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Frontiers in Endocrinology 2022Idiopathic premature adrenarche (IPA) is considered a normal variant of puberty, presenting more commonly in female patients. There are concerns as to whether IPA alters...
INTRODUCTION
Idiopathic premature adrenarche (IPA) is considered a normal variant of puberty, presenting more commonly in female patients. There are concerns as to whether IPA alters the final height of these girls. Our main objectives were to (a) compare the adult height of girls with IPA against their target height and (b) design a mathematical model to predict adult height at diagnosis in female patients with IPA.
MATERIALS AND METHODS
A cohort study of girls with IPA was conducted from the time of IPA diagnosis until adult height. The following data were collected: target height, perinatal history, anthropometric and biochemical variables and bone age at diagnosis, age at Tanner stage 2 and menarcheal age, and adult height. First, we performed a univariate statistical analysis after which we carried out a multiple linear regression analysis using adult height as the dependent variable.
RESULTS
We obtained data from 79 female patients diagnosed with IPA with a mean adult height of 164.6 cm (95% CI: 163.36-165.85 cm). The mean follow-up time was 6.60 years. Average age at Tanner stage 2 was 9.71 years. Mean menarcheal age was 11.64 years. There were no significant differences between target height and adult height. Of the several predictive models designed for these patients, one of them, which included bone age, obtained an value of 71%.
CONCLUSIONS
Although slightly advanced puberty was observed among the girls with IPA, their adult height was preserved. The use of predictive models of adult height on diagnosis of IPA could facilitate closer follow-up of girls at risk of reduced adult height.
Topics: Adrenarche; Body Height; Child; Cohort Studies; Female; Humans; Male; Puberty; Puberty, Precocious
PubMed: 35311244
DOI: 10.3389/fendo.2022.852422 -
Clinical Endocrinology Mar 1995Previous reports of endocrinological profiles in children presenting with premature adrenarche have not shown consistent abnormalities. We therefore aimed to review the...
OBJECTIVE
Previous reports of endocrinological profiles in children presenting with premature adrenarche have not shown consistent abnormalities. We therefore aimed to review the clinical and biochemical aspects of a large number of patients presenting with premature adrenarche without virilization and determine the relation between clinical and biochemical characteristics and the frequency of adrenal steroid disorders.
DESIGN AND PATIENTS
Eighty-eight patients presenting with adrenarche without virilization during 1985-1992 were retrospectively reviewed. There were 72 girls and 16 boys. All were normotensive and had either prepubertal breasts or testes < 4 ml. In patients with high adrenal androgen levels, adrenal tumours had been excluded by either adrenal ultrasound or CT scan.
MEASUREMENT
We recorded clinical manifestations, auxological data, bone age, biochemical results including basal 17OH-progesterone (b17OHP), dehydroepiandrosterone sulphate (DHEAS), androstenedione (delta 4A), testosterone, cortisol and stimulated 17OHP and cortisol. ACTH stimulation tests (using soluble Synacthen 250 micrograms intramuscularly and collecting blood at 0, 30 and 60 minutes) were performed when clinically indicated. 17OH-Pregnenolone (17OHPreg) was also measured during ACTH stimulation tests in 13 individuals to look for abnormalities of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD).
RESULTS
The age of onset ranged from 3 to 9.5 years (mean 6.8 +/- 1.3). There were no significant differences by sex for height SDS, weight SDS or % ideal body weight, but bone age advancement was greater in males (P < 0.02). The most common presenting clinical manifestation was premature appearance of pubic hair in 93.8%, the other 6.2% presenting with body odour, acne and/or hirsutism. Twelve patients had b17OHP > 6 nmol/l of whom 5 were diagnosed as having congenital adrenal hyperplasia (CAH) resulting from 21-hydroxylase deficiency after ACTH stimulation tests. A further 33 patients who had b17OHP < 6 nmol/l had normal 17OHP and cortisol responses to ACTH stimulation. Patients, after excluding those with CAH, were divided on the basis of their DHEAS levels into prepubertal (< 1.5 mumol/l), pubertal (1.5-6 mumol/l) and above pubertal range (> 6 mumol/l). The 8 patients with DHEAS values above the pubertal range were described as having 'exaggerated adrenarche'. There were no significant clinical differences between these 3 groups, but significant differences were found for bone age advancement and the steroids, b17OHP, delta 4A and testosterone. There was a strong correlation between DHEAS and delta 4A (r = 0.623, P < 0.001). The 'exaggerated adrenarche' group had higher 17 OHPreg/17OHP ratios at 60 minutes after stimulation but these were not diagnostic for 3 beta-HSD deficiency.
CONCLUSION
The value of assessing basal steroids in children presenting with premature adrenarche is demonstrated in this series with 5.7% being diagnosed with 21-hydroxylase deficiency and 9.1% with 'exaggerated adrenarche'. No relation was found between adrenal steroids and clinical features except for the acceleration of bone age. The relation between 'exaggerated adrenarche' and future ovarian hyperandrogenism needs further evaluation.
Topics: 17-alpha-Hydroxypregnenolone; 17-alpha-Hydroxyprogesterone; Adrenal Cortex Diseases; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adrenal Gland Diseases; Adrenal Hyperplasia, Congenital; Age Determination by Skeleton; Androstenedione; Child; Child, Preschool; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Hydroxyprogesterones; Male; Retrospective Studies; Testosterone
PubMed: 7758231
DOI: 10.1111/j.1365-2265.1995.tb01874.x -
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 -
Hormone Research in Paediatrics 2020Recent studies have shown 11-oxygenated androgens (11oAs) are the dominant androgens in premature adrenarche (PA). Our objective was to compare 11oAs and conventional...
INTRODUCTION
Recent studies have shown 11-oxygenated androgens (11oAs) are the dominant androgens in premature adrenarche (PA). Our objective was to compare 11oAs and conventional androgens in a well-defined cohort of children with PA or premature pubarche (PP) and correlate these androgens with metabolic markers.
METHODS
A prospective cross-sectional study was conducted at a university hospital. Fasting early morning serum steroids (including 11oAs) and metabolic biomarkers were compared and their correlations determined in children ages 3-8 years (F) or 3-9 years (M) with PA or PP (5 M and 15 F) and healthy controls (3 M and 8 F).
RESULTS
There were no differences between PA, PP, and controls or between PA and PP subgroups for sex, BMI z-score, or criteria for childhood metabolic syndrome. Dehydroepiandrosterone sulfate (DHEAS) was elevated only in the PA subgroup, as defined. 11oAs were elevated versus controls in PA and PP although no differences in 11oAs were noted between PA and PP. Within the case cohort, there was high correlation of T and A4 with 11-ketotestosterone and 11β-hydroxyandrostenedione. While lipids did not differ, median insulin and HOMA-IR were higher but not statistically different in PA and PP.
CONCLUSIONS
PA and PP differ only by DHEAS and not by 11oAs or insulin sensitivity, consistent with 11oAs - rather than DHEAS - mediating the phenotypic changes of pubarche. Case correlations suggest association of 11oAs with T and A4. These data are the first to report the early morning steroid profiles including 11oAs in a well-defined group of PA, PP, and healthy children.
Topics: Adrenal Glands; Androgens; Case-Control Studies; Child; Child, Preschool; Female; Humans; Male; Puberty, Precocious
PubMed: 33530089
DOI: 10.1159/000513236 -
The Journal of Pediatrics Apr 1979
Topics: Adrenal Cortex; Estradiol; Female; Humans; Puberty, Precocious
PubMed: 430320
DOI: 10.1016/s0022-3476(79)80052-9 -
Reviews in Endocrine & Metabolic... Mar 2009Nonclassic adrenal hyperplasia is most commonly attributable to mutations in CYP21A2 (also termed CYP21) encoding steroid 21-hydroxylase. Partial deficiency of this... (Review)
Review
Nonclassic adrenal hyperplasia is most commonly attributable to mutations in CYP21A2 (also termed CYP21) encoding steroid 21-hydroxylase. Partial deficiency of this enzyme causes an imbalance in cortisol synthesis with consequent adrenal androgen excess. Unlike more severe forms of congenital adrenal hyperplasia, this condition is rarely recognized in infants, but rather is a potential cause of premature adrenarche and pubarche in children, virilization in young women, and variable symptoms in young men. This article will review relevant clinical, hormonal and genetic aspects of nonclassic adrenal hyperplasia.
Topics: Adrenal Hyperplasia, Congenital; Female; Humans; Male; Steroid 21-Hydroxylase
PubMed: 18690539
DOI: 10.1007/s11154-008-9097-x -
Hormone Research in Paediatrics 2017The aim of this study was to investigate the cardiovascular risk of children with premature adrenarche (PA). (Clinical Trial)
Clinical Trial
AIM
The aim of this study was to investigate the cardiovascular risk of children with premature adrenarche (PA).
METHODS
A total of 75 children (44 with PA and 31 control subjects) aged 6-10 years were included in the study. Their metabolic, anthropometric, and echocardiographic parameters were recorded and compared.
RESULTS
Triglyceride, DHEA-SO4, and 17-hydroxyprogesterone levels were significantly higher in the PA group (p = 0.04, p = 0.002, and p = 0.01, respectively). The echocardiographic assessments revealed that the left ventricular end-diastolic diameter (LVEDD) (p < 0.001), left ventricle (LV) and right ventricle (RV) ejection times (p = 0.031 and p = 0.035, respectively), and LV and RV Tei index measurements (p = 0.033 and p = 0.006, respectively) were significantly higher in the PA group than in the control group, whereas the E/e' ratio of the mitral lateral annulus was significantly lower in the PA group (p = 0.006). Additionally, carotid intima-media thickness and epicardial adipose tissue measurements were significantly increased in the PA group compared to the control group (p < 0.001).
CONCLUSION
Early atherosclerotic changes and subclinical impairment of cardiac function were observed in children with PA. It is possible that these children are on a course for early cardiovascular disease.
Topics: Adipose Tissue; Adrenarche; Atherosclerosis; Carotid Intima-Media Thickness; Child; Dehydroepiandrosterone Sulfate; Echocardiography; Female; Humans; Male; Pericardium; Stroke Volume; Triglycerides
PubMed: 27871080
DOI: 10.1159/000452445 -
Journal of Pediatric Endocrinology &... Aug 2021Premature adrenarche may be associated with an intrauterine programmed metabolic syndrome which should be considered as a warning sign for coronary heart disease due to...
OBJECTIVES
Premature adrenarche may be associated with an intrauterine programmed metabolic syndrome which should be considered as a warning sign for coronary heart disease due to accelerated atherosclerosis, hypertension, type 2 diabetes mellitus (DM), and polycystic ovary syndrome.
METHODS
Seventy-three patients with premature adrenarche were evaluated for metabolic parameters and aortic elasticity to evaluate the susceptibility to atherosclerosis and compared with a control group. The patients were examined in two groups as overweight and nonoverweight, and metabolic and cardiac parameters were also compared among these groups. Strain, distensibility, and stiffness index parameters were used to evaluate aortic elasticity.
RESULTS
Biochemical parameters and cardiac measurements were not statistically different between patients and controls. They also did not differ between patients with normal weight and overweight groups. Atherogenic index and insulin resistance were closely related and a positive correlation between cholesterol and triglyceride, and ascending aortic stiffness was found.
CONCLUSIONS
The results may suggest that cholesterol and triglyceride-related arterial involvement is more involved in the pathogenesis of arterial stiffness. It can be considered that 'being overweight' or 'having metabolic profile characterized by insulin resistance and dyslipidemia' are the major coexisting factors influencing the vascular structure, rather than increased androgens and premature adrenarche itself.
Topics: Adrenal Gland Diseases; Adrenarche; Atherosclerosis; Case-Control Studies; Child; Female; Follow-Up Studies; Humans; Insulin Resistance; Male; Metabolic Syndrome; Overweight; Prognosis; Risk Factors; Vascular Stiffness
PubMed: 34167179
DOI: 10.1515/jpem-2021-0160 -
Journal of Pediatric Endocrinology &... 2000The growth and pubertal development of patients with premature adrenarche are reported to be normal, but the effects of this condition on pubertal growth are not well...
The growth and pubertal development of patients with premature adrenarche are reported to be normal, but the effects of this condition on pubertal growth are not well documented. In the present study the growth kinetics of a group of 38 female patients with isolated premature adrenarche followed in our institution for a period of 5.77 (SD=1.7) yr were evaluated to assess whether and how premature adrenarche affects pubertal growth and final height. Birth weight and length, height, skeletal maturation, onset of puberty, age at menarche, height prognosis and final height were documented. To examine the shape of growth kinetics, growth profiles of each girl were fitted with Preece-Baines nonlinear function (PB1) and mean constant curves were obtained by a 2-stage linear model. The biokinetic constants of the patients were compared both with those obtained by Preece and Baines in normal British girls participating in the Harpenden study and by Milani et al. in normal Italian girls. Birth weight and length of premature adrenarche patients were within the normal range for a northern Italian population [+0.29 (1.57) and -0.40 (1.49) SDS, respectively]. Analysis of the biokinetic constants showed that in PA girls the prepubertal component of height velocity, ie. the one preceding the diagnosis of PA, was consistently higher than that of both normal Italian and Harpenden girls, accounting for the increased height of the patients at the beginning of puberty. In contrast, the pubertal component of height velocity was reduced with respect to control groups, leading to a final height similar to the one estimated by the PB1 model and to the target height. In conclusion, the transient acceleration of growth and bone maturation observed in girls with premature adrenarche did not negatively influence the onset and progression of puberty but modified the growth pattern of these patients. Prepubertal growth was enhanced with respect to normal controls, and this enhancement was compensated for by a reduction of the pubertal growth component leading to a final height in accordance with the target height. This abnormal growth shape is not due to an altered tempo of growth but it is rather a consequence of premature adrenarche.
Topics: Body Height; Child; Female; Humans; Kinetics; Nonlinear Dynamics; Puberty; Puberty, Precocious; Reference Values; Time Factors
PubMed: 11117663
DOI: No ID Found -
Hormone Research 2008Adrenarche is the direct consequence of the organogenesis of the zona reticularis (ZR). Proliferation of cortical cells could take place in the outermost layers of the... (Review)
Review
Adrenarche is the direct consequence of the organogenesis of the zona reticularis (ZR). Proliferation of cortical cells could take place in the outermost layers of the adrenal cortex. Cells could then migrate to differentiate the zona glomerulosa (ZG) and zona fasciculata (ZF) during fetal life, and the ZR during postnatal life. After adrenarche, there are detectable increases in circulating DHEA and DHEA-S. Adrenarche could result from an increase in 17,20-lyase activity of P450c17 secondary to high levels of cytochrome b(5) expression, and from a decrease in 3betaHSD2 expression along with an increase in the expression of SULT2A1 in the ZR. The GH-IGF system and insulin, among other factors, might also modulate adrenal androgen production. Furthermore, high concentrations of estradiol enhance basal and ACTH-stimulated DHEA-S production, while aromatase expression was observed in the human adrenal medulla but not in the ZR, suggesting that estrogens produced in the adrenal medulla might be involved in the regulation of androgen production in the ZR. Premature adrenarche might be associated with ovarian hyperandrogenism and polycystic ovarian syndrome in females, as well as with insulin resistance in both sexes. However, many questions remain, transforming adrenal androgens into markers of diseases important for human health.
Topics: Adrenal Cortex; Adrenal Medulla; Adrenarche; Adult; Androgens; Cell Differentiation; Child; Child, Preschool; Dehydroepiandrosterone; Estrogens; Female; Human Growth Hormone; Humans; Male; Puberty, Precocious; Somatomedins; Steroid 17-alpha-Hydroxylase; Zona Reticularis
PubMed: 18824863
DOI: 10.1159/000157871