Bone mass and hormone analysis in patients with spinal cord injury: evidence for a gonadal axis disruption.

CONTEXT: Bone loss is a constant finding in patients with spinal cord injury (SCI). OBJECTIVE: We sought to evaluate potential modifiable factors that could lead to bone loss in complete motor paraplegia by examining gonadal axis hormones, vitamin D status, and bone markers. DESIGN: This is a cross sectional. SETTING: It includes SCI Outpatient. PATIENTS AND OTHER PARTICIPANTS: Twenty-nine chronic male patients with SCI were compared with 17 age-matched, able-bodied men. MAIN OUTCOME MEASURE: The bone mineral density (BMD) of lower limbs and lumbar spine were measured using dual x-ray absorptiometry. Parathormone, 25-hydroxyvitamin D [25(OH)D], collagen type I C-terminal telopeptide (CTX), and sexual hormone were measured. RESULTS: Patients with SCI had lower BMD at the inferior limbs sites. CTX showed an inverse relationship with the time since injury. Patients had lower free T levels (SCI, 12.00 ± 2.91 vs controls, 19.51 ± 5.72; P ≤ .001), and the majority (72%) had normal/low levels of gonadotropins. Low T, however, was not related to low bone mass in patients with SCI. In the controls, the 25(OH)D level was positively correlated with the T and with the lumbar spine BMD, but these correlations were not observed in the SCI. CONCLUSIONS: Impairment of testicular function after SCI was indicated by the low levels of T and the loss of correlation between T and 25(OH)D levels; this correlation was present in the able-bodied controls. Inappropriate levels of gonadotropins were identified in most patients, featuring a hypogonadotropic hypogonadism and suggesting a disruption of the pituitary-gonadal axis. T concentrations might not be an effective target for bone loss therapy.

Feminization and altered gonadal gene expression profile by ethinylestradiol exposure to pejerrey, Odontesthes bonariensis, a South American teleost fish.

In pejerrey (Odontesthes bonariensis), ovarian differentiation has been associated with gonadal aromatase expression. It is also known that exposure of pejerrey larvae to estradiol (E(2)) produces all female populations. During the last few years, the presence of ethinylestradiol (EE(2)), a synthetic E(2) analogue, has been reported in water reservoirs of different parts of the world. In the present study, the effects of EE(2) were assessed on sex ratio bias and gene expression levels of gonadal aromatase (cyp19a1a), 11ß-hydroxysteroid dehydrogenase type 2 (hsd11b2), estrogens (erα, erß1), and androgen receptors (arα, arß). Pejerrey larvae were fed with commercial food containing EE(2) (0.1 and 1 µg/g) and E(2 ) (50 µg/g) as a positive control for six weeks after hatching. The gonadal histological analysis showed that 42 to 46% of the fish had clearly differentiated ovaries in both the EE(2) - and E(2) -treated groups, compared with 27% in the control group. Moreover, in the EE(2) - (1 µg/g) and E(2) -treated groups, no fish presented signs of testicular development compared with controls. In addition, expression of cyp19a1a and hsd11b2 was significantly up- and downregulated, respectively, by EE(2) and E(2) . The authors' results suggested that the feminization process driven by EE(2) depends on the positive balance of cyp19a1a in relation to hsd11b2. Thus, these genes can be used as early indicators of exposure to xenoestrogens in this species.

Avaliação tardia do eixo hipofisário-gonadal em pacientes adultos que sofreram traumatismo cranioencefálico grave / Late evaluation of the pituitary-gonadal axis in survivors of severe traumatic brain injury

OBJETIVO: Avaliar a função hipofisária-gonadal nos pacientes vítimas de TCE graves ocorridos na Grande Florianópolis, entre 2000 e 2004. MÉTODOS: Foram estudados 30 pacientes, sendo 22 homens e 8 mulheres, submetidos à avaliação clínica e laboratorial em seguimento médio de 4 anos após a data do traumatismo. RESULTADOS: Os homens possuíam em média 38 anos no ano da avaliação, enquanto as mulheres, 42 anos. A maioria dos traumatismos está relacionada aos acidentes de trânsito (63,3 por cento). Três pacientes (10 por cento) estavam com valores de FSH abaixo do normal e apenas 1 paciente (3,3 por cento) apresentou LH alterado. Nas mulheres avaliadas, os níveis de estradiol foram normais. Na população masculina, foi evidenciado nível de testosterona baixo em 2 pacientes (9,1 por cento). Todos os pacientes apresentavam normoprolactinemia. CONCLUSÃO: Dois casos de hipogonadismo masculino (9,1 por cento) foram diagnosticados neste estudo. Isso indica a necessidade de atenção aos pacientes sobreviventes de TCE grave para realizar diagnóstico precoce de hipogonadismo.

OBJECTIVE: The purpose of this study is to evaluate pituitary function impairment in order to verify the prevalence of sex hormone deficiency and to analyze the profile of TBI population. METHODS: Thirty patients were studied, 22 were male and 8 were female. All patients had their gonadal function assessed and they were evaluated at a median of 4 years post-trauma. RESULTS: The average age of the men was 38 years at the time of the evaluation, while the mean age of women was 42 years. The majority of TBI was related to traffic accidents (63.3 percent). Three patients (10 percent) had low FSH and only 1 patient (3.3 percent) had low LH. There was no biochemical evidence of hypogonadism in women. Two male patients presented low testosterone (9.1 percent) and were diagnosed with hypogonadism. Prolactin levels were normal in all patients. CONCLUSION: Two cases of hypogonadism (9.1 percent) were diagnosed among men in this study. It is therefore necessary that medical professionals involved in the management of TBI patients are aware of hypogonadism as a complication of TBI, in order to diagnose it early.

[Late evaluation of the pituitary-gonadal axis in survivors of severe traumatic brain injury]. / Avaliação tardia do eixo hipofisário-gonadal em pacientes adultos que sofreram traumatismo cranioencefálico grave.

OBJECTIVE: The purpose of this study is to evaluate pituitary function impairment in order to verify the prevalence of sex hormone deficiency and to analyze the profile of TBI population. METHODS: Thirty patients were studied, 22 were male and 8 were female. All patients had their gonadal function assessed and they were evaluated at a median of 4 years post-trauma. RESULTS: The average age of the men was 38 years at the time of the evaluation, while the mean age of women was 42 years. The majority of TBI was related to traffic accidents (63.3%). Three patients (10%) had low FSH and only 1 patient (3.3%) had low LH. There was no biochemical evidence of hypogonadism in women. Two male patients presented low testosterone (9.1%) and were diagnosed with hypogonadism. Prolactin levels were normal in all patients. CONCLUSION: Two cases of hypogonadism (9.1%) were diagnosed among men in this study. It is therefore necessary that medical professionals involved in the management of TBI patients are aware of hypogonadism as a complication of TBI, in order to diagnose it early.

Effect of nutritional stress on the hypothalamo-pituitary-gonadal axis in the growing male rat.

BACKGROUND/OBJECTIVE: Nutritional dwarfing (ND) consists of a decrease in weight and height gain and delayed onset of puberty. The aim of the present investigation was to study the modifications induced in male rats by the nutritional stress of a mere 20% reduction in food intake which, however, started immediately after weaning. MATERIALS AND METHODS: At weaning, male Wistar rats were divided into two groups: Control (C) and ND. C rats were fed ad libitum with a balanced rodent diet. ND received 80% of the diet consumed by C for 4 weeks (T4); then they were fed ad libitum for another 4 (T8) and 8 weeks (T12). The rats were studied at T0, T4, T8 and T12 for the effects of nutritional stress and refeeding on nutritional status, body composition, hypothalamic-pituitary-gonadal axis, and sperm morphology and concentration. RESULTS: ND body weight and length diminished vs. C (p < 0.001). ND body fat percentage decreased 40% (p < 0.001) without change in the percentage of body protein content. The hypothalamic content of LHRH did not change. However, FSH, LH and testosterone serum levels had significantly decreased (p < 0.001) at T4 in ND rats. A 48.4 % decrease in serum leptin in the ND group was observed at T4 (p < 0.05). The absolute testicular and seminal vesicle weight was significantly decreased by ND at T4 (p < 0.001). At T4 the percentage of anomalies of caudal spermatozoa increased in about 64% (p < 0.001) of ND vs. C rats, despite the unchanged sperm concentrations. All parameters normalized during refeeding. CONCLUSION: In this model, a decrease in leptin due to nutritional stress could be responsible, at least in part, for the inhibition of reproductive function. Refeeding normalized all parameters studied.

Genitália ambígua: diagnóstico diferencial e conduta / Ambiguous genitalia: differential diagnosis and management

As ambiguidades genitais têm-se constituído em uma verdadeira emergência pediátrica e a adequada avaliaçäo decada caso pode evitar que o paciente seja criado num sexo inadequado, com interferência importante na sua saúde bio-psico-social. Os autores fazem uma abordagem da fisiopatologia da determinaçäo gonadal, bem como dos mecanismos envolvidos na diferenciaçäo sexual e fornecem elementos para o diagnóstico diferencial e conduta terapêutica.

A funçäo gonadal do homem obeso / Gonadal function of the obese man

Em homens obesos, os níveis séricos de globulina ligadora de hormônios sexuais (GLHS), bem como de testosterona total, (TT) estão diminuídos. Dados relativos aos níveis séricos de testosterona livre (TL) são controversos. Homens com obesidade mórbida apresentam valores plasmáticos de testosterona livre diminuídos, levando à alteração dos mecanismos de retro-regulação. O decréscimo funcional da amplitude do pulso de LH, bem como a diminuição dos níveis de LH, seriam a causa do hipoandrogenismo. Estudamos dois grupos de homens obesos: Grupo 1 (IMC /= 35kg/m 2 ) antes e após seis meses de dieta hipocalórica (1.200Kcal/dia). Todos os pacientes utilizaram dexfenfluramina (15mg 2x ao dia) durante todo o período do estudo. Níveis plasmáticos de insulina, bem como valores séricos de testosterona total, testosterona livre e LH foram dosados antes e após a perda de peso. Pacientes com obesidade moderada (IMC = 32,3 +/- 1,9kg/m 2 ) apresentaram diminuição significativa na concentração sérica de TT (390 +/- 120ng/dL), bem como de TL (média +/- DP 16,0 +/- 4,8pg/mL) quando comparados a normais. A concentração de LH sérico (4,5 +/- 2,9mIU/mL) foi considerada normal. Níveis de insulina mostravam-se elevados em todos os pacientes (46,3 +/- 30,1µU/mL). Após a perda de peso, notou-se aumento significante (p < 0,01) dos níveis séricos de LH, TT e TL concomitante à queda da concentração de insulina plasmática. Em homens com obesidade de grande porte (IMC = 43,0 +/- 6,7kg/m 2 ), os níveis de TT (320 +/- 110ng/dL), TL (11,0 +/- 2,1pg/mL) e LH (3,1 +/- 1,3mIU/mL) mostraram-se significativamente menores quando comparados ao Grupo 1 e aos controles normais. Como esperado, após a perda de peso, os níveis séricos de TT, TL e LH aumentaram significativamente enquanto a concentração plasmática de insulina diminuiu. Concluímos que os níveis de TL são dependentes do grau de obesidade: homens com obesidade de grande porte (IMC >/= 35kg/m 2 ) são considerados como candidatos a apresentarem baixos valores séricos de TL.

Función gonadal y tiroidea en pacientes infantojuveniles renales crónicos tratados con eritropoyetina / Gonadal and thyroid function in children and young patients with chronic kidney failure treated with erythropoietin

Antecedentes y Objetivos: A partir de un estudio realizado sobre factores de riesgo coronario, en el que habíamos observado asociaciones significativas entre hipertensión arterial y diversas alteraciones metabólicas, surgió la inquietud de buscar un factor fisiopatogénico que las vinculara. La bibliografía mostró como posible factor fisiopatogénico a la insulinorresistencia, encontrando opiniones divididas frente a esta teoría. Fue así como nos planteamos que, si esta teoría fuera cierta, entonces los pacientes con hiperinsulinismo debían tener una mayor prevalencia de hipertensión arterial y de alteraciones metabólicas. Material y Métodos: Realizamos un análisis retrospectivo de la base de datos Tucumán del estudio multicéntrico de factores de riesgo SAC88. El índice de sensibilidad a la insulina (ISI) se calculó en base a la fórmula de Breglund y Lithell. Para el análisis estadístico se utilizó el test de chi cuadrado para las variables nominales y con el anova y el test de Krusker-Wakis para las cualitativas, considerándose significativa una diferencia de p = o < 0,05. Resultados: Pudimos observar que las personas con ISI anormal tienen mayor prevalencia de hipertensión arterial y de alteraciones metabólicas que comprenden: hipertrigliceridemia, hiperglucemia, aumento de colesterol total y disminución del HDL-col., sin diferencias significativas en el LDL-col. Además, se observó una relación de ISI con el sexo masculino, el envejecimiento, el tabaquismo y la menopausia. Conclusiones: Este trabajo avala la teoría que señala a la resistencia a la insulina como factor fisiopatogénico de la hipertension arterial y los cambios metabólicos que la acompañan. (AU)

Función gonadal y tiroidea en pacientes infantojuveniles renales crónicos tratados con eritropoyetina / Gonadal and thyroid function in children and young patients with chronic kidney failure treated with erythropoietin

Antecedentes y Objetivos: A partir de un estudio realizado sobre factores de riesgo coronario, en el que habíamos observado asociaciones significativas entre hipertensión arterial y diversas alteraciones metabólicas, surgió la inquietud de buscar un factor fisiopatogénico que las vinculara. La bibliografía mostró como posible factor fisiopatogénico a la insulinorresistencia, encontrando opiniones divididas frente a esta teoría. Fue así como nos planteamos que, si esta teoría fuera cierta, entonces los pacientes con hiperinsulinismo debían tener una mayor prevalencia de hipertensión arterial y de alteraciones metabólicas. Material y Métodos: Realizamos un análisis retrospectivo de la base de datos Tucumán del estudio multicéntrico de factores de riesgo SAC'88. El índice de sensibilidad a la insulina (ISI) se calculó en base a la fórmula de Breglund y Lithell. Para el análisis estadístico se utilizó el test de chi cuadrado para las variables nominales y con el anova y el test de Krusker-Wakis para las cualitativas, considerándose significativa una diferencia de p = o < 0,05. Resultados: Pudimos observar que las personas con ISI anormal tienen mayor prevalencia de hipertensión arterial y de alteraciones metabólicas que comprenden: hipertrigliceridemia, hiperglucemia, aumento de colesterol total y disminución del HDL-col., sin diferencias significativas en el LDL-col. Además, se observó una relación de ISI con el sexo masculino, el envejecimiento, el tabaquismo y la menopausia. Conclusiones: Este trabajo avala la teoría que señala a la resistencia a la insulina como factor fisiopatogénico de la hipertension arterial y los cambios metabólicos que la acompañan.

Hypothalamic-pituitary-gonadal function in prepubertal boys and girls with chronic renal failure.

Hypothalamic-pituitary-gonadal function was evaluated in 24 prepubertal children with chronic renal failure (CRF). Among the 17 boys, 5 were receiving conservative treatment and four long-term dialysis. Another eight boys were studied 6 months to 3.3 years after renal transplantation; their ages ranged from 5 years 8 months to 15 1/2 years. Among the girls, two patients were receiving conservative treatment and five long-term dialysis; their ages ranged from 3 1/2 years to 11 years 2 months. In boys with CRF, but not in those after transplantation, mean serum follicle-stimulating hormone 60 minutes after administration of gonadotropin releasing hormone (GnRH) was lower than in 18 control prepubertal boys (mean +/- SD: 2.53 +/- 1.34 vs 6.25 +/- 2.84 IU/L, respectively; p < 0.01). Testosterone steroidogenic capacity after 1 week of stimulation with human chorionic gonadotropin and androgen sensitivity (percentage of decrease of serum sex hormone-binding globulin 1 week after intramuscular administration of testosterone enanthate) were normal. In girls, no difference between those with CRF and a control group of 19 girls was found after intravenous administration of GnRH. However, after intramuscular administration of GnRH agonist, serum follicle-stimulating hormone concentration was lower in girls with CRF than in control girls (p < 0.02); six of seven control girls had an increase of serum estradiol to more than 55 pmol/L, whereas three of seven girls with CRF had no response, and serum follicle-stimulating hormone failed to increase after GnRH agonist therapy in two of these patients. We conclude that hypothalamic-pituitary function is not normal in some prepubertal boys and girls with CRF, particularly in those with low serum albumin concentrations. On the other hand, testicular and ovarian steroidogenic capacity is not impaired, and the biologic response to androgens in boys is preserved.

Conceptos recientes sobre el descenso testicular / Recent concepts of testicular descent

Se presenta una revisión de los conocimientos actuales sobre el descenso testicular. La gónada inicia su diferenciación hacia la sexta semana, orientada por el mesonefros. En la siguiente semana e l antígeno H-Y y la gonadotropina coriónica definen la organogénesis testicular. Entre las semanas octava y duodécima ocurren importantes cambios en la gónada, las estructuras mesonéfricas y el primordio o anclaje perineal, que influyen decisivamente en la estructura y la función testiculares. Durante el segundo trimestre se realiza la proliferación gubernacular y, finalmente, en las últimas doce semanas desempeñan su propia función la pared abdominal y la contracción gubernacular, influída esta última por la gonadotropinahipofisiaria fetal. El maldescenso testicular puede deberse a defectos en la organogénesis gonadal durante las primeras doce semanas, o bien originarse en imperfecciones del mecanismo de descenso a nivel de la pared abdominal o del propio gubernáculo.(au)