[Effects of growth hormone on anthropometric and metabolic parameters in android obesity]. / Efeito do hormônio de crescimento sobre parâmetros antropométricos e metabólicos na obesidade andróide.

The aim of the study was to evaluate the effect of GH on body weight, body composition and cardiovascular risk factors in android obese men. Forty non-diabetic subjects aged 20 to 50 years-old with android obesity (WHR > 1) were divided in two groups, on a prospective randomized double-blind basis to receive treatment with GH (0.050 U/kg/day) or placebo for three months. Bioimpedance analysis, DEXA, indirect calorimetry and cardiovascular risk factors were done at the beginning and at the end of the study. Anthropometric measurements were evaluated monthly. Body weight was reduced (3.5 +/- 2.9 kg), as well as BMI (1.2 +/- 1.0 kg/m2), WHR (0.04 +/- 0.01) and fat mass (2.4 +/- 1.0 kg), total cholesterol (4.0 +/- 3.3 mg/dL) and LDL-cholesterol (5.7 +/- 2.7 mg/dL) in GH-treated patients. Percentual changes were statistically different from placebo. Benefits and risks of long-term GH use in obese patients are still largely unknown.

Prevalence of subclinical hypothyroidism in a morbidly obese population and improvement after weight loss induced by Roux-en-Y gastric bypass.

BACKGROUND: There are many studies concerning thyroid function in obesity, and some of them describe higher TSH levels in obese subjects. Few studies evaluated long-term changes in thyroid function caused by weight loss after bariatric surgery. Our aims were to evaluate the prevalence of subclinical hypothyroidism (SH) in a morbidly obese population and to analyze the effect of weight loss induced by Roux-en-Y gastric bypass (RYGBP) on TSH and thyroid hormone (TH) levels. METHODS: TSH, free thyroxine (fT4) and total triiodothyronine (T3) levels were analyzed before and 12 months after RYGBP in patients with grade III or grade II obesity with co-morbidities. Subjects taking TH and/or with positive antithyroid antibodies and/or with overt hypothyroidism were excluded. RESULTS: 72 subjects (62F/10M), with mean age 39.6+/-9.8 years and mean BMI 53.0+/-10.4 kg/m2 were studied. The prevalence of SH before RYGBP was 25% (n=18). There was a significant post-surgical decrease in BMI in the whole population, as well as in SH patients. In the SH group and normal TSH group, there was a decrease in TSH and T3, but not in fT4. TSH was not correlated with initial BMI or percent change in BMI. TSH concentrations reached normal values in all SH patients after RYGBP. CONCLUSION: Our data confirm that severe obesity is associated with increased TSH. The decrease in TSH was independent of BMI, but occurred in all SH patients. A putative effect of weight reduction on the improvement of SH in all patients may be an additional benefit of bariatric surgery.

Novel inactivating mutations in the GH secretagogue receptor gene in patients with constitutional delay of growth and puberty.

BACKGROUND: A limited number of mutations in the GH secretagogue receptor gene (GHSR) have been described in patients with short stature. Objective To analyze GHSR in idiopathic short stature (ISS) children including a subgroup of constitutional delay of growth and puberty (CDGP) patients. SUBJECTS AND METHODS: The GHSR coding region was directly sequenced in 96 independent patients with ISS, 31 of them with CDGP, in 150 adults, and in 197 children with normal stature. The pharmacological consequences of GHSR non-synonymous variations were established using in vitro cell-based assays. RESULTS: Five different heterozygous point variations in GHSR were identified (c.-6 G>C, c.251G>T (p.Ser84Ile), c.505G>A (p.Ala169Thr), c.545 T>C (p.Val182Ala), and c.1072G>A (p.Ala358Thr)), all in patients with CDGP. Neither these allelic variants nor any other mutations were found in 694 alleles from controls. Functional studies revealed that two of these variations (p.Ser84Ile and p.Val182Ala) result in a decrease in basal activity that was in part explained by a reduction in cell surface expression. The p.Ser84Ile mutation was also associated with a defect in ghrelin potency. These mutations were identified in two female patients with CDGP (at the age of 13 years, their height SDS were -2.4 and -2.3). Both patients had normal progression of puberty and reached normal adult height (height SDS of -0.7 and -1.4) without treatment. CONCLUSION: This is the first report of GHSR mutations in patients with CDGP. Our data raise the intriguing possibility that abnormalities in ghrelin receptor function may influence the phenotype of individuals with CDGP.

Efeito do hormônio de crescimento sobre parâmetros antropométricos e metabólicos na obesidade andróide / Effects of growth hormone on anthropometric and metabolic parameters in android obesity

O objetivo do estudo foi avaliar os efeitos do GH sobre peso, composição corporal, metabolismo de repouso e fatores de risco cardiovascular na obesidade visceral. O estudo foi prospectivo randomizado duplo-cego em 40 homens não diabéticos de 20 a 50 anos com RAQ (relação abdômen-quadril) > 1 tratados com GH (0,050 U/kg/dia) ou placebo por três meses. Foram avaliados peso, composição corporal por bioimpedância e DEXA, metabolismo de repouso através da calorimetria indireta e exames de fatores de risco cardiovasculares no início e fim do tratamento. O grupo de obesos tratados com GH teve reduções de peso (3,5 ± 2,9 kg), IMC (1,2 ± 1,0 kg/m²), RAQ (0,04 ± 0,01) e massa adiposa (2,4 ± 1,0 kg). As reduções porcentuais foram significantemente diferentes das observadas no grupo placebo. Também houve diminuição nos níveis de colesterol total (4,0 ± 3,3 mg/dL) e LDL-colesterol (5,7 ± 2,7 mg/dL) no grupo GH, em relação ao grupo placebo. Os outros fatores de risco não se alteraram significantemente. Concluímos que obesos tratados com GH por três meses apresentaram uma redução significante de peso corporal, gordura visceral e massa adiposa, e melhora do perfil lipídico. O benefício/risco do GH a longo prazo em obesos é desconhecido.