Effect of recombinant growth hormone on leptin, adiponectin, resistin, interleukin-6, tumor necrosis factor-α and ghrelin levels in growth hormone-deficient children.

BACKGROUND: Treatment with GH promotes linear growth and decreases body fat in patients with isolated GH deficiency (GHD). However, few studies have analyzed how GH replacement modifies ghrelin levels and the adipokine profile and the relationship of these modifications with the metabolic changes. AIMS: To analyze the eventual differences between serum levels of leptin, leptin soluble receptor (sOBR), resistin, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), total (TG) and acylated ghrelin (AG) and lipid and glycemic profiles in children with GHD, as well as to determine the effect of GH replacement on these parameters during the first year of therapy. SUBJECTS AND METHODS: Thirty pre-pubertal (Tanner stage I) GHD children and 30 matched controls were enrolled. Children with GHD were studied before and after 6 and 12 months of GH treatment. Weight, height, BMI, fasting glucose, insulin, lipid profile and serum levels of adipokines and ghrelin were studied at every visit. Adi - pokines, insulin and ghrelin levels were determined by using commercial radio- and enzymoimmunoassays. RESULTS: At baseline children with GHD had significantly higher sOBR (p<0.01) and adiponectin (p<0.01) levels than controls. Treatment with GH resulted in a decline in leptin (p<0.05) and TG (p<0.001) levels, an increase of homeostasis model assessment index and restored IGF-I levels (p<0.001). CONCLUSIONS: These data indicate that GH replacement has a negative effect on leptin levels and may also produce a slight unfavorable effect on carbohydrate metabolism. In addition, the changes observed in the adipokine profile appear to be independent of body mass index.

Estadios de Tanner y niveles de sulfato de dehidroepiandrosterona (DHEA-S) en niños sanos de la provincia de Granada / Tanner´s staging and dehydroepiandrosterone sulphate (DHEA-S) levels in healthy children from Granada province

En el curso del crecimiento del individuo existen cambiosque implican el desarrollo sexual hasta el cuerpo adulto. Duranteeste desarrollo la maduración de la corteza suprarrenal conla consiguiente producción de DHEA (adrenarquia), precede a lapubertad. Durante la gonadarquia, cuyo inicio está mediado porhormonas hipotalámicas, es cuando tiene lugar la adquisiciónde la fertilidad y la capacidad reproductiva; para esto el DHEA,una vez sulfatado a nivel gonadal, es usado como sustrato en laproducción de andrógenos y estrógenos principales responsablesde la maduración sexual. La adrenarquia y la gonadarquiason dos acontecimientos de inicio y regulación independientepero que guardan una relación temporal directa. En este trabajohemos comparado los niveles séricos de DHEA-S de 215niños sanos de la provincia de Granada con la edad fisiológica yel desarrollo de sus caracteres sexuales. En el estudio se concluyela existencia de una dependencia entre las concentracionesséricas de DHEA-S y las edades fisiológica y ósea y el gradode madurez sexual según los estadios de Tanner, mientrasque no la hay con el sexo; además se obtienen los limites dereferencia de DHEA-S para distintos grupos de edades fisiológicay ósea y para los estadios de Tanner

The human body undergoes various changes during itsgrowth and development into sexual adolescence. In this processthe maturation of the suprarenal complex and the productionof DHEA (adrenarche) precedes the puberty. During thegonadarche, which is initiated and regulated by the hypothalamichormones, the human body reaches its fertility and reproductiveability. This involves sulfation of DHEA at gonadal leveland its use as a substrate for the production of androgenes andestrogenes, the main substances responsible for the sexualmaturation. Adrenarche and gonadarche are two independentmajor events in terms of their initiation and regulation, however,they have a temporary direct relation. In this work we haveanalysed the serum levels of DHEA-S in 215 healthy childrenresiding in the Granada province in association with their ageand signs of sexual maturation. In this study we found a correlationbetween the serum concentration of DHEA-S and thephysiological and bone age, and the stage of sexual maturationaccording to Tanner´s. However, there is no correlation with thesex. In addition, we have established limits of reference ofDHEA-S for different groups of physiologic and bone ages, aswell as for stages according to Tanner´s

Phenotypic analysis and growth response to different growth hormone treatment schedules in two siblings with an inactivating mutation in the growth hormone-releasing hormone receptor gene.

Mutations in the GHRH receptor (GHRHR) gene (GHRHR) are emerging as a common cause of familial isolated growth hormone deficiency (IGHD) type IB. The use of gonadotropin-releasing hormone (GnRH) analogues has been advocated as a tool to delay puberty in patients with isolated GH deficiency (IGHD), allowing longer time for the beneficial effect of exogenous human GH (hGH) treatment on growth. We describe two male siblings with IGHD due to a homozygous missense GHRHR mutation who, because they were started on hGH therapy at different ages, presented with different height SDS at the onset of puberty and therefore had different predicted target heights. The shorter brother was treated with GnRH analogue plus hGH for 3 years, whereas the other brother received only hGH. Despite different predicted heights at the onset of puberty, they attained similar final heights. We conclude that in patients with IGHD, GnRH analogue treatment should be considered to delay puberty and obtain a maximal growth response if hGH treatment is started in late childhood and the predicted height at puberty onset is below the genetic target.