Hiperplasia suprarrenal congénita debida a deficiencia de 17 -hidroxilasa: a propósito de una nueva mutación en el gen CYP17A1 / Congenital adrenal hyperplasia due to lack of 17 -hydroxylase: A report of a new mutation in the gene CYP17A1

La enzima P450c17 cataliza 2 reacciones diferentes: 17alfa-hidroxilación de la progesterona y pregnenolona y segmentación de la unión del carbono 17-20 a partir de la 17,20 liasa para producir andrógenos suprarrenales. Esta enzima está codificada por el gen CYP17A1. Se presenta una paciente de 14 años con retraso en el desarrollo puberal y presión arterial elevada para su talla y edad. Cariotipo 46,XX. En el estudio hormonal destaca hipogonadismo hipergonadotropo, así como una insuficiencia suprarrenal y exceso mineralocorticoideo. El estudio genético mostró una mutación en homozigosis en el gen CYP17A1 (c.753+1G>A), no descrita previamente, la cual es responsable de la fisiopatología de la deficiencia de 17alfa-hidroxilasa. Esta entidad es una forma rara de hiperplasia suprarrenal congénita. Normalmente la enfermedad suele pasar desapercibida hasta la adolescencia o el inicio de la vida adulta y se debería sospechar ante individuos 46,XY con genitales ambiguos o 46,XX con retraso puberal que asocia hipertensión y/o hipopotasemia

P450c17 enzyme catalyses two different reactions: the 17Alpha-hydroxylation of progesterone and pregnenolone, and segmenting the carbon 17-20 binding from the 17,20 lyase producing adrenal androgens. This enzyme is coded by the CYP17A1 gene. The case is presented of a 14 year old patient with delayed pubertal development and a high blood pressure for height and age. 46,XX karyotype. Hormonal studies highlighted hypergonadotropic hypogonadism, adrenal insufficiency and mineralocorticoid excess. Subsequent genetic studies showed a homozygous mutation in the CYP17A1 gene (c.753+G>A), not previously described, which is responsible for the pathophysiology of 17Alpha-hydroxylase deficiency. This entity is a rare form of congenital adrenal hyperplasia. The disease often goes unnoticed until adolescence or early adult life, and should be suspected in 46,XY individuals with ambiguous genitalia or 46,XX with delayed puberty associated with hypertension and/or hypokalaemia

[Congenital adrenal hyperplasia due to lack of 17α-hydroxylase: a report of a new mutation in the gene CYP17A1]. / Hiperplasia suprarrenal congénita debida a deficiencia de 17α-hidroxilasa: a propósito de una nueva mutación en el gen CYP17A1.

P450c17 enzyme catalyses two different reactions: the 17α-hydroxylation of progesterone and pregnenolone, and segmenting the carbon 17-20 binding from the 17,20lyase producing adrenal androgens. This enzyme is coded by the CYP17A1 gene. The case is presented of a 14 year old patient with delayed pubertal development and a high blood pressure for height and age. 46,XX karyotype. Hormonal studies highlighted hypergonadotropic hypogonadism, adrenal insufficiency and mineralocorticoid excess. Subsequent genetic studies showed a homozygous mutation in the CYP17A1 gene (c.753+G>A), not previously described, which is responsible for the pathophysiology of 17α-hydroxylase deficiency. This entity is a rare form of congenital adrenal hyperplasia. The disease often goes unnoticed until adolescence or early adult life, and should be suspected in 46,XY individuals with ambiguous genitalia or 46,XX with delayed puberty associated with hypertension and/or hypokalaemia.

Diferente expresividad de la mutacion Asn264LysfsX35 del gen GNAS en una familia afecta de pseudohipoparatiroidismo / Different expression of the Asn264LysfsX35 mutation of the GNAS gene in a family with pseudohypoparathyroidism

El pseudohipoparatiroidismo (PHP) comprende un grupo heterogéneo de enfermedades endocrinológicas que se caracterizan por la existencia de hipocalcemia, hiperfosfatemia y resistencia tisular a la hormona paratiroidea. Se distinguen diferentes formas de PHP. El PHP-Ia es la forma más frecuente y asocia resistencia hormonal múltiple, signos clínicos de osteodistrofia hereditaria de Albright (OHA) y mutaciones en el gen GNAS codificador de la proteína Gsα. El pseudoPHP (PPHP) asocia igualmente mutaciones en el gen GNAS pero cursa con OHA aislada sin anomalías endocrinas. Se presenta una familia con madre afecta de PPHP y dos hijas con PHP-Ia que comparten la misma mutación inactivadora en heterocigosis en el gen GNAS (Asn264LysfsX35). Se discute la diferente expresividad clínica así como el modelo de herencia dominante con impronta genética en el que el fenotipo de la descendencia está deteminado por el sexo del progenitor afecto (AU)

Pseudohypoparathyroidism (PHP) is a heterogeneous group of endocrine diseases characterised by hypocalcaemia, hyperphosphataemia and resistance to PTH. There are different forms of PHP. PHP-Ia is the most frequent form and shows multi-hormonal resistance, GNAS (Gsα) mutations and signs of Albright́s hereditary osteodystrophy (AHO). PseudoPHP (PPHP) have isolated AHO without hormonal resistance and it is also caused by GNAS mutations. We present a family that share the same inactivating GNAS mutation (Asn264LysfsX35); the mother being affected with PPHP and the two daughters with PHP-Ia. We discuss the different clinical phenotypes and the dominant mode of inheritance with genetic imprinting where the phenotype of the offspring depends on the sex of the parent affected (AU)

[Study of bone mass in patients with growth hormone deficiency]. / Estudio de la masa ósea en el déficit de hormona de crecimiento.

OBJECTIVES: To evaluate bone mineral density by radiogrametric study of metacarpal bone diameter and cortical thickness in patients with growth hormone deficiency (GHD) before and during treatment with growth hormone (GH). PATIENTS AND METHODS: We studied 92 children with GHD (60 boys and 32 girls) divided into two groups: group I: 66 previously untreated patients (42 boys and 24 girls) aged between 3 and 14 years old; group II: 66 patients (42 girls and 24 boys) treated with GH and with a mean age of 10.2 +/- 3.1 years at treatment onset. Bone mass was studied indirectly by radiogrametry; the bone diameter and cortical thickness of the 2nd-3rd and 4th metacarpal bones were measured with a magnifying glass. As reference standards we used the Spanish longitudinal growth and development study (Andrea Prader Center, Zaragoza) in children aged between 0.5 and 9 years and the Swiss longitudinal standards in children aged 10 years of age and older. Statistical significance was set at p < 0.05. RESULTS: Group I (spontaneous evolution): cortical thickness values were below the mean with statistically significant differences al 11, 12 and 13 years of age in girls and at 12, 13 and 14 years in boys. Bone diameter was diminished compared with controls in all the study periods and was significantly reduced at 8, 9, 10 and 11 years of age in girls and at 8, 10, 11, 12, 13 and 14 years in boys. Group II: (effect of GH treatment): cortical regression analysis showed a sharp increase in the first year of treatment with a subsequent moderate increase, which was statistically significant. Bone diameter showed a similar pattern with a significant increase which was more pronounced in the first period. CONCLUSIONS: Children with GHD have decreased bone mass before initiation of treatment and therefore show deficient acquisition of peak bone mass, which in normal conditions occurs during in the first 4-5 years of life and during adolescence. GH replacement therapy leads to recovery of bone mass, which is more pronounced in the first year of treatment and prevents the progressive reduction that appears in untreated patients. Therefore, GH treatment plays an important role in peak bone mass acquisition in children with GHD.

Estudio de la masa ósea en el déficit de hormona del crecimiento / Study of bone mass in patients with growth hormone deficiency

Objetivos. Evaluar la masa ósea con la medida de la cortical y el diámetro metacarpianos en pacientes con déficit de hormona de crecimiento (GH), antes y durante el tratamiento con GH. Pacientes y métodos. Se ha estudiado una población de 92 niños (60 varones, 32 mujeres) con déficit de GH, distribuidas en los siguientes grupos: grupo I, 66 pacientes (42 varones, 24 mujeres) que no habían recibido previamente tratamiento entre 3-14 años de edad; grupo II, 66 pacientes (42 varones, 24 mujeres) tratadas con GH, edad de inicio del tratamiento 10,2 6 3,1 años. La masa ósea se evaluó indirectamente por radiogrametría midiendo en la radiografía de la mano la cortical y el diámetro de 3 metacarpianos con una lupa de aumento. Como estándar de referencia se tomaron los propios españoles del estudio longitudinal del Centro Andrea Prader entre los 0,5 y los 9 años y los suizos de 10 años en adelante. La significación estadística p < 0,05. Resultados. Grupo I (evolución espontánea): la cortical evoluciona por debajo de la media y está disminuida significativamente a los 11, 12 y 13 años en las chicas y 12, 13 y 14 años en los chicos. El diámetro se encuentra disminuido en relación a los controles durante todo el período de observación y está disminuido significativamente a los 8, 9, 10 y 11 años en las chicas y a los 8, 10, 11, 12, 13 y 14 años en los chicos. Grupo II (impacto del tratamiento con GH): la cortical en su ecuación de regresión muestra un incremento brusco durante el primer año de tratamiento y a partir de allí mantiene un crecimiento moderado; estadísticamente es significativo. El diámetro sigue una evolución similar, aumenta de manera significativa de forma más marcada durante el primer período. Conclusiones. Los niños con déficit de GH, presentan un descenso de la masa ósea antes de iniciar el tratamiento, y por lo tanto, una adquisición deficiente del pico de masa ósea, que ocurre normalmente durante los primeros 4 y 5 años y durante la adolescencia. El tratamiento sustitutivo con GH provoca una recuperación de la masa ósea, más intensa durante el primer año de tratamiento y evita el deterioro progresivo que se aprecia en los pacientes no tratados y así desempeña un papel importante en la adquisición del pico de masa ósea en los niños con déficit de GH

Objectives. To evaluate bone mineral density by radiogrametric study of metacarpal bone diameter and cortical thickness in patients with growth hormone deficiency (GHD) before and during treatment with growth hormone (GH). Patients and methods. We studied 92 children with GHD (60 boys and 32 girls) divided into two groups: group I: 66 previously untreated patients (42 boys and 24 girls) aged between 3 and 14 years old; group II: 66 patients (42 girls and 24 boys) treated with GH and with a mean age of 10.2 6 3.1 years at treatment onset. Bone mass was studied indirectly by radiogrametry; the bone diameter and cortical thickness of the 2nd-3rd and 4th metacarpal bones were measured with a magnifying glass. As reference standards we used the Spanish longitudinal growth and development study (Andrea Prader Center, Zaragoza) in children aged between 0.5 and 9 years and the Swiss longitudinal standards in children aged 10 years of age and older. Statistical significance was set at p < 0.05. Results. Group I (spontaneous evolution): cortical thickness values were below the mean with statistically significant differences al 11, 12 and 13 years of age in girls and at 12, 13 and 14 years in boys. Bone diameter was diminished compared with controls in all the study periods and was significantly reduced at 8, 9, 10 and 11 years of age in girls and at 8, 10, 11, 12, 13 and 14 years in boys. Group II: (effect of GH treatment): cortical regression analysis showed a sharp increase in the first year of treatment with a subsequent moderate increase, which was statistically significant. Bone diameter showed a similar pattern with a significant increase which was more pronounced in the first period. Conclusions. Children with GHD have decreased bone mass before initiation of treatment and therefore show deficient acquisition of peak bone mass, which in normal conditions occurs during in the first 4-5 years of life and during adolescence. GH replacement therapy leads to recovery of bone mass, which is more pronounced in the first year of treatment and prevents the progressive reduction that appears in untreated patients. Therefore, GH treatment plays an important role in peak bone mass acquisition in children with GHD

[Study of bone mass in Turner syndrome]. / Estudio de la masa ósea en el síndrome de Turner.

OBJECTIVES: To evaluate bone mass in patients with Turner syndrome by measuring metacarpal cortical thickness and bone diameter before and after treatment with oxandrolone, growth hormone (GH) and estrogens. PATIENTS AND METHODS: We studied 42 girls with Turner syndrome divided into the following groups: group I: 31 patients aged between 3 and 15 years who were not treated before the study; group II: 15 patients treated with GH at start ages of between 5.2-14.8 years; group III: 17 patients treated with oxandrolone at start ages of between 5.3 and 15.2 years; group IV: 17 patients treated with estrogens and divided in different subgroups: IVa: seven patients treated with GH and estrogens at start ages of between 6.1 and 12.9 years; IVb: five patients treated with oxandrolone and estrogens at start ages of between 13.4 and 17.4 years, and IVc: five patients treated with oxandrolone, GH and estrogens at start ages of between 10.3 and 16.1 years. Bone mass was evaluated by a radiogrammetric method that measures the cortical thickness and bone diameter of three metacarpal bones with a magnifying glass. The results are expressed in SD according to Spanish longitudinal reference standards (Andrea Prader Center of Growth and Development) from 0.5 to 9 years of age and to Swiss standards from the age of 10 years onwards. Statistical significance was set at p < 0.05. RESULTS: Group I (spontaneous development): cortical development was below the mean and was significantly diminished at the ages of 9, 13 and 14 years; bone diameter was decreased in relation to controls throughout the study period; group II (impact of GH treatment): cortical thickness showed a nonsignificant increase of 0.6 SD from baseline to years 3-4 of treatment and diameter increased by 0.5 SD from baseline to year 4 of treatment; group III (impact of oxandrolone): cortical thickness increased from -0.8 SD before treatment to 0.0 SD at years 2 and 3 of treatment; bone diameter increased from -1.5 SD at baseline to -1 SD at 3 years of treatment; group IV (impact of treatment with estrogens); IVa: cortical thickness and bone diameter increased; IVb: cortical thickness increased but bone diameter was unchanged; IVc: both cortical thickness and bone diameter increased. CONCLUSIONS: The results of this study show that cortical thickness and bone diameter are decreased in untreated girls with Turner syndrome; cortical thickness was significantly decreased at the ages of 9, 13 and 14 years, while bone diameter was diminished at all ages, suggesting the presence of osteopenia in these patients. GH treatment produced a nonsignificant increase in cortical thickness and bone diameter. Oxandrolone treatment showed a positive effect on bone mass during the first few years of therapy. Because of the small number of patients, conclusions cannot be reached on the effectiveness of estrogens.

Estudio de la masa ósea en el síndrome de Turner / Study of bone mass in Turner syndrome

Los cuidados paliativos son esenciales en las unidades de cuidados intensivos pediátricos (UCIP). Dada la frecuencia de la muerte en las UCIP y la presencia de condiciones médicas que amenazan la vida del niño mientras este está ingresado, existe una necesidad de que el pediatra esté preparado para proporcionar cuidados paliativos, con independencia de los tratamientos curativos. En este artículo se revisan algunos temas, como el proceso de toma de decisiones en la UCIP, las necesidades psicosociales del personal sanitario y la vulnerabilidad al burnout, y los sentimientos y actitudes del personal sanitario ante la muerte del niño. Se proporcionan recomendaciones sobre cómo actuar cuando un niño muere, para concertar reuniones post mortem con los padres y para llevar a cabo el seguimiento del duelo, y se sugieren estrategias que pueden ayudar a afrontar las múltiples pérdidas que experimenta el pediatra de la UCIP

Palliative care is essential in the pediatric intensive care unit (PICU). Because of the mortality rates and the presence of life-threatening conditions in children admitted to the PICU, pediatricians must be prepared to provide palliative care independently of cure-directed therapies. The present article reviews certain issues, including the decision- making process in the PICU, psychosocial needs and susceptibility to burnout among PICU staff, and the emotions and attitudes of the staff when a child dies. We provide some guidelines on how to act when a child dies, how to meet with parents after the child’s death and how to follow- up parental bereavement. Strategies that can help PICU pediatricians to cope with the numerous loses they experience are suggested

[Hormonal reference values for adrenocortical function in healthy children from Zaragoza]. / Valores de referencia hormonales de función corticosuprarrenal en niños sanos zaragozanos.

OBJECTIVE: Estimation of reference values for basal serum concentrations of adrenocorticotropic hormone (ACTH), cortisol, 11-deoxycortisol, 17-OH-progesterone (17-OHP), plasma renin activity (PRA), aldosterone, -4-androstendione ( 4A) and dehydroepiandrosterone sulphate (DHA-S) in healthy children from Zaragoza. METHODS: Reference population were healthy children aged 0 to 14, with normal weight and height, living in the metropolitan area of Zaragoza (Spain). It is a transversal study. Reference values and ranges for ACTH, cortisol, 11-deoxycortisol, 17-OHP, PRA, aldosterone, 4A and DHA-S were estimated, and changes in concentrations were analyzed in relation to age, sex and puberal stage. RESULTS: Reference values have been classified by puberal stage and age in eleven groups for every sex: Tanner I (umbilical cordon, 3 days, 4-30 days, 1-6 months, 6 months-4 years, 4-7 years, 7-10 years, 10-14 years), Tanner II, Tanner III and Tanner IV-V. Sex did not influence ACTH, cortisol, 17-OHP and PRA concentrations, and there are punctual differences in 11-deoxycortisol, aldosterone, 4A and DHA-S levels. 17-OHP, 11-deoxycortisol and aldosterone concentrations significantly decreased from birth to 6 months-4 years and subsequently kept steady. The maximal concentration of ACTH, and ARP in blood cord significantly decreased until the period 6 months-4 years, and subsequent differences among different age groups, and between prepuberal and puberal groups are scarce. The highest concentration of 4A and DHA-S were observed in blood cord and third day of life, decreased until the lowest level in 6 months-4 years and progressively increased with age in prepuberty, and between prepuberty and puberty. The lowest concentration of cortisol was detected in 4-30 days, increased until 6 months-4 years and kept steady along the prepuberty and puberty. CONCLUSION: It is necessary that every population establish own reference values for ACTH, cortisol, 11-deoxycortisol, 17-OHP, PRA, aldosterone, 4A and DHA-S during infancy, childhood and adolescence, according to age, sex and puberal stage.

Valores de referencia hormonales de función corticosuprarrenal en niños sanos zaragozanos / Hormonal reference values for adrenocortical function in healthy children from Zaragoza (Spain)

Objetivo : Estimar los valores de referencia de las concentraciones séricas/plasmáticas basales de hormona corticotropa (ACTH), cortisol, 11-desoxicortisol, 17-OH-progesterona (17-OHP), actividad renina plasmática (ARP), aldosterona, (4-androstendiona (4A) y sulfato de dehidroepiandrosterona (DHA-S) en niños sanos zaragozanos. Métodos La población de referencia de este estudio transversal han sido niños sanos de 0-14 años, con peso y talla normales, residentes en el área urbana de Zaragoza. Se han estimado los valores e intervalos de referencia de ACTH, cortisol, 11-desoxicortisol, 17-OHP, ARP, aldosterona, 4A y DHA-S. Resultados Los valores de referencia se han clasificado por estadios puberales y edad, en 11 grupos para cada sexo: Tanner I (cordón umbilical, 3 días, 4-30 días, 1-6 meses, 6 meses-4 años, 4-7 años, 7-10 años, 10-14 años), Tanner II, Tanner III y Tanner IV-V. No existen diferencias entre sexos para ACTH, cortisol, 17-OHP y ARP, y las diferencias son puntuales para 11-desoxicortisol, aldosterona, 4A y DHA-S. Las concentraciones de 17-OHP, 11-desoxicortisol y aldosterona disminuyen significativamente con la edad desde el nacimiento hasta el período 6 meses-4 años y posteriormente se estabilizan. Las concentraciones de ACTH y ARP de cordón umbilical descienden significativamente hasta el período 6 meses-4 años, con escasas diferencias puntuales entre edades prepuberales y entre prepúberes y púberes. Las concentraciones máximas de 4A y DHA-S se aprecian en cordón y al tercer día, disminuyen hasta el nivel mínimo del período 6 meses-4 años y aumentan progresivamente con la edad en prepubertad y entre prepúberes y púberes. La concentración mínima de cortisol en el grupo 4-30 días aumenta hasta el período 6 meses-4 años en que se alcanzan los niveles estables de la prepubertad y pubertad. Conclusiones Las diferencias en los valores de referencia de ACTH, cortisol, 11-desoxicortisol, 17-OHP, ARP, aldosterona, 4A y DHA-S durante la infancia, niñez y adolescencia hacen necesario que cada población establezca sus propios valores en función de edad, sexo y estadio puberal, y para cada método de cuantificación utilizado (AU)

[Reference values of FSH, LH, total testosterone, free testosterone, 17-beta-estradiol and SHBG in healthy children in Zaragoza]. / Valores de referencia de FSH, LH, testosterona total, testosterona libre, 17-beta-estradiol y SHBG en niños sanos zaragozanos.

OBJECTIVE: Our purpose was to estimate reference values for basal serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, free testosterone, 17-beta-estradiol (E2) and sex steroid binding globulin (SHBG) in healthy children of Zaragoza. PATIENTS AND METHODS: The reference population consisted of healthy children between 0 and 14 years of age with normal weight and height and living in the metropolitan area of Zaragoza (Spain). It was a transversal study. Basal serum concentrations of FSH, LH and SHBG were measured by immunoradiometric assay. Basal serum concentrations of total testosterone, free testosterone and E2 were analyzed by radioimmunoassay. Reference values and ranges were estimated according to the recommendations of the International Federation of Clinical Chemistry. RESULTS: Reference values have been classified by age, sex and pubertal stage. Serum concentrations of FSH, LH, total testosterone, free testosterone and E2 increase during the first six months, remain low in infancy and rise during puberty. All of these concentrations showed marked differences according to sex. Serum SHBG levels are influenced by age and during puberty by sex. CONCLUSIONS: Differences in reference values for gonadotrophins, sex steroids and SHBG during infancy, childhood and adolescence makes it necessary for every population to establish their own reference values according to age, sex and pubertal stage.

[Reference values for IGF-I, IGFBP-1, IGFBP-3 and osteocalcin in healthy children in Zaragoza]. / Valores de referencia de IGF-I, IGFBP-1, IGFBP-3 y osteocalcina en niños sanos zaragozanos.

OBJECTIVE: Our aim was to estimate reference values for basal serum concentrations of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-1, IGFBP-3 and osteocalcin in healthy children of Zaragoza. PATIENTS AND METHODS: The reference population consisted of healthy children between 0 and 14 years of age with normal weight and height and living in the metropolitan area of Zaragoza (Spain). It was a transversal study. Immunoradiometric assays were used to determine basal serum IGF-I, IGFBP-1, IGFBP-3 and osteocalcin concentrations. Reference values and ranges were estimated according to the recommendations of the International Federation of Clinical Chemistry. RESULTS: Reference values have been classified according to age, sex and pubertal stage. IGF-I, IGFBP-1, IGFBP-3 and osteocalcin concentrations differ during the pubertal period according to age. There are differences in IGF-I, IGFBP-3 and osteocalcin levels between prepuberty and puberty and differences in IGF-I and osteocalcin levels among the pubertal stages. Sex did not influence IGF-I or IGFBP-1 concentrations and there were punctual differences in IGFBP-3 and osteocalcin levels between girls and boys. CONCLUSIONS: Sincere there are differences in IGF-I, IGFBP-1, IGFBP-3 and osteocalcin reference values according to age, sex, pubertal stage and immunoassays, it is necessary to establish the reference values for each population and laboratory in accordance with these parameters.

[Reference values for thyroid hormones, thyrotropin and thyroglobulin in healthy children of Zaragoza]. / Valores de referencia de hormonas tiroideas, tirotropina y tiroglobulina en niños sanos zaragozanos.

OBJECTIVE: The purpose of this study was to estimate the basal serum concentration reference values for total T3 (T3), total T4 (T4), free T4 (FT4), thyrotropin (TSH) and thyroglobulin (Tg) in healthy children of Zaragoza. PATIENTS AND METHODS: Healthy children aged 0 to 14, with normal weight and height, living in the metropolitan area of Zaragoza (Spain) were the reference population of this transversal study. Basal serum concentrations of T3, T4 and FT4 were measured by radioimmunoassay and of TSH and Tg by immunoradiometric assay. Reference values and ranges were estimated according to the recommendations of the International Federation of Clinical Chemistry. RESULTS: Reference values have been classified according to age, sex and pubertal stage. There are differences in T3, T4, FT4 TSH and Tg concentrations during the prepubertal period according to age, but not to sex, and between the prepubertal period and puberty. Sex and Tanner stage influence T3 and T4 concentrations during puberty. CONCLUSIONS: Since there are differences in T3, T4, FT4, TSH and Tg reference values according to age, sex, pubertal stage and immunoassays, it is necessary to establish reference values for every population and laboratory in accordance with these parameters.

[Bone mass evolution in patients with precocious and advanced puberty treated with LHRH analogs]. / Evolución de la masa ósea de pacientes con pubertad precoz y pubertad adelantada tratados con análogos de LHRH.

OBJECTIVE: Our aim was to know the long-term effects of treatment with LHRH analogs on the bone mass of patients with precocious or advanced puberty. PATIENTS AND METHODS: Forty-six patients (11 boys and 35 girls) received a-LHRH throughout a 2-year period. The diagnoses were precocious or advance puberty alone or associated to other pathologies. The bone mass was indirectly estimated by measuring the cortical thickness (CT) and the metacarpal diameter (BD) of the 2nd, 3rd, and 4th metacarpals, taking as a reference values the results of the longitudinal Aragonese study of the "Andrea Prader" Center. RESULTS: The CT was 1.3 SD at the beginning and decreased to 0.3 SD (p < 0.002) by the end of therapy and continuing losing to reach 0.1 SD after withdrawal. The BA decreased from 0.8 SD to 0.7 SD (p < 0.0002) and continued decreasing to reach 0.5 SD after withdrawal (p < 0.05). The BD went from -0.64 to -0.62 and to -0.9 SD (p < 0.04) after withdrawal. The longitudinal study of the same 18 cases gave similar results. No significant difference was found between sexes. CONCLUSIONS: In precocious or advance puberty, the bone age and the cortical thickness are increased. After two years of treatment with a-LHRH both decreased significantly and stabilized one year after its suppression. The BD does not change during the treatment, but continues losing value thereafter. This loss of bone mass, not well known in this pediatric situation, is probably related to estrogen deprivation and needs the attention of the physician in order to take possible preventative measures.

[Reduced erythrocyte glutathione and urinary thioethers in children undergoing treatment with paracetamol]. / Glutation reducido eritrocitario y tioeteres urinarios en niños tratados con paracetamol.

In the present study the objective was to evaluate whether therapeutic doses of paracetamol in children has an impact on the concentrations of erythrocyte reduced glutathione (GSH) and urinary thioethers (UT), used as indicators of internal exposure to electrophiles, as well as to establish the association between the two parameters. The population sample consisted of 40 children. From each patient, two blood and two urine samples were taken. Sample A was obtained one week after completing treatment and sample B was taken two hours after taking the last dose of paracetamol. The total group was divided into three subgroups according to age: subgroup I from 9 to 8 months, subgroup II from 19 to 72 months and subgroup III from 73 to 132 months. The concentrations of GSH and UT have been determined in blood and urine, respectively. The results demonstrate that after treatment with paracetamol for a period of days (3.57 +/- 0.86) an elevation in GSH was produced in the total group (Z = -2.40, p < 0.05). A significant and positive association (r = 0.52) existed between the GSH and UT values. No correlation was observed either between plasma levels, or the duration of treatment and the effects observed on GSH and UT.