RESUMEN
OBJECTIVE: To assess whether the presence of high DHEAS (HD) at 7 years determines different timing, sequence, and rate of pubertal events, and whether it is associated with adrenal and/or ovarian hyperandrogenism and changes in ovarian morphology throughout puberty. METHODS: In a longitudinal study of 504 girls, clinical evaluation was performed every 6 months after 7 years of age to detect Tanner stages; hormonal and anthropometric measurements were conducted at thelarche (B2), breast Tanner 4 (B4), and 1 year after menarche; ultrasonographic evaluation was also performed after menarche. The girls were classified as HD if their DHEAS level was >42.1 µg/dL (>75th percentile) around 7 years. RESULTS: HD around 7 years is associated with a younger age at thelarche, pubarche, and menarche. Girls with HD had higher androstenedione and total testosterone levels, and a higher free androgen index (FAI), and lower levels of antimüllerian hormone (AMH) at B2, and higher levels of androstenedione and FAI at B4 and after menarche. All these results were significant even after adjusting for body mass index, age at first DHEAS determination, and birth weight. One year after menarche, polycystic ovarian morphology was detected in 7.6 and 7.3% of the HD and the normal DHEAS group, respectively. Ovarian volume was correlated with AMH, testosterone, androstenedione, and LH but not with DHEAS around 7 years. CONCLUSION: Prepubertal HD in normal girls was associated with earlier thelarche, pubarche, and menarche, and a mild androgen increase throughout puberty. We believe continuous follow-up of this cohort is important to prospectively address the interrelationships between biochemical adrenarche and early growth as determinants of ovarian function.
Asunto(s)
Adrenarquia/sangre , Andrógenos/sangre , Sulfato de Deshidroepiandrosterona/sangre , Ovario , Pubertad Precoz , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Ovario/metabolismo , Ovario/patología , Pubertad Precoz/sangre , Pubertad Precoz/patologíaRESUMEN
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.
Asunto(s)
Adrenarquia/sangre , Hormona Antimülleriana/sangre , Predisposición Genética a la Enfermedad , Madres , Núcleo Familiar , Síndrome del Ovario Poliquístico/sangre , Pubertad/sangre , Biomarcadores/sangre , Índice de Masa Corporal , Niño , Femenino , Humanos , Síndrome del Ovario Poliquístico/etiología , Síndrome del Ovario Poliquístico/genética , RadioinmunoensayoRESUMEN
BACKGROUND: Accelerated weight and height gain in infancy have been associated with premature adrenarche. However, the exact tempo of these events remains undefined. Thus, our goal was to assess the relationship between early BMI and height growth in different periods before 7 years of age and plasma DHEAS levels at 7 years of age. METHODS: This is a longitudinal follow-up of participants of the Growth and Obesity Chilean Cohort Study (GOCS) that represents Chilean children from low- to middle-income families. The subjects were 972 children (48% girls) with birth weights of 2,500-4,500 g for whom serial weight and height measurements from birth until 7 years were available. At 7 years of age, we also measured DHEAS, IGF-I, leptin, insulin, and other metabolic markers in serum. The main outcome of interest was plasma DHEAS concentrations at 7 years of age. RESULTS: At 7 years of age, children with DHEAS >75th percentile of the sample were taller and fatter and presented higher HOMA-IR and IGF-I than their counterparts (p < 0.05). Children with higher DHEAS were heavier at 4 years of age and beyond compared to their counterparts (higher BMI [BMI SDS at 4 years: 1.16, 95% CI 1.02-1.29 vs. 0.83, 95% CI 0.76-0.91, p < 0.001]) and taller at 7 years of age (height SDS at 7 years: 0.19, 95% CI -0.08 to 0.31 vs. -0.001, 95% CI -0.06 to 0.06, p < 0.005). CONCLUSIONS: We observed weight and BMI from 2 to 4 years, and height gains from 4 to 7 years were associated with higher DHEAS levels at 7 years.
Asunto(s)
Adrenarquia/sangre , Estatura , Índice de Masa Corporal , Sulfato de Deshidroepiandrosterona/sangre , Niño , Chile , Femenino , Humanos , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Leptina/sangre , MasculinoRESUMEN
OBJECTIVE: To evaluate the effect of premature adrenarche (PA) on prepubertal growth. STUDY DESIGN: The prepubertal growth of 54 girls with PA and 52 control girls was analyzed retrospectively. Birth measures were noted, and childhood length/height and weight were measured annually until age 5 years and at the current visit (at a median age of 7.6 years). The growth variables were correlated with serum insulin-like growth factor (IGF)-1, dehydroepiandrosterone sulfate, and insulin concentrations. RESULTS: There were no significant differences in birth length or weight standard deviation scores (SDSs) between the 2 study groups. The girls with PA demonstrated a significant length SDS increment during the first 2 years of life (median +1.0 SDS; P < .001). Compared with controls, they were taller (median current height 1.2 vs 0 SDS; P < .001) and gained more weight throughout childhood. The difference in weight-for-height became significant at a later age compared with the difference in height. Median serum IGF-1 concentration adjusted for both age and body mass index SDS was higher in the PA group (24 vs 19 nmol/L; P < .031). CONCLUSIONS: PA was not associated with small birth size in our population. Girls with PA had enhanced growth already in early childhood, which was not explained by weight gain. Enhanced IGF-1 production may contribute to the prepubertal growth acceleration in PA.
Asunto(s)
Adrenarquia/fisiología , Crecimiento/fisiología , Adrenarquia/sangre , Edad de Inicio , Peso al Nacer , Estatura , Peso Corporal , Niño , Preescolar , Sulfato de Deshidroepiandrosterona/sangre , Estradiol/sangre , Femenino , Humanos , Recién Nacido , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Pubertad Precoz/sangre , Pubertad Precoz/fisiopatologíaRESUMEN
Prader-Willi syndrome (PWS) is a genetic disorder characterized by dysmorphic features, obesity, hypogonadism, hypotonia and mental retardation. Obesity has been linked to insulin resistance and the latter has also been associated with premature adrenarche. Since up to date a controlled study to investigate adrenarche and its hormonal regulation was lacking in PWS, our aim was to assess whether prepubertal PWS patients develop premature adrenarche and its relationship with markers of insulin sensitivity. Fourteen prepubertal children with PWS (6 M, 8 F) and 10 non-syndromal simple obese matched controls (5 M, 5 F) participated (mean age: 7.62 +/- 1.84 years). A fasting blood sample was obtained for adrenal and ovarian androgens, sex hormone binding globulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1, leptin, adiponectin and a lipid profile. Thereafter an oral glucose tolerance test was performed. PWS patients were smaller at birth and a higher proportion displayed premature pubarche. No differences were found in testosterone, androstenedione, sex hormone binding globulin, free androgen index, homeostatic model assessment-IR, 2-hour insulin, leptin or adiponectin levels. 17-hydroxyprogesterone and DHEAS levels however, were significantly higher in PWS. IGF-I levels were significantly lower in PWS and correlated significantly with height SDS (p < 0.05). In conclusion, a higher proportion of premature adrenarche in our PW patients was observed, which was not explained by differences in insulin sensitivity or plasma levels of adipokines and IGF-I.