Deficiencia de hormona de crecimiento (GH) en la edad pediátrica / Growth hormone (GH) deficiency in the pediatric age

La deficiencia de hormona de crecimiento (DGH) provoca manifestaciones clínicas distintas, según su etiología y la etapa del desarrollo, pero siempre existe un denominador común: Las otras manifestaciones clínica dependerán d ela etiología (genética, adquirida o idiopática), de la intensidad de la deficienica y de si es la única hormona hipofisaria afectada o existe afectación de otras hormonas hipofisarias. Los avances de los últimos años han ampliado el conocimiento de sus bases moleculares y han caracterizado mejor las formas adquiridas. Sin embargo, la mayor parte de DGH no tienen una causa conocida y son catalogadas como idiopáticas. Mientras que los criterios clínicos y moleculares del diagnóstico de DGH están bien establecidos, los criterios hormonales continúan siendo un rompecabezas a esar de los esfuerzos realizados para armonizar las técnicas bioquímicas de análisis de GH y de IGF-1. Los diagnósticos basados en los estímulos secretores de GH han demostrado ser la escasa utilidad clínica para predecir la respueta terapéutica a la GH (AU)

Growth hormone (GH) deficiency manifests differently according to the individual´s developmental stage. During the paediatric period, one of the msot prominent clincial features is chronic skeletal growth retardation. Clinical signs also depend on the cause (genetic, acquired or idiopathic), deficiency intensity and whether GH is the only pituitary-affected hormone or is combined with that of other pituitary hormones. Growing knowledge of the genetic basis of GH deficiency continues to provide us with useful information to further characterise to provide us with useful information to further characterise mutation types and mechanisms for prevously-described and new candidate genes. Despite these advances, a high proportion of GH deficiencies with no recognisable acquired basis continue to be labelled as idiopathic. The hormonal diagnoses continue to be a conundrum despite efforts to harmonise biochemical assays for GH and IGF-1 analysis, and the diagnosis based on the so-called GH secretion stimulation tests with prove to be of limited usefulness for predicting response to GH therapy (AU)

Height gain at adult-height age in 184 short patients treated with growth hormone from prepubertal age to near adult-height age is not related to GH secretory status at GH therapy onset.

BACKGROUND: GH release after stimuli classifies short children as severe idiopathic isolated GH deficiency (IIGHD), mild IIGHD, dissociated GH release (DGHR) and normal GH release (NGHR) and anthropometric birth data as adequate for gestational age (AGA) or small for gestational age (SGA). GH release after stimuli classifies AGA patients as IIGHD or as idiopathic short stature (ISS). AIM: To compare height gain induced by GH therapy (31.8 ± 3.5 µg/kg/day, 7.7 ± 1.6 years) started at prepubertal age and stopped at near adult-height age. METHODS: A retrospective longitudinal multicenter study including 184 short patients classified as severe IIGHD n = 25, mild IIGHD n = 75, DGHR n = 55 and NGHR n = 29; or as IIGHD n = 78, ISS n = 57 and SGA n = 49. Height gain was evaluated throughout GH therapy and at adult-height age. RESULTS: Height-SDS gain at adult-height age was similar among severe IIGHD (1.8 ± 0.8 SDS), mild IIGHD (1.6 ± 0.6 SDS), DGHR (1.7 ± 0.7 SDS) and NGHR (1.6 ± 0.7 SDS), or among IIGHD (1.7 ± 0.7 SDS), ISS (1.7 ± 0.6 SDS) and SGA (1.6 ± 0.8 SD). CONCLUSION: GH-release stimuli are of little help for deciding on GH therapy in the clinical management of prepubertal children with IIGHD, ISS or SGA.

SRD5A2 gene mutations and polymorphisms in Spanish 46,XY patients with a disorder of sex differentiation.

One hundred and forty-six index patients with 46,XY DSD in whom gonads were confirmed as testes were consecutively studied for a molecular diagnosis during the period 2002-2010. AR gene was analysed in all patients as the first candidate gene, yielding a mutation in 42.5% of cases and SRD5A2 gene was analysed as the second candidate gene, resulting in the characterization of 10 different mutations (p.Y91D, p.G115D, p.Q126R, p.R171S, p.Y188CfsX9, p.N193S, p.A207D, p.F219SfsX60, p.R227Q and p.R246W) in nine index patients (6.2% of the total number of 46,XY DSD patients). One of the mutations (p.Y188CfsX9) has never been reported. In addition, we genotyped SRD5A2 gene p.V89L and c.281+15T>C polymorphisms in 46,XY DSD and in 156 normal adult males and found that patients with SRD5A2 mutations or without a known molecular diagnosis presented a higher frequency of homozygous p.L89, homozygous TT and combined CCTT genotypes compared with controls. This result suggests that 46,XY DSD patient phenotypes may be influenced by SRD5A2 polymorphism genotypes. SRD5A2 gene mutations may not be as infrequent as previously considered in 46,XY DSD patients with variable degrees of external genitalia virilization at birth and normal T production and appears to be the second aetiology in our series.

Growth hormone secretory status evaluated by growth hormone peak after two pharmacological growth hormone release stimuli did not significantly influence the two-year catch-up growth induced by growth hormone therapy in 318 prepubertal short children with idiopathic growth retardation.

BACKGROUND/AIMS: In prepubertal short children with idiopathic growth retardation, growth hormone (GH) peak after GH release stimuli classifies patients as growth hormone- deficient (GHD) or non-GHD. This study compared a 2-year growth response to GH therapy in 318 prepubertal short children. METHODS: Patients were classified as: severe GHD (GH peaks <5 ng/ml after 2 stimuli; n = 54), mild GHD (GH peaks <10 ng/ml, but one or two between 5 and 10 ng/ml; n = 140), dissociated GH release (GH peak ≥ 10 ng/ml after 1 stimulus and <10 ng/ml after the other; n = 89), and normal GH release (GH peaks ≥ 10 ng/ml after 2 stimuli; n = 35). RESULTS: Two-year height gain did not differ statistically among the 4 groups: 1.39 ± 0.51 SD, 16.4 ± 2.3 cm; 1.23 ± 0.56 SD, 15.8 ± 2.1 cm; 1.18 ± 0.53 SD, 15.3 ± 2.0 cm, and 1.14 ± 0.53 SD, 15.4 ± 2.0 cm, respectively, as was also the case for bone age gain: 2.5 ± 0.6, 2.4 ± 0.7, 2.6 ± 0.7 and 2.3 ± 0.5 years, respectively. CONCLUSIONS: Our results suggest that GH release stimuli are of little help for deciding on GH therapy in the clinical management of prepubertal short children with idiopathic growth retardation, while well-defined anthropometric and biochemical criteria may be useful.

Retinol-binding protein 4 levels in obese children and adolescents with glucose intolerance.

BACKGROUND: Retinol-binding protein 4 (RBP4) is known to be involved in obesity-associated insulin resistance. AIMS: To study the relationships between the degree of adiposity, insulin resistance indices, plasma lipids, inflammatory parameters, glucose intolerance (GI) status and plasma RBP4 levels in obese children and adolescents. PATIENTS AND METHODS: Prospective study comprising 199 obese patients (95 boys) aged 8-16 years (11.8 +/- 1.9). Fifty-three subjects (23 boys) of similar mean age, 11.3 +/- 2.1 years, served as controls. BMI, waist and hip circumferences, plasma lipids, and inflammatory parameters were measured and patients underwent an oral glucose tolerance test. Plasma RBP4 levels were determined by nephelometry. RESULTS: Plasma RBP4 levels (pg/ml) in obese patients with GI (n = 15) were higher (45.0 +/- 14.1) compared with those of obese patients without GI (35.9 +/- 11.7, p = 0.02; n = 184) and controls (31.5 +/- 12.3, p = 0.04) in a generalized linear model adjusted for age, sex, BMI and pubertal status. A negative correlation was found between the skeletal muscle insulin resistance index and RBP4; positive correlations were found between the RBP4 and BMI Z-score (r = 0.213, p < 0.001), waist circumferences (r = 0.135, p < 0.05), plasma triglycerides (r = 0.187, p = 0.005) and apolipoprotein B (0.187, p = 0.007). CONCLUSIONS: Our results suggest a direct relationship between circulating insulin and RBP4 levels, which indicates that this protein might contribute to the development of muscle insulin resistance.

Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development.

BACKGROUND: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic women [complete androgen insensitivity syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). OBJECTIVE: The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46,XY DSD in a series of Spanish patients. SETTING: We studied a series of 133 index patients with 46,XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis. METHODS: The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in family members of 61% of AR-mutated gene patients. RESULTS: AR gene mutations were found in 59 individuals (44.4% of index patients), of whom 46 (78%) were CAIS and 13 (22%) PAIS. Fifty-seven different mutations were found: 21.0% located in exon 1, 15.8% in exons 2 and 3, 57.9% in exons 4-8, and 5.3% intronic. Twenty-three mutations (40.4%) had been previously described and 34 (59.6%) were novel. CONCLUSIONS: AR gene mutation is the most frequent cause of 46,XY DSD, with a clearly higher frequency in the complete phenotype. Mutations spread along the whole coding sequence, including exon 1. This series shows that 60% of mutations detected during the period 2002-2009 were novel.

The exon 3-deleted/full-length growth hormone receptor polymorphism did not influence growth response to growth hormone therapy over two years in prepubertal short children born at term with adequate weight and length for gestational age.

CONTEXT: Consensus is lacking as to whether the exon 3-deleted (d3)/full-length (fl) GH receptor (GHR) polymorphism is associated with responsiveness to GH therapy. OBJECTIVE: Our objective was to evaluate, in short, prepubertal, appropriate-for-gestational age (AGA) patients, 2-yr growth response to GH therapy (31.7+/-3.5 microg/kg.d) according to exon 3-deleted/full-length GHR genotypes. DESIGN: We conducted a retrospective study. PATIENTS: We studied 106 short AGA children, 58 boys and 48 girls, 7.8+/-2.3 yr, (d3/d3 n=18, d3/fl n=42, and fl/fl n=46). The GH response to two provocative stimuli were under 10 ng/ml in 65 and one or both over 10 ng/ml in 41 patients. MAIN OUTCOME MEASURES: Patients were followed by a single clinical team and remained prepubertal during the study. The exon 3-deleted/full-length GHR genotypes were determined and analyzed in the same hospital. RESULTS: Growth velocity significantly (P<0.0001) increased during the first and second years of therapy, as did height sd score (SDS). These increases were similar in each exon 3-deleted/full-length GHR genotype. Total 2-yr height gain (SDS) did not differ statistically among genotypes: 15.5+/-2.2 cm and 1.2+/-0.5 SDS in d3/d3, 15.9+/-2.0 cm and 1.3+/-0.4 SDS in d3/fl, and 15.4+/-2.1 cm and 1.1+/-0.3 SDS in fl/fl. No significant differences among the three genotypes were found in both sexes or in patients with different GH peak response to provocative stimuli for these parameters. An analysis of previously published studies was also performed. CONCLUSIONS: These results confirm in AGA patients those previously found by us and others in small-for-gestational-age patients and suggest that neither sex nor GH peaks after provocative stimuli might influence significantly the responsiveness to GH therapy according to the exon 3-deleted/full-length GHR genotypes.

Changes in oxidant-antioxidant status in young diabetic patients from clinical onset onwards.

Oxidative stress has been implicated as a mechanism underlying hyperglycaemia-associated cellular damage and could play a role in the development of diabetes-related complications. This study aimed to evaluate the significance of changes in oxidant-antioxidant status in 176 child and adolescent diabetic patients at clinical onset, during disease progression and when early microvascular complications appeared. Indicative lipid and protein oxidation markers and antioxidant defence activity were measured in plasma and correlated with clinical data, diabetes duration, long-term glycometabolic control and serum lipids. Compared with their respective age-matched controls, diabetic patients had greater oxidative damage to lipids and proteins, demonstrated through the analysis of hydroperoxides, lipoperoxides and oxidation protein products, all of which were significantly raised at onset, decreased during the first 1.5 years of evolution and rose progressively thereafter. Plasma levels of oxidizable lipids were significantly associated with lipid and protein oxidation products. Overall, plasma antioxidant capacity was significantly and consistently lower from clinical onset onwards. These results suggest that insulin therapy in the first year improved metabolic and oxidant homeostasis and consequently hyperglycaemia-derived biomolecular oxidative damage. Diabetes-associated hyperlipidaemia is related to lipid and protein oxidation processes, which supports the concept of glucose toxicity and lipotoxicity being interrelated. The greatest increase in lipid and protein oxidative damage biomarkers in young diabetic patients with premature microangiopathy points to oxidative stress as a possible contributing mechanism of microvascular dysfunction. Consequently, tight lipid and glycometabolic control may have therapeutic potential by diminishing oxidative tissue-damaging effects of hyperglycaemia.

Hemiagenesia tiroidea en pacientes pediátricos / Thyroid hemiagenesis in paediatric patients

La hemiagenesia tiroidea es una rara malformación congénita, caracterizada por la ausencia o hipoplasia de uno de los lóbulos tiroideos, se localiza con más frecuencia en el lado izquierdo. El diagnóstico suele establecerse de forma casual, mediante ecografía tiroidea, en el estudio de concentraciones plasmáticas elevadas de hormona hipofisaria estimulante del tiroides (TSH) o por la existencia de un bocio unilateral. Con frecuencia existe hipertrofia compensadora del único lóbulo existente. La función tiroidea suele estar conservada en la mayoría de los casos, aunque un porcentaje elevado de pacientes presenta cifras de TSH superiores a las de individuos con tiroides íntegros. El diagnóstico de esta entidad obliga a mantener un estrecho control de la función tiroidea a largo plazo. Se revisan las características clínicas y hormonales de cinco pacientes en edad pediátrica diagnosticados en nuestro centro (el Hospital Materno Infantil «Valld'Hebronl») en los últimos 15 años

Thyroid hemiagenesis is a rare congenital abnormality, with a prevalence of 0.05%, that is characterized by the absence or hypoplasia of one of the thyroid lobes, more frequently the left lobe. It is usually discovered by chance, on thyroid ultrasound performed during the assessment of elevated plasma thyroid-stimulating hormone (TSH) concentrations or because of the presence of unilateral goiter. Compensatory hypertrophy of the existing lobe frequently develops, probably due to thyroid tissue over stimulation by endogenous TSH. Thyroid function remains normal in the majority of cases, but these patients usually have higher levels of TSH. Clase long-term follow-up is necessary in all cases of thyroid hemiagenesis to prevent future complications. We review the clinical features and hormonal status of a group of five children diagnosed in our center over the last 15 year

The long-term strength of Europe and its implications for plate-forming processes.

Field-based geological studies show that continental deformation preferentially occurs in young tectonic provinces rather than in old cratons. This partitioning of deformation suggests that the cratons are stronger than surrounding younger Phanerozoic provinces. However, although Archaean and Phanerozoic lithosphere differ in their thickness and composition, their relative strength is a matter of much debate. One proxy of strength is the effective elastic thickness of the lithosphere, Te. Unfortunately, spatial variations in Te are not well understood, as different methods yield different results. The differences are most apparent in cratons, where the 'Bouguer coherence' method yields large Te values (> 60 km) whereas the 'free-air admittance' method yields low values (< 25 km). Here we present estimates of the variability of Te in Europe using both methods. We show that when they are consistently formulated, both methods yield comparable Te values that correlate with geology, and that the strength of old lithosphere (> or = 1.5 Gyr old) is much larger (mean Te > 60 km) than that of younger lithosphere (mean Te < 30 km). We propose that this strength difference reflects changes in lithospheric plate structure (thickness, geothermal gradient and composition) that result from mantle temperature and volatile content decrease through Earth's history.

Trastornos de la conducta alimentaria en la diabetes mellitus tipo 1. Revisión bibliográfica / Eating disorders in type 1 diabetes mellitus. A literature review

El buen control del paciente con diabetes está directamente relacionado con su alimentación. Los aspectos de la diabetes tipo 1 y su tratamiento que se han descrito como un incremento del riesgo de presentar un trastorno de la conducta alimentaria incluyen: a) la pérdida de peso al inicio de la enfermedad y el consecuente aumento cuando se inicia el tratamiento insulínico; b) la tendencia a aumentar el índice de masa corporal asociado al tratamiento insulínico intensivo; c) la sensación de hambre asociada con las hipoglucemias; d) la dieta necesaria para el tratamiento de la diabetes, y e) la posibilidad de disminuir u omitir dosis de insulina como método de control de peso. Estas desviaciones de la forma natural de la conducta alimentaria perturban la relación normal del paciente diabético con su peso y con sus sensaciones de hambre y saciedad, promueven unos modelos anormales de alimentación y aumentan el riesgo de trastornos de la conducta alimentaria. Este trabajo pretende hacer una recopilación de los estudios de trastornos de la conducta alimentaria realizados en pacientes diabéticos, un problema real pero poco estudiado en la población española (AU)

Patrones antropométricos de los recién nacidos pretérmino y a término (24-42 semanas de edad gestacional) en el Hospital Materno-Infantil Vall d'Hebron (Barcelona) (1997-2002) / Anthropometric growth patterns of preterm and full-term newborns (24-42 weeks´ gestational age) at the Hospital Materno Infantil Vall D´Hebron (Barcelona, Spain) 1997-2002

Antecedentes y objetivo La edad gestacional, el peso y la longitud al nacimiento son factores predictivos de morbilidad neonatal y en la edad adulta. Hemos valorado estos parámetros en una población de recién nacidos pretérmino y a término. Sujetos y métodos Análisis retrospectivo del peso, longitud vértice-talón y perímetro cefálico al nacimiento, en 1.470 recién nacidos vivos de gestaciones únicas de 24-36 semanas de edad gestacional, entre 1997 y 2002. Análisis prospectivo de los mismos parámetros en 1.786 recién nacidos vivos de gestaciones únicas de 37 a 42 semanas de curso no complicado, durante 2001 y 2002. Todos nacieron en el Hospital Materno-Infantil Vall d'Hebron de Barcelona y únicamente se han incluido recién nacidos de raza blanca de padres nacidos en España. En el grupo de 37-42 semanas de edad gestacional todas las mediciones fueron realizadas por un único investigador. Resultados Se presentan los valores de la media y desviación estándar, y los de la distribución percentilada del peso, longitud y perímetro craneal en los recién nacidos de ambos sexos según su edad gestacional. Existe un incremento progresivo con la edad gestacional y un dimorfismo sexual a partir de la semana 30 de gestación con diferencias estadísticamente significativas para todos los parámetros (p 0,05). Los valores del percentil 10 (P10) de peso y longitud de nuestra población son superiores a los de otras poblaciones de España publicadas en 1988 y 1996. Conclusiones Existe un dimorfismo sexual en los parámetros antropométricos de los recién nacidos y éstos varían con el devenir del tiempo, siendo precisa su actualización periódica (AU)

[Anthropometric growth patterns of preterm and full-term newborns (24-42 weeks' gestational age) at the Hospital Materno-Infantil Vall d'Hebron (Barcelona)(1997-2002]. / Patrones antropométricos de los recién nacidos pretérmino y a término (24-42 semanas de edad gestacional) en el Hospital Materno-Infantil Vall d'Hebron (Barcelona) (1997-2002).

BACKGROUND AND OBJECTIVE: Gestational age and neonatal anthropometric parameters are significant predictive factors of neonatal and adult morbidity. Our objective was to evaluate these parameters in a population of preterm and full-term newborns. SUBJECTS AND METHOD: We retrospectively analyzed neonatal anthropometric parameters (weight, vertex-heel length and head circumference) in 1470 live preterm neonates born at 24-36 weeks' gestation between 1997 and 2002. The same parameters were prospectively analyzed in 1786 live newborns born at 37-42 weeks after uncomplicated pregnancies between 2001 and 2002. All preterm and full-term neonates were the result of single pregnancies and were born at the Hospital Materno-Infantil Vall d'Hebron in Barcelona. Only Caucasian neonates whose parents were born in Spain were included. In the group of full-term neonates all measurements were made by the same researcher. RESULTS: The mean and standard deviation and percentile distribution values of weight, length and head circumference according to sex and gestational age are presented. These parameters progressively increased with gestational age and sexual dimorphism from the 30th week of gestation onwards, with statistically significant differences (p < 0.05) for all parameters at 38-42 weeks' gestational age. The mean gains in male full-term newborns compared with female full-term newborns were: 129.1 g of weight, 0.68 cm of length and 0.45 cm of head circumference (P < 0.05). In our population, 10th percentile values for weight and length were higher than those in other Spanish populations reported in 1988 and 1996. CONCLUSIONS: Sexual dimorphism was found in intrauterine anthropometric growth parameters. These parameters change over time and should be updated periodically.

Unidad de adolescentes en un hospital de tercer nivel / No disponible

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Endocrinopatías y masa ósea / Endocrinopathies and bone mass

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Valores de contenido mineral óseo (CMO), densidad mineral ósea (DMO) y densidad mineral ósea volumétrica (DMOv) en niños y adolescentes a nivel de la columna lumbar y femoral / Bone mineral conten (BMC), bone mineral density (BMD) and volumetric bone mineral density (vBMD) values in children and adolescents in the lumbar spine and femoral

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Hyperinsulinemia in pre- and post-pubertal children born small for gestational age.

BACKGROUND: Reduced fetal growth is a potential risk factor for development of metabolic abnormalities in later life. The relationship between low birthweight and impaired glucose tolerance, type 2 diabetes and insulin resistance in adulthood has been well documented. PURPOSE: Assuming that fetal undernutrition is associated with insulin resistance in middle age, we elected to study whether this process may already be present in young adults and adolescents born small for gestational age (SGA). SUBJECTS AND METHODS: Children born in Vall d'Hebron Hospital Infantil, Barcelona, between 1986 and 1989 and between 1978 and 1983 with birthweights below the third centile for the local standard values, were invited to participate in the present study. Of those, 51 (22 girls and 29 boys) were pre-pubertal with 9.4 +/- 0.2 years of age and 49 (29 girls and 20 boys ) were post-pubertal, with 17.3 +/- 0.3 years of age. All patients underwent a standard, 2-hour oral glucose tolerance test. Insulin and glucose responses were compared with our previously published data in control children with normal birthweight. RESULTS: The insulin response at 30 min after glucose load was significantly higher (p < 0.001) in pre- and post-pubertal girls and boys formerly SGA than in controls. In addition, the girls also had a higher insulin response at 60 and 120 min. Mean serum insulin (MSI), the area under the insulin curve during the glucose challenge, was statistically increased in pre- and post-pubertal boys and girls born SGA when compared to controls. CONCLUSION: The presence of high insulin levels after an oral glucose challenge in children and adolescents born SGA might be considered as an early marker of subsequent insulin resistance in adulthood. Furthermore, our population offers the opportunity to study the natural course of hyperinsulinemia and its outcome. Follow-up of this cohort may be helpful in distinguishing a subset of young children and adolescents in whom therapeutic intervention could be done.

Spontaneous, but not induced, puberty permits adequate bone mass acquisition in adolescent Turner syndrome patients.

Lumbar L2-L4 bone mineral density (BMD) values were measured in 37 adolescent and young adult Turner syndrome patients. Nine had developed spontaneous puberty and had had regular menses since menarche (12.55 years +/- 1.17 years) to the time of BMD evaluation (14.96 years +/- 1.26 years). In the other 28, puberty was induced with increasing doses of oral ethinyl estradiol (2.5-10.0 microg/day, for 2 years) and later administration of estrogen/gestagen therapy up to the time of BMD evaluation. In 18, the adolescent group, menarche appeared at 14.68 years +/- 0.63 years and BMD was evaluated at 17.77 years +/- 0.70 years, and in the other 10, the young adult group, menarche appeared at 14.47 years +/- 0.53 years and BMD was evaluated at 20.90 years +/- 0.68 year. BMD values were in the normal range in those who had developed spontaneous puberty (Z score values, -0.24 +/- 0.22) and in the osteopenia range in those in whom puberty was induced (Z score values, -2.09 +/- 0.79 and -2.18 +/- 0.32 for the adolescent and young adult groups, respectively) p < 0.0001. Height Z score values were similar in all three groups (-3.45 +/- 0.77, -3.15 +/- 0.83, and -3.08 +/- 0.33, respectively). No significant differences in calcium intake or physical activity were found among groups. Neither the karyotype distribution nor growth hormone (GH) therapy (five in the spontaneous puberty and six in the induced puberty groups had been treated for a 3.5- to 4.4-year period) explained the differences in BMD values. Because the main difference between groups was the availability of estrogens to bone tissue from infancy to menarche and of estrogens/gestagens from then on up to the time of BMD evaluation, our results suggest that normal gonadal function from infancy to adulthood may be required for adequate bone mass peaking. Early detection of osteopenia and improvement in general measures for adequate bone mass peaking (calcium intake and physical activity) should be considered mandatory in the health care of these patients.

Low areal bone mineral density values in adolescents and young adult turner syndrome patients increase after long-term transdermal estradiol therapy.

OBJECTIVE: To study the effects of long-term estradiol therapy on areal bone mineral density (aBMD) values in young adult Turner syndrome patients. METHODS: The effects of 2-year transdermal estradiol administration on lumbar, L2-L4, aBMD values were evaluated in 12 Turner syndrome patients, 15.41-21.85 years old, who had reached adult height and had low aBMD values. Puberty was induced in all at a chronological age above 12 years and menarche appeared between 13.82 and 15.40 years. The patients were on oral estrogen/gestagen therapy from then until the start of the study. Adhesive patches of 17-beta-estradiol designed to be worn for 72 h and deliver 100 microg of estradiol per day, which results in a steady mean serum estradiol level of 75 pg/ml, were used for 21 days. From day 11 to day 21, 10 mg of oral didrogesterone were also added. Nutritional and physical activity habits were evaluated at the beginning, after 1 year and at the end of the study. RESULTS: aBMD values significantly increased from 0.910 +/- 0.065 to 1.005 +/- 0.086 g/cm2 (10.06 +/- 3.37%) and the z-score from -2.38 +/- 0.63 to -1.54 +/- 0.71 (0.81 +/- 0.30 z-score). No significant differences were observed in body mass index, calcium intake and physical activity habits at the start, during and at the end of the study. CONCLUSION: In summary, our results underline the importance of estrogens for bone mass peaking and suggest that this therapeutic protocol may be useful in the therapy of Turner syndrome patients with low bone mass.