenarche can be indicative of future onset of adult diseases, thus increasing the clinical relevance of adrenarche. The physiological triggers of adrenarche and the role(s) of DHEA-S remain speculative. However, the biochemical pathways that define adrenarche have been characterized in detail, and the appearance of key enzymes and cofactors in the adrenal zona reticularis track with the progression of adrenarche. This article reviews the clinical manifestations of adrenarche, the biochemistry of the enzymes involved in DHEA-S production, and the cell biology of the adrenal zona reticularis.
Topics: Adolescent; Adrenal Cortex Diseases; Adrenal Cortex Hormones; Child; Child Development; Dehydroepiandrosterone Sulfate; Female; Hair; Humans; Male; Puberty; Zona Reticularis
PubMed: 15008992
DOI: 10.1046/j.1365-2265.2003.01858.x -
Journal of the Endocrine Society Jan 2021The conclusion of Panayiotopoulos that glucocorticoid resistance accounted for 57% to 67% of their premature adrenarche and polycystic ovary syndrome cases cannot be...
The conclusion of Panayiotopoulos that glucocorticoid resistance accounted for 57% to 67% of their premature adrenarche and polycystic ovary syndrome cases cannot be accepted from the data presented. This is because proper validation of their method for determining glucocorticoid sensitivity is not presented. Furthermore, the method seems insensitive to physiologic glucocorticoid concentrations.
PubMed: 33367193
DOI: 10.1210/jendso/bvaa163 -
International Journal of Pediatric... 2020Premature adrenarche has been described as clinical and biochemical hyperandrogenism before the age of 8 years in girls and 9 years in boys and absence of signs of...
BACKGROUND
Premature adrenarche has been described as clinical and biochemical hyperandrogenism before the age of 8 years in girls and 9 years in boys and absence of signs of true puberty. Adrenal pathology such as adrenal tumors or non-classical congenital adrenal hyperplasia (NCCAH) and exogenous androgen exposure need to be excluded prior to diagnosing (idiopathic) premature adrenarche. Premature adrenarche is more common among black girls compared to white girls and other racial groups. Adrenal pathology such as NCCAH is less common as a cause for premature adrenarche compared with idiopathic premature adrenarche. The evaluation guidelines for premature adrenarche however are not individualized based on racial/ethnic differences. Few studies have been done to evaluate a largely black population with premature adrenarche to assess the incidence of adrenal pathology.
METHODS
This cross-sectional retrospective study evaluated characteristics of prepubertal patients seen in an endocrine clinic for premature adrenarche.
RESULTS
Two hundred and seventy three subjects had signs of early adrenarche. Three subjects were found to have CAH (2 with NCCAH and 1 with late diagnosis classical CAH). None were black. Exogenous androgen exposure was etiology in 4 additional subjects. These 7 patients were excluded from further analysis. The remaining subjects had idiopathic PA ( = 266); 76.7% were females. The mean age at initial visit was 6.42 +/- 1.97 years (with no racial difference) although black subjects were reported symptom onset at a significantly younger age compared to non-Hispanic white patients.
CONCLUSIONS
Our study showed organic pathology was very uncommon in a predominantly black population with premature adrenarche. Patient factors that influence the probability of an underlying organic pathology including race/ ethnicity should be considered to individualize evaluation.
PubMed: 32165891
DOI: 10.1186/s13633-020-0075-8