Chronic renal failure and growth hormone: effects on GH-IGF axis and leptin

AIM: To analyze the changes in IGF-1, IGFBP-3, leptin and insulin after replacement doses of recombinant human growth hormone (rhGH) in short prepubertal children with chronic renal failure (CRF). PATIENTS AND METHODS: Eleven children (3F:8M), with mean age of 9.6 years, were treated with rhGH (0.23 mg/Kg weekly for 12 months). Serum leptin, insulin, glucose, IGF-1 and IGFBP-3 were measured before, 6 and 12 months after beginning rhGH treatment. RESULTS: The serum levels of leptin, insulin and glucose did not vary during the treatment; normal leptin and glucose levels and high insulin were observed. There was a significant increment of IGF-1 and IGFBP-3 during the use of rhGH. CONCLUSIONS: The replacement doses of rhGH during 12 months in a selected group of CRF children determined an increment in IGF-1 and IGFBP-3, associated to normal serum leptin and insulin resistance.OBJETIVO: Avaliar as alterações de IGF-1, IGFBP-3, leptina e insulina após o uso de doses de reposição de hormônio de crescimento recombinante humano (rhGH) em crianças baixas pré-púberes com insuficiência renal crônica (IRC). CASUÍSTICA E MÉTODOS: Em 11 crianças (3F:8M), com idade média de 9,6 anos, em uso de rhGH (0,23mg/Kg/semana) por 12 meses, foram dosados (antes, 6 e 12 meses após o início do tratamento com rhGH) leptina, insulina, glicemia, IGF-1 e IGFBP-3. RESULTADOS: As concentrações séricas de leptina, insulina e glicemia não variaram significativamente no decorrer do uso do rhGH, sendo observado o padrão de leptina e glicemia normais, com hiperinsulinemia. Houve aumento significativo da IGF-1 e IGFBP-3 durante o uso do rhGH. CONCLUSÕES: O uso de doses de reposição de rhGH durante 12 meses em um grupo selecionado de crianças com IRC propiciou aumento significativo da concentração sérica de IGF-1 e IGFBP-3, com leptinemia normal e resistência insulínica.96497

Assessment Of Serum Chromogranin-a As Prognostic Factor In High-risk Prostate Cancer.

The presence of neuroendocrine differentiation may play a key role in androgen-independent tumor progression. The prognostic significance of plasma chromogranin-A (CgA) was assessed in a series of consecutive patients with high-risk prostate cancer (PCa). Twenty-three patients presenting high-risk PCa and 8 healthy individuals, as control group, had their blood samples collected to evaluate CgA, free and total prostate specific antigen, and free and total testosterone in a pilot study. The correlations of serum CgA levels with PSA, testosterone, Gleason score, number of foci of hypercaptation in bone scan, age, and outcomes were evaluated at baseline and after 12 months. Patients with PCa had significantly higher levels of plasma CgA (mean, 8.7; range, 1.9-73) than healthy patients (mean, 3.45; range, 0.6-5.6), P = 0.02. Analyzing only the patients group through correlation of the ranks, it was observed that CgA has low, insignificant correlations with PSA (P = 0.07) and with metastatic extension (P = 0.09). No association was found between the plasma CgA levels and the Gleason score (P = 0.20), age (P = 0.15), or disease progression (P = 0.27). The serum levels of CgA were significantly increased in the group with PCa compared with the healthy group. However, there were low correlations between serum CgA and known prognostic factors (such as total and free PSA, age, Gleason score, and bone metastases) or clinical deterioration. Although future studies are needed with larger samples and longer follow-up, the presented data envisage a limited role to serum CgA as high-risk PCa prognostic factor.58957-6

[5alpha-reductase Type 2 Deficiency: Experiences From Campinas (sp) And Salvador (ba)].

To report the experience regarding patients with steroid 5alpha-reductase type 2 deficiency from three different clinical services in Brazil. Twenty five patients with clinical and hormonal features of 5alpha-reductase deficiency from 23 families (15 from Bahia, 7 from São Paulo and 1 from Minas Gerais) were included in this study. Clinical, hormonal and molecular data were evaluated. The molecular analysis of the five exons of the SRD5A2 gene was done by automatic or manual sequencing of PCR products. In ten families, SRD5A2 mutations were found in homozygosis (5 with G183S, 2 with R246W, 1 with G196S, 1 with del642T, 1 with 217_218insC), in three in compound heterozygosis (1 with Q126R/IVS3+1G>A, 1 with Q126R/del418T, 1 with Q126R/G158R) while other three were heterozygous, with only one deleterious mutation (1 with G196S, 1 with A207D, and 1 with R246W). In seven cases, no sequencing abnormalities were detected. The G183S substitution was the most frequently found among miscegenated patients (Afro-Euro-Brazilians) from Bahia. Hormonal and clinical findings did not differ between patients with or without mutations, exception made to a higher frequency of consanguinity and greater severity of genital ambiguity in the first group. Our results reinforce the importance of molecular investigation for the diagnosis of this disease and point out to the finding of a very frequent mutation (G183S) in our series, especially in patients with mixed ethnic background from Bahia, and the description of mutations that have only been reported in Brazilian patients so far.49103-1