The Effect and Potential Mechanism Analysis of Growth Hormone-Secreting Pituitary Adenomas on Thyroid Function.

OBJECTIVE: Current studies on the effect of high growth hormone (GH)/insulin-like growth factor (IGF)-1 on thyroid function are inconsistent. The aim was to explore the effect and potential mechanism of high GH/IGF-1 on thyroid function by analyzing the changes of thyroid function in patients with growth hormone-secreting pituitary adenoma (GHPA). METHODS: This was a retrospective cross-sectional study. Demographic and clinical data of 351 patients with GHPA who were first admitted to Beijing Tiantan Hospital, Capital Medical University, from 2015 to 2022 were collected to analyze the relationship between high GH/IGF-1 levels and thyroid function. RESULTS: GH was negatively correlated with total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH). IGF-1 was positively correlated with total triiodothyronine (TT3), free triiodothyronine (FT3), and FT4 and negatively correlated with TSH. Insulin-like growth factor-binding protein (IGFBP)-3 was positively correlated with TT3, FT3, and FT3:FT4 ratio. The FT3, TT3, TSH, and FT3:FT4 ratio of patients with GHPA and diabetes mellitus (DM) were significantly lower than those with GHPA but without DM. With the increase of tumor volume, thyroid function gradually decreased. GH and IGF-1 were correlated negatively with age in patients with GHPA. CONCLUSION: The study emphasized the complex interaction between the GH and the thyroid axes in patients with GHPA and highlighted the potential effect of glycemic status and tumor volume on thyroid function.

Combined diagnostic value of insulin-like growth factor-1, insulin-like growth factor binding protein-3, and baseline luteinizing hormone levels for central precocious puberty in girls.

OBJECTIVES: The golden standard test for diagnosing central precocious puberty (CPP) is the gonadotropin releasing hormone stimulation test, which has many limitations. This study aimed to investigate the value of insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), and basal luteinizing hormone (LH) levels in diagnosing CPP. METHODS: Cross-sectional study of the levels of IGF-1, IGFBP-3, and basal LH in girls with a chief complaint of premature breast development. Seventy-nine girls with CPP and 37 girls with premature thelarche (PT) diagnosed at West China Second University Hospital from January 2016 to October 2018 were recruited. All patients underwent physical examination, laboratory tests, uterine and ovarian ultrasound, and bone age tests, only CPP patients underwent pituitary magnetic resonance imaging (MRI). Statistical analysis was performed using the SPSS software 21.0. A receiver operating characteristic curve was used to determine diagnostic value. RESULTS: The anthropometric data and hormone indicators between CPP and PT were statistically different (p<0.001), except for peak follicle stimulating hormone (FSH) levels (p=0.181). IGF-1, IGFBP-3, and basal LH levels were significantly higher in the subjects with CPP than in those with PT; IGF-1 and basal LH were positively correlated with peak LH and LH/FSH (peak) (p<0.001). The area under the curve (AUC) of IGF-1, IGFBP-3, and basal LH were 0.880, 0.853, and 0.915, respectively. When combined, the AUC reached the highest value of 0.978. CONCLUSIONS: IGF-1, IGFBP-3, and baseline LH levels were useful in diagnosing CPP. The combined analysis improved the diagnostic effectiveness.

BMI and Contraceptives Affect New Age-, Sex-, and Puberty-adjusted IGF-I and IGFBP-3 Reference Ranges Across Life Span.

CONTEXT: Various clinical factors influencing serum levels of insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) are not entirely consistently described. OBJECTIVE: We asked whether body mass index (BMI), contraceptive drugs (CDs), and hormone replacement therapy (HRT) have potential effects on data for interpreting new age-, sex-, and puberty-adjusted reference ranges for IGF-I and IGFBP-3 serum levels. DESIGN AND SETTING: Subjects were mainly participants from 2 population-based cohort studies: the LIFE Child study of children and adolescents and the LIFE Adult study. PARTICIPANTS: We investigated 9400 serum samples from more than 7000 healthy and 1278 obese subjects between 3 months and 81 years old. MAIN OUTCOME MEASURES: Associations between IGF-I or IGFBP-3, measured with a new electrochemiluminescence immunoassay, and the predictors BMI and CDs were estimated using hierarchical linear modeling. RESULTS: During infancy, obese children had up to 1 SD score (SDS) higher mean predicted IGF-I values, converging with levels of normal-weight subjects up to 13 years old. Between 20 and 40 years of age, obesity was related to up to -0.5 lower IGF-I SDS values than the predicted values. Obesity had less impact on IGFBP-3. Estrogen- and progestin-based CDs, but not HRT, decreased IGF-I and increased IGFBP-3 (P < 0.01) in adolescents (ß IGF-I = -0.45, ß IGFBP-3  = 0.94) and adults (ß IGF-I = -0.43, ß IGFBP-3  = 1.12). Conversely, progestin-based CDs were significantly positive associated with IGF-I (ß IGF-I  =0.82). CONCLUSIONS: BMI and CDs must be considered when assessing and interpreting the clinical relevance of IGF-I and IGFBP-3 measurements.

Growth Hormone and Thyroid Function in Children With Attention Deficit Hyperactivity Disorder Undergoing Drug Therapy.

CONTEXT: The trends in hormone indices of children with attention deficit hyperactivity disorder (ADHD) who received long-term medication treatment remains controversial. OBJECTIVE: This prospective study aimed to examine the changes in the growth hormone and thyroid hormone systems among children with ADHD undergoing various medication treatments. METHODS: In total, 118 children who were diagnosed with ADHD and were drug-naive were observed naturalistically over 12 months. Of them, 22 did not receive any medication, while 39, 40, and 17 were treated with low doses of short-acting methylphenidate (MPH) (14 ±â€…6.7 mg/day), osmotic-release oral system (OROS) long-acting MPH (32 ±â€…9.6 mg/day), and atomoxetine (29.2 ±â€…9.7 mg/day), respectively. Blood samples were obtained at both the baseline and the endpoint (month 12) to measure serum levels of insulin-like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), prolactin, thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and free T4. RESULTS: Trends for IGF-1, IGFBP-3, prolactin, TSH, T3, T4, and free T4 levels were similar among the 4 groups. Changes in serum levels of IGF-1 were positively correlated with changes in height and weight of all the children with ADHD. However, patients who received MPH treatment had less body weight gain than the nonmedicated group. The ratio of MPH doses to body weight was inversely correlated with the increment in height. CONCLUSION: There were no changes in thyroid or growth hormones associated with the low doses of ADHD medications used in this study within 1 year's duration. Nonetheless, patients' growth and the appropriateness of drug dosage should be closely monitored.

Energy homeostasis genes modify the association between serum concentrations of IGF-1 and IGFBP-3 and breast cancer risk.

Breast cancer is a multifactorial disease in which the interplay among multiple risk factors remains unclear. Energy homeostasis genes play an important role in carcinogenesis and their interactions with the serum concentrations of IGF-1 and IGFBP-3 on the risk of breast cancer have not yet been investigated. The aim of this study was to assess the modifying effect of the genetic variation in some energy homeostasis genes on the association of serum concentrations of IGF-1 and IGFBP-3 with breast cancer risk. We analyzed 78 SNPs from 10 energy homeostasis genes in premenopausal women from the 4-Corner's Breast Cancer Study (61 cases and 155 controls) and the Mexico Breast Cancer Study (204 cases and 282 controls). After data harmonization, 71 SNPs in HWE were included for interaction analysis. Two SNPs in two genes (MBOAT rs13272159 and NPY rs16131) showed an effect modification on the association between IGF-1 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). In addition, five SNPs in three genes (ADIPOQ rs182052, rs822391 and rs7649121, CARTPT rs3846659, and LEPR rs12059300) had an effect modification on the association between IGFBP-3 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). Our findings showed that variants of energy homeostasis genes modified the association between the IGF-1 or IGFBP-3 serum concentration and breast cancer risk in premenopausal women. These findings contribute to a better understanding of this multifactorial pathology.

Association of significantly elevated plasma levels of NGAL and IGFBP4 in patients with diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a type of progressive kidney disease affecting approximately 40% of patients with diabetes. Current DN diagnostic criteria predominantly rely on albuminuria and serum creatinine (sCr) levels. However, the specificity and reliability of both markers are limited. Hence, reliable biomarkers are required for early diagnosis to effectively manage DN progression. METHODS: In this study, a cohort of 159 individuals were clinically evaluated and the plasma levels of NGAL, IGFBP-1, IGFBP-3, and IGFBP-4 were determined using Multiplexing Assays. Additionally, the association between the plasma levels of NGAL, IGFBP-1, IGFBP-3, and IGFBP-4 in patients with DN were compared to those in patients with T2D without kidney disease and control participants. RESULTS: Circulating level of NGAL were significantly higher in people with DN compared to people with T2D and non-diabetic groups (92.76 ± 7.5, 57.22 ± 8.7, and 52.47 ± 2.9 mg/L, respectively; p <  0.0001). IGFBP-4 showed a similar pattern, where it was highest in people with DN (795.61 ng/ml ±130.7) compared to T2D and non-diabetic people (374.56 ng/ml ±86.8, 273.06 ng/ml ±27.8 respectively, ANOVA p <  0.01). The data from this study shows a significant positive correlation between NGAL and IGFBP-4 in people with DN (ρ = .620, p <  0.005). IGFBP-4 also correlated positively with creatinine level and negatively with eGFR, in people with DN supporting its involvement in DN. CONCLUSION: The data from this study shows a parallel increase in the plasma levels of NGAL and IGFBP-4 in DN. This highlights the potential to use these markers for early diagnosis of DN.

Circulating Insulin-Like Growth Factor 1-Related Biomarkers and Risk of Lethal Prostate Cancer.

Background: Experimental and epidemiologic evidence supports the role of circulating insulin-like growth factor-1 (IGF-1) levels with the risk of prostate cancer. Most circulating IGF-1 is bound to specific binding proteins, and only about 5% circulates in a free form. We explored the relation of free IGF-1 and other components of the IGF system with lethal prostate cancer. Methods: Using prospectively collected samples, we undertook a nested case-only analysis among 434 men with lethal prostate cancer and 524 men with indolent, nonlethal prostate cancer in the Physicians' Health Study and the Health Professionals Follow-up Study. Prediagnostic plasma samples were assayed for free IGF-1 and total IGF-1, acid labile subunit, pregnancy-associated plasma protein A (PAPP-A), and intact and total IGF binding protein 4. We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the associations between IGF-1-related biomarkers and lethal prostate cancer using unconditional logistic regression models adjusted for age, height, and body mass index. Results: Men in the highest quartile of PAPP-A levels had 42% higher odds of lethal prostate cancer (pooled adjusted OR = 1.42, 95% CI = 1.04 to 1.92) compared with men in the lowest 3 quartiles. There were no statistically significant differences in the other plasma analytes. The positive association between PAPP-A and lethal prostate cancer was present among men with intact PTEN but not among those with tumor PTEN loss (2-sided P interaction = .001). Conclusions: Our study provides suggestive evidence that among men who later develop prostate cancer, higher plasma PAPP-A levels measured prior to diagnosis are associated with increased risk of lethal compared with indolent disease.

Dynamic Changes in Serum IGF-I and Growth During Infancy: Associations to Body Fat, Target Height, and PAPPA2 Genotype.

CONTEXT: IGF-I is important for postnatal growth and may be of diagnostic value in infants suspected of pituitary disease; however, little is known about the impact of IGF-I and its determinants on infant growth. Importantly, detailed reference ranges for IGF-I and IGF binding protein-3 (IGFBP-3) concentrations during infancy are lacking. OBJECTIVE: To evaluate the rapid changes in weight and length as well as their determinants in healthy infants, and to establish age- and sex-specific reference curves for IGF-I and IGFBP-3 in children aged 0 to 1 years. DESIGN: Prospective longitudinal study. SETTING: Cohort study. PARTICIPANTS: A total of 233 healthy children (114 girls) with repeated blood samples during the first year of life. MAIN OUTCOME MEASURE(S): Serum concentrations of IGF-I and IGFBP-3, length velocity, weight velocity, and PAPPA2 (rs1325598) genotype. RESULTS: Individual trajectories of length and weight velocities were sex specific. We provide detailed reference curves based on longitudinal data for IGF-I and IGFBP-3 during infancy. In both girls and boys, IGF-I decreased during infancy, whereas IGFBP-3 remained stable. IGF-I and IGFBP-3, but not PAPPA2 genotype, were positively associated with weight gain, but not with longitudinal growth. When stratified by sex, the association between weight gain and IGF-I only remained significant in girls. CONCLUSIONS: Interestingly, we found a significant association between IGF-I and infant weight gain in girls, but not with longitudinal growth in the first year of life. Our findings highlight the role of IGF-I as an important anabolic hormone that is not limited to linear growth.

Myokine Expression and Tumor-Suppressive Effect of Serum after 12 wk of Exercise in Prostate Cancer Patients on ADT.

PURPOSE: Although several mechanisms have been proposed for the tumor-suppressive effect of exercise, little attention has been given to myokines, even though skeletal muscle is heavily recruited during exercise resulting in myokine surges. We measured resting serum myokine levels before and after an exercise-based intervention and the effect of this serum on prostate cancer cell growth. METHODS: Ten prostate cancer patients undertaking androgen deprivation therapy (age, 73.3 ± 5.6 yr) undertook a 12-wk exercise-based intervention including supervised resistance training, self-directed aerobic exercise, and protein supplementation. Body composition was assessed by dual-energy x-ray absorptiometry and muscle strength by the one-repetition maximum method. Fasting blood was collected at baseline and postintervention, and serum levels of myokines-secreted protein acidic and rich in cysteine, oncostatin M (OSM), decorin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 (IGFBP-3)-were measured. The growth of the prostate cancer cell line DU145 with baseline and postintervention serum was measured. RESULTS: Body weight (P = 0.011), fat mass (P = 0.012), and percent body fat (P = 0.033) were reduced, whereas percent lean mass (P = 0.001) increased, as did strength (leg press, P = 0.006; chest press, P = 0.020) across the intervention. Serum OSM levels (P = 0.020) and relative serum OSM levels (P = 0.020) increased compared with baseline. A significant reduction in DU145 Cell Index (P = 0.012) and growth rate (P = 0.012) was observed after applying postintervention serum compared with baseline serum. CONCLUSIONS: This study provides evidence for enhanced myokine expression and tumor-suppressive effects of serum from chronically exercise-trained prostate cancer patients on androgen deprivation therapy.

Malnutrition in children associated with low insulin-like growth factor binding protein-3 (IGFBP-3) levels.

OBJECTIVE: This study aimed to compare serum levels of Insulin-like Growth Factor Binding Protein-3 in children with malnutrition and good nutritional status. METHOD: This cross-sectional study included 41 participants consisting of 31 malnourished, 10 well-nourished children aged between 36 and 60 months. Demographic data of participants were obtained utilizing a questionnaire. Nutritional status was determined by calculating the Z-score of body weight for age, height for age, and body weight for height indices using the WHO classification. IGFBP-3 levels were determined by the Enzyme-Linked Immunosorbent Assay (ELISA) method. RESULT: Median serum IGFBP-3 levels in malnourished children were found to be lower i.e. 0.35mcg/mL (minimum-maximum: 0.04-1.52mcg/mL) compared to well-nourished children 1.52ng/mL (minimum-maximum 0.47-3.17mcg/mL). CONCLUSION: Serum IGFBP-3 levels can be used as indicators to assess nutritional status.

GH Responsiveness in Children With Noonan Syndrome Compared to Turner Syndrome.

Background: Despite different genetic background, Noonan syndrome (NS) shares similar phenotype features to Turner syndrome (TS) such as short stature, webbed neck and congenital heart defects. TS is an entity with decreased growth hormone (GH) responsiveness. Whether this is found in NS is debated. Methods: Data were retrieved from combined intervention studies including 25 children diagnosed with NS, 40 diagnosed with TS, and 45 control children (all prepubertal). NS-children and TS-girls were rhGH treated after investigation of the GH/IGFI-axis. GH was measured with poly- and monoclonal antibodies; 24hGH-profile pattern analysed by PULSAR. The NS-children were randomly assigned to Norditropin® 33 or 66 µg/kg/day, and TS-girls were consecutively treated with Genotropin® 33 or 66 µg/kg/day. Results: Higher PULSAR-estimates of 24h-profiles were found in both NS-children and TS-girls compared to controls: Polyclonal GHmax24h-profile (Mean ± SD) was higher in both groups (44 ± 23mU/L, p<0.01 in NS; 51 ± 47, p<0.001 in TS; compared to 30 ± 23 mU/L in controls) as was GH-baseline (1.4 ± 0.6 mU/L in NS; 2.4 ± 2.4 mU/L in TS, p<0.01 for both, compared to 1.1 ± 1.2 mU/L in controls). Pre-treatment IGFISDS was 2.2 lower in NS-children (-1.7 ± 1.3) compared to TS-girls (0.6 ± 1.8, p<0.0001). GHmax, IGFI/IGFBP3-ratioSDS, and chronological age at start of GH accounted for 59% of the variance in first-year growth response in NS. Conclusion: Both prepubertal NS-children and TS-girls had a high GH secretion, but low IGFI/IGFBP3 levels only in NS-children. Both groups presented a broad individual response. NS-children showed higher response in IGFI and growth, pointing to higher responsiveness to GH treatment than TS-girls.

Maternal Plasma and Amniotic Fluid LBP, Pentraxin 3, Resistin, and IGFBP-3: Biomarkers of Microbial Invasion of Amniotic Cavity and/or Intra-amniotic Inflammation in Women with Preterm Premature Rupture of Membranes.

BACKGROUND: We sought to determine whether lipopolysaccharide binding protein (LBP), pentraxin 3, resistin, and insulin-like growth factor binding protein (IGFBP)-3 in plasma and amniotic fluid (AF) can predict microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI), and microbial-associated IAI in women with preterm premature rupture of membranes (PPROM). METHODS: This was a retrospective cohort study involving 168 singleton pregnant women with PPROM. AF obtained via amniocentesis was cultured and assayed for interleukin (IL)-6 to define IAI and for IL-8 to compare with AF biomarkers. Plasma samples were collected at the time of amniocentesis, and C-reactive protein (CRP) levels in serum were compared with plasma biomarkers. The stored plasma and AF samples were assayed for LBP, pentraxin 3 (PTX3), resistin, and IGFBP-3 by ELISA. RESULTS: Multivariate logistic regression analysis revealed that: 1) elevated plasma and AF levels of LBP were independently associated with increased risks of MIAC, IAI, and microbial-associated IAI; 2) elevated AF, but not plasma, PTX3, and resistin levels were independently associated with increased risks of MIAC, IAI, and microbial-associated IAI; 3) decreased IGFBP-3 levels in the plasma were independently associated with only IAI, whereas those in the AF were associated with only microbial-associated IAI. Among the tested biomarkers, AF PTX3 and resistin had the highest predictive performance for MIAC, IAI, and microbial-associated IAI (area under the curves [AUC] = 0.85-0.95), which is similar to the performance of AF IL-8. The AUCs of the plasma LBP and IGFBP-3 were similar to that of serum CRP with respect to IAI. CONCLUSION: Maternal plasma LBP and IGFBP-3 are potential biomarkers for the non-invasive identification of IAI in women with PPROM, with a similar accuracy to the serum CRP level. AF LBP, PTX3, resistin, and IGFBP-3 may be involved in the intra-amniotic inflammatory responses in PPROM complicated by MIAC.

Evaluation of circulating IGF-I and IGFBP-3 as biomarkers for tumors in dogs.

BACKGROUND: Serum-based parameters are considered non-invasive biomarkers for cancer detection. In human studies, insulin-like growth factor-I and II (IGF-I and IGF-II) and insulin-like growth factor binding protein-3 (IGFBP-3) are useful as diagnostic or prognostic markers and potential therapeutic targets. OBJECTIVES: This study examined the diagnostic utility of circulating IGF-I, IGF-II, and IGFBP-3 levels in healthy dogs and dogs with tumors. METHODS: The serum concentrations of these biomarkers in 86 dogs with tumors were compared with those in 30 healthy dogs using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The ELISA results showed no difference between healthy dogs and dogs with tumors in the serum IGF-II concentrations. On the other hand, there was a significant difference in the circulating IGF-I and IGFBP-3 levels between healthy dogs and dogs with tumors. The concentrations of serum IGF-I (median [interquartile range], 103.4 [59.5-175] ng/mL) in dogs with epithelial tumors were higher than those (58.4 ng/mL [43.5-79.9]) in healthy dogs. Thus, the concentrations of serum IGFBP-3 (43.4 ng/mL [33.2-57.2]) in dogs with malignant mesenchymal tumors were lower than those (60.8 ng/mL [47.6-70.5]) in healthy dogs. CONCLUSIONS: The serum IGF-I and IGFBP-3 levels can be used as diagnostic biomarkers in dogs with tumors.

Effects of raloxifene administration on serum levels of insulin-like growth factor-1 and insulin-like growth factor-binding protein 3 levels: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To ascertain the clinical magnitude of raloxifene administration on insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) levels. METHODS: A systematic comprehensive search was performed without language limitation up to 14 December 2020. We included only trials that assessed the effect of raloxifene on IGF-1 and IGFBP-3 in adults. Meta-analysis was performed using the Stata software (Stata Corp. College Station, Texas, USA). RESULTS: Seven arms were included, encompassing postmenopausal women with type 2 diabetes mellitus, postmenopausal women with breast cancer, healthy postmenopausal women, and healthy elderly men. Raloxifene therapy significantly reduced IGF-1 levels (WMD: -2.92 nmol/L, 95% CI: -3.49, -2.35, p < 0.001) compared to placebo. Raloxifene dosage ˃60 mg/day (WMD: -3.29 ng/mL, 95% CI: -3.50 to -3.08, I2 = 0.0%) decreased IGF-1 levels more than 60 mg/day (WMD: -2.29 ng/mL, 95% CI: -2.90 to -1.69, I2 = 16%). Moreover, intervention duration ˃26 weeks (WMD: -3.48 ng/mL, 95% CI: -5.26 to -1.69, I2 = 0.0%) reduced IGF-1 levels more than ˂26 weeks (WMD: -2.55 ng/mL, 95% CI: -3.31 to -1.79, I2 = 92%). In contrast, overall results from the random-effects model did not suggest a significant change in IGFBP-3 levels upon raloxifene therapy. CONCLUSION: Raloxifene therapy significantly reduced serum levels of IGF-1 levels but without changes in IGFPB-3 levels.

Serum IGF-I concentrations are low in female bodybuilders in the pre-contest phase.

Bodybuilding involves athletes performing a series of poses/postures on the stage so that they can be classified according to their best esthetic and physical appearance during the competition. In the weeks prior to the target competition, the athletes subject themselves to restrictive diets and different physical training methods, as well as using dietary supplementation and, in some cases, anabolic steroids, to reduce body fat to low levels and maintain or increase muscle mass. On the other hand, it is known that physical training is a potent stimulator for releasing the components of the GH/IGF-I axis that are directly linked to the anabolic process. Based on these assumptions, this study aimed to verify the kinetics of IGF-I and of its binding protein IGFBP-3 in female bodybuilders. Serum IGF-I and IGFBP-3 concentrations were recorded before and after standardized training sessions at two different times: in the initial phase (phase 1) and in the final phase of the pre-contest (phase 2) of a 12-week training season. It was possible to conclude that there was a significant reduction in serum IGF-I values at the end of the pre-contest phase that preceded the athletes' participation in a competition. With relation to the serum IGF-I and IGFBP-3 values measured before and after the standardized training session, it was only possible to verify significant changes in the IGF-I values in the initial phase of the pre-contest. It seems reasonable to suggest that the caloric restriction used by bodybuilders may be related to the decrease in IGF-I values verified at the end of the pre-contest phase.

Evaluation of neurotrophic factors and education level as predictors of cognitive decline in alcohol use disorder.

Cognitive reserve (CR) is the capability of an individual to cope with a brain pathology through compensatory mechanisms developed through cognitive stimulation by mental and physical activity. Recently, it has been suggested that CR has a protective role against the initiation of substance use, substance consumption patterns and cognitive decline and can improve responses to treatment. However, CR has never been linked to cognitive function and neurotrophic factors in the context of alcohol consumption. The present cross-sectional study aims to evaluate the association between CR (evaluated by educational level), cognitive impairment (assessed using a frontal and memory loss assessment battery) and circulating levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in patients with alcohol use disorder (AUD). Our results indicated that lower educational levels were accompanied by earlier onset of alcohol consumption and earlier development of alcohol dependence, as well as impaired frontal cognitive function. They also suggest that CR, NT-3 and BDNF may act as compensatory mechanisms for cognitive decline in the early stages of AUD, but not in later phases. These parameters allow the identification of patients with AUD who are at risk of cognitive deterioration and the implementation of personalized interventions to preserve cognitive function.

High-intensity interval training or resistance training versus usual care in men with prostate cancer on active surveillance: a 3-arm feasibility randomized controlled trial.

This study assessed the feasibility of a phase II randomized controlled trial of high-intensity interval training (HIIT), resistance training (RT), and usual care (UC) in men with prostate cancer (PCa) on active surveillance and evaluated changes in clinically relevant outcomes. Eighteen men undergoing active surveillance for PCa were randomized to HIIT (n = 5), RT (n = 7), or UC (n = 6). Exercise participants attended 2 supervised sessions weekly and were instructed to complete 1 home-based session weekly for 8 weeks. UC participants were provided with physical activity guidelines. Feasibility was met for attendance, compliance, and retention, but not recruitment. HIIT increased leg press (mean: +8.2 kg, 95% CI 1.1 to 15.3) from baseline to 8 weeks. RT increased seated row (mean: +11.7 kg, 95% CI 6.1 to 17.3), chest press (mean: +10.4 kg, 95% CI 5.3 to 15.5), leg press (mean: +13.1 kg, 95% CI 5.9 to 20.3), serum insulin-like binding protein-3 (IGFBP-3) (mean: +400.0 ng/mL, 95% CI 94.5 to 705.5), and decreased interferon-γ (mean: -3.1 pg/mL, 95% CI -5.7 to -0.4). No changes were observed in the UC group. HIIT and RT may be effective strategies for improving muscle strength; however, only RT may increase serum IGFBP-3. Strategies that can enhance recruitment in men on active surveillance are important prior to conducting a phase II trial. Trial registration number: ClinicalTrials.gov number NCT04266262. Novelty: High-intensity interval training or resistance training are feasible during active surveillance for prostate cancer. Resistance training may suppress the tumour-promoting effects of insulin-like growth factor-I (IGF-I) via increased expression of IGFBP-3.

Associations of genetically predicted circulating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 with bladder cancer risk.

Insulin-like growth factors (IGF) play important roles in carcinogenesis. The associations of circulating IGF-1 and insulin-like growth factor-binding protein-3 (IGFBP-3) with the risks of bladder cancer remain unclear. In this large case control study of 2011 bladder cancer cases and 2369 heathy controls, we assessed the associations of circulating IGF-1 and IGFBP-3 with bladder cancer risks using a Mendelian randomization approach, which uses genetic variants as instruments to study causal relationship between risk factors and diseases. We first constructed a weighted genetic risk score (GRS) predictive of circulating IGF-1 and IGFBP-3 using 413 genome-wide association study-identified single nucleotide polymorphisms (SNPs) associated with IGF-1 and four SNPs with IGFBP-3, respectively. We found that higher GRS for IGF-1 was associated with a significantly reduced bladder cancer risk (odds ratio [OR] = 0.66 per SD increase, 95% confidence interval [CI], 0.54-0.82, p < 0.001). We then used a summary statistics-based MR method, inverse-variance weighting (IVW), and found a similar risk estimate (OR = 0.67 per SD increase, 95% CI = 0.54-0.83, p < 0.001). When we categorized individuals into high and low IGF-1 groups using the median GRS value in the controls, the high GRS group had a 21% reduced bladder cancer risk (OR = 0.79, 95% CI = 0.70-0.89) compared to the low GRS group. Genetically predicted circulating IGFBP-3 was not associated with bladder cancer risk. In conclusion, our data demonstrated for the first time a strong inverse relationship between circulating IGF-1 level and bladder cancer risk.

Insulin-like Growth Factor 1, but Not Insulin-Like Growth Factor-Binding Protein 3, Predicts Central Precocious Puberty in Girls 6-8 Years Old: A Retrospective Study.

BACKGROUND: Central precocious puberty (CPP) in females is characterized by thelarche before 8 years of age. Evidence of reproductive axis activation confirms the diagnosis (basal serum luteinizing hormone (LH) ≥0.3 IU/L or LH-releasing hormone (LHRH)-stimulated LH ≥5 IU/L). Stimulation testing is the diagnostic gold standard but is time-consuming and costly. Serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) are increased in girls with CPP. OBJECTIVE: The aim of the study was to assess the utility of serum IGF-1 and IGFBP-3 in identifying CPP in girls aged 6-8 years. METHODS: The study was a single-center retrospective study. Girls with confirmed CPP (n = 44) and isolated premature precocious adrenarche/ precocious thelarche (PA/PT, n = 16) had baseline biochemical profiling and LHRH stimulation testing. Serum IGF-1 and IGFBP-3 results were converted to standard deviation scores (SDS). Correlations were calculated and receiver operating characteristic curves were plotted. RESULTS: Girls with CPP had higher basal and peak LH, IGF-1 SDS, and growth velocity (p < 0.05). IGF-1 SDS correlated positively with basal and peak LH (p < 0.05). IGF-1 SDS (1.75-2.15) differentiated CPP and PA/PT with 89% sensitivity and 56% specificity (basal LH) and 94% specificity and 55% sensitivity (peak LH). IGFBP-3 SDS did not differ between groups or by CPP parameters. CONCLUSIONS: In clinical practice, IGF-1 SDS may be an additional tool for identifying CPP in girls aged 6 to 8 years when baseline clinical and laboratory diagnostic criteria are inconclusive, possibly avoiding more time-consuming and costly procedures.