Endocrine Abstracts

Background: In addition to its normal spectrum of metabolic effects, insulin has been identified as a growth factor capable of promoting mitogenic activities. Thus, hyperinsulinemia, a consequence of insulin resistance, is regarded as a potential risk factor for the development of cancer in patients with diabetes. However, the mechanism of action of insulin in prostate cancer has not yet been completely elucidated. The aim of this study was to investigate whether insulin can d...

Background: IGF1R targeting emerged in recent years as a promising therapeutic approach in prostate cancer (PCa). The insulin receptor (IR) shares high structure homology with the IGF1R and activates similar signaling cascades. In recent studies we have shown that insulin’s mitogenic activities in PCa cells are mediated via the IR. Given the central role of IR in regulation of metabolism, most anti-IGF1R therapeutic strategies were designed to specifically inhibit IGF1R, ...

One major issue regarding the clinical use of many peptides is their short half-life span in the body, due to the rapid clearance from the circulation. Thus, at the clinical level, there is a need for a regime of frequent injections of the peptides into the patients to overcome this low stability factor. To overcome this problem, we succeeded to add the signal sequence of O-linked oligosaccharides to the coding sequence of the hormones. The cassette gene that has been u...

Objective: The concentration of GH (hGH) is important in the attribution of hGH therapy, for which in The Netherlands a national committee is responsible. Without this authorization re-imbursement is impossible. Therapy is permitted if all hGH concentrations after two stimulation tests are below 20 mU/l and in some clinical conditions independent of hGH. However, different assays produce different results and nationwide hGH results varied with CV ~30%. Consequently, authorizat...

Ghrelin requires a fatty acid modification for binding to the GH secretagogue receptor. Octanoylation of the Ser3 residue of ghrelin is essential for ghrelin-mediated stimulation of GH secretion and regulation of energy homeostasis via increased food intake and adiposity. Other than octanoylation (C8:0), the hormone is subject to other types of acyl modification, decanoylation (C10:0), and possibly decenoylation (C10:1). The fatty acid substrate that contributes to ghrelin acy...

Objectives: Angiotensin II (AngII) induces renal premature senescence by multiple mechanisms including by increasing oxidative stress. Recent study revealed that growth hormone secretagogue ghrelin exerts anti-senescence effects. In this study, we examined whether ghrelin inhibits AngII-induced renal senescence and damages.Methods: Renal senescence was induced by infusion of Ang II in C57BL/6 mice with osmotic mini-pump. Ghrelin was administered by the d...

Aim: We investigated the influence of mitochondrial dysfunction associated with aging on physical performance in mice, and the effect of hormone replacement on physical performance.Method: Using 8, 20, 50 and 100 week-old C57bl6 mice, we evaluated skeletal muscle mass, mitochondrial activity, glucose tolerance and physical performance (muscle power and exercise endurance). In addition, we treated 50-week-old mice with ghrelin or insulin like growth facto...

Background: About 3% of all children are short statured. Clinically GH deficiency (GHD) or idiopathic short stature (ISS) is frequently diagnosed. GH (GH−) treatment, which is primarily indicated for GHD patients, is provided not only to increase height, but also to improve psychological functioning and raise health related quality of life. The present study examines these psychosocial outcomes in young German patients and their parents, and analyzes differences accordin...

Introduction: Acromegalic patients have an increased risk of developing colorectal neoplasms (CN). A common polymorphism (C677T) in gene coding for methylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism and in DNA synthesis, reparation and methylation, has been associated with CN risk in general population, but its role in acromegalic patients has never been explored yet.Aim: To investigate the contribution of MTHFR C677T polymorp...

Context: Ectopic GHRH secretion is a rare cause of acromegaly described mainly in isolated case reports.Setting: From the registry of the sole laboratory performing plasma GHRH assays in France, we identified cases of ectopic GHRH secretion presenting with acromegaly between 1983 and 2008.Patients: In total, 21 patients aged 14–77 years, from 12 French hospitals. Median GHRH was 548 ng/l (270–9779)....

Aim: GH is used to treat short stature in children with GH deficiency (GHD), Turner syndrome (TS) and born small for gestational age (SGA). As GH is injected daily, treatment adherence may be problematic. To maximise adherence, improvements in injection devices have been targeted. This report compares intuitiveness and ease of use of two disposable GH devices: Norditropin NordiFlex (NF; Novo Nordisk A/S, Bagsværd, Denmark) and GoQuick (GQ, Pfizer, Inc., New York, USA).</p...

Although GH has been implicated in the pathogenesis of retinopathy in diabetic subjects, the frequency of retinopathy in diabetic acromegalic subjects is deemed to be rare. The aim of our study is to evaluate the prevalence of retinopathy in hypersomatotropic patients.Subjects and methods: In total, 40 acromegalic diabetic patients (21 M, 19 F, mean age=50 years) underwent funduscopy to search for diabetic retinopathyResults: Among...

In children whose height is substantially below norms, behavioural and emotional problems can be experienced. When evaluating the outcomes of treatments or making treatment decisions, health related quality of life (HrQoL) should be taken into consideration. At present, no standardised HrQoL instrument for short stature youth exists. Through consensus building in five countries, the objective of this study was to develop and psychometrically test a growth-related HrQoL instrum...

Background: GH replacement during the childhood-adult transition period is important for somatic maturation. The aim of the study was to explore the factors influencing IGF1 response to GH during transition.Methods: KIMS (Pfizer International Metabolic Study) database in UK was interrogated, and 98 patients (55 male, median age 20.7 years (15.7–25.8)) with childhood-onset GH deficiency (Co-GHD), who were started on adult dose of GH during transition...

GH is used primarily to increase adult height in short children with GHD/NSD with little knowledge about the impact of GH on health-related quality of life (HRQoL). Therefore this study was carried out to evaluate HRQoL in adult patients with childhood onset GHD/NSD at the end of GH therapy.HrQoL was measured by patient self-report using two generic questionnaires, SF36 and NHP. Patient data were compared to representative norm data. Clinical data as wel...

Studies showed an increase of cardiovascular risk (CVR) and reduction of the life expectancy observed in the anterior pituitary insufficiency (API) subjects. The morbimortality would be related to GH deficiency not substituted.Aim: To seek the frequency of the hypertension and analyse the predictive factors in subjects with API.A retrospective study relating 55 (47 women, eight men) subjects with API: interrupted pituitarystalk n:6...

In pigs, the assembly of primordial follicles and their subsequent transition to the primary stage occur in the late gestational and neonatal period. Previously, we reported the presence of androgen receptors in the porcine fetal ovary on different days of gestation, which suggests a fetus capacity to respond to androgens. Since testosterone was detected in the plasma of porcine female fetuses during the second half of pregnancy, it is possible that androgens are involved in p...

Introduction: The GH/insulin-like growth factor 1 (IGF1) system may modulate the pituitary-gonadal axis in males. Direct pituitary and/or testicular effects might be involved, as well as indirect effects on sex hormone binding globulin (SHBG) and aromatase activity.Methods/design: Nine healthy male volunteers (mean age 37, range 29–49 years) were treated in random order with increasing doses of GH for three weeks (1st week 0.01, 2nd week 0.02, 3rd 0...

Patients with craniopharyngioma (CP) are more often operated by transcranial route than patients with nonfunctioning pituitary adenoma (NFPA), have higher prevalence of pituitary deficiencies, are more obese and dyslipidemic and have a higher mortality rate. A previous study in a large group of GHD subjects, showed that the effects of 2-year rhGH replacement are similar in patients operated for CP and in patients operated for NFPA, except for less reduction in fat mass in CP p...

Introduction: Pegvisomant is indicated for acromegaly. Doses >20 mg are not commercially available, although daily doses up to 30 mg are approved.Objectives: 1. To estimate the relative bioavailability (relBA) of single-dose pegvisomant s.c. administrations, one injection of 30 mg/ml (1×30) vs two injections of 15 mg/ml (2×15), and 2. To evaluate their pharmacokinetics (PK), safety and tolerability.Methods: This was a...

Alterations in the thyroid axis have been reported following GH therapy both in adults and children with GH deficiency (GHD), even if the clinical significance of these changes, in small and short-term studies, remains uncertain. To evaluate the impact of GH replacement on thyroid status in a large selected cohort of prepubertal children with idiopathic GHD during a 3-years follow-up. Study outcome considered FT3, FT4 and TSH modifications (delta) during therapy and their corr...

IGF1 represent an important key player in several physiologic process, so it can be implicated in different pathologies among delays of growth. A comparative study was realized comparing a group of healthy Algerian children of normal size (n: 266) and a group presenting a GH deficiency (GHD n: 107)to a group of healthy westerners children of normal size(Serie of ROSENFIELD).The results are as follows: Before the age of 04 years, there is a ...

One of the most clinical characteristic of Turner’s syndrome is the final short stature.In order to cure this handicap, several teams were interested to treat these patients by the GH.We report two cases of Turner syndrome associated with GH deficiency.In the first, a 17 years old girl, having a delayed growth lower than −4 S.D. associated with delayed puberty and dysmorphic syndrome...