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PURPOSE: Little attention has been directed towards examining the impact of predictors on change in health-related quality of life (HRQOL) within the course of growth hormone (GH) treatment in pediatric short stature. We aimed to assess changes in HRQOL and its sociodemographic, clinical and psychosocial predictors in children and adolescents diagnosed with growth hormone deficiency (GHD), and born short for gestational age (SGA) before and 12-month after start of GH treatment from the parents' perspective. Results were compared with an untreated group with idiopathic short stature (ISS). In this prospective multicenter study, 152 parents of children/adolescents (aged 4-18 years) provided data on their children's HRQOL at baseline and at 12-month follow-up. METHOD: Repeated-measures multivariate analyses of covariance were performed to examine parent-reported HRQOL changes from baseline to 1-year after treatment and hierarchical linear regressions to identify the predictors of HRQOL changes. RESULTS: Results showed that parents of children that were treated with GH report an increase in their children's HRQOL after 1 year. Changes in HRQOL were mostly explained by psychosocial predictors followed by sociodemographic and clinical variables. Specifically, the diagnosis SGA significantly predicted a greater increase in parent-reported HRQOL. Furthermore, a lower caregiving burden significantly predicted a decrease in parent-reported HRQOL. CONCLUSION: In conclusion, a substantial percentage of explained variance in HRQOL relates to psychosocial and sociodemographic predictors. However, there appears to be other important factors that are predictors of HRQOL, which need to be determined in large, population-based samples.
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Enanismo Hipofisario/psicología , Hormona de Crecimiento Humana/administración & dosificación , Padres/psicología , Calidad de Vida , Encuestas y Cuestionarios/estadística & datos numéricos , Adolescente , Estatura , Niño , Preescolar , Enanismo Hipofisario/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Estudios Prospectivos , PsicometríaRESUMEN
BACKGROUND: 21-Hydroxylase deficient (21-OHD) classic congenital adrenal hyperplasia (CAH) is a potentially lethal inherited endocrine disorder. It is included in many neonatal screening programs to prevent morbidity and mortality from salt-wasting and to reduce long-term health problems. This paper presents a population-based evaluation of CAH screening quality and outcome in Bavaria between 1999 and 2011 including long-term follow-up of patients. METHODS: Screening process quality, clinical complications during the neonatal period, treatment and development of patients up to the age of 4 years were analysed. RESULTS: Among 1 420 102 screened infants, 114 cases of 21-OHD classic CAH were detected (prevalence 1:12 457). Mean age at start of treatment was 7 days. However, in 29 cases (25.4%), age at start of treatment was 12 days or more. The frequency of neonatal salt-wasting increased with age at start of treatment, but all neonatal salt-wasting episodes and crises were managed successfully. Up to the age of 4 years, developmental assessment of the CAH cohort yielded normal results. DISCUSSION: Epidemiological and screening effectiveness results are in keeping with other publications. For the most part, screening process times were compliant with guidelines. The Bavarian CAH screening and tracking system proved successful, but there were process delays and complications which might have been avoidable. The outcome supports the benefits of CAH screening, but further research is necessary to increase CAH screening effectiveness and to evaluate long-term effects.
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Hiperplasia Suprarrenal Congénita/diagnóstico , Tamizaje Neonatal , Hiperplasia Suprarrenal Congénita/epidemiología , Hiperplasia Suprarrenal Congénita/terapia , Factores de Edad , Preescolar , Estudios Transversales , Femenino , Alemania , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Garantía de la Calidad de Atención de SaludRESUMEN
BACKGROUND: The German study group for quality assurance in pediatric endocrinology and the University of Ulm have established a software ("Hypo Dok") for the documentation of longitudinal data of patients with congenital primary hypothyroidism (CH). Aim of this study was to analyse the long-term follow-up of patients with CH and to compare treatment with current guidelines. METHODS/PATIENTS: Anonymised data of 1,080 patients from 46 centres were statistically analysed. RESULTS: Newborn screening result was available at a mean age of 7.3 days. Confirmation of the diagnosis was established at 8.4 days and therapy was started at 11 days. The average screening TSH was 180.0 mIU/L. During the first 3 months mean levothyroxine (LT4) dose was 10.7 µg/kg/day or 186.0 µg/m²/day. Weight-, BMI- and height-SDS did not differ significantly from the normal population. Only 25% of the patients (n=262) underwent formal EQ/IQ-testing. Their average IQ was 98.8 ± 13.2 points. DISCUSSION: In Germany screening, confirmation and start of treatment of CH are within the recommended time frame of 14 days. Initial LT4-doses are adequate. The auxological longterm outcome of young CH patients is normal. The implementation of standardized IQ testing has to be improved in routine patient care. CONCLUSION: Longitudinal data of patients with CH was analysed and compared to current guidelines. Confirmation and start of treatment are according to the recommendations. However standardised IQ testing requires improvement.
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Hipotiroidismo Congénito/tratamiento farmacológico , Cuidados a Largo Plazo , Sistema de Registros , Programas Informáticos , Tiroxina/uso terapéutico , Hipotiroidismo Congénito/diagnóstico , Femenino , Alemania , Adhesión a Directriz , Humanos , Lactante , Recién Nacido , Inteligencia/efectos de los fármacos , Estudios Longitudinales , Masculino , Tamizaje Neonatal , Garantía de la Calidad de Atención de Salud , Resultado del TratamientoRESUMEN
Over the last years concerns have been raised about the health effects particularly on young climbers due to the observation of short stature with low body weight and body fat in sports climbers. The aim of this study was to investigate anthropometric and hormonal data for climbers of the German Junior national team. 16 climbers were compared with 14-age matched nonclimbers with respect to several anthropometric variables, leptin level, and climbing characteristics. Height, weight and body mass index (BMI) standard deviation scores (SDS) for boys were not significantly different from the controls, whereas girls had significantly lower SDS-values for weight and BMI. In comparison with the control group boys and girls had a lower skinfold thickness. The leptin values were lower than the calculated leptin levels but only reached significance for the girls. The young athletes of the GJNT were neither of short stature nor thin when compared with a physically active control group. The low body fat in boys and girls was within expected limits. The lower leptin levels might be attributed to a decrease in total body fat.
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Pesos y Medidas Corporales , Ghrelina/sangre , Leptina/sangre , Montañismo/fisiología , Adolescente , Adulto , Estatura , Índice de Masa Corporal , Peso Corporal , Dieta , Femenino , Alemania , Humanos , Masculino , Factores Sexuales , Grosor de los Pliegues Cutáneos , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Adulto JovenRESUMEN
INTRODUCTION: Irradiation of brain tumors (BT) in children can lead to the loss of pituitary function, predominantly manifesting as deficiencies in GH and ACTH. OBJECTIVE: To assess the incidence and nature of pituitary deficiency in relation to initial tumor location in children after radiotherapy of BT. METHODS: Twenty survivors (16 males and 4 females) of radiation-treated BT aged 1.4-10.9 (median 3.6) yr at diagnosis were studied, 10 with supratentorial and 10 with infratentorial BT. Radiation doses to the hypothalamus- pituitary (HP) area ranged from 30 to 54 (median 45) Gray. Follow-up was 9.4-16.9 (median 12.2) yr. Basal pituitary hormone levels were measured every 6 months. When growth failure became evident or pituitary deficiency was suspected, provocation tests of the HP axis were performed to assess GH, ACTH, and TSH function. RESULTS: GH deficiency (GHD) developed in 17/20 (85%) children. In 10 patients, it occurred 4 yr after radiotherapy and in 2, 11 and 12 yr after radiotherapy. Six (30%) patients developed secondary hypothyroidism and 4 (20%) developed ACTH deficiency. Precocious puberty occurred in 2 girls. The course of development and the severity of hormone deficiencies were similar for supratentorial and infratentorial tumors. CONCLUSION: The major hormonal effect of BT irradiation in children is GHD, which may sometimes take more than 10 yr to manifest. We confirm findings by others that ACTH insufficiency occurs less frequently in children than reported for adults. Tumor location has no prognostic significance regarding the loss of HP function.
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Hormona Adrenocorticotrópica/deficiencia , Neoplasias Encefálicas/radioterapia , Irradiación Craneana , Hormona de Crecimiento Humana/deficiencia , Hipófisis/efectos de la radiación , Traumatismos por Radiación/etiología , Hormona Adrenocorticotrópica/metabolismo , Niño , Preescolar , Femenino , Hormona de Crecimiento Humana/metabolismo , Humanos , Hipotálamo/efectos de la radiación , Hipotiroidismo/etiología , Lactante , Masculino , Hipófisis/metabolismo , Traumatismos por Radiación/metabolismo , Estudios RetrospectivosRESUMEN
Children with chronically endocrine diseases should be treated as young adults by adult endocrinologists. To optimize the transfer from the pediatric to adult endocrinologist, the model of a common transition clinic has been developed. Within this setting it should be possible to exchange experiences, extend the knowledge and understanding of the disease with the other side, and to provide for the patient an optimal outpatient care. This model, however, has only been sporadically realized to date. To set an example for the problems of the transition into adult endocrinology, we used two different endocrine diseases, the classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency, and the childhood-onset growth hormone deficiency. Specific problems for this transfer to adult care are the fixation of the patients to their pediatricians and the lack of comprehension in the need of a long term and continuous therapy. The consequence is a dramatic impairment in the quality of the therapy.
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Servicios de Salud del Adolescente/tendencias , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/terapia , Atención a la Salud/tendencias , Transición de la Salud , Medicina Interna/tendencias , Síndrome de Laron/diagnóstico , Síndrome de Laron/terapia , Adolescente , Adulto , Alemania , Necesidades y Demandas de Servicios de Salud/tendencias , Humanos , Pediatría/tendencias , Adulto JovenRESUMEN
BACKGROUND: Information about treatment of adult male patients with congenital adrenal hyperplasia (CAH) and testicular adrenal rest tumors (TART) is scarce. Diagnostic and therapeutic guidelines do not exist. The aim of this review is to evaluate the current state of therapeutic options in adult male patients with CAH. METHODS: We performed an extensive search of the literature of the last 10 years by using PubMed/MEDLINE. RESULTS: The aims of treatment in adult male patients with CAH are prevention of adrenal crisis and TART, improvement of general well-being, good quality of life and sexual well-being, fertility, and prevention of side effects of gluco- and mineralocorticoid therapy. However, fertility is impaired in these patients and correlates with TART. The current therapeutic concepts are discussed. CONCLUSIONS: A future system of regular follow-up visits and standards in therapeutic concepts is needed to guarantee an improved fertility and lifelong good quality of life in adult male patients with CAH.
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Tumor de Resto Suprarrenal/terapia , Neoplasias Testiculares/terapia , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/patología , Hiperplasia Suprarrenal Congénita/terapia , Tumor de Resto Suprarrenal/diagnóstico , Tumor de Resto Suprarrenal/patología , Glucocorticoides/administración & dosificación , Humanos , Infertilidad Masculina/etiología , Masculino , Mineralocorticoides/administración & dosificación , Orquiectomía , Pronóstico , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patología , Testículo/patologíaAsunto(s)
Hiperplasia Suprarrenal Congénita/genética , Síndrome Adrenogenital/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/efectos adversos , Tamización de Portadores Genéticos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prednisona/efectos adversos , Esteroide 21-Hidroxilasa/genética , Síndrome de Abstinencia a Sustancias/genética , Hiperplasia Suprarrenal Congénita/diagnóstico , Hormona Adrenocorticotrópica , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Preescolar , Análisis Mutacional de ADN , Dexametasona/administración & dosificación , Asesoramiento Genético , Predisposición Genética a la Enfermedad/genética , Humanos , Hidrocortisona/sangre , Enfermedad Iatrogénica , Masculino , Prednisona/administración & dosificación , Análisis de Secuencia de ADN , Síndrome de Abstinencia a Sustancias/diagnósticoRESUMEN
Androgen insensitivity syndrome (AIS) is characterized by deficient or absent virilization in 46,XY individuals despite normal or even elevated androgen levels. AIS is usually caused by mutations in the androgen receptor (AR) gene. We aimed at contrasting clinical, biochemical, and molecular genetic characteristics of three patients (P1-P3) with clinically evident partial (P1) and complete (P2, P3) AIS with and without AR gene mutations. AR expression was studied in cultured genital skin fibroblasts (GSF) by Western immunoblotting, ligand binding analyses, Northern blotting, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), and RT-PCR spanning exons 1-8. AR gene DNA sequence was analyzed by single-strand conformation analysis (SSCA), and DNA sequencing. GSF revealed reduced (P1) or absent (P2, P3) ligand binding. Northern blots showed either slightly reduced hybridization of the 10.5-kb AR transcript (P3) or no hybridization (P1, P2), as confirmed by semiquantitative RT-PCR. RT-PCR spanning exons 1-8 detected single AR mRNA bands in P1-P3 excluding splicing errors. Western analyses showed either low (P1) or no (P2, P3) AR protein. While SSCA initially did not reveal any molecular abnormality, sequencing showed a novel CAG (Gln) to TAG (stop) mutation at codon 59 (P3) and a previously described 2-bp deletion at codon 472, leading to a frameshift and premature stop in codon 499 (P2). Intriguingly, P1 showed an unaltered DNA sequence of the coding region of the AR gene including all intron-exon boundaries. In conclusion, patients with clinically evident complete AIS are likely to harbor an AR gene mutation, demanding that the two polymorphic regions must always be included in molecular analyses of the AR gene. Moreover, our data support the concept that in a subset of AIS patients, particularly those with partial AIS, molecular alterations outside the coding region of the AR gene must be presumed.
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Síndrome de Resistencia Androgénica/genética , Mutación , Fenotipo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Síndrome de Resistencia Androgénica/diagnóstico , Western Blotting , Células Cultivadas , Preescolar , Trastornos del Desarrollo Sexual/genética , Trastornos del Desarrollo Sexual/metabolismo , Exones , Fibroblastos/citología , Fibroblastos/metabolismo , Humanos , Recién Nacido , Cariotipificación , Imagen por Resonancia Magnética , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , UltrasonografíaRESUMEN
Purpose: This guideline of the German Society of Pediatric Endocrinology and Diabetology (DGKED) is designed to be experts' opinion on the current concept of prenatal therapy for congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH). Several scientific medical societies have also participated in the guideline. It aims to offer guidance to physicians when they counsel affected families about prenatal therapy. Methods: The experts commissioned by the medical societies developed a consensus in an informal process. The consensus was subsequently confirmed by the steering committees of the respective medical societies. Recommendations: Prenatal CAH therapy is an experimental therapy. We recommend designing and using standardized protocols for the prenatal diagnosis, therapy and long-term follow-up of women and children treated prenatally with dexamethasone. If long-term follow-up is not possible, then prenatal therapy should not be performed.
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Idiopathic intrauterine growth restriction (IUGR) is a result of impaired placental nutrient supply. Newborns with IUGR exhibiting postnatal catch-up growth are of higher risk for cardiovascular and metabolic co-morbidities in adult life. Mammalian target of rapamycin (mTOR) was recently shown to function as a placental nutrient sensor. Thus, we determined possible correlations of members of the placental mTOR signaling cascade with auxologic parameters of postnatal growth. The protein expression and activity of mTOR-pathway signaling components, Akt, AMP-activated protein kinase α, mTOR, p70S6kinase1 and insulin receptor substrate-1 were analysed via western blotting in IUGR v. matched appropriate-for-gestational age (AGA) placentas. Moreover, mTOR was immunohistochemically stained in placental sections. Data from western blot analyses were correlated with retrospective auxological follow-up data at 1 year of age. We found significant catch-up growth in the 1st year of life in the IUGR group. MTOR and its activated form are immunohistochemically detected in multiple placental compartments. We identified correlations of placental mTOR-pathway signaling components to auxological data at birth and at 1 year of life in IUGR. Analysis of the protein expression and phosphorylation level of mTOR-pathway components in IUGR and AGA placentas postpartum, however, did not reveal pathognomonic changes. Our findings suggest that the level of activated mTOR correlates with early catch-up growth following IUGR. However, the complexity of signals converging at the mTOR nexus and its cellular distribution pattern seem to limit its potential as biomarker in this setting.
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Desarrollo Infantil/fisiología , Retardo del Crecimiento Fetal/metabolismo , Placenta/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Lactante , Recién Nacido , Proteínas Sustrato del Receptor de Insulina/metabolismo , Embarazo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Transducción de SeñalRESUMEN
Prenatal diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency by amniotic fluid (AF) steroid analysis is not possible in those cases in which prenatal dexamethasone (DEX) therapy is initiated to prevent virilization of female CAH fetuses because AF steroid levels are suppressed if DEX therapy is continued beyond amniocentesis (AC). In order to use AF steroids for prenatal diagnosis, it is necessary to discontinue DEX therapy for 5 days before AC. To study the effects of this interruption on AF steroid levels, we measured levels of aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone (170HP), 11-deoxycortisol, cortisol, and cortisone as well as androstenedione (delta 4-A) in AF samples (16-18 weeks) obtained from 25 pregnancies at risk for CAH treated with Dex (daily dosage: 1.0-1.5 mg). The prenatal diagnosis of 14 normal fetuses and 11 affected CAH fetuses was postnatally confirmed in all cases. Additionally, steroid levels were measured in AF samples (16-18 weeks) from 8 untreated CAH fetuses and in 19 AF samples (weeks 16-20) obtained in normal pregnancies. In 17/19 prenatally diagnosed CAH fetuses, the affected sibs had the salt wasting (SW)-form, in 2 cases the simple virilizing (SV)-form. All steroids were measured by RIA after extraction and Sephadex LH-20 chromatography. AF levels of aldosterone, corticosterone, deoxycorticosterone, progesterone, cortisol, cortisone, and 11-deoxycortisol were not different between CAH fetuses, prenatally DEX-treated normal fetuses and untreated controls. The 170HP-levels of the CAH-SW-fetuses (range: 19.9-59.8 mmol/L) were clearly above the normal range (3.74-11.6), but normal in the SV-fetuses (10.9, 11.5), whereas delta-4 A-levels (normal range: 0.87-5.13 mmol/L) were elevated both in the SW-(range: 6.53-37.6) and the SV-form (9.37,6.25) of CAH. 170HP and delta-4 A levels of prenatally DEX-treated pregnancies with normal fetuses were not different from levels found in normal pregnancies. Mean 170HP and delta-4 A AF steroid levels of prenatally DEX-treated CAH-pregnancies were slightly lower (NS) than levels of untreated CAH-pregnancies (170HP: 30.5 vs. 40.7; delta-4 A: 15.8 vs. 21.1). 170HP levels are elevated in the SW-form of CAH, but not in the SV-form. However, with the combination of 170HP and delta-4 A levels it is possible to diagnose prenatally both forms. There is no rebound phenomenon of AF steroid levels if DEX therapy is interrupted 5 days before amniocentesis.
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Hiperplasia Suprarrenal Congénita , Hiperplasia Suprarrenal Congénita/prevención & control , Líquido Amniótico/química , Dexametasona/uso terapéutico , Esteroides/metabolismo , 17-alfa-Hidroxiprogesterona , Hiperplasia Suprarrenal Congénita/diagnóstico , Aldosterona/análisis , Aldosterona/metabolismo , Amniocentesis , Androstenodiona/análisis , Androstenodiona/metabolismo , Corticosterona/análisis , Corticosterona/metabolismo , Cortisona/análisis , Cortisona/metabolismo , Cortodoxona/análisis , Cortodoxona/metabolismo , Femenino , Edad Gestacional , Humanos , Hidrocortisona/análisis , Hidrocortisona/metabolismo , Hidroxiprogesteronas/análisis , Hidroxiprogesteronas/metabolismo , Embarazo , Segundo Trimestre del Embarazo , Diagnóstico Prenatal , Factores de Riesgo , Esteroides/análisisRESUMEN
Androstenedione and testosterone were measured in whole adrenal glands of 56 previously healthy boys who died suddenly between birth and 2 yr of age. In each adrenal gland, the concentration of androstenedione considerably exceeded that of testosterone. The highest concentrations were found during the first week of life (median, 295 ng/g; range, 98-320 ng/g). Thereafter, values decreased rapidly until the end of the first year of life (median, 10 ng/g; range, 4.4-22.7 ng/g). Adrenal testosterone concentrations averaged 15% of those of androstenedione in the same gland and similarly decreased until the end of the first year. The decrease of adrenal androgen concentrations paralleled the involution of the fetal adrenal zone. A close correlation existed between the concentration of androstenedione in adrenal tissue and plasma. However, no correlation existed between adrenal and plasma testosterone. When the adrenals and testes of the same infant were compared, there was 10 times more androstenedione in the adrenals than in the testes during the first 2 yr of life. The testes contained more testosterone than the adrenals only during the first 4 months. Thus, in infant boys the adrenals are the main source of androstenedione during the first 2 yr. After the sixth month of life, they also are the main source of testosterone.
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Glándulas Suprarrenales/metabolismo , Androstenodiona/biosíntesis , Testosterona/biosíntesis , Envejecimiento , Androstenodiona/sangre , Preescolar , Humanos , Hidrocortisona/sangre , Lactante , Recién Nacido , Masculino , Tamaño de los Órganos , Testículo/metabolismo , Testosterona/sangreRESUMEN
GH deficiency (GHD) in patients with myelomeningocele leads to the question of whether these disabled patients should be treated with human GH. To date, only a few short-term reports of GH therapy are available in the literature, and long-term data for final height are lacking. We report auxological and laboratory data for seven prepubertal myelomeningocele patients with proven GHD (idiopathic GHD or neurosecretory dysfunction) during GH treatment. All patients (five males and two females; median chronological age, 6.6 yr) had shunted hydrocephalus and were treated with GH (0.5 IU/kg x week; 0.15 mg/kg x week; daily sc injections) over a median period of 38 months (range, 35-49 months). GH secretion was analyzed by measurement of spontaneous overnight GH secretion and two standard stimulation tests. Auxological parameters, bone age, serum levels of insulin-like growth factor I and insulin-like growth factor-binding protein-3, and neurological and orthopedic status were documented regularly. Median growth velocity of supine length improved during treatment (at start, 3.7 cm/yr; after 36 months, 5.7 cm/yr; P < 0.05), with highest levels 6 months after the start of therapy (8.1 cm/yr). The growth velocity of arm span was greater than these values. Supine length SD score for chronological age increased from -4.71 (at start) to -3.35 (after 36 months; P = NS), length SD score for bone age increased from -2.70 to -2.23 (P = NS), and arm span SD score increased from -2.98 to -1.75 (P < 0.05). The growth velocities of length and arm span remained significantly above the pretreatment values (P < 0.05). Symptomatic tethered cord associated with progression of scoliosis developed in two of seven children. GH treatment significantly improved the growth velocities of body length and arm span. However, the increase in length SD score was not significant, whereas arm span SD scores significantly improved over the study period.
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Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Hipopituitarismo/complicaciones , Hipopituitarismo/tratamiento farmacológico , Meningomielocele/complicaciones , Estatura , Preescolar , Femenino , Crecimiento/efectos de los fármacos , Humanos , Hipopituitarismo/fisiopatología , Lactante , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Masculino , Meningomielocele/fisiopatología , Factores de TiempoRESUMEN
Testosterone and androstenedione were measured in testicular and epididymal tissue of 37 previously healthy infants between 1 and 24 months of age who died suddenly. In half of the patients elevated plasma levels of cortisol and androstenedione suggested preterminal stress. Plasma testosterone levels, however, did not differ from those in healthy infants. Testicular testosterone concentrations were maximal in boys from 1-3 months of age (median, 36.6 ng/g; range, 7-380 ng/g) with peak values similar to those found in pubertal or even adult testes. Thereafter testicular testosterone concentrations decreased and after the age of 6 months all values were below 12.5 ng/g, which corresponds to the low normal range of older prepubertal boys. Plasma testosterone and testicular testosterone correlated significantly (P less than 0.001). On average the testicular concentrations were 36.4 times higher than the corresponding plasma concentrations. Testicular androstenedione was low but correlated significantly with testicular testosterone (P less than 0.001). Epididymal testosterone concentrations were surprisingly high (1-3 months: median, 10.3 ng/g; range, 4-42.7 ng/g) and averaged 30% of the testicular testosterone concentration. Thus, epididymal testosterone concentrations were significantly higher than the circulating plasma testosterone levels, indicating the capacity of the infant epididymis to accumulate androgens. These findings suggest that high local testosterone concentrations during early infancy are important not only for the testis itself but particularly for the developing epididymis.
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Envejecimiento , Androstenodiona/metabolismo , Epidídimo/metabolismo , Testículo/metabolismo , Testosterona/metabolismo , Androstenodiona/sangre , Preescolar , Humanos , Hidrocortisona/sangre , Lactante , Masculino , Testosterona/sangreRESUMEN
To determine the origin of estrogens in infant blood, we measured estrone (E1) and estradiol (E2) in the gonads of 50 girls and 64 boys who died suddenly between birth and 2 yr of age as well as in the adrenals of 18 of these infant girls and 16 of the boys. In the adrenals, E1 [median, 2.8 ng/g (10.4 pmol/g); range, 1.1-4.8 ng/g (4.1-17.8 pmol/g)] and E2 [median, 3.0 ng/g (10.9 pmol/g); range, 1.2-5.3 ng/g (4.4-19.5 pmol/g)] were found in similar concentrations and were independent of age and sex. In the gonads, E2 was the major estrogen, but the concentrations differed markedly between the sexes; E2 exceeded E1 almost 10-fold in the ovaries and 2-fold in the testes. On the average, the gonads of the infant girls had 5 times more E2 and 2 times more E1 than those of the boys. As in plasma, E2 concentrations were highest in the ovaries of 1- to 6-month-old girls [median, 10.5 ng/g (38.5 pmol/g); range, 1.1-55.1 ng/g (4.0-202.0 pmol/g)] and in testes of 1- to 3-month-old boys [median, 1.8 ng/g (6.6 pmol/g); range, 0.6-6.4 ng/g (2.3-23.5 pmol/g)]. Ovarian E2 concentrations declined to less than 3.0 ng/g (11.0 pmol/g) by the end of the first year of life, and testicular E2 declined to less than 1.0 ng/g (3.7 pmol/g) after only 6 months of age. Gonadal estrogen concentrations paralleled changes in gonadal morphology. Ovarian weights varied in a pattern of rise and fall similar to that of ovarian E2 concentrations; the biggest ovaries contained multiple macroscopic cysts. Testicular E2 closely correlated with Leydig cell development and testicular testosterone concentrations. We infer, therefore, that the surge of plasma E2 in infant girls originates from ovarian follicles and that of boys from testicular Leydig cells, and that these both occur as a result of the postnatal surge in gonadotropin secretion. The basal plasma E1 and E2 pool, however, is derived from the adrenals and remains at a comparatively constant level in both sexes.
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Glándulas Suprarrenales/metabolismo , Estradiol/metabolismo , Estrona/metabolismo , Ovario/metabolismo , Testículo/metabolismo , Glándulas Suprarrenales/crecimiento & desarrollo , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Concentración Osmolar , Ovario/crecimiento & desarrollo , Testículo/crecimiento & desarrolloRESUMEN
We reported previously reference values for seven corticosteroids in the plasma of term neonates and their mothers, including values for aldosterone (Aldo) that appeared high compared to the values in the literature. Plasma 11-deoxycortisol (S) was not measured in that longitudinal study. Using an improved technique of chromatographic separation of Aldo and S, the Aldo levels were measured again, and S levels were newly determined in stored plasma samples of the 12 newborn infants of our original report. The mean concentrations were: (Formula: see text). These plasma Aldo values should replace those of our original report. Thus, both plasma Aldo and S levels decline in the first week of life in normal infants.
Asunto(s)
17-Hidroxicorticoesteroides/sangre , Aldosterona/sangre , Cortodoxona/sangre , Recién Nacido/sangre , Cromatografía en Gel , Femenino , Humanos , EmbarazoRESUMEN
Cortisol reduces the activity of the PG-inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH) in human placental cells. The objective was to investigate a possible relation between 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), converting cortisol to cortisone, and PGDH gene expression in the placenta of patients with preeclampsia. In placental tissue taken from 20 healthy women with normal pregnancy, 20 premature babies born after labor before term, and 18 neonates after preeclamptic pregnancy, 11beta-HSD2 and PGDH messenger RNA (mRNA) expression was determined using quantitative TaqMan real-time PCR and quantitative competitive PCR. When comparing matched pairs, there were 3-fold lower 11beta-HSD2/glyceraldehyde-3-phosphate dehydrogenase (11beta-HSD2/GAPDH) mRNA levels in placentas of patients with preeclampsia than in controls [0.18 +/- 0.04 relative units (RU) and 0.61 +/- 0.10 RU, P = 0.0003]. We also found a 2-fold reduction in placental PGDH/GAPDH mRNA concentrations (0.28 +/- 0.15 RU and 0.50 +/- 0.18 RU, P = 0.0003). PGDH and 11beta-HSD2 mRNA levels correlated significantly (r = 0.66, P < 0.0001). In term placenta, 11beta-HSD2/GAPDH, but not PGDH, showed a significant correlation to birth weight (r = 0.43, P = 0.01) and to placental weight (r = 0.47, P = 0.01). Results could be confirmed by competitive PCR. We conclude that, in preeclampsia, 11beta-HSD2 mRNA expression is reduced, leading to the known decrease of 11beta-HSD2 activity. By means of an autocrine or paracrine mechanism, the diminished conversion of placental cortisol may lead to reduced PGDH mRNA expression as found in the present study.
Asunto(s)
Expresión Génica , Hidroxiprostaglandina Deshidrogenasas/genética , Hidroxiesteroide Deshidrogenasas/genética , Placenta/enzimología , Preeclampsia/enzimología , 11-beta-Hidroxiesteroide Deshidrogenasas , Adolescente , Adulto , Peso al Nacer , Cortisona/metabolismo , Femenino , Edad Gestacional , Humanos , Hidrocortisona/metabolismo , Recién Nacido , Recien Nacido Prematuro , Reacción en Cadena de la Polimerasa , Embarazo , Proteinuria , ARN Mensajero/análisisRESUMEN
Corticosteroids (CS) are essential for fetal organ maturation; yet, knowledge of endogeneous CS and precursor levels throughout fetal life is limited. Therefore, unconjugated aldosterone (Aldo), corticosterone (B), 11-deoxycorticosterone (DOC), progesterone (P), 17 alpha-hydroxyprogesterone (17-OHP), 11-deoxycortisol (S), cortisol (F), and cortisone (E) were simultaneously determined by RIA after automated Sephadex LH-20 chromatography in 70 control samples of amniotic fluid (AF) obtained at all gestational ages between 14-42 weeks. Levels of the progestins P and 17-OHP slowly increased from means (+/- SE) of 14.7 +/- 2.8 and 1.63 +/- 0.21 ng/ml, respectively, in early gestation to maximum levels of 32.4 +/- 3.5 and 3.80 +/- 0.74 ng/ml at 36-38 weeks (P less than 0.005), then dropped significantly (P less than 0.01) to 19.2 +/- 2.2 and 1.58 +/- 0.22 ng/ml at term. All CS levels except E rose very markedly by 3- to 12-fold (P less than 0.0001) from the weeks 14-16 (DOC, 0.44 +/- 0.08; B, 1.49 +/- 0.23; Aldo, 0.043 +/- 0.012; S, 0.51 +/- 0.10; F, 5.96 +/- 0.93 ng/ml) until the 36-38th weeks (DOC, 3.50 +/- 0.66; B, 4.60 +/- 0.78; Aldo, 0.530 +/- 0.109; S, 6.00 +/- 0.75; F, 60.8 +/- 8.9 ng/ml). Term levels were significantly reduced (P less than 0.01) in the less active CS DOC (0.51 +/- 0.07 ng/ml), B (2.35 +/- 0.35 ng/ml), and S (1.14 +/- 0.14 ng/ml), whereas those of the biologically most potent CS Aldo and F declined less markedly (0.272 +/- 0.053 and 23.0 +/- 0.75 ng/ml, respectively, at 39-42 weeks). Levels of the inactive glucocorticoid E rose from 8.83 +/- 1.08 ng/ml at 14-16 weeks to 16.8 +/- 2.6 ng/ml at 31-35 weeks (P less than 0.01), then remained rather constant around 11.5 ng/ml until term. It is concluded that after the 25th week, large amounts of biologically active CS are available in AF which probably directly induce the final epithelial maturation of fetal lungs and intestinal tract.
Asunto(s)
Corticoesteroides/análisis , Líquido Amniótico/análisis , Embarazo , Aldosterona/análisis , Corticosterona/análisis , Cortisona/análisis , Cortodoxona/análisis , Desoxicorticosterona/análisis , Femenino , Humanos , Hidrocortisona/análisis , Hidroxiprogesteronas/análisis , Progesterona/análisis , Factores de TiempoRESUMEN
The characteristic excess production of androgens in the cortisol 21-hydroxylase defect is generally considered to be secondary to ACTH stimulation of alternate pathways. Whenever a morphological examination of the adrenals has been possible in this disorder, adrenocortical hyperplasia was a constant finding. The availability of methods for the prenatal diagnosis of the 21-hydroxylase defect has made it possible to examine some of the manifestations of this disorder during fetal life. We studied a severely virilized 20-week-old aborted female fetus with the 21-hydroxylase defect whose adrenals were neither grossly enlarged nor microscopically hyperplastic. In a pregnancy at risk for congenital adrenal hyperplasia due to a 21-hydroxylase deficiency, amniocentesis was performed in the 18th week of gestation. The 21-hydroxylase defect was established by HLA typing and highly elevated levels of 17-hydroxyprogesterone, testosterone, and androstendione in amniotic fluid. After counselling, the parents, who already had a girl with the salt-wasting form of 21-hydroxylase deficiency, wished termination of the pregnancy. The aborted 20-week-old fetus was within the normal range for gestational age in weight and height. The external genitalia were ambiguous and extremely virilized, with an enlarged clitoris and fused labioscrotal folds. A urogenital sinus opened at the base of the clitoris. The internal organs were female, with a normal uterus and ovaries. Both adrenals were normal in size and weight for their gestational age. Histological examination of the adrenals revealed no abnormalities, and no hyperplasia was detectable. Thus, the adrenals in the 21-hydroxylase defect during fetal life secrete excessive amounts of androgens and cause virilization in the absence of adrenocortical hyperplasia.