[Efficacy, safety and compliance of long-term growth hormone (GH) replacement therapy in adults with GH deficiency]. / Eficácia, segurança e aderência ao tratamento de longo prazo com hormônio de crescimento (GH) em adultos com deficiência de GH.

AIM: To study efficacy, safety and compliance of GH therapy for 4 years in 18 GH deficient (GHD) adults [12 women; mean age 50.5 yrs (25-66 yrs)]. METHODS: Clinical, biochemical and body composition (DXA) measurements were performed before and every year after GH therapy. Ecocardiography was performed at baseline and after 4 years. Dose of GH was 0.2 mg/day during the first year with subsequent titration to attain normal IGF-1 levels. RESULTS: There was a significant reduction of total body fat (mean 2.8 kg), truncal fat (mean 1.9 kg) and an increase of lean body mass (mean 0.8 kg) and bone mineral density (BMD) on lumbar spine and femur, particularly in sites with T-score<-1,0 at baseline. Insulin levels and HOMA index worsened in the first year, but at the end no changes were noted on glucose, insulin, HOMA index and glycosylated hemoglobin. Two patients with altered glucose tolerance at baseline developed type 2 diabetes during follow-up. Total and LDL-cholesterol were significantly lower after therapy, with changes directly associated with baseline values. Cardiac parameters did not change. Side effects were mild and disappeared spontaneously. Tumor recurrence was not observed. Low compliance (estimated by low IGF-1 levels) was observed in 4 (22%), 2 (11%) and 6 (33%) patients at the end of second, third and fourth year, respectively. CONCLUSIONS: Four years of GH therapy in GHD adults had a positive impact on body composition, BMD and lipid profile, with no effects on insulin sensitivity and heart. Glucose tolerance should be monitored carefully during long-term GH therapy.

Eficácia, segurança e aderência ao tratamento de longo prazo com hormônio de crescimento (GH) em adultos com deficiência de GH / Efficacy, safety and compliance of long-term growth hormone (GH) replacement therapy in adults with GH deficiency

OBJETIVO: Avaliar a eficácia, a segurança e a aderência de quatro anos de tratamento com GH em 18 adultos [12 mulheres, 6 homens, com idade média de 50,5 anos (25-66 anos)] com deficiência grave de GH (DGH). MÉTODOS: Avaliações clínica, laboratorial e de composição corporal (DXA) realizadas antes e anualmente após o início do GH, e ecocardiografia realizada antes e após quatro anos de tratamento. Dose de 0,2 mg GH/dia mantida fixa no primeiro ano, com posteriores ajustes para normalizar IGF-1. RESULTADOS: Redução significativa da gordura corporal total (média 2,8 kg) e da gordura truncal (média 1,9 kg), associadas com aumento da massa magra (média 0,8 kg) e aumento da densidade mineral óssea (DMO) em coluna lombar e fêmur, particularmente nos sítios com T-escore menor que 1,0 na avaliação basal. Houve piora dos níveis de insulina e HOMA no primeiro ano de terapia, mas ao final do quarto ano os valores de glicose, insulina, HOMA e hemoglobina glicosilada não eram diferentes dos basais. Desenvolveram diabetes tipo 2 no seguimento dois pacientes com intolerância à glicose pré-tratamento. O colesterol total e o LDL colesterol reduziram significativamente, e as mudanças foram proporcionais aos valores basais. Os parâmetros ecocardiográficos não se alteraram. Os efeitos colaterais foram leves e bem tolerados. Não foi observada recorrência tumoral. Baixa adesão ao tratamento (estimada por níveis baixos de IGF-1) ocorreu em quatro (22 por cento), dois (11 por cento) e seis (30 por cento) pacientes ao final do segundo, terceiro e quarto ano, respectivamente. CONCLUSÕES: Quatro anos de tratamento com GH em adultos com DGH teve impacto positivo sobre a composição corporal, a DMO e o perfil lipídico, e nenhum efeito sobre sensibilidade insulínica e o coração. A intolerância à glicose deve ser cuidadosamente monitorada no tratamento de longo prazo.

AIM: To study efficacy, safety and compliance of GH therapy for 4 years in 18 GH deficient (GHD) adults [12 women; mean age 50.5 yrs (25-66 yrs)]. METHODS: Clinical, biochemical and body composition (DXA) measurements were performed before and every year after GH therapy. Ecocardiography was performed at baseline and after 4 years. Dose of GH was 0.2 mg/day during the first year with subsequent titration to attain normal IGF-1 levels. RESULTS: There was a significant reduction of total body fat (mean 2.8 kg), truncal fat (mean 1.9 kg) and an increase of lean body mass (mean 0.8 kg) and bone mineral density (BMD) on lumbar spine and femur, particularly in sites with T-score < -1,0 at baseline. Insulin levels and HOMA index worsened in the first year, but at the end no changes were noted on glucose, insulin, HOMA index and glycosylated hemoglobin. Two patients with altered glucose tolerance at baseline developed type 2 diabetes during follow-up. Total and LDL-cholesterol were significantly lower after therapy, with changes directly associated with baseline values. Cardiac parameters did not change. Side effects were mild and disappeared spontaneously. Tumor recurrence was not observed. Low compliance (estimated by low IGF-1 levels) was observed in 4 (22 percent), 2 (11 percent) and 6 (33 percent) patients at the end of second, third and fourth year, respectively. CONCLUSIONS: Four years of GH therapy in GHD adults had a positive impact on body composition, BMD and lipid profile, with no effects on insulin sensitivity and heart. Glucose tolerance should be monitored carefully during long-term GH therapy.

One year of GH replacement therapy with a fixed low-dose regimen improves body composition, bone mineral density and lipid profile of GH-deficient adults.

OBJECTIVE: We have studied the effects on body composition and metabolism of a fixed low dose of growth hormone (GH), 0.6 IU (0.2 mg)/day, administered for 12 months to GH-deficient (GHD) adults. DESIGN AND METHODS: Prospective open-label study, using 18 GHD patients (11 women, 7 men; aged 21-58 years). All investigations were performed at baseline and after 12 months. Body composition was determined by dual energy X-ray absorptiometry. RESULTS: Total body fat decreased (-1.74+/-2.87%) and lean body mass (LBM) increased (1.27+/-2.08 kg) after therapy (P < 0.05). Changes in truncal fat did not reach statistical significance, but a decrease varying from 0.72 to 2.78kg (1 to 8.7%) was observed in 13 (72%) patients. Bone mineral density (BMD) increased at lumbar spine, total femur and femoral neck (P < 0.05). Levels of total and low-density lipoprotein (LDL)-cholesterol were lower after therapy (P < 0.05), and their changes were directly associated with values at baseline. Insulin levels increased and the insulin resistance index worsened at 12 months (P < 0.05). Median IGF-I s.d. score was -4.30 (range, -11.03 to -0.11) at baseline and -1.73 (range, -9.80 to 2.26) at 12 months. Normal age-adjusted IGF-I levels were obtained with therapy in 5 of 11 patients who had low IGF-I levels at baseline. Changes in IGF-I levels were not correlated with any biological end point, except changes in LBM (r = 0.53, P = 0.02). Side effects were mild and disappeared spontaneously. CONCLUSIONS: One-year of a fixed low-dose GH regimen in GHD adults resulted in a significant reduction in body fat, total cholesterol and LDL-cholesterol, and a significant increase in LBM and BMD at lumbar spine and femur, regardless of normalization of IGF-I levels. This regimen led to an elevation of insulin levels and a worsening of the insulin resistance index.