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ABSTRACT: 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 (Gs(α)) 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.
Anales de Pediatría 12/2010; 74(2):116-21. · 0.77 Impact Factor
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ABSTRACT: Traditionally, it has been assumed that intellectual development in children with growth hormone deficiency (GHD) is distributed between ranges of a normal population based on the observation that it does not differ substantially from that of children of the same age. Nevertheless, few studies have investigated this assumption. This Spanish Collaborative study was prospectively planned with two main purposes: to study a possible influence of GHD on intelligence quotient (IQ), personality traits and adaptative capacity and to study the evolution of these parameters during substitution therapy with growth hormone (GH). Although the overall intellectual ability of children with GHD is comparable to that of a normal reference population, some areas such the motor-component scale (evaluated by McCarthy test) and performance IQ (evaluated by WISC-R) were below the mean at the beginning of the study, showing significant improvement during therapy. Emotional adjustment (normal at study start) also improved significantly during treatment. Females showed better adjustment capacity before and during GH therapy. Longer studies with an increased number of cases are needed to confirm these effects of GHD and its treatment in children.
Pediatric endocrinology reviews: PER 06/2010; 7(4):328-38.
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ABSTRACT: 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).
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.
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.
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.
Anales de Pediatría 09/2005; 63(3):219-23. · 0.77 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Anales de Pediatría 05/2005; 62(5):441-9. · 0.77 Impact Factor
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ABSTRACT: Mutations in the GHRH receptor (GHRHR) gene (GHRHR) are emerging as a common cause of familial isolated growth hormone deficiency (IGHD) type IB. The use of gonadotropin-releasing hormone (GnRH) analogues has been advocated as a tool to delay puberty in patients with isolated GH deficiency (IGHD), allowing longer time for the beneficial effect of exogenous human GH (hGH) treatment on growth. We describe two male siblings with IGHD due to a homozygous missense GHRHR mutation who, because they were started on hGH therapy at different ages, presented with different height SDS at the onset of puberty and therefore had different predicted target heights. The shorter brother was treated with GnRH analogue plus hGH for 3 years, whereas the other brother received only hGH. Despite different predicted heights at the onset of puberty, they attained similar final heights. We conclude that in patients with IGHD, GnRH analogue treatment should be considered to delay puberty and obtain a maximal growth response if hGH treatment is started in late childhood and the predicted height at puberty onset is below the genetic target.
Journal of pediatric endocrinology & metabolism: JPEM 06/2004; 17(5):793-800. · 0.88 Impact Factor
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ABSTRACT: Congenital adrenal hyperplasia is a general term applied to several disorders caused by inherited recessive defects of cortisol synthesis. The most common form is 21-hydroxylase deficiency, accounting for 95% of cases. The classical forms have an incidence of one in 15,000 and the non-classical forms about one in 1,000. The classical or severe phenotype presents in the newborn period or early infancy with virilization and adrenal insufficiency, with or without salt-losing; the non-classical or mild phenotype presents in late childhood or early adulthood with signs of hyperandrogenism. This wide range of clinical expression is explained by genetic variation. Although there is a certain amount of genotype-phenotype correlation, discrepancies have been described. During the last 30 years there has been a substantial improvement in diagnosis and treatment of this disease, and patients with CAH now reach adulthood. Treatment of this condition is intended to reduce excessive corticotropin secretion and replace glucocorticoids and mineralocorticoids as physiologically as possible. Clinical management is often complicated by periods of inadequately treated hyperandrogenism, iatrogenic hypercortisolism, or both. Long-term consequences in adult life may include short stature, obesity, diminished bone mass, gonadal dysfunction with low fertility rates and psychosexual dysfunction in females. New treatment approaches are under investigation, such as the use of anti-androgens, inhibitors of estrogen production and adrenalectomy for severely resistant cases.
Journal of pediatric endocrinology & metabolism: JPEM 04/2004; 17 Suppl 3:411-22. · 0.88 Impact Factor
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ABSTRACT: The possible impact of IUGR on the intellectual outcome of children born with IUGR gives special relevance to this condition. In order to determine the psychomotor and intellectual development of such children, we analyzed the evolution of 60 children through appropriate tests, along the years, and the possible influence of two factors, the socio-economic status of the family, and whether or not there was catch-up growth. Our results show a negative impact of IUGR on the intellectual outcome of these children, independent of catch-up growth, although those with catch-up growth showed better evolution. The socio-economic status plays a limited role only at older age. Those children followed longitudinally for 1 year did not show any amelioration of their IQ.
Journal of pediatric endocrinology & metabolism: JPEM 04/2004; 17 Suppl 3:457-62. · 0.88 Impact Factor
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A Ferrández Longás
Journal of pediatric endocrinology & metabolism: JPEM 04/2004; 17 Suppl 3:381-4. · 0.88 Impact Factor
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ABSTRACT: We studied the rate of apoptosis in the placental tissue of pregnancies complicated with intrauterine growth retardation (IUGR) and compared it with the results obtained in normal placentas. Our results clearly demonstrate a strongly increased rate of apoptosis in placentas of children born with IUGR, suggesting severe placental dysfunction. The significance of these findings needs further study.
Journal of pediatric endocrinology & metabolism: JPEM 04/2004; 17 Suppl 3:451-6. · 0.88 Impact Factor
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ABSTRACT: To investigate the possibility of altered gene expression of growth factors in prenatal growth retardation, we assessed expression of the genes for insulin-like growth factor-I (IGF-I) and epidermal growth factor receptor (EGFR) by RT-PCR from human placentas at term delivery in two groups: appropriate for gestational age (AGA) and pregnancies complicated with IUGR. The placentas from IUGR gestations showed reduced IGF-I expression with a significance of p = 0.008, whereas we did not find any significant differences in EGFR gene expression.
Journal of pediatric endocrinology & metabolism: JPEM 04/2004; 17 Suppl 3:445-50. · 0.88 Impact Factor
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Journal of pediatric endocrinology & metabolism: JPEM 01/2004; 17(2):451. · 0.88 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the physical condition of young adults with childhood-onset growth hormone deficiency (GHD) before and after 6 months of hGH therapy. Ten men and three women, aged 22.3 +/- 3.3 years, previously treated with hGH for 8.6 +/- 4.07 years at a dose of 0.5 IU/kg/week with a minimun of 2.5 years without treatment at the time of study, were studied. Nine patients presented isolated GHD and four patients had combined pituitary hormone deficiencies; they were treated with hGH at a dosage of 0.125 IU/kg/week for the first month and 0.25 IU/kg/week for the following 5 months. The tests performed were: exercise test, heart rate, rating of perceived exertion, blood lactate analysis, jump test and hand grip. Body composition was also analyzed using Holtain Body Analysis. Skinfold thickness was measured at four sites (triceps, biceps, subscapular and suprailiac). After 6 months of treatment a significant increase in lean body mass (42.0 +/- 7.72 to 46.2 +/- 8.01 kg, p = 0.004) and decrease in fat mass (19.6 +/- 10.01 to 16.1 +/- 10.79 kg, p = 0.01) were observed. The initial physical condition of these patients was lower than expected, and improved after treatment with an increase in maximum oxygen consumption from 2.0 +/- 1.2 to 2.33 +/- 0.68 l x min(-1) (p = 0.01). Maximum heart rate increased significantly from 189 +/- 14.8 to 193 +/- 11.7 beats x min(-1) (p = 0.03). No modifications were observed in anaerobic threshold (4 mmol x l(-1)). Only slight, non-significant increases were observed in jump and strength tests. We conclude that a) adults with childhood-onset growth hormone deficiency present a deficient physical condition and lower than expected for age and sex; b) this condition improves after 6 months of treatment, particularly in the aerobic aspect; c) changes observed in strength tests were discrete and of little significance; and d) the increase observed in lean body mass plays an important role in these changes. Further studies investigating GH action on maximum oxygen consumption are required, once its basic mechanism of action has been determined, either in the heart or peripheral factors.
Journal of pediatric endocrinology & metabolism: JPEM 02/2003; 16(1):27-34. · 0.88 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Anales espanoles de pediatria 03/2000; 52(2):106-15.
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ABSTRACT: 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.
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.
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.
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.
Anales espanoles de pediatria 12/1999; 51(5):499-504.
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ABSTRACT: 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.
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.
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.
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.
Anales espanoles de pediatria 11/1999; 51(4):361-8.
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ABSTRACT: 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.
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.
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.
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.
Anales espanoles de pediatria 09/1999; 51(2):167-74.
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ABSTRACT: 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.
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.
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.
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.
Anales espanoles de pediatria 09/1999; 51(2):159-66.
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ABSTRACT: Constitutional delay in growth and puberty (CDGP) is one of the principal causes of consultation due to short height. Frequently familial short stature is associated with the CDGP. The predicted final height is reached in the majority of the cases but some individuals do not achieve their target height. Poor growth, especially during the pubertal years, as well as a short or growth delayed mother are some of the negative factors for final outcome. Some prepubertal children show a transient diminished GH secretion that normalizes during puberty. Therapy with hGH or oxandrolone increases growth velocity but does not ameliorate final height. The psychosocial situation of the children is the most important condition to treat with testosterone, estrogens or oxandrolone. In view of the results hGH should not be administered routinely to these cases. It remains open which children could benefit from hGH therapy.
Journal of pediatric endocrinology & metabolism: JPEM 07/1996; 9 Suppl 3:345-57. · 0.88 Impact Factor
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