Ángel Ferrández

Longitudinal Pubertal Growth According to Age at Pubertal Growth Spurt Onset: Data from a Spanish Study Including 458 Children (223 Boys and 235 Girls)

BACKGROUND Age at pubertal growth spurt (PGS) onset varies and is sex-dependent. We present anthropometric pubertal growth data for five 1-year interval age maturity groups: very early, early, intermediate, late and very late. METHODS Longitudinal growth study of 458 healthy children (223 boys, 235 girls). Ages at PGS onset and at adult height attainment, total pubertal growth (TPG), and peak height velocity (PHV) were evaluated. PGS begins between the ages of 10 and 15 in boys and 8 and 13 in girls; children were allocated to the corresponding 1-year interval age maturity group. RESULTS For each sex, the earlier the start of PGS onset, the higher were PHV and TPG gain. However, adult heights were similar among the five pubertal maturity groups. Height SDS values for mean values of the very early, early, late and very late maturity groups calculated according to data from the five pubertal maturity groups taken together as a single group differed from zero in both sexes, mainly during the pubertal years for the very early (> +1) and very late (> -1) maturers. These differences disappeared at adult height. CONCLUSIONS Our data might contribute to better clinical evaluation of pubertal growth according to individual pubertal maturity tempo.

Influencia de la edad de inicio del brote de crecimiento puberal en la talla adulta

Fundamento y objetivo: En ambos sexos la duracion del crecimiento posnatal difiere entre los sujetos sanos debido a diferencias en la edad a la que inician el crecimiento puberal. Sin embargo, poco se conoce sobre la influencia de este hecho en la estatura adulta. Nuestro objetivo ha sido comparar la talla adulta entre cada uno de los 5 grupos madurativos en los que se inicia el crecimiento puberal. Sujetos y metodo: Dos pediatras realizaron un seguimiento longitudinal de 230 personas (115 mujeres y 115 varones) sanas y sin medicaciones cronicas desde el nacimiento hasta la talla adulta. Se midio la estatura 1-3 veces/ano y se obtuvieron las correspondientes curvas de crecimiento. A partir de ellas se evaluaron la velocidad de crecimiento (cm/ano), la edad al inicio del crecimiento puberal (anos), el crecimiento puberal (cm) y la talla adulta (cm). Segun la edad de inicio del crecimiento puberal, los participantes se agruparon en 5 grupos: 8-9 anos (n = 10), 9-10 anos (n = 29), 10-11 anos (n = 45), 11-12 anos (n = 23) y 12-13 anos (n = 8) en las mujeres, y 10-11 anos (n = 10), 11-12 anos (n = 26), 12-13 anos (n = 45), 13-14 anos (n = 27) y 14-15 anos (n = 7) en los varones. Resultados: En ambos sexos se observaron diferencias estadisticamente significativas para la media de las estaturas al inicio del crecimiento puberal (p < 0,01) y para la media del crecimiento puberal total (p < 0,0001) cuando se comparan entre si los 5 grupos madurativos. Sin embargo, estas diferencias no se observaron entre la media de las tallas adultas cuando se comparan los 5 grupos madurativos entre si, ni cuando se comparo cada grupo con el conjunto de la muestra, ni cuando se comparo cada grupo con las medias obtenidas en estudios recientes de crecimiento de la poblacion espanola. En ambos sexos se observo una correlacion positiva y estadisticamente significativa (p # 0,03) entre la talla al inicio del crecimiento puberal y la talla adulta. Sin embargo, esta correlacion no se observo entre las edades de inicio del crecimiento puberal y las correspondientes estaturas adultas. Conclusiones: En ambos sexos, los factores geneticos, pero no la edad al inicio del crecimiento puberal, influyen en la talla adulta. Aunque la duracion del crecimiento posnatal es menor en las personas con maduracion precoz que en aquellas con maduracion mas tardia, las primeras tienen un desarrollo puberal mas prolongado, ganan mas centimetros de altura y finalizan su crecimiento con una estatura adulta similar.

Pubertal Growth and Adult Height According to Age at Pubertal Growth Spurt Onset: Data from a Spanish Study Including 540 Subjects (281 Boys and 259 Girls)

Longitudinal growth studies show that age at pubertal growth spurt onset occurs as a continuum and is sex dependent. However, mainly due to the scant number of subjects included, these studies tend to present data on pubertal growth as for a single group, without considering the different maturity tempo of each subject included in them. Here, we present anthropometric pubertal growth data for five 1-year-interval age maturity groups, very early, early, intermediate, late, and very late, from a longitudinal growth study of 540 healthy subjects (281 girls and 259 boys). The onset of pubertal growth spurt began between the ages of 8 and 13 in girls and 10 and 15 in boys. According to age at pubertal growth spurt onset, subjects were allocated to the corresponding 1-year-interval age maturity group: very early, early, intermediate, late, and very late. A significant number of subjects were included in each group (75–101 for girls and 59–106 for boys) except in the very early (27 girls and 25 boys) and very late (19 girls and 17 boys) groups. Anthropometric pubertal data (total pubertal growth gain (cm), pubertal growth peak (cm/year), and adult height) were obtained for each of the five pubertal maturity groups in both sexes. In both sexes, the earlier the start of pubertal growth spurt was, the higher the peak height velocity, the total pubertal height gain, and the puberty duration were. Height at onset of pubertal growth spurt was lower in the early than in the late maturity groups. Adult heights were similar and did not differ significantly among the five pubertal maturity groups. Values for all five groups taken together, as a single group, were also similar to those of the intermediate group. Height-for-age and growth velocity-for-age growth charts for the early, intermediate, and late pubertal maturity groups were made. In summary, anthropometric data on pubertal growth are reported for five 1-year-interval age maturity groups according to age at pubertal growth spurt onset. These data might contribute to better clinical evaluation of pubertal growth according to the individual pubertal maturity tempo of each subject and help to avoid the mistakes currently made in the evaluation of pubertal growth when only one pubertal pattern (based on the data of the five groups taken together) is used.

Crecimiento puberal de 1.453 niños sanos según la edad de inicio de la pubertad. Estudio longitudinal de Barcelona

INTRODUCTION Pubertal growth pattern differs according to age at pubertal growth spurt onset which occurs over a five years period (girls: 8-13 years, boys: 10-15 years). The need for more than one pubertal reference pattern has been proposed. We aimed to obtain five 1-year-age-interval pubertal patterns. SUBJECTS AND METHODS Longitudinal (6 years of age-adult height) growth study of 1,453 healthy children to evaluate height-for-age, growth velocity-for-age and weight-for-age values. According to age at pubertal growth spurt onset girls were considered: very-early matures (8-9 years, n=119), early matures (9-10 years, n=157), intermediate matures (10-11 years, n=238), late matures (11-12 years, n=127) and very-late matures (12-13 years, n=102), and boys: very-early matures (10-11 years, n=110), early matures (11-12 years, n=139), intermediate matures (12-13 years, n=225), late matures (13-14 years, n=133) and very-late matures (14-15 years, n=103). Age at menarche and growth up to adult height were recorded. RESULTS In both sexes, statistically-significant (P<.0001) and clinically-pertinent differences in pubertal growth pattern (mean height-for-age, mean growth velocity-for-age and mean pubertal height gain, values) were found among the five pubertal maturity groups and between each group and the whole population, despite similar adult height values. The same occurred for age at menarche and growth from menarche to adult height (P<.05). CONCLUSIONS In both sexes, pubertal growth spurt onset is a critical milestone determining pubertal growth and sexual development. The contribution of our data to better clinical evaluation of growth according to the pubertal maturity tempo of each child will obviate the mistakes made when only one pubertal growth reference is used.

Clinical challenges in the management of isolated GH deficiency type IA in adulthood

Summary Isolated GH deficiency type IA (IGHDIA) is an infrequent cause of severe congenital GHD, often managed by pediatric endocrinologists, and hence few cases in adulthood have been reported. Herein, we describe the clinical status of a 56-year-old male with IGHDIA due to a 6.7 kb deletion in GH1 gene that encodes GH, located on chromosome 17. We also describe phenotypic and biochemical parameters, as well as characterization of anti-GH antibodies after a new attempt made to treat with GH. The height of the adult patient was 123 cm. He presented with type 2 diabetes mellitus, dyslipidemia, osteoporosis, and low physical and psychological performance, compatible with GHD symptomatology. Anti-GH antibodies in high titers and with binding activity (>101 IU/ml) were found 50 years after exposure to exogenous GH, and their levels increased significantly (>200 U/ml) after a 3-month course of 0.2 mg/day recombinant human GH (rhGH) treatment. Higher doses of rhGH (1 mg daily) did not overcome the blockade, and no change in undetectable IGF1 levels was observed (<25 ng/ml). IGHDIA patients need lifelong medical surveillance, focusing mainly on metabolic disturbances, bone status, cardiovascular disease, and psychological support. Multifactorial conventional therapy focusing on each issue is recommended, as anti-GH antibodies may inactivate specific treatment with exogenous GH. After consideration of potential adverse effects, rhIGF1 treatment, even theoretically indicated, has not been considered in our patient yet. Learning points Severe isolated GHD may be caused by mutations in GH1 gene, mainly a 6.7 kb deletion. Appearance of neutralizing anti-GH antibodies upon recombinant GH treatment is a characteristic feature of IGHDIA. Recombinant human IGF1 treatment has been tested in children with IGHDIA with variable results in height and secondary adverse effects, but any occurrence in adult patients has not been reported yet. Metabolic disturbances (diabetes and hyperlipidemia) and osteoporosis should be monitored and properly treated to minimize cardiovascular disease and fracture risk. Cerebral magnetic resonance imaging should be repeated in adulthood to detect morphological abnormalities that may have developed with time, as well as pituitary hormones periodically assessed.