Association between anthropometric hormonal measurements and bone mineral density in puberty and constitutional delay of growth and puberty / Asociación entre las mediciones hormonales antropométricas y la densidad mineral ósea en la pubertad y el retraso constitucional del crecimiento y la pubertad

The aim of this study is to evaluate the acquisition of bone mineral in healthy children throughout puberty and in children with constitutional delay of growth and puberty (CDGP), and to relate changes in bone mass to age, weight, height, sitting height, body mass index and sex hormones in healthy boys. A total of 90 boys: 15 boys with CDGP and 75 healthy boys in different pubertal stages were examined. The number of children assigned to each Tanner stages was 15. Although bone age, weight and Body Mass Index (BMI) were significantly higher in stages II, III, IV, V compared to stage I and CDGP, mean height and sitting height values were higher in stages III, IV, V compared to stage I and CDGP. Also, serum FSH, LH, oestradiol, total and free testosterone levels progressively increased, although serum sex hormone binding globulin (SHBG) levels decreased, in healthy children with progression of sexual development. Significant increase was observed for serum oestradiol levels at stage II and above (p < 0.001), for serum total and free testosterone levels at stage III and above (p < 0.001), for serum FSH and LH levels at stage IV and above (p < 0.01 and p < 0.001) respectively. Also, it was shown that bone mineral content (BMC) and bone mineral density (BMD) measurements were significantly higher for pubertal stage lll and above groups according to both the CDGP group and stage I group. When BMD and BMC measurements of children with CDGP (0.62 ± 0.05 gr/cm² and 23.4 ± 2.8 gr) were compared with bone age, age, BMI and height-matched controls, there was no significant difference between children with CDGP and controls, except for age. Bone mineral density and BMC measurements in children with CDGP were significantly lower than those of age-matched controls (for pubertal stage lll: p < 0.05, for pubertal stage IV: p < 0.01). The strongest correlation coefficients were found between BMD and height among auxological parameters (r = 0.63, p < 0.001) and serum oestradiol levels among hormones (r = 0.55, p < 0.001). The most important findings of this investigation was the determination of body composition and hormonal measurement changes during puberty in boys; oestradiol was the most potent determinant of BMD among pubertal boys. We suggested that there is a critical age period for accumulation of bone mass according to the results. Longitudinal studies will elucidate why sufficient mineralization does take place after puberty starts in CDGP.

El objetivo de este estudio es evaluar la adquisición de mineral óseo del hueso en niños saludables a través de la pubertad y en niños varones con retraso constitucional del crecimiento y la pubertad (RCCP), y relacionar los cambios de masa ósea a la edad, el peso, la altura, la altura sentado, el índice de masa corporal, y las hormonas del sexo en niños varones saludables. Examinamos un total de 90 niños, 15 niños con RCCP y 75 niños saludables en diferentes etapas de la pubertad. El número de niños asignados a cada etapa de Tanner fue 15. Aunque la edad ósea, el peso y el IMC fueron significativamente más altos en las etapas II, III, IV, V, comparados con la etapa I y el RCCP; la altura promedio y los valores de la altura sentado fueron más altos en las etapas III, IV, V, comparados con la etapa I y el RCCP. Por otra parte, los niveles séricos de HEF, HL, estradiol y testosterona total y libre, aumentaron progresivamente, aunque los niveles séricos de SHBG disminuyeron en los niños saludables con el avance del desarrollo sexual. Se observó un aumento significativo en los niveles de estradiol sérico en la etapa II y por encima (p <0.001), en los niveles séricos de testosterona libre y total en la etapa II y por encima (p < 0.001), y en los niveles séricos de HEF, HL en la etapa IV y por encima (p < 0.01 y p < 0.001). Además se observó que las mediciones del contenido mineral óseo (CMO) y la densidad mineral ósea (DMO) fueron significativamente mayores en la etapa III de la pubertad y grupos por encima, de acuerdo tanto con el grupo de RCCP cómo el grupo de la etapa I. Cuando las mediciones de DMO y CMO de niños con RCCP (0.62 ± 0.05 gr/cm² y 23.4 ± 2.8 gr) fueron comparadas con la edad ósea, la edad, IMC y los controles pareados por altura, no se halló ninguna diferencia significativa entre los niños con RCCP y los controles, excepto la edad. Las mediciones de DMO y CMO en niños con RCCP fueron significativamente más bajas que las de los controles pareados por edad (para la etapa III de la pubertad: p < 0.05; para la etapa IV de la pubertad: p < 0.01). Los coeficientes de correlación más fuertes se encontraron entre la DMO y la altura entre los parámetros auxológicos (r = 0.63, p < 0.001), los niveles séricos de estradiol entre las hormonas (r = 0.55, p < 0.001). Los hallazgos más importantes de esta investigación fueron la determinación de la composición corporal y los cambios en la medición hormonal durante la pubertad en los muchachos; el estradiol fue el determinante más potente de la DMO entre los niños en la pubertad. Sugerimos que hay un periodo de edad crítico para la acumulación de masa ósea de acuerdo con nuestros resultados. Los estudios longitudinales esclarecerán por qué se produce suficiente mineralización después de que la pubertad empieza en RCCP.

Association between anthropometric hormonal measurements and bone mineral density in puberty and constitutional delay of growth and puberty.

The aim of this study is to evaluate the acquisition of bone mineral in healthy children throughout puberty and in children with constitutional delay of growth and puberty (CDGP), and to relate changes in bone mass to age, weight, height, sitting height, body mass index and sex hormones in healthy boys. A total of 90 boys: 15 boys with CDGP and 75 healthy boys in different pubertal stages were examined. The number of children assigned to each Tanner stages was 15. Although bone age, weight and Body Mass Index (BMI) were significantly higher in stages II, III, IV V compared to stage I and CDGI mean height and sitting height values were higher in stages III, IV V compared to stage I and CDGP Also, serum FSH, LH, oestradiol, total and free testosterone levels progressively increased, although serum sex hormone binding globulin (SHBG) levels decreased, in healthy children with progression of sexual development. Significant increase was observed for serum oestradiol levels at stage II and above (p < 0.001), for serum total and free testosterone levels at stage III and above (p < 0.001), for serum FSH and LH levels at stage IV and above (p < 0.01 and p < 0.001) respectively. Also, it was shown that bone mineral content (BMC) and bone mineral density (BMD) measurements were significantly higher for pubertal stage III and above groups according to both the CDGP group and stage I group. When BMD and BMC measurements of children with CDGP (0.62 +/- 0.05 gr/cm2 and 23.4 +/- 2.8 gr) were compared with bone age, age, BMI and height-matched controls, there was no significant difference between children with CDGP and controls, except for age. Bone mineral density and BMC measurements in children with CDGP were significantly lower than those of age-matched controls (for pubertal stage III: p < 0.05, for pubertal stage IV: p < 0.01). The strongest correlation coefficients were found between BMD and height among auxological parameters (r = 0.63, p < 0.001) and serum oestradiol levels among hormones (r = 0.55, p < 0.001). The most important findings of this investigation was the determination of body composition and hormonal measurement changes during puberty in boys; oestradiol was the most potent determinant of BMD among pubertal boys. We suggested that there is a critical age period for accumulation of bone mass according to the results. Longitudinal studies will elucidate why sufficient mineralization does take place after puberty starts in CDGP

Association between bone turnover markers and bone mineral density in puberty and constitutional delay of growth and puberty / Asociación entre los marcadores de turnover óseo y la densidad mineral ósea en la pubertad y en el retraso constitucional del crecimiento y la pubertad

The aim of this study was to evaluate associations between the markers of bone formation and resorption and bone mineral density in healthy children throughout puberty and in children with constitutional delay of growth and puberty (CDGP). For this reason, 15 boys with CDGP and 75 other boys in different pubertal stages were included in this study. Although mean serum phosphorus level was higher in stages II, III, IV, V compared to stage I and CDGP, mean bone specific akaline phosphatase (b-AP), parathyroid hormone (PTH), bone mineral density (BMD), bone mineral content (BMC) levels were higher in stages III, IV, V compared to stage I and CDGP. Mean serum calcium (Ca) levels were lower in stages III, IV, V compared to stage I and CDGP. During puberty, urine DPry/Cr levels were not significant. The peak level of b-AP occurred at stage IV. Serum PTH, Ca, b-AP levels, urine Ca/Cr ratio, BMC and BMD measurements significantly changed during puberty in healthy children. While serum Ca levels progressively decreased, serum b-AP, PTH levels, urine Ca/Cr ratio and bone mineralization increased in healthy children with the level of sexual development. The only significant correlation is found between serum PTH levels and bone mineral density (p < 0.05). In our opinion, PTH may be a potent stimulator of skeletal dynamics in boys and may be associated with substantial increases in lumbar spine. We conclude that PTH behaved as a valuable marker in bone mineralization during puberty. Accelerated bone mineralization is reflected by high levels of serum PTH during puberty. All values of the markers of bone formation and bone resorption in children with CDGP were similar to those of prepubertal children. Children with CDGP had prepubertal properties. We suggest that there is a critical age period for accumulation of bone mass according to the results in this study.

El objetivo de este estudio fue evaluar las asociaciones entre los marcadores de formación y resorción ósea y la densidad mineral ósea en niños saludables a lo largo de la pubertad y en niños con retraso constitucional del crecimiento y la pubertad (RCCP). Por esta razón, 15 muchachos con RCCP y otros 75 muchachos en diferentes etapas de la pubertad, fueron incluidos en este estudio. Aunque el nivel medio de fósforo sérico fue más alto en las etapas II, III, IV, V en comparación con la etapa 1 y el RPC, la fosfatasa alcalina especifica ósea media, la hormona paratiroidea (HPT), la densidad mineral ósea (DMO), y los niveles de contenido mineral óseo (CMO) fueron más altos en las etapas III, IV, V en comparación con la etapa I y el RCCP. Los niveles medio de calcio (Ca) en suero fueron más bajos en las etapas II, IV, V en comparación con la etapa I y el RPC. Durante la pubertad, los niveles de orina DPry/Cr no fueron significativos. El nivel pico de b-AP ocurrió en la etapa IV. Los niveles séricos de HPT, Ca, y BAP, el índice Ca/Cr en orina, y las mediciones del CMO y el DMO, cambiaron significativamente durante la pubertad en los niños saludables. Mientras que los niveles de calcio en suero disminuyeron progresivamente, los niveles séricos de BAP y HPT, el índice Ca/Cr en orina, y la mineralización ósea aumentaron en los niños saludables con el nivel de desarrollo sexual. La única correlación significativa se halló entre los niveles de HPT en suero y la densidad mineral ósea (p < 0.05). En nuestra opinión, la HPT puede ser un potente estimulador de la dinámica del esqueleto en los muchachos y puede asociarse con los aumentos sustanciales de la espina lumbar. Concluimos que la HPT se comportó como un valioso marcador de la mineralización ósea durante la pubertad. La mineralización ósea acelerada es reflejada por los altos niveles séricos de HPT durante la pubertad. Todos los valores de los marcadores de formación y resorción ósea en los niños con RCCP fueron similares a los de los niños en la prepubertad. Los niños con RCCP mostraron características prepubertales. Sugerimos que hay un periodo de edad crítico para la acumulación de masa ósea, de acuerdo con los resultados en este estudio.

Association between bone turnover markers and bone mineral density in puberty and constitutional delay of growth and puberty.

The aim of this study was to evaluate associations between the markers of bone formation and resorption and bone mineral density in healthy children throughout puberty and in children with constitutional delay of growth and puberty (CDGP). For this reason, 15 boys with CDGP and 75 other boys in different pubertal stages were included in this study. Although mean serum phosphorus level was higher in stages II, III, IV, V compared to stage I and CDGP, mean bone specific akaline phosphatase (b-AP), parathyroid hormone (PTH), bone mineral density (BMD), bone mineral content (BMC) levels were higher in stages III, IV, V compared to stage I and CDGP Mean serum calcium (Ca) levels were lower in stages III, IV, V compared to stage I and CDGP. During puberty, urine DPry/Cr levels were not significant. The peak level of b-AP occurred at stage IV. Serum PTH, Ca, b-AP levels, urine Ca/Cr ratio, BMC and BMD measurements significantly changed during puberty in healthy children. While serum Ca levels progressively decreased, serum b-AP, PTH levels, urine Ca/Cr ratio and bone mineralization increased in healthy children with the level of sexual development. The only significant correlation is found between serum PTH levels and bone mineral density (p < 0.05). In our opinion, PTH may be a potent stimulator of skeletal dynamics in boys and may be associated with substantial increases in lumbar spine. We conclude that PTH behaved as a valuable marker in bone mineralization during puberty. Accelerated bone mineralization is reflected by high levels of serum PTH during puberty. All values of the markers of bone formation and bone resorption in children with CDGP were similar to those of prepubertal children. Children with CDGP had prepubertal properties. We suggest that there is a critical age period for accumulation of bone mass according to the results in this study.

Male pubertal development and the role of androgen therapy.

In boys, the hormonal changes that accompany normal puberty are well defined, as are the physical signs of pubertal development and the kinetics of the growth spurt. Most androgens are derived from the testes, although adrenal androgens may also contribute; testosterone can also be aromatized to estrogen to exert important effects during puberty. Androgens, but especially their conversion to estrogens by aromatase, have a major role in the dramatic changes in linear growth, secondary sexual characteristics, and changes to bone, muscle and fat distribution that occur during puberty. Androgen therapy for delayed puberty should permit full normal pubertal development and thereby also address some of the associated psychosocial problems. Adolescent boys with conditions of permanent hypogonadism (hypogonadotropic or hypergonadotropic) or transient hypogonadotropic hypogonadism (constitutional delay of growth and puberty) can benefit from testosterone therapy. Long-term testosterone therapy should be given for hypothalamic or pituitary gonadotropin deficiency, or for primary hypogonadism such as for adolescents with Klinefelter syndrome, if endogenous testosterone levels drop or levels of luteinizing hormone rise. Intramuscular administration every few weeks is effective, but newer cutaneous forms, for example, gels or patches, also show promise in permitting adolescent males to reach adult body composition.

Evaluation of the buserelin stimulation test in diagnosing gonadotropin deficiency in males with delayed puberty.

OBJECTIVE: To assess the efficacy of the gonadotropin-releasing hormone (GnRH) agonist buserelin in a stimulated gonadotropin test for the investigation of delayed puberty in males. STUDY DESIGN: Prepubertal males (n = 31; age range, 10.3 to 17.2 years) were studied; buserelin (100 microg) was administered subcutaneously, with blood sampling at 0 and 4 hours for serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH). At follow-up (mean, 4.2 years), 8/31 (26%) failed to progress into puberty, constituting hypogonadotropic hypogonadism (HH), but 23/31 (74%) had testicular enlargement (> or =8 mL) consistent with a normal hypothalamic-pituitary-gonadal (HPG) axis. RESULTS: Stimulated serum LH response to buserelin was lower in males with HH (mean +/- standard error under the mean for HH, 1.4 +/- 0.5 U/L, compared with a normal HPG axis of 17.4 +/- 2.0 U/L; P < .0001). Stimulated serum FSH response was nondiscriminatory (HH, 7.7 +/- 2.2 U/L; normal HPG axis, 11.5 +/- 1.6 U/L; P = .27). All males with HH had a stimulated serum LH level <5 U/L, whereas only 1/23 with a normal HPG axis had a stimulated serum LH below this level. Using this value as the criterion for diagnosing HH, the buserelin stimulation test yielded a sensitivity of 100%, specificity of 96%, and positive predictive value of 89%. CONCLUSIONS: The buserelin stimulation test is a highly specific and sensitive GnRH agonist test for the investigation of males with delayed puberty.

Basal ultrasensitive LH assay: a useful tool in the early diagnosis of male pubertal delay?

The aim of this study was to evaluate the usefulness of basal measurements of gonadotropins in distinguishing between constitutionally delayed puberty (DP) and hypogonadotropic hypogonadism (HH), comparing its diagnostic efficiency with that of the dynamic GnRH infusion test (0.83 microg/min during 120 min). We studied 20 males, chronological age (CA) 14-18 years, with a final diagnosis of DP (n = 8), partial HH (n = 5) and complete HH (n = 7), confirmed by follow-up. We also evaluated basal samples of ultrasensitive LH and FSH in 117 healthy control males (CA 2-19 yr), classified according to Tanner stage. In the control group, ROC plot analysis showed a cutoff to differentiate prepuberty from puberty of 0.65 IU/l for LH (sensitivity: 91%, specificity: 98%). Differences were found (p < 0.05) in basal LH and in maximal responses to GnRH in complete HH in relation to DP and partial HH. The diagnostic efficiency of the GnRH infusion test was 85%. For basal LH, a cut-off limit of 0.65 IU/l showed a diagnostic efficiency of 85% for complete HH and 100% for partial HH and DP. We conclude that, in our experience, basal LH levels above 0.65 IU/l measured by ultrasensitive assay would rule out a complete deficiency. It was not possible to differentiate DP from partial HH, either in basal samples or with the infusion test.

Sickle Cell Disease and age at menarche in Jamaican girls: observations from a cohort study

AIMS: (1) To investigate the distribution of age at menarche in a representative sample of 99 patients with homozygous sickle cell disease (ss), 69 with sickle cell haemoglobin C (sc) disease, and 100 controls with a normal haemoglobin (AA) genotype followed in a cohort study from birth. (2) To explore the determinants of the age menarche. METHODS: Children ascertained in a new-born screening programme were followed prospectively from birth to age 18-26.5 years with regular assessments of height, weight, puberal stage, and haematological indices at the Sickle Cell Clinic of the University Hospital of the West Indies. RESULTS: All subjects have now reached menarche and the mean age in normal controls (13.0 years) was significantly earlier than in SC disease (13.5 years) or SS disease (15.4 years). Greater weight and earlier age at menarche was the only association significant across all genotypes although additional contributions occured from fetal haemoglobin and red cell count in SS disease. Alpha thalassaemia, which ameliorates many of the effects of SS disease, had no discernible effect on menarche. CONCLUSIONS: Mean age at menarche is delayed by 0.5 years in SC disease and by 2.4 years in SS disease. Weight appears to be the principle determinant of age at menarche. (AU)

Sickle cell disease and age at menarche in Jamaican girls: observations from a cohort study.

AIMS: (1) To investigate the distribution of age at menarche in a representative sample of 99 patients with homozygous sickle cell (SS) disease, 69 with sickle cell haemoglobin C (SC) disease, and 100 controls with a normal haemoglobin (AA) genotype followed in a cohort study from birth. (2) To explore the determinants of the age at menarche. METHODS: Children ascertained in a newborn screening programme were followed prospectively from birth to age 18-26.5 years with regular assessments of height, weight, pubertal stage, and haematological indices at the Sickle Cell Clinic of the University Hospital of the West Indies. RESULTS: All subjects have now reached menarche and the mean age in normal controls (13.0 years) was significantly earlier than in SC disease (13.5 years) or SS disease (15.4 years). Greater weight and earlier age at menarche was the only association significant across all genotypes although additional contributions occurred from fetal haemoglobin and red cell count in SS disease. Alpha thalassaemia, which ameliorates many of the effects of SS disease, had no discernible effect on menarche. CONCLUSIONS: Mean age at menarche is delayed by 0.5 years in SC disease and by 2.4 years in SS disease. Weight appears to be the principle determinant of age at menarche.

Use of the gonadotropin-releasing hormone agonist triptorelin in the diagnosis of delayed puberty in boys.

To differentiate gonadotropin deficiency from delayed puberty in teenage boys, 0.1 mg/m2 of triptorelin, a gonadotropin-releasing hormone agonist, was administered subcutaneously at 4 AM. Serum gonadotropins and testosterone levels were determined at baseline and 4 hours after the injection. The increase in blood gonadotropin and testosterone levels was significantly greater in patients with delayed puberty than in those with gonadotropin deficiency.

[Delayed constitutional puberty or hypogonadotrophic hypogonadism?]. / Pubertad retrasada constitucional o hipogonadismo hipogonadotrófico?

This review is focused on the diagnosis, clinical and general therapeutic approach of constitutional growth and puberty delay and hypogonadotrophic hypogonadism in males, two entities that are difficult to distinguish. Clinical history and physical examination must be carefully performed. Delayed puberty is due to constitutional growth and puberty delay in the vast majority of children. These must be distinguished from a small fraction of boys with hypogonadism, a pathological condition. A number of laboratory test allow the prediction of puberty onset and progression. Nevertheless, the advent of highly sensitive immunoassay and radiometric immunoassay systems for LH, FSH and testosterone has not entirely solved the problems, since their values may overlap between normal and pathological conditions.

[Pharmacologic stimulation in delayed female sexual development (response of androstenedione vs. 17 beta-estradiol). Presentation of 2 cases]. / Estímulo farmacológico en el desarrollo sexual femenino retrasado (respuesta de androstendiona vs. 17 beta-estradiol). Presentación de dos casos.

Two girls of 13 and 18 years of age, XX chromosomic pattern, complaining of delay in sexual development (Stage 1) and primary amenorrhea, were studied. Height, weight and surface area in the 13 years subject were three standard deviations below the anthropometric characteristics of already menstruating girls of the same age. Presence of uterus and ovarian tissue was demonstrated by laparoscopy in both, and afterwards, simultaneous measurements of androstenedione (delta 4) and 17 beta-estradiol (E2) were performed in peripheral blood, before and after: placebo, clomiphene (25 and 50 mg), LH-RH, FSH/LH. Under this trials the gonadal structures produced delta 4 and E2, being the former in many instances a good index of ovarian steroid production and associated to growth of pubic and axillary hair. In the patient whose menstruation began after the pharmacologic stimuli, the steroid production was higher as compared to the one, with initiation of no menstrual bleeding. Critical aspects of the various phases of the study are revised to better understand the physiology of some biological processes.

Relationship of somatomedin-C concentrations to pubertal changes.

The plasma somatomedin-C concentration increases above adult values during the teenage years. We studied the relationship of pubertal variables and the adolescent growth spurt to the changes in plasma total Sm-C concentration in normal volunteers and in boys with delayed puberty. The rise in plasma Sm-C concentrations was gradual and correlated positively with pubertal variables rather than with age. By midpuberty, plasma Sm-C had usually risen twofold. The Sm-C level in midpubertal girls (3.1 +/- 1.1, SD, U/ml) was greater than that in midpubertal boys (1.9 +/- 0.50, P less than 0.05). The Sm-C concentration in sexually mature teenagers was two to three times greater than that of adults. Both estrogens and androgens correlated independently with the plasma Sm-C concentration. The data are compatible with the hypothesis that pubertal estrogen or testosterone levels cause an increase in Sm-C, an effect possibly mediated by stimulation of growth hormone secretion, whereas greater estrogen exposure inhibits Sm-C generation, possibly by a direct effect. Plasma Sm-C concentrations correlated significantly with linear growth velocity until the age of peak pubertal growth velocity. Maximum Sm-C values were observed after the peak pubertal growth velocity was achieved, as height velocity was decelerating, and remained above adult levels for at least two to six years, at which time linear growth had virtually ceased. In boys with delayed puberty, Sm-C values resembled those of boys of like pubertal stage more closely than those of boys of similar age. Depressed plasma Sm-C values were found in some boys with delayed puberty; however, these did not preclude subsequent normal linear growth during sexual maturation.