Hormone research最新文献

Background: The most effective growth hormone (GH) treatment regimen for increasing height in short children born small for gestational age (SGA) has not been well defined.

Methods: Short SGA children (n = 151, age 3-8 years, height less than -2.5 standard deviation scores) were randomised to receive low-dose GH for 2 years (0.033/0.033 mg/kg/day, n = 51), high-dose GH for 1 year and then no treatment for 1 year (0.100/0 mg/kg/day, n = 51) or were untreated for 1 year then received mid-dose GH for 1 year (0/0.067 mg/kg/day, n = 47). Height, bone age and adverse events were determined at check-ups every 3 months.

Results: The mean +/- SD additional height gain with GH after 1 year, relative to untreated controls, was higher with discontinuous high-dose than with continuous low-dose GH (6.5 +/- 0.2 vs. 3.3 +/- 0.2 cm). After 2 years, the additional height gain was similar between high- and low-dose GH groups (between-group treatment difference = 0.2, 95% CI = -0.8 to 1.2 cm, p = 0.702). Patients treated exclusively in the last year had a similar height gain to those in the other treatment groups (p = 0.604).

Conclusions: In short SGA children, continuous low-dose and discontinuous high-dose GH regimens were associated with similar height gain. Treatment with mid-dose GH for 1 year also led to a similar improvement in growth.

Aims: To compare the short- and long-term effects of intervention programs on body weight and cardiometabolic risk factors.

Methods: 162 obese children (6-11 years) were randomly assigned to three 12-week interventions with a 9-month follow-up period: exercise (E): 90 min moderate exercise 3 days/week (n = 52); diet (D): balanced hypocaloric diet, weekly meetings with dietician (n = 55), and diet + exercise (D+E) (n = 55). Changes in anthropometric variables, cardiometabolic profile and psychological outcome were assessed.

Results: At 12 weeks BMI-SDS, cardiometabolic profiles, and psychological score improved in all groups. The decrease in BMI-SDS was greater in D and D+E compared with E (p < 0.001), without a significant difference between the first two groups. Waist circumference and LDL cholesterol decreased more in D+E compared with E (p = 0.026 and p = 0.038, respectively). The increase in adiponectin was greater in D and D+E compared with E (p = 0.004). Anthropometric and cardiometabolic variables regressed without significant differences between groups after 9 months. However, BMI-SDS, body fat percentage and LDL cholesterol were lower compared to baseline.

Conclusions: Diet alone or combined with exercise are the most effective short-term interventions for weight loss and improved cardiometabolic profiles, without a difference between them. In the long term, obese children need the long-term support of maintenance approaches.

Aim: This phase III clinical study in growth hormone deficiency (GHD) children with growth retardation was designed to compare efficacy and safety of Omnitrope((R)) with Genotropin((R)) and assess the long-term safety and efficacy of Omnitrope((R)). The results of 7 years of treatment with Omnitrope((R)) are presented.

Patients and methods: Eighty-nine treatment-naïve, prepubertal children with GHD were randomized (part 1) to Omnitrope((R)) lyophilisate (group A, n = 44) or Genotropin((R)) (group B, n = 45) for 9 months and received a subcutaneous dose of 0.03 mg/kg/day. In part 2, patients receiving Omnitrope((R))lyophilisate continued the same treatment for a further 6 months, while patients on Genotropin((R)) were switched to Omnitrope((R)) liquid for the subsequent 6 months. In part 3, patients in both groups received Omnitrope((R))liquid for a period up to 69 months.

Results: The development of the 4 auxological parameters (height, height SD score, height velocity and height velocity SD score) and IGF-1 and IGFBP-3 levels were comparable between both groups of patients and confirmed the well-known growth response of GHD children to recombinant human GH treatment. Omnitrope((R)) was well tolerated and safe over 7 years of treatment.

Conclusion: The clinical comparability between Omnitrope((R)) and Genotropin((R)) was demonstrated within 9 months of treatment. Long-term safety and efficacy of 7 years of treatment with Omnitrope((R)) was proven.

Background/aims: Determine (1) frequency of attention-deficit hyperactivity disorder (ADHD) treatment and (2) growth responses in growth hormone (GH)-treated children who are receiving ADHD medication versus GH alone.

Methods: Prepubertal children with idiopathic short stature (ISS) or GH deficiency (IGHD) enrolled in Genentech's National Cooperative Growth Study. ADHD treatment was determined by documentation of psycho-stimulant medication use at enrollment.

Results: ADHD medication use increased from 0.8% (7/850) in 1985 to 5.8% (752/12,113) in 2005. First-year GH treatment response for ADHD + IGHD versus IGHD: 8.5 +/- 2.0 vs. 9.4 +/- 2.6 cm/year, but when adjusted for age, sex, and enrollment body mass index, the difference is clinically insignificant (-0.4 cm/year). First-year growth was similar in all ISS: 8.1 +/- 1.9 versus 8.6 +/- 2.1 cm/year (ADHD + ISS vs. ISS, an adjusted -0.2-cm/year difference).

Conclusion: Increasing numbers of GH-treated children are taking ADHD medications and their growth responses during the first year of GH therapy are similar to those not taking ADHD medications.

Background: Sotos syndrome is an autosomal dominant disease characterized by tall stature, advanced bone age, typical morphological abnormalities of the face and developmental delay. It is caused by mutations in the NSD1 gene located on chromosome 5. NSD1 mutations are detected in the majority of the Sotos patients, and include intragenic NSD1 mutations and microdeletions in the 5q35 region. Cardiovascular and urogenital symptoms are more frequent in the microdeletion group.

Methods: Mutation analysis was performed in 4 patients with Sotos syndrome with typical phenotypic characteristics.

Results: In each of the 4 patients a NSD1 mutation was found (2 frame shifts, 1 nonsense and 1 missense mutation). Two of our patients presented dysplastic kidneys with cysts and psychosis, respectively.

Conclusions: We describe 4 Greek patients with Sotos syndrome. Apart from the typical phenotypic characteristics, 2 of our patients presented rare clinical manifestations such as dysplastic kidneys and psychosis. The 3 detected mutations are novel.

Noonan syndrome (NS) is one of the most common syndromes transmitted by a mendelian mode. In recent years, germline mutations that affect components of the RAS-MAPK (mitogen-activated protein kinase) pathway were shown to be involved in the pathogenesis of NS and four rare syndromes with clinical features overlapping with NS: Leopard syndrome, cardio-facio-cutaneous syndrome, Costello syndrome and neurofibromatosis type 1. Several hormones act through receptors that stimulate the RAS-MAPK pathway, and therefore, NS and related disorders represent a remarkable opportunity to study the implication of the RAS-MAPK pathway in different endocrine systems. Additionally, children with NS frequently are referred to the endocrinologist because of short stature, delayed puberty and/or undescended testes in males. In this paper, we review the diagnostic, clinical and molecular aspects of NS and NS-related disorders.

Background/aims: Type 1 diabetes (T1DM) is associated with autoimmune thyroid, celiac, autoimmune gastric and Addison's disease. Our aim was to investigate the prevalence of associated autoantibodies in relation to the demographic and beta-cell autoantibody status (anti-GAD).

Methods: Antibodies against thyroid peroxidase (anti-TPO), thyroglobulin (anti-Tg), tissue transglutaminase (anti-tTG IgA), parietal cells (APCA) and adrenal tissue (AAA) were measured in 144 children with T1DM with a mean +/- SD age of 12.3 +/- 4.6 years and a diabetes duration of 4.6 +/- 3.8 years.

Results: The prevalence of antibody positivity among our patients was: anti-GAD 53.2%, anti-thyroid (anti-TPO 17.4%, anti-Tg 11.1%); anti-tTG IgA 7.6%, APCA 4.0%, and AAA 0%. Among the children with positive anti-thyroid antibodies, 60% developed autoimmune thyroiditis, while among those anti-tTG IgA positive, 62.5% developed biopsy-confirmed celiac disease. Female gender was more frequent among anti-tTG IgA-positive patients (OR 4.47, p = 0.068), while increasing age was associated with anti-Tg positivity (OR 22.9, p = 0.041). The presence of anti-thyroid antibodies was associated with the presence of anti-GAD (OR 1.45, p = 0.01) and parietal cell antibodies (OR 4.98, p = 0.09).

Conclusion: Among T1DM patients, the prevalence rates of anti-thyroid and parietal cell antibodies increased with age and diabetes duration. As the presence of anti-GAD was associated with gastric and thyroid autoimmunity, it could serve as marker for the development of additional autoimmunity in adolescents with diabetes.

Background: Valproic acid (VPA), a widely used antiepileptic drug, has broad-spectrum activity against both generalized and partial epilepsy. Among the side effects of VPA, weight gain is frequently reported, although the real incidence and magnitude of this problem is unknown. Its pathogenesis is most likely multifactorial, and is controversial.

Methods: In order to evaluate the role of hyperinsulinemia and related hormonal abnormalities in VPA-induced obesity, data from the existing literature have been analyzed and discussed critically.

Results: Patients suffering from weight gain show various metabolic and endocrinologic abnormalities. The most frequent are hyperinsulinemia and insulin resistance, hyperleptinemia and leptin resistance, and an increase in the availability of long-chain free fatty acids. Significant weight gain is associated with increased levels of insulin and leptin, suggesting a close relationship between obesity-induced hyperinsulinemia and hyperleptinemia. VPA can directly stimulate pancreatic beta-cells and indirectly enhance insulin resistance by suppressing insulin-mediated peripheral glucose uptake. Leptin activation seems to be similar in obese VPA-treated subjects to that seen in otherwise obese subjects.

Conclusions: The mechanisms of hyperinsulinemia in VPA-induced weight gain remain unclear, although it is likely that obesity is the cause of hyperinsulinemia and all related metabolic changes. However, this heterogeneous metabolic disorder requires further research.

Unlabelled: Preterm ovarian hyperstimulation syndrome (POHS) is a rare condition in which immaturity of the gonadal axis is accepted as the cause. Based on our case and 8 cases from the literature, we made an attempt to specify the mechanisms underlying the syndrome and its pathognomonic signs. All POHS newborns were born between 24 and 31 weeks postconception age (WPCA) and developed vulvar, hypogastric and upper leg swelling, and ovarian follicular cyst/cysts (10-40 mm in diameter) with mildly or considerably elevated E(2) concentrations (80-5,300 pmol/l) between 35 and 39 WPCA. The GnRH test, performed in 5 cases, confirmed gonadal axis activation. In our case the observed normalization of elevated gonadotropin values by 43 WPCA, accompanied by a simultaneously increasing E(2) value (approximately 800 pmol/l), could correspond with the maturation of the gonadal steroid-dependent negative-feedback mechanism. The continuously increasing E(2) levels after this period (maximum 1,300 pmol/l) suggest its autonomous secretion. In all the cases, including 3 neonates treated with medroxyprogesterone and surgery, the swelling resolved by 6 months.

Conclusions: A pathognomonic sign of POHS is swelling which develops around 37 +/- 3 WPCA, and the syndrome is only infrequently diagnosed when the swelling is profound. The direct etiologic factor here is not E(2). POHS does not require therapy as long as there is no danger of cyst torsion.

Background: With a reported incidence of 1 to 2 cases per million, adrenocortical cancer (ACC) is a rare disease with poor prognosis. Age distribution shows two peaks: early childhood and between age 40 and 50 years, with females more frequently affected. Sequelae can include Cushing syndrome, virilization and hypertension or local symptoms consistent with abdominal obstruction. Although most cases of ACC are of sporadic origin, they may also occur as part of a congenital or familial disease in which the genetic abnormalities are well established. ACC can also be discovered incidentally in asymptomatic individuals. In sporadic ACC, some molecular modifications are commonly observed (i.e., overexpression of insulin-like growth factor II or vascular endothelial growth factor and somatic mutations of tumor protein 53). When surgical resection of the tumor is impossible or ineffective, chemotherapy with etoposide, doxorubicin and cisplatin plus mitotane or with streptozotocin plus mitotane is frequently used; however, the overall survival rates are disappointing.

Conclusions: Hormonal evaluation is essential to diagnose ACC and the prognosis depends on many factors. New treatments, such as insulin-like growth factor I receptor antibodies, tyrosine kinase inhibitors and other antiangiogenic compounds, are now being intensively investigated to identify better therapies for this extremely severe malignant neoplasia.