Serum Insulin-like Growth Factor-1 Concentrations Research Articles

Safety, tolerability, and preliminary efficacy of an IGF-1 mimetic in patients with spinal and bulbar muscular atrophy: a randomised, placebo-controlled trial

Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by CAG repeat expansion in the androgen receptor gene. Patients with this disease have low concentrations of insulin-like growth factor-1 (IGF-1), and studies of overexpression and administration of IGF-1 showed benefit in a transgenic model; thus the IGF-1 pathway presents as a potential treatment target. We assessed safety, tolerability, and preliminary efficacy of BVS857, an IGF-1 mimetic, in patients with spinal and bulbar muscular atrophy. In this randomised, double-blind, placebo-controlled trial, we recruited patients from neuromuscular centres in Denmark (Copenhagen), Germany (Ulm), Italy (Padova), and three sites within the USA (Bethesda, MD; Irvine, CA; and Columbus, OH). Eligible patients were 18 years or older with a confirmed genetic diagnosis of spinal and bulbar muscular atrophy, were ambulatory, had symptomatic weakness, and had serum IGF-1 concentrations of 170 ng/mL or lower. Patients were randomly assigned (2:1) to study drug or placebo by a number scheme. Patients, investigators, and study personnel were masked to treatment assignment. After a safety and tolerability assessment with eight patients, BVS857 was administered once a week (0·06 mg/kg intravenously) for 12 weeks. Primary outcome measures were safety, tolerability, and the effects of BVS857 on thigh muscle volume (TMV) measured by MRI. The ratio of TMV at day 85 to baseline was analysed with ANCOVA per protocol. Secondary outcomes of muscle strength and function were measured with the Adult Myopathy Assessment Tool, lean body mass through dual energy x-ray absorptiometry, and BVS857 pharmacokinetics. This trial was registered with ClinicalTrials.gov, NCT02024932. 31 patients were assessed for eligibility, 27 of whom were randomly assigned to either BVS857 treatment (n=18) or placebo (n=9), and 24 were included in the preliminary efficacy analysis (BVS857 group, n=15; placebo group, n=9). BVS857 was generally safe with no serious adverse events. No significant differences were found in adverse events between the BVS857 and placebo groups. Immunogenicity was detected in 13 (72%) of 18 patients in the BVS857 group, including crossreacting antibodies with neutralising capacity to endogenous IGF-1 in five patients. TMV decreased from baseline to day 85 in the placebo group (-3·4% [-110 cm3]) but not in the BVS857 group (0% [2 cm3]). A significant difference in change in TMV was observed in the BVS857 group versus the placebo group (geometric-mean ratio 1·04 [90% CI 1·01-1·07]; p=0·02). There were no differences between groups in measures of muscle strength and function. TMV remained stable in patients with spinal and bulbar muscular atrophy after being given BVS857 for 12 weeks. The intervention was associated with high incidence of immunogenicity and did not improve muscle strength or function. Additional studies might be needed to assess the efficacy of activating the IGF-1 pathway in this disease. Novartis Pharmaceuticals and the US National Institutes of Health.

The relationship between serum insulin-like growth factor-1 (IGF-1) concentration and reproductive performance, and genome-wide associations for serum IGF-1 in Holstein cows

The objectives of this study were to determine (1) factors associated with serum concentration of insulin-like growth factor-1 (IGF-1); (2) the relationship between serum IGF-1 concentration during the first week postpartum and ovarian cyclicity status by 35 d postpartum (DPP); (3) an optimum serum IGF-1 concentration threshold predictive of pregnancy to first artificial insemination (P/AI), including its diagnostic values; (4) the associations among categories of serum IGF-1 concentration and reproductive outcomes (P/AI and pregnancy risk up to 150 and 250 DPP); and (5) single nucleotide polymorphisms (SNP) associated with phenotypic variation in serum IGF-1 concentration in dairy cows. Serum IGF-1 concentration was determined at 7 (±2.4; ±standard error of the mean) DPP in 647 lactating Holstein cows (213 primiparous, 434 multiparous) from 7 herds in Alberta, Canada. The overall mean, median, minimum, and maximum serum IGF-1 concentrations during the first week postpartum were 37.8 (±1.23), 31.0, 20.0, and 225.0 ng/mL, respectively. Herd, age, parity, precalving body condition score, and season of blood sampling were all identified as factors associated with serum IGF-1 concentrations. Although serum IGF-1 concentration during the first week postpartum had no association with ovarian cyclicity status by 35 DPP in primiparous cows, it was greater in cyclic than in acyclic multiparous cows (32.2 vs. 27.4 ng/mL, respectively). The optimum serum IGF-1 thresholds predictive of P/AI were 85.0 ng/mL (sensitivity = 31.9%; specificity = 89.1%) and 31.0 ng/mL (sensitivity = 45.5%; specificity = 66.9%) for primiparous and multiparous cows, respectively. When cows were grouped into either high or low IGF-1 categories (greater or less than or equal to 85.0 ng/mL for primiparous cows and greater or less than or equal to 31.0 ng/mL for multiparous cows, respectively), primiparous cows with high IGF-1 had 4.43 times greater odds of P/AI and a tendency for higher pregnancy risk up to 150 DPP than those with low IGF-1, but not up to 250 DPP. Likewise, multiparous cows with high IGF-1 had 1.61 times greater odds of P/AI than those with low IGF-1. Pregnancy risk up to 150 and 250 DPP, however, did not differ between IGF-1 categories in multiparous cows. Moreover, 37 SNP across 10 Bos taurus autosomes were associated with variation in serum IGF-1 concentration, and 4 previously identified candidate genes related to fertility that were in linkage disequilibrium with some of these SNP were also identified.

Trajectories of Growth and Serum DHEAS and IGF-1 Concentrations in Girls With a History of Premature Adrenarche: Attenuation of the Phenotype by Adulthood.

Background: It has been speculated that premature adrenarche (PA) could lead to unfavorable outcome, including shorter adult stature, but longitudinal follow-up data are insufficient.Methods: This prospective case-control study included 30 PA and 42 control females who were born mostly full-term and appropriate for gestational age. They were examined first at the median age of 7.6 years and now at 18.1 years. Main outcome measures were height, body mass index (BMI), age at menarche, and serum dehydroepiandrosterone sulfate (DHEAS) and insulin-like growth factor 1 (IGF-1) concentrations.Results: The PA and control females had comparable mean (standard deviation) adult height [167.2 (6.8) vs. 164.5 (5.1) cm, P = 0.059] and median (25th–75th percentiles) BMI [22.8 (21.1–28.9) vs. 21.6 (19.8–24.3) kg/m2, P = 0.068, respectively]. Adult heights were comparable with the mid-parental heights in both study groups. The PA females were taller than the controls until the age of 12 years and they lacked a distinct pubertal growth spurt. Serum DHEAS and IGF-1 concentrations did not differ between the PA and control groups at the age of 18 years. Median (range) age at menarche was significantly lower in the PA than control females [11.5 (9.5–15.0) vs. 13.0 (10.0–15.0), P = 0.001].Conclusions: Although PA girls have advanced growth and earlier pubertal development together with a tendency to be more overweight, their height, BMI, and serum DHEAS and IGF-1 concentrations are comparable to those of their peers at the age of 18 years. Our findings indicate a benign outcome of PA in appropriate for gestational age -born females concerning adult height and adrenal androgen secretion.

Growth Hormone Treatment in Children Born Small for Gestational Age (SGA).

Abstract Introduction: Growth failure is a common consequence in small for gestational age (SGA) children. Patients and Methods: The growth patterns and serum insulin like growth factor 1 (IGF1) concentrations before and after the 1st year under growth hormone treatment of 32 short stature SGA born children have been evaluated. In addition, we investigated the insulin like growth factor 1 receptor (IGF1R) exon 2 as a hotspot for IGF1R genetic alterations. It is of note that no dysmorphic features were observed in this group of children. Results: The tests for pituitary reserve were within normal ranges for all 32 patients. Growth hormone (GH) treatment (0.037 mg/kg/day) was initiated at the mean age of 9.32±3.19 years. Growth velocity increased yearly from −1.80 SDS after the first year to −0.03 SDS in the sixth year of treatment. Their IGF1 serum concentrations before treatment were age and sex appropriate, while during treatment a significant increase was observed fitting in the upper third of the normal range: before the treatment IGF1 SDS was 0.84±1.78 after 1st year the concentrations increased to IGF1 SDS 0.94±2.23. No genetic alterations were found in the IGF1R exon 2 by PCR analysis. Conclusions: Herein we present 32 short stature SGA children with no dysmorphic features treated with GH. They all had increased growth velocity and entered the normal growth range on their growth charts. No side-effects were observed. GH treatment in children with no genetic alterations on the IGF1R exon 2 is safe and efficient in treating SGA children with short stature.

Methyl donors dietary supplementation to gestating sows diet improves the growth rate of offspring and is associating with changes in expression and DNA methylation of insulin-like growth factor-1 gene.

The study aimed to investigate the effects of maternal dietary methyl donors on the performance of sows and their offspring, and the associated hepatic insulin-like growth factor-1 (IGF-1) expression of the offspring. A total of 24 multiparous sows were randomly fed the control (CON) or the CON diet supplemented with methyl donors (MD) at 3g/kg betaine, 15mg/kg folic acid, 400mg/kg choline and 150μg/kg VB12 , from mating until delivery. After farrowing, sows were fed a common lactation diet through a 28-days lactation period and six litters per treatment were selected to be fed until at approximately 110kg BW. Maternal MD supplementation resulted in greater birthweight (p<0.05) and increased the piglet weights (p<0.01) and litter weights (p<0.05) at the age of day 28, compared with that in CON group. The offspring pigs in the MD group had greater ADG (p<0.05) and tended to lower F:G ratio (p=0.07) compared with that of CON group from day 28 to 180 of age. The offspring pigs from MD group had greater serum IGF-1 concentrations and expressions of hepatic IGF-1 gene and muscular IGF-1 receptor (IGF-1r) protein at birth (p<0.05), and greater hepatic IGF-1 protein (p=0.03) and muscular IGF-1r gene expressions (p<0.05) at slaughter, than that from the CON group. Moreover, the methylation at the promoter of IGF-1 gene in the liver of newborn piglets and finishing pigs was greater in the MD group than that of the CON group (p<0.05). In conclusion, maternal MD supplementation throughout gestation could enhance the birthweight and postnatal growth rate of offspring, associated with an increased expression of the IGF-1 gene and IGF-1r, as well as the altered DNA methylation of IGF-1 gene promotor.

Changes in hormone profiles, growth factors, and mRNA expression of the related receptors in crop tissue, relative organ weight, and serum biochemical parameters in the domestic pigeon (Columba livia) during incubation and chick-rearing periods under artificial farming conditions.

The present study was conducted to determine the changes in concentrations of hormones and growth factors and their related receptor gene expressions in crop tissue, relative organ weight, and serum biochemical parameters in male and female pigeons during incubation and chick-rearing periods under artificial farming conditions. Seventy-eight pairs of 60-week-old White King pigeons with 2 fertile eggs per pair were randomly divided into 13 groups by different breeding stages. Serum prolactin and insulin-like growth factor-1 (IGF-1) concentrations in crop tissue homogenates were the highest in both male and female pigeons at 1 d of chick-rearing (R1), while epidermal growth factor (EGF) in female pigeons peaked at d 17 of incubation (I17) (P < 0.05). mRNA expression of the prolactin and EGF receptors in the crop tissue increased at the end of incubation and the early chick-rearing stage in both sexes. However, estrogen, progesterone, and growth hormone receptor expression each decreased during the early chick-rearing stage (P < 0.05). In male pigeons, IGF-1 receptor gene expression reached its peak at R7, while in female pigeons, it increased at the end of incubation. The relative weight of breast and abdominal fat in both sexes and thighs in the males was lowest at R7, and then gradually increased to the incubation period level. Serum total protein, albumin, and globulin concentrations increased to the highest levels at I17 (P < 0.05). Total cholesterol, triglyceride, and low-density lipoprotein reached their highest values at I17 in male pigeons and R25 in female pigeons (P < 0.05). In conclusion, hormones, growth factors, and their receptors potentially underlie pigeon crop tissue development. Changes in organs and serum biochemical profiles suggested their different breeding-cycle patterns with sexual effects.

Evaluation of serum insulin-like growth factor-1 and 26S proteasome concentrations in healthy dogs and dogs with chronic diseases depending on body condition score

In patients suffering from chronic diseases, the objective assessment of metabolic states could be of interest for disease prognosis and therapeutic options. Therefore, the aim of this study was to assess insulin-like growth factor-1 (IGF-1) and 26S proteasome (26SP) in healthy dogs and dogs suffering from chronic diseases depending on their body condition score (BCS) and to examine their potential for objective assessment of anabolic and catabolic states. Serum concentrations of IGF-1, an anabolic hormone, and 26SP, a multiprotein complex which is part of the ubiquitin-proteasome pathway, by which the majority of endogenous proteins including the muscle proteins are degraded, were measured in 21 healthy dogs and 20 dogs with chronic diseases by canine ELISA. The concentrations of IGF-1, 26SP and their ratio (IGF-1/26SP) were set in relationship to the BCS of the dogs. When examining healthy and chronically diseased dogs separately, a positive correlation between IGF-1 and the BCS was observed in the healthy group and a negative correlation between 26SP and the BCS was noted in dogs with chronic diseases. Further, dogs suffering from chronic diseases showed higher 26SP concentrations and lower values for IGF-1/26SP than the healthy dogs. Overall, we detected a negative correlation between 26SP and the BCS and a positive correlation between IGF-1/26SP and the BCS. The results of our study indicate usability of IGF-1 for description of anabolic states, while 26SP could be useful for detection and description of catabolic states. Finally, the ratio IGF-1/26SP seems to be promising for assessment of metabolic states.

Relative Bioavailability of a Single 4-mg Dose of Somatropin Administered by Subcutaneous Injection or by Needle-free Device and Coadministered With the Growth Hormone Inhibitor Octreotide Acetate in Healthy Adult Subjects

PurposeSomatropin, used to treat growth hormone deficiency, has been traditionally administered by subcutaneous (SC) injection with needle and syringe. Needle-free devices offer ease of administration and may improve adherence and outcomes. This study evaluated the relative bioavailability of somatropin delivered with a needle-free device compared with traditional SC injection. MethodsIn this randomized, single-dose, crossover study, healthy adults aged 18 to 35 years received single 4-mg doses of somatropin via a needle-free device or SC injection, along with octreotide to suppress endogenous growth hormone production. Blood samples were analyzed for serum somatropin and insulin-like growth factor-1 (IGF-1) concentrations over 24 hours after somatropin dosing. Pharmacokinetic and pharmacodynamic parameters were evaluated by using noncompartmental methods, and bioequivalence was determined based on ln transformation of the AUC0–24, AUC0–∞, Cmax, area under the effect-time curve from time 0 to 24 hours (AUEC0–24), and maximum effect concentration (Emax). Bioequivalence was concluded if the 90% CIs of the needle-free device compared with the SC injection, constructed by using the two 1-sided hypotheses at the α = 0.05 level, for these pharmacokinetic/pharmacodynamic parameters fell within the 80.00% to125.00% regulatory acceptance range. FindingsA total of 57 subjects completed both study periods and were included in the pharmacokinetic analyses. Point estimates (90% CIs) of the geometric mean ratio (needle-free device/SC injection) based on serum somatropin were 1.013 (0.987–1.040) for AUC0–24, 1.012 (0.986–1.038) for AUC0–∞, and 1.200 (1.137–1.267) for Cmax. For IGF-1, baseline-corrected point estimates (90% CIs) were 0.901 (0.818–0.993) for AUEC0–24 and 0.867 (0.795–0.946) for Emax. Non–baseline-corrected values were 0.978 (0.953–1.004) for AUEC0–24 and 0.953 (0.923–0.984) for Emax. Both treatments were well tolerated; blood glucose levels increased in nearly all subjects (98.3%). All adverse events were mild and resolved spontaneously within 24 hours. ImplicationsBioequivalence was shown for a single 4-mg dose of somatropin delivered by using a needle-free device compared with SC injection based on ln-transformed AUC0–24 and AUC0–∞ but not ln-transformed Cmax.

The Impact of Continuous Positive Airway Pressure on Circulating IGF-1 in Patients With Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a disease with metabolic and cardiovascular consequences and is associated with decreased serum concentrations of insulin-like growth factor-1 (IGF-1). The aim of this study was to investigate whether continuous positive airway pressure (CPAP) will increase serum IGF-1 concentration in patients with OSA. Patients with moderate to severe OSA were recruited from a sleep clinic and serum IGF-1 was measured before initiation of CPAP and at follow-up after 4.8 ± 2.5 months. Patients adherent to CPAP treatment (usage ≥ 4 h/night) were compared with those considered to be nonadherent (usage < 4 h/night). Complete data were obtained from 69 patients (86% male, age 56 ± 12 years, respiratory event index 43 ± 21 events/h, Epworth Sleepiness Scale score 12 ± 5). In those adherent to CPAP (n = 42), there was an increase in serum IGF-1 concentration with 21.1 (95% confidence interval [CI]: 13.1 to 29.2) μg/L compared to 4.7 (95% CI: -4.1 to 13.5) μg/L in the nonadherent group (n = 27) (P = .0083). In a linear multivariate model adjusting for sex, age, body mass index, respiratory event index, and mean oxygen saturation during the night recording, the change in serum IGF-1 concentration was significantly associated with adherence to CPAP treatment (adjusted β coefficient: 21.8, 95% CI: 10.2 to 33.4) and inversely associated with change in body mass index (adjusted β coefficient: -7.1, 95% CI: -11.3 to -3.0) and change in hemoglobin A1c (adjusted β coefficient: -1.8, 95% CI: -33 to -0.3). CPAP usage ≥ 4 h/night is associated with increased serum IGF-1 concentration in male patients with OSA.

Upregulation of GH, but not IGF1, in the hippocampus of the lactating dam after kainic acid injury

Lactation embodies a natural model of morphological, neurochemical, and functional brain plasticity. In this reproductive stage, the hippocampus of the female is less sensitive to excitotoxins in contrast to nulliparity. Growth hormone (GH) and insulin-like growth factor 1 (IGF1) are known to be neuroprotective in several experimental models of brain lesion. Here, activation of the GH–IGF1 pituitary–brain axis following kainic acid (7.5 mg/kg i.p. KA) lesion was studied in lactating and nulliparous rats. Serum concentrations of GH and IGF1 were uncoupled in lactation. Compared to virgin rats, the basal concentration of GH increased up to 40% but IGF1 decreased 58% in dams, and only GH increased further after KA treatment. In the hippocampus, basal expression of GH mRNA was higher (2.8-fold) in lactating rats than in virgin rats. GH mRNA expression in lactating rats increased further after KA administration in the hippocampus and in the hypothalamus, in parallel to GH protein concentration in the hippocampus of KA-treated lactating rats (43% vs lactating control), as detected by Western blot and immunofluorescence. Except for the significantly lower mRNA concentration in the liver of lactating rats, IGF1 expression was not altered by the reproductive condition or by KA treatment in the hippocampus and hypothalamus. Present results indicate upregulation of GH expression in the hippocampus after an excitotoxic lesion, suggesting paracrine/autocrine actions of GH as a factor underlying neuroprotection in the brain of the lactating dam. Since no induction of IGF1 was detected, present data suggest a direct action of GH.

Diagnostic Usefulness of Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor Binding Protein 3 in Children with Suspected Pituitary Dwarfism

Pituitary dwarfism (also known as short stature) is a medical condition in which the pituitary gland does not produce enough growth hormone (GH). To confirm the diagnosis of growth hormone deficiency the overnight profile of GH secretion and GH provocative tests are usually performed; however, due to wide GH fluctuations throughout the day and night and the invasiveness of stimulation tests, their clinical utility is limited. Therefore, screening for IGF-1 (insulin-like growth factor 1) and IGFBP-3 (insulin-like growth factor binding protein type 3) is proposed, suggesting that these tests provide a more accurate reflection of the mean plasma GH level, although the results of these tests are still problematic. In this context, the aim of this study was to assess the diagnostic usefulness of IGF-1 and IGFBP-3 in children with suspected pituitary dwarfism. Studies were carried out in 127 children with abnormal growth and low spontaneous 24-hour plasma GH profiles and abnormal results of GH stimulation tests. Fasting serum IGF-1 and IGFBP-3 were determined by chemiluminescent quantitative measurement using the IMMULITE 1000 IGF-1 and IGFBP-3 kits (Siemens Healthcare Diagnostics, United Kingdom) on the IMMULITE 1000 analyzer (Siemens Healthcare Diagnostics, USA). Results were compared to the normal range by children's age. Mean serum IGF-1 concentrations were within the lower normal range (41.7% cases), and 58.3% results were below the normal reference range in the study group. The average serum IGFBP-3 levels were within the lower normal range. We conclude that IGF-1 test can be a useful tool in the diagnosis of pituitary dwarfism in children suspected of this condition, but due to relatively poor sensitivity the testing cannot be performed alone, but in combination with other tests. The IGFBP-3 test is not useful for the diagnosis of this disease.

Polymorphisms of the IGF1 gene and their association with growth traits, serum concentration and expression rate of IGF1 and IGF1R in buffalo.

The insulin-like growth factor 1 (IGF1) gene is a member of the group of somatotropin axis genes that play a significant role in cell proliferation and growth of muscles. Here, we searched for polymorphisms in buffalo IGF1 and found two novel single nucleotide polymorphisms (SNPs), G64A and G280A, in the noncoding sequences of exon 1 and exon 4, respectively. Statistical analysis of different genotypes showed that the individuals with GG genotypes had significantly (P<0.05) higher body weight (BW) and average daily gain (ADG) than those with other genotypes at ages of 3-6 months in G64A SNP and 6-9 months in G280A SNP. The combined genotypes of these two SNPs produced three haplotypes, GG/GG, AG/AG, and AA/AA, which were significantly associated (P<0.0001) with BW and ADG at an age from 3 to 12 months. Buffaloes with the homozygous GG/GG haplotype showed higher growth performance than other buffaloes. The two SNPs were correlated with mRNA levels of IGF1 and IGF1 receptor (IGF1R) in semitendinosus muscle as well as with the serum concentration level of IGF1. Also, buffaloes with GG/GG haplotype showed higher mRNA and serum concentration levels. The data revealed that these two SNPs could be valuable genetic markers for selection of Egyptian buffaloes for better performance in the population.

Associations of lifestyle factors with serum dehydroepiandrosterone sulphate and insulin-like growth factor-1 concentration in prepubertal children.

Little is known about the relationships of dietary factors, physical activity and sedentary behaviour to dehydroepiandrosterone sulphate (DHEAS) and insulin-like growth factor-1 (IGF-1) concentrations among prepubertal children. Therefore, we studied the associations of these lifestyle factors with serum DHEAS and IGF-1 in children. Cross-sectional analysis of a population sample of 431 prepubertal children aged 6-9years. Assessment of dietary factors by food records and physical activity and sedentary behaviour by a combined heart rate and movement monitor and a questionnaire. Measurement of serum DHEAS and IGF-1. Consumption of low-fibre grain products (standardized regression coefficient β=.118, P=.017) and intake of vegetable protein (β=.100, P=.045) was positively and consumption of sugar-sweetened beverages (β=-.117, P=.018) was inversely associated with DHEAS after adjustment for sex, age and body fat percentage. Energy intake (β=.160, P=.001) was positively associated with IGF-1 adjusting for sex, age and body fat percentage. Vigorous physical activity was inversely associated with DHEAS after adjustment for sex and age (β=-.120, P=.027), and total (β=-.137, P=.007), moderate (β=-.130, P=.012), vigorous (β=-.136, P=.011) and moderate to vigorous physical activity (β=-.160, P=.003) were inversely and total sedentary behaviour (β=.151, P=.003) was positively associated with IGF-1 adjusting for sex and age. None of physical activity measures was associated with DHEAS or IGF-1 after additional adjustment for body fat percentage. Lifestyle factors have weak and moderate associations with biochemical markers of adrenarche in prepubertal children. These associations indicate body fat independent and dependent influences of diet and physical activity, respectively.

The key role of targeted betacarotene supplementation on endocrine and reproductive outcomes in goats: Follicular development, ovulation rate and the GH-IGF-1 axis

The possible effects of betacarotene (BC) supplementation on the secretion pattern of growth hormone (GH) and insulin-like growth factor-1 (IGF-1), and their possible relationship with total ovarian activity (TOA), was evaluated in adult goats during the breeding season. In October, goats [n=22, 3.5y. old, 7/8 Sannen-Alpine] were randomly assigned to: a) Betacarotene group [BC, n=10; 45.9±1.97kg live weight (LW), 3.04±0.08 units, body condition score (BCS), supplemented with 50mg of BC goat day−1], and b) Control group [CONT, n=12; 46.2±2.04kg LW, 3.0±0.08 units, BCS]. An ultrasonographic scan was performed to evaluate corpus luteum number (OR) and antral follicle number (AF); TOA=OR+AF. Average LW and BCS did not differ (p>0.05) during the experimental period, yet BC-goats reflected an increased OR (3.4±0.2 vs. 2.8±0.2), AF (5.0±0.6 vs. 3.4±0.6) and TOA (8.4±0.5 vs. 6.2±0.6). Regarding the endocrine profile, the lowest (p<0.05) serum GH average concentrations (10.0 vs. 14.3±1.0ngmL−1; p=0.01) and GH-AUC (3670.4 vs. 5235.7±369.8 units; p=0.01), were observed in the BC-supplemented group. Neither serum IGF-1 concentrations (254.6±28.9ngmL−1 p>0.05) nor GH-PULSE (1.4±0.5 pulses 6h−1 p>0.05) differed between treatments. We document a potential role of BC as modulator of somatotrophic function, decreasing mean serum concentration and the area under the curve of GH, while also noting a positive action upon ovarian function with increases in ovulation rate and antral follicular development; such outcomes may embrace not only physiologic significance but also potential translational applications.

Factors associated with survival after pancreatic cancer surgical resection

The elevation of insulin-like growth factor 1 (IGF-1) and adipokine retinol-binding protein 4 (RBP-4) is known to be associated with the risk of many cancers. The aim of this study was to evaluate the serum concentrations of IGF-1 and RBP-4 in patients with PDAC and chronic pancreatitis (CP).The study included 43 patients with PDAC, 39 patients with CP and 10 controls. The concentrations of IGF-1 and RBP-4 were obtained using the ELISA method (Corgenix UK Ltd R&D Systems). The study protocol was approved by the Bioethics Committee at the Medical University of Lodz.In PDAC patients the serum IGF-1 level was significantly higher than in patients with CP (107.79 ± 66.40 ng/ml vs 89.91 ± 74.06 ng/ml; P < 0.05). Patients with both CP and diabetes mellitus (DM) were noted to have a significantly lower level of IGF-1 compared with those who only had CP (51.33 ± 24.30 ng/ml vs 108.42 ± 82.39 ng/ml; P = 0.01). The same result was obtained for men with and without DM (58.05 ± 32.44 ng/ml vs 98.79 ± 79.47 ng/ml, P = 0.05). As regards the serum level of RBP-4, the PDAC and CP groups were not significantly different from each other.Diabetes accompanying PDAC does not influence the level of IGF-1 as opposed to diabetes in the course of CP. The IGF-1 level can be useful for early diagnosis of PDAC. High concentration of RBP-4 is not specific to pancreatic cancer, so it does not appear to be a useful biomarker for PDAC.

Hepatic modification of pancreatic exosomes in experimental acute pancreatitis

The elevation of insulin-like growth factor 1 (IGF-1) and adipokine retinol-binding protein 4 (RBP-4) is known to be associated with the risk of many cancers. The aim of this study was to evaluate the serum concentrations of IGF-1 and RBP-4 in patients with PDAC and chronic pancreatitis (CP).The study included 43 patients with PDAC, 39 patients with CP and 10 controls. The concentrations of IGF-1 and RBP-4 were obtained using the ELISA method (Corgenix UK Ltd R&D Systems). The study protocol was approved by the Bioethics Committee at the Medical University of Lodz.In PDAC patients the serum IGF-1 level was significantly higher than in patients with CP (107.79 ± 66.40 ng/ml vs 89.91 ± 74.06 ng/ml; P < 0.05). Patients with both CP and diabetes mellitus (DM) were noted to have a significantly lower level of IGF-1 compared with those who only had CP (51.33 ± 24.30 ng/ml vs 108.42 ± 82.39 ng/ml; P = 0.01). The same result was obtained for men with and without DM (58.05 ± 32.44 ng/ml vs 98.79 ± 79.47 ng/ml, P = 0.05). As regards the serum level of RBP-4, the PDAC and CP groups were not significantly different from each other.Diabetes accompanying PDAC does not influence the level of IGF-1 as opposed to diabetes in the course of CP. The IGF-1 level can be useful for early diagnosis of PDAC. High concentration of RBP-4 is not specific to pancreatic cancer, so it does not appear to be a useful biomarker for PDAC.

Role of faecal elastase in predicting echoendoscopic findings in chronic pancreatitis

The elevation of insulin-like growth factor 1 (IGF-1) and adipokine retinol-binding protein 4 (RBP-4) is known to be associated with the risk of many cancers. The aim of this study was to evaluate the serum concentrations of IGF-1 and RBP-4 in patients with PDAC and chronic pancreatitis (CP).The study included 43 patients with PDAC, 39 patients with CP and 10 controls. The concentrations of IGF-1 and RBP-4 were obtained using the ELISA method (Corgenix UK Ltd R&D Systems). The study protocol was approved by the Bioethics Committee at the Medical University of Lodz.In PDAC patients the serum IGF-1 level was significantly higher than in patients with CP (107.79 ± 66.40 ng/ml vs 89.91 ± 74.06 ng/ml; P < 0.05). Patients with both CP and diabetes mellitus (DM) were noted to have a significantly lower level of IGF-1 compared with those who only had CP (51.33 ± 24.30 ng/ml vs 108.42 ± 82.39 ng/ml; P = 0.01). The same result was obtained for men with and without DM (58.05 ± 32.44 ng/ml vs 98.79 ± 79.47 ng/ml, P = 0.05). As regards the serum level of RBP-4, the PDAC and CP groups were not significantly different from each other.Diabetes accompanying PDAC does not influence the level of IGF-1 as opposed to diabetes in the course of CP. The IGF-1 level can be useful for early diagnosis of PDAC. High concentration of RBP-4 is not specific to pancreatic cancer, so it does not appear to be a useful biomarker for PDAC.

Zeb1 in stromal myofibroblasts fosters Kras-driven pancreatic cancer development

The elevation of insulin-like growth factor 1 (IGF-1) and adipokine retinol-binding protein 4 (RBP-4) is known to be associated with the risk of many cancers. The aim of this study was to evaluate the serum concentrations of IGF-1 and RBP-4 in patients with PDAC and chronic pancreatitis (CP).The study included 43 patients with PDAC, 39 patients with CP and 10 controls. The concentrations of IGF-1 and RBP-4 were obtained using the ELISA method (Corgenix UK Ltd R&D Systems). The study protocol was approved by the Bioethics Committee at the Medical University of Lodz.In PDAC patients the serum IGF-1 level was significantly higher than in patients with CP (107.79 ± 66.40 ng/ml vs 89.91 ± 74.06 ng/ml; P < 0.05). Patients with both CP and diabetes mellitus (DM) were noted to have a significantly lower level of IGF-1 compared with those who only had CP (51.33 ± 24.30 ng/ml vs 108.42 ± 82.39 ng/ml; P = 0.01). The same result was obtained for men with and without DM (58.05 ± 32.44 ng/ml vs 98.79 ± 79.47 ng/ml, P = 0.05). As regards the serum level of RBP-4, the PDAC and CP groups were not significantly different from each other.Diabetes accompanying PDAC does not influence the level of IGF-1 as opposed to diabetes in the course of CP. The IGF-1 level can be useful for early diagnosis of PDAC. High concentration of RBP-4 is not specific to pancreatic cancer, so it does not appear to be a useful biomarker for PDAC.

Metachronous liver metastasis seven years after a whipple procedure for ductal adenocarcinoma of the pancreas

The elevation of insulin-like growth factor 1 (IGF-1) and adipokine retinol-binding protein 4 (RBP-4) is known to be associated with the risk of many cancers. The aim of this study was to evaluate the serum concentrations of IGF-1 and RBP-4 in patients with PDAC and chronic pancreatitis (CP).The study included 43 patients with PDAC, 39 patients with CP and 10 controls. The concentrations of IGF-1 and RBP-4 were obtained using the ELISA method (Corgenix UK Ltd R&D Systems). The study protocol was approved by the Bioethics Committee at the Medical University of Lodz.In PDAC patients the serum IGF-1 level was significantly higher than in patients with CP (107.79 ± 66.40 ng/ml vs 89.91 ± 74.06 ng/ml; P < 0.05). Patients with both CP and diabetes mellitus (DM) were noted to have a significantly lower level of IGF-1 compared with those who only had CP (51.33 ± 24.30 ng/ml vs 108.42 ± 82.39 ng/ml; P = 0.01). The same result was obtained for men with and without DM (58.05 ± 32.44 ng/ml vs 98.79 ± 79.47 ng/ml, P = 0.05). As regards the serum level of RBP-4, the PDAC and CP groups were not significantly different from each other.Diabetes accompanying PDAC does not influence the level of IGF-1 as opposed to diabetes in the course of CP. The IGF-1 level can be useful for early diagnosis of PDAC. High concentration of RBP-4 is not specific to pancreatic cancer, so it does not appear to be a useful biomarker for PDAC.

Pachydermoperiostosis: a rare mimicker of acromegaly.

Pachydermoperiostosis is a very rare osteoarthrodermopathic disorder whose clinical and radiographic presentations may mimic those of acromegaly. In the evaluation of patients with acromegaloid appearances, pachydermoperiostosis should be considered as a differential diagnosis. In this article, we report a 17-year-old boy who presented with 2-year history of acral enlargement and facial appearance changes associated with joint pain and excessive sweating. He had been investigated extensively for acromegaly, and the final diagnosis was pachydermoperiostosis.Learning pointsThere is a broad range of differential diagnosis for acromegaloid features such as acromegaly, pseudoacromegaly with severe insulin resistance, Marfan’s syndrome, McCune–Albright and a rare condition called pachydermoperiostosis.Once a patient is suspected to have acromegaly, the first step is biochemical testing to confirm the clinical diagnosis, followed by radiologic testing to determine the cause of the excess growth hormone (GH) secretion. The cause is a somatotroph adenoma of the pituitary in over 95 percent of cases.The first step is measurement of a serum insulin-like growth factor 1 (IGF1). A normal serum IGF1 concentration is strong evidence that the patient does not have acromegaly.If the serum IGF1 concentration is high (or equivocal), serum GH should be measured after oral glucose administration. Inadequate suppression of GH after a glucose load confirms the diagnosis of acromegaly.Once the presence of excess GH secretion is confirmed, the next step is pituitary magnetic resonance imaging (MRI).Atypical presentation warrants revision of the diagnosis. This patient presented with clubbing with no gigantism, which is expected in adolescent acromegalics as the growth spurt and epiphyseal plate closure have not taken place yet.