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      La hormona de crecimiento durante el período de transición

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          Abstract

          La etapa de transición ha sido definida como el período de la vida que comienza hacia el fin de la pubertad y finaliza cuando se adquiere la maduración adulta completa. Esta fase dura aproximadamente 6 a 8 años y durante la misma se producen una serie de modificaciones cuantitativas y cualitativas en la esfera física y psíquica, caracterizadas por la adquisición de la talla y composición corporal adulta, del pico de masa ósea, la obtención de una plena capacidad fértil y, finalmente, de las características psicosociales propias del adulto. Deben recordarse los efectos que la hormona de crecimiento (GH) ejerce a lo largo de toda la vida del sujeto sobre el metabolismo, función y estructura cardíaca, hueso, composición corporal y calidad de vida. Sin embargo, hay datos conflictivos sobre la necesidad de continuar, sin interrupción, con la terapia de GH durante la etapa de transición. Se debe tener en cuenta, también, que existe un grupo de pacientes que adquieren la insuficiencia de GH durante el período de transición. Si bien existen claras evidencias que indican no discontinuar el tratamiento luego de haber finalizado la etapa de crecimiento, los pacientes deben ser reevaluados previamente para constatar si el déficit es suficientemente severo como para justificar mantener la terapéutica con GH. La respuesta a gran parte de estas dudas podrá resolverse con estudios randomizados y observacionales a largo plazo, desarrollados por equipos multidisciplinarios especializados.

          Translated abstract

          Transition phase has been defined as the period of life starting in late puberty and ending with full adult maturation. This phase extends over approximately 6 to 8 years. A number of quantitative and qualitative changes occur during this phase both in physical and psychic aspects, which are characterized by attainment of adult height and body composition, peak bone mass, full reproductive potential and, finally, psychosocial characteristics inherent to adults. We should remember the effects exerted by growth hormone (GH) throughout the life of a subject on metabolism, cardiac function and structure, bone, body composition and quality of life. However, there are controversial data on the need to continue GH therapy during the transition period with no discontinuation. We should also take into account that there is a group of patients who develop GH deficiency during the transition period. Even if there is clear evidence against discontinuation of therapy after completion of the growth period, patients should be previously reevaluated to confirm if GH deficiency is severe enough to warrant continuation of GH therapy. The response to many of these issues may be obtained from long-term randomized and observational studies conducted by specialized multidisciplinary teams.

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          Most cited references59

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          Consensus statement on the management of the GH-treated adolescent in the transition to adult care.

          The European Society for Paediatric Endocrinology held a consensus workshop in Manchester, UK in December 2003 to discuss issues relating to the care of GH-treated patients in the transition from paediatric to adult life. Clinicians experienced in the care of paediatric and adult patients on GH treatment, from a wide range of countries, as well as medical representatives from the pharmaceutical manufacturers of GH participated.
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            Comparison of continuation or cessation of growth hormone (GH) therapy on body composition and metabolic status in adolescents with severe GH deficiency at completion of linear growth.

            Although GH replacement improves the features of GH deficiency (GHD) in adults, it has yet to be established whether cessation of GH at completion of childhood growth results in adverse consequences for the adolescent with GHD. Effects of continuation or cessation of GH on body composition, insulin sensitivity, and lipid levels were studied in 24 adolescents (13 males, 11 females, aged 17.0 +/- 0.3, yr, mean +/- se, puberty stage 4 or 5) in whom height velocity was less than 2 cm/yr. Provocative testing confirmed severe GHD [peak GH < 9 mU/liter (3 microg/liter)] in all cases and was followed by a lead-in period of 3 months during which the pediatric dose of GH continued unchanged. Baseline investigations were then performed using dual-energy x-ray absorptiometry (body composition), lipid measurements, and assessment of insulin sensitivity by both homeostasis model assessment and a short insulin tolerance test. Twelve patients remained on GH (0.35 U/kg.wk), and 12 patients ceased GH treatment. The groups were followed up in parallel with repeat observations made after 6 and 12 months. No endocrine differences were evident between the groups at baseline. GH cessation resulted in a reduction of serum IGF-I Z score [-1.62 +/- 0.29, baseline vs. -2.52 +/- 0.12, 6 months (P < 0.05) vs. -2.52 +/- 0.10, 12 months (P < 0.01)] but values remained unchanged in those continuing GH replacement. Lean body mass increased by 2.5 +/- 0.5 kg ( approximately 6%) over 12 months in those receiving GH but was unchanged after GH discontinuation. Cessation of GH resulted in increased insulin sensitivity [short insulin tolerance test, 153 +/- 22 micromol/liter.min, baseline vs. 187 +/- 20, 6 months (P < 0.05) vs. 204 +/- 14, 12 months (P = 0.05)], but no significant change was seen during 12 months of GH continuation. Lipid levels remained unaltered in both groups. Continuation of GH at completion of linear growth resulted in ongoing accrual of lean body mass (LBM), whereas skeletal muscle mass remained static after GH cessation in these adolescents with GHD. This divergence of gain in LBM is of potential importance because increases in LBM occur as a feature of healthy late adolescent development. GH is a major mediator of insulin sensitivity, independent of body composition in adolescents. Further studies are required to determine whether discontinuation of GH in the adolescent with severe GHD once linear growth is complete results in long-term irreversible adverse physical and metabolic consequences and to determine conclusively the benefits of continuing GH therapy.
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              Effect of growth hormone (GH) treatment on bone in postpubertal GH-deficient patients: a 2-year randomized, controlled, dose-ranging study.

              GH treatment in children with GH deficiency is frequently terminated at final height. However, in healthy individuals bone mass continues to accrue until peak bone mass is achieved. Because no prospective data specifically prove the role of GH in attainment of peak bone mass, we performed a multinational, controlled, 2-yr study in patients who had terminated pediatric GH at final height. Patients were randomized to: GH at 25.0 microg/kg x day (pediatric dose, n = 58) or 12.5 microg/kg x day (adult dose, n = 59), or no GH treatment (control, n = 32). Bone mineral content (BMC) and density were measured by dual-energy x-ray absorptiometry and evaluated centrally. Laboratory measurements were also performed centrally. After 2 yr, significant increases were seen with both GH treatments, compared with control in bone-specific alkaline phosphatase (P = 0.004) and type I collagen C-terminal telopeptide:creatinine ratio (P < 0.001), but there were no significant dose effects. Total BMC increased by 9.5 +/- 8.4% in the adult dose group, 8.1 +/- 7.6% in the pediatric dose group, and 5.6 +/- 8.4% in controls (analysis of covariance, P = 0.008), with no significant GH dose effect. BMC increased predominantly at the lumbar spine (11.0 +/- 10.6%, P = 0.015) rather than at the femoral neck or hip. In contrast, a significant dose-dependent increase was seen in IGF-I concentrations (adult dose: 114.5 +/- 119.4 microg/liter; pediatric dose: 178.5 +/- 143.7 microg/liter; P = 0.023). There were no gender-related differences in BMC changes with either dose, whereas the IGF-I increase was significantly higher with the pediatric than with the adult dose in females (P < 0.001) but not males (P = 0.606). In summary, reinstitution of GH replacement after final height in severely GH-deficient patients induced significant progression toward peak bone mass. Although there was a by-gender dose effect on IGF-I concentration, the treatment effect on bone was obtained in both males and females with the adult GH dose regimen.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                rvdem
                Revista Venezolana de Endocrinología y Metabolismo
                Rev. Venez. Endocrinol. Metab.
                Sociedad Venezolana de Endocrinología y Metabolismo (Mérida )
                1690-3110
                October 2014
                : 12
                : 3
                : 148-156
                Affiliations
                [1 ] Hospital T. Álvarez Argentina
                Article
                S1690-31102014000300002
                f86389fc-be00-4ccf-9273-881c98a9fbd6

                http://creativecommons.org/licenses/by/4.0/

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                SciELO Venezuela

                Self URI (journal page): http://www.scielo.org.ve/scielo.php?script=sci_serial&pid=1690-3110&lng=en
                Categories
                ENDOCRINOLOGY & METABOLISM

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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