Adrenarche and pubarche in girls with turner syndrome during growth-promoting therapy with human growth hormone.

BACKGROUND: Data on adrenarche and pubarche in girls with Turner syndrome (TS) are inconsistent in the literature. METHODS: The cohort consisted of 94 girls and young women with TS born between 1971 and 2001 (age range: 3.1-23.2 yrs.), who were treated with human growth hormone and regularly presented at our outpatient clinic every 4 to 6 months.The longitudinal data of all patients were ascertained retrospectively from patient charts. The data collection ended in January 2016. Adrenarche was assessed by serum DHEAS levels and pubertal status by Tanner stages. Pubarche was defined as the appearance of pubic hair (PH2), whereas spontaneous puberty was defined as Tanner stage B2. The patients were retrospectively subdivided in two groups with regard to pubertal development: group 1 (n = 21) with spontaneous puberty and group 2 (n = 70) with induced puberty. Since blood samples were not taken at every visit, we generated seven groups according to the age of the children at which the blood samples were taken: 3-5, 5-7, 7-9, 9-11, 11-13, 13-15, and 15-17 yrs. Serum DHEAS and follicle-stimulating hormone (FSH) levels were measured by chemiluminescence immunoassay and compared with those of a control group of healthy girls. RESULTS: Adrenarche started in TS girls between 5 and 7 years. TS girls had higher DHEAS levels than the control group, with statistically significant differences in the age groups 7 to 17 years. No differences were determined between the TS girls with spontaneous puberty and those with POI. TS girls in group 2 reached the Tanner stages PH2 (p < 0.04), PH3 (p < 0.01), PH4 and PH5 (p < 0.001) markedly later than TS girls in group 1. CONCLUSIONS: The onset of adrenarche in girls with TS undergoing GH therapy does not differ from that in healthy girls. However, adrenarche is more pronounced in girls with TS. There is no difference in DHEAS levels between the TS girls with spontaneous puberty and the TS girls with primary ovarian insufficiency (POI), while the tempo of pubarche is markedly slower in the girls with POI.

Adrenarche in Silver-Russell Syndrome: Timing and Consequences.

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.

Crecimiento compensador, adrenarca y función hipotálamo-hipofiso-gonadal en función del polimorfismo del gen del receptor de Hormona de Crecimiento en nacidos pequeños para edad gestacional / Compensatory growth, adrenarche, and hypothalamic-pituitary-gonadal function as a function of growth hormone receptor gene polymorphism in small-for-gestational-age infants

INTRODUCCIÓN El receptor de la hormona de crecimiento (GHR) presenta un polimorfismo causado por la deleción del exon 3 que simula un splicing alternativo. Este polimorfismo ha sido asociado con aumento de la respuesta al tratamiento con rhGH en pacientes pequeños para edad gestacional (PEG). Sin embargo, existen pocos datos acerca del crecimiento compensador espontáneo y la adrenarca en relación con las variantes alélicas de GHR en esta población y se ahn reportado datos controversiales acerca de su influencia en la edad de inicio puberal. OBJETIVO El objetivo del estudio es evaluar la relación entre las variantes polimórficas de GHR y la adrenarca, edad de inicio puberal y el crecimiento compensador en pacientes PEG. DISEÑO Estudio descriptivo de corte transversal. Se incluyeron sesenta (60) pacientes púberes y prepúberes (38 varones) que asistieron al servicio de endocrinología de un hospital pediátrico de alta complejidad. Se tipificaron las variantes de GHR mediante PCR-duplex. Se documentaron los datos antropométricos y la edad de inicio puberal establecida utilizando parámetros clínicos y hormonales mediante la determinación de los niveles séricos de gonadotrofinas, testosterona y estradiol. Los niveles séricos de DHEAS fueron utilizados para evaluar la adrenarca. RESULTADOS La proporción de pacientes que presentaron crecimiento compensador fue significativamente mayor en los portadores de al menos un alelo d3 (GHRd3/-)(n=11/22; 50%) cuando se los compraró con el grupo de pacientes GHRfl/fl (n=7/38; 18%) p= 0,02. En concordancia, los valores de IGF1 séricos ajustados por edad fueron más elevados en los pacientes GHR d3/- (-0.25 ±0.96) cuando se los comparó con los portadores del genotipo GHRfl/fl (-0.46 ±1.09 ), p=0.03. No se encontraron diferencias en la edad de inicio puberal ni en los valores séricos de DHEAS entre los diferentes genotipos. DISCUSIÓN En pacientes PEG, la deleción del exón 3 de GHR se asocia un mayor crecimiento compensador y a niveles sericos mas elevados de IGF1 en función del sexo y la edad. Los resultados del estudio permiten proponer que la delecion del exón 3 en el genotipo del GHR podría ser una variable involucrada en el crecimiento compensador de los PEG. Sin embargo este polimorfismo no estaría asociado al inicio de la adrenarca humana

Regulation of human 3ß-hydroxysteroid dehydrogenase type 2 by adrenal corticosteroids and product-feedback by androstenedione in human adrenarche.

In human adrenarche during childhood, the secretion of dehydroepiandrosterone (DHEA) from the adrenal gland increases due to its increased synthesis and/or decreased metabolism. DHEA is synthesized by 17α-hydroxylase/17,20-lyase, and is metabolized by 3ß-hydroxysteroid dehydrogenase type 2 (3ßHSD2). In this study, the inhibition of purified human 3ßHSD2 by the adrenal steroids, androstenedione, cortisone, and cortisol, was investigated and related to changes in secondary enzyme structure. Solubilized, purified 3ßHSD2 was inhibited competitively by androstenedione with high affinity, by cortisone at lower affinity, and by cortisol only at very high, nonphysiologic levels. When purified 3ßHSD2 was bound to lipid vesicles, the competitive Ki values for androstenedione and cortisone were slightly decreased, and the Ki value of cortisol was decreased 2.5-fold, although still at a nonphysiologic level. The circular dichroism spectrum that measured 3ßHSD2 secondary structure was significantly altered by the binding of cortisol, but not by androstenedione and cortisone. Our import studies show that 3ßHSD2 binds in the intermitochondrial space as a membrane-associated protein. Androstenedione inhibits purified 3ßHSD2 at physiologic levels, but similar actions for cortisol and cortisone are not supported. In summary, our results have clarified the mechanisms for limiting the metabolism of DHEA during human adrenarche.

Adrenarche and puberty in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

UNLABELLED: There have been only a few studies on adrenarche in girls with classic congenital adrenal hyperplasia (CAH) showing that dehydroepiandrosterone sulfate (DHEAS) levels did not rise at the physiological age of adrenarche. OBJECTIVE: Longitudinal analysis of serum DHEAS levels and Tanner stages in CAH children. DESIGN: We studied 98 CAH patients (52 females), aged between 1 month and 18.0 years. All patients had genetically proven classic CAH and received steroid substitution therapy. RESULTS: Serum DHEAS levels did not differ between CAH children and healthy children from the age of 1 year until 5-6 years. Beginning at the age of 7-8 years, there was a continuous but blunted increase in DHEAS levels in CAH boys and girls compared to healthy children. There was no correlation of DHEAS levels with the genotype, glucocorticoid dosage, auxological data, or quality of metabolic control. Pubarche (PH2) as well as gonadarche (G2) and thelarche (B2) occurred significantly earlier in CAH boys and girls than in the reference group, but timing of menarche was normal. CONCLUSIONS: Pubarche and adrenarche are dissociated in classic CAH: earlier pubarche, gonadarche and thelarche, respectively, in both sexes contrast with the absence of typical adrenarche.