Measurement Of Insulin-like Growth Factor Research Articles

Challenges Confounding Biochemical Diagnosis of Acromegaly.

Abstract:
 Acromegaly is a disorder caused by growth hormone (GH) hypersecretion resulting in excessive release of insulin like growth factor-1 (IGF-1). Both GH and IGF-1 measurements are crucial in its accurate diagnosis and in differentiating it from pseudoacromegaly. Early diagnosis is frequently restricted by its subtle, unnoticeable pathological changes; hence, clinical presentation is often late. Therefore, biochemical diagnosis is critical. However, the straightforward interpretation of these markers are hindered by factors that contribute to GH – IGF-1 discordance observed both in static and in dynamic function tests. These factors include both markers biological variation and their analytical assay limitations, which lead to false positive and negative results. This review is describing the pitfalls and challenges confounding the biochemical diagnosis of acromegaly. Despite these interpretive challenges, we strongly believe that interpretation of these results could be facilitated by effective clinician-laboratory professional communications which is the highlight of this review.
 
 Keywords: Acromegaly, growth hormone (GH), insulin like growth factor-1 (IGF-1), IGF-binding proteins (IGFBP)

The Association Between Preoperative Insulin-Like Growth Factor 1 Levels and the Total Body Weight Loss in Women Post Laparoscopic Sleeve Gastrectomy.

Despite the well-described optimal initial clinical response of sleeve gastrectomy (SG) in the treatment of obesity, some patients do not achieve optimal initial clinical response. Insulin-like growth factor-1 (IGF-1) has currently shown an association with post-bariatric surgery weight loss. This study aimed to assess the IGF-1 levels in female patients with obesity, the change after surgery, and their association with the metabolic profile and weight loss after surgery. This was a prospective study that was conducted on adult female patients who were recruited for SG. The patients underwent clinical and laboratory investigations that included the IGF-1 measurement. At the 1-year follow-up, the same clinical and laboratory measures were repeated. This study included 100 female patients. At the 1-year follow-up, there was a statistically significant reduction in body mass index (BMI) (p < 0.001), fasting HbA1C levels (p < 0.001), and triglycerides (p < 0.001), as well as a statistically significant increase in HDL (p < 0.001) and IGF-1 (p < 0.001). Multiple regression analysis revealed that, among the patients baseline characteristics, the significant predictors for the percentage of total weight loss (%TWL) were the patients' BMI (p < 0.001) and IGF-1 levels (p < 0.001). The ROC curve showed that an IGF1 cutoff value of ≤ 23ng/ml detected suboptimal initial clinical response, with a sensitivity of 95.35% and a specificity of 100%. This study underscores the significant impact of SG on weight loss and metabolic improvements in female patients. Baseline IGF-1 levels emerged as a crucial predictor of optimal initial clinical response.

Diagnostic significance and considerations of growth hormone stimulation testing and insulin-like growth factor 1 in growth hormone deficiency

The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is an essential component of the hypothalamic-pituitary growth hormone axis and plays a crucial role in childhood growth and development. Disruptions and abnormalities in the GH/IGF-1 signaling pathway and its pathways typically manifest as short stature in children. Children with short stature often undergo GH stimulation testing and IGF-1 level measurements to differentiate growth hormone deficiency (GHD) from other causes of growth delay. This article aims to analyze and elucidate the values of GH stimulation testing and IGF-1 measurement, providing reference for the diagnosis of GHD in children.

A-049 Inter-assay Variation of Insulin-like Growth Factor-1 Remains an Issue

Abstract Background Human insulin-like growth factor-1 (IGF-1) is the main mediator of the somatotropic effects of growth hormone (GH). Accurate measurement of IGF-1 is required for the diagnosis and management of GH secretion disorders. Several commercial vendors and laboratories have standardized their IGF-1 assays to the WHO International Standard 02/254. This standardization does not prohibit the existence of significant inter-assay variability in IGF-1 measurements. Such concentration variance can lead to inaccurate patient case decision making. The IGF-1 testing performed in our laboratory was recently migrated from an Immulite 2000 platform to a CobasPro system. This shift in vendor necessitated an investigation of the inter-assay variability between these standardized tests. This relative variance was established through a validation of the analytical performance of the CobasPro IGF-1 assay. Methods Reportable range, intra-day precision and accuracy of IGF-1 measurements using the CobasPro (Roche Diagnostics) system were determined. Patient correlation studies between the CobasPro and an Immulite 2000 (Siemens Healthcare Diagnostics) instrument was also performed. The concentration of IGF-1 in a subset of these correlation study specimens was also quantified by liquid chromatography mass spectrometry (LC-MS) assays from two different reference laboratories. Results The CobasPro assay had a verified linear range of 7–1443 ng/mL (R2 = 0.9998, slope = 0.9915). At IGF-1 concentrations of 54 and 345 ng/mL the intra-day precision (%CV, N = 10) of the CobasPro assay did not exceed 0.9%. Patient specimen correlations between the CobasPro and Immulite 2000 assays showed significant bias (Deming regression: y = 1.543x − 48.61, N = 128, R = 0.9641). This method bias was exacerbated at Immulite 2000 derived IGF-1 concentrations &amp;gt;100 ng/mL (Deming regression: y = 1.662x − 84.29, N = 93, R = 0.9492, CobasPro range = 77–910 ng/mL, Immulite 2000 range = 103–539 ng/mL). Patient specimen correlations between the CobasPro and LC-MS assay from reference laboratory A showed a positive bias (Deming regression: y = 1.375x − 64.5, N = 19, R = 0.9210). An analogous correlation with reference laboratory B demonstrated a higher level of concordance (Deming regression: y = 1.005x + 10.2, N = 16, R = 0.9499). The CobasPro and Immulite 2000 assays both produced acceptable result when challenged by multiple external quality assurance (EQA) specimens provided by the College of American Pathologists (CAP). However, the observed relative trends in IGF-1 concentrations from these challenges were opposite to our observations with authentic patient specimens. The CobasPro assay consistently produced lower IGF-1 concentrations relative to the Immulite 2000 assay for these EQA specimens. Conclusion The CobasPro IGF-1 assay offered acceptable analytical performance. Although both assays were traceable to a reference standard, a significant positive concentration bias was observed between the CobasPro and Immulite 2000 assays. Standardization efforts have not eliminated inter-assay IGF-1 variability. A careful evaluation of the impact of this variance on the diagnosis and management of GH deficiency and acromegaly must be considered when IGF-1 testing platforms are changed.

Method Validation and Establishment of Reference Intervals for an Insulin-like Growth Factor-1 Chemiluminescent Immunoassay in Cats.

Previously, radioimmunoassay (RIA) has been the only assay to measure insulin-like growth factor-1 (IGF-1) to diagnose hypersomatotropism (HS). Due to radiation concerns, availability, and the cost of IGF-1 RIA, validation of assays for automated analysers such as a chemiluminescent immunoassay (CLIA) is needed. The aim of this study was to validate a CLIA for measurement of feline IGF-1 (IMMULITE 2000® XPi, Siemens Medical Solutions Diagnostics, Malvern, PA, USA) compared to IGF1 RIA, establish reference interval (RI), and determine a cut-off value for diagnosis of HS in diabetic cats. Validation of assay performance included precision, linearity, and recovery studies. Right-sided RI was determined using surplus serum of 50 healthy adult cats. Surplus serum samples of diabetic cats with known IGF-1 concentration with (n = 32/68) and without HS (n = 36/68) were used for method comparison with RIA. The cut-off for diagnosis of HS was established using receiver operating characteristic (ROC) analysis. The intra-assay coefficient of variation (CV) was ≤4.7%, and the inter-assay CV was ≤5.6% for samples with low, medium, and high IGF-1 concentration. Linearity was excellent (R2 > 0.99). The correlation between CLIA and RIA was very high (rs = 0.97), with a mean negative bias for CLIA of 24.5%. The upper limit of RI was 670 ng/mL. ROC analysis showed an area under the curve of 0.94, with best cut-off for diagnosis of HS at 746 ng/mL (sensitivity, 84.4%; specificity, 97.2%). The performance of CLIA was good, and the RI and cut-off for HS diagnosis established in this study allow for CLIA to be used in routine work-up of diabetic cats.

Elevated IGF-1 concentrations in children with low grade glioma: A descriptive analysis in a retrospective national cohort.

Children with low grade glioma (LGG) may present with, or develop, elevated concentrations of insulin-like growth factor 1 (IGF-1). The prevalence, pathophysiology, or its possible clinical effects are poorly understood. Our aim was to evaluate the prevalence of such elevated IGF-1 concentrations and to describe its association with linear growth, body mass index (BMI), pituitary outcome, and tumor behavior in a large retrospective national cohort. From a nationwide retrospective cohort of pediatric brain tumor survivors diagnosed between 2002 and 2012, tumor, treatment, endocrine, and auxological data of children with LGG were collected (n = 358). Prevalence and risk factors for elevated IGF-1 concentrations, as well as the association between having elevated IGF-1 concentrations and receiving tumor treatment, were explored. IGF-1 concentrations had only been measured in 45.5% of cases (n = 163/358). In 18.4% of 163 children with available IGF-1 measurements, IGF-1 concentrations were found elevated. No association was described between having an elevated IGF-1 concentration and tumor behavior or height SDS at last moment of follow-up. Multivariate logistic regression identified posterior pituitary disorder (OR 6.14 95% CI: 2.21-17.09) and BMI SDS at follow-up (OR 1.56 95% CI: 1.09-2.20) to be significantly associated with elevated IGF-1 concentrations. In this retrospective cohort of children with LGG, IGF-1 was found elevated in 18.4% of children with available IGF-1 measurements. Elevated IGF-1 seems to be related to hypothalamic dysfunction worsening over time. Larger prospective cohort studies are needed.

Dynamic of irisin secretion change after moderate-intensity chronic physical exercise on obese female.

Exercise is one of the beneficial mediators for the regulation and prevention of obesity through the role of irisin, so it potentially enhances metabolism health. This study aims to investigate the dynamic of irisin secrecy change after chronic exercise in obese females. Thirty-one female adolescents aged 20-22 years enrolled in the study and were given interventions aerobic, resistance, and a combination of aerobic and resistance training. The exercises were performed at moderate-intensity, for 35-40 min per session, and three times a week for four weeks. The measurement of irisin level, IGF-1 level, and bio-anthropometry was carried out before and after the four weeks of exercise. The bio-anthropometry measurement was carried out using seca mBCA 514, while the measurement of insulin-like growth factor 1 (IGF-1) and irisin was completed using an enzyme-linked immunosorbent assay (ELISA). The obtained data were analyzed using a one-way ANOVA test with 5 % significance. Our results indicated higher dynamic of irisin and IGF-1 increases in the group with a combination of aerobic and resistance training exercises than the other two groups with a different exercise. Further, we also observed different dynamics of irisin and IGF-1 level increase (p<0.05). Besides, the irisin was also correlated with the IGF-1 and bio-anthropometric parameters (p<0.05). The combination of aerobic and resistance training exercises is considered as the alternative for enhancing the dynamic of irisin and IGF-1 increase. Thus, itcan be used to prevent and regulate obesity.

The impact of different calibration matrices on the determination of insulin-like growth factor 1 by high-resolution-LC-MS in acromegalic and growth hormone deficient patients

ObjectivesCalibration is an important source of variability in liquid chromatography mass spectrometry (LC-MS) methods for insulin-like growth factor 1 (IGF-1). This study investigated the impact of different calibrator matrices on IGF-1 measurements by LC-MS. Moreover, the comparability of immunoassays and LC-MS was assessed. Design & MethodsCalibrators from 12.5 to 2009 ng/ml were prepared by spiking WHO international Standard (ID 02/254 NIBSC, UK) into the following matrices: native human plasma, fresh charcoal-treated human plasma (FCTHP), old charcoal-treated human plasma, deionized water, bovine serum albumin (BSA), and rat plasma (RP). A validated in-house LC-MS method was calibrated repeatedly with these calibrators. Then, serum samples from 197 growth hormone excess and deficiency patients were analysed with each calibration. ResultsThe seven calibration curves had different slopes leading to markedly different patient results. The largest differences in IGF-1 concentration from the median (interquartile range) was observed with the calibrator in water and the calibrator in RP (336.4 [279.6–417.0] vs. 112.5 [71.2–171.2], p < 0.001). The smallest difference was observed with calibrators in FCTHP and BSA (141.8 [102.0–198.5] vs. 127.9 [86.9–186.0], p < 0.049). Compared to LC-MS with calibrators in FCTHP, immunoassays showed relevant proportional bias (range: −43% to −68%), constant bias (range: 22.84 to 57.29 ng/ml) and pronounced scatter. Comparing the immunoassays with each other revealed proportional bias of up to 24%. ConclusionsThe calibrator matrix is critical for the measurement of IGF-1 by LC-MS. Regardless of the calibrator matrix, LC-MS shows poor agreement with immunoassays. Also, the agreement between different immunoassays is variable.

Insulin-Like Growth Factor 1 and Risk of Cardiovascular Disease: Results From the UK Biobank Cohort Study.

Relationships between insulin-like growth factor 1 (IGF-1) levels and cardiovascular disease (CVD) in the general population remain unclear. This study aims to investigate the association of circulating IGF-1 concentrations with CVD from a population-based cohort study. A total of 394 082 participants without CVD and cancer at baseline from UK Biobank were included with measurements of serum IGF-1 at baseline. Main outcomes were incidence of CVD, including CVD mortality, coronary heart disease (CHD), myocardial infarction (MI), heart failure (HF), and stroke. Over a median 11.6 years of follow-up, UK Biobank documented 35 803 incident CVD cases, including 4231 from CVD-related death, 27 051 from CHD, 10 014 from MI, 7661 from HF, and 6802 from stroke. Dose-response analysis showed a U-shaped relationship between IGF-1 levels and cardiovascular events. Compared with the third quintile of IGF-1, the lowest category of IGF-1 was associated with increased risk of CVD (hazard ratio 1.128; 95% CI, 1.093 to 1.164), CVD mortality (1.294; 1.181 to 1.418), CHD (1.118; 1.078 to 1.159), MI (1.071; 1.008 to 1.139), HF (1.185; 1.107 to 1.268), and stroke (1.149, 1.070 to 1.235); also, the highest category was associated with increased risk of CVD (1.056; 1.020 to 1.094), CVD mortality (1.111; 1.000 to 1.236), CHD (1.070; 1.028 to 1.114), MI (1.111; 1.041 to 1.187) and HF (1.098; 1.015 to 1.188) after multivariable adjustment. This study indicates that both low and high levels of circulating IGF-1 are associated with increased risk of CVD in general population. These results highlight the importance of monitoring IGF-1 status on cardiovascular health.

Growth hormone deficiency in adult survivors of childhood brain tumors treated with radiation.

Growth hormone deficiency (GHD) is the most common endocrine late effect in irradiated survivors of childhood brain tumors. This study aimed to determine the prevalence of GHD in adults treated with proton or photon irradiation for a brain tumor in childhood and to detect undiagnosed GHD. This study is a cross-sectional study. We investigated GHD in 5-year survivors from two health regions in Denmark treated for childhood brain tumors with cranial or craniospinal irradiation in the period 1997-2015. Medical charts were reviewed for endocrinological and other health data. Survivors without a growth hormone (GH) test at final height were invited to a GH stimulation test. Totally 41 (22 females) survivors with a median age of 21.7 years (range: 15.1-33.8 years) at follow-up and 14.8 years (range: 5.1-23.4 years) since diagnosis were included; 11 were treated with proton and 30 with photon irradiation; 18 of 21 survivors were previously found to have GHD; 16 of 20 survivors with no GH test at final height were tested, 8 (50 %) had GHD. In total, 26 of 41 patients (63%) had GHD. Insulin-like growth factor-1 (IGF-1) is associated poorly with the insulin tolerance test (ITT). This study identified a high prevalence of undiagnosed GHD in survivors with no GH test at final height. The results stress the importance of screening for GHD at final height in survivors of childhood brain tumors with prior exposure to cranial irradiation, irrespective of radiation modality and IGF-1. This cross-sectional study reports a prevalence of 63% of GHD in irradiated childhood brain tumor survivors. Furthermore, the study identified a considerable number of long-term survivors without a GH test at final height, of whom, 50% subsequently were shown to have undiagnosed GHD. Additionally, this study confirmed that a normal serum IGF-1 measurement cannot exclude the diagnosis of GHD in irradiated survivors. This illustrates the need for improvements in the diagnostic approach to GHD after reaching final height in childhood brain tumor survivors at risk of GHD. In summary, our study stresses the need for GHD testing in all adult survivors treated with cranial irradiation for a brain tumor in childhood irrespective of radiation modality.

Discordance of insulin-like growth factor-1 results and interpretation on four different platforms

ObjectiveInconsistent Insulin-like Growth Factor 1 (IGF-1) measurements among different platforms have been observed. In this study, we compared the IGF-1 assay on four different platforms. MethodsA total of 110 serum specimens were analyzed in this comparison study. IGF-1 was measured on the three different chemiluminescent automated immunoassay of Siemens Immulite 2000 XPi, DiaSorin Liaison XL, IDS iSYS and LC-MS/MS method. Results were compared with Weighted Deming regression. Bias was evaluated using the Bland-Altman method. ResultsWeighted Deming regression analysis showed approximately 36 % negative variation on Immulite, compared to Liaison (Immulite = 0.64 * DiaSorin + 2.95, r2 = 0.95); 8 % negative variation on iSYS, compared to Liaison (iSYS = 0.92 * DiaSorin + 0.51, r2 = 0.97); 17 % negative variation on LC-MS/MS, compared to Liaison (LC-MS/MS = 0.83 * DiaSorin-11.23, r2 = 0.93); 34 % positive variation on LC-MS/MS compared to Immulite (LC-MS/MS = 1.34 * Immulite-21.97, r2 = 0.96); 81 % positive variation on IDS iSYS compared to Immulite (IDS iSYS = 1.81 * Immulite-117.65, r2 = 0.83).The Bland-Altman plot showed a significant negative variation of Immulite versus DiaSorin and positive variation of IDS iSYS versus Immulite. Overall agreement between different platforms was poor, which reflected systematic difference. The variation between platforms increased as IGF-1 values increased. ConclusionsThere are wide variations between different platforms for IGF-1 measurement. The lack of standardization in IGF-1 measurement creates a challenge for clinicians to monitor IGF-1 and treat patients with pituitary disorders, when switching from one platform to another. The potential impact of the variations in IGF-1 measurement between different platforms should be taken into consideration when managing patients.

PMON117 IGF-1 Testing: Diagnostic Pitfalls

Abstract Introduction Acromegaly is a rare endocrine disorder, with an incidence of 5.3/million/year, that results from persistent hypersecretion of growth hormone (GH), which stimulates hepatic secretion of insulin-like growth factor-1 (IGF-1). The best single test for the diagnosis of acromegaly is measurement of serum IGF-1; however, the result must be interpreted with caution, with understanding of potential pitfalls. Here we present a case of falsely elevated IGF-1 levels. Case Description A 43-year-old female with medical history of prediabetes, sleep apnea, and headaches was referred to endocrine clinic for evaluation of possible acromegaly. Patient had been evaluated by her primary care physician for frequent headaches, unintentional weight gain, and bilateral leg and hand swelling. Patient endorsed being unable to wear her wedding ring for a few years. Initial laboratory evaluation by primary care physician 3 months prior revealed normal thyroid function, prolactin, FSH, LH, random cortisol, but elevated IGF-1 of 310 ng/mL (normal 71-258 ng/mL), with negative pregnancy test. Brain MRI at that time revealed a pineal gland cyst but no pituitary abnormality. During her initial endocrine visit, IGF-1 was repeated, which was again elevated but improved to 283 ng/mL (normal 71-258 ng/mL). Other pertinent labs included a normal random ACTH of 18 pg/mL (normal &amp;lt;47 pg/mL), and pm cortisol of 2.4 mcg/dL (normal 2.9-17.3 mcg/dL). Physical examination was notable for a few light purple striae on abdomen, acanthosis nigricans, and mild limb edema, but no macrognathia, enlarged hands or feet. Given patient's lack of typical features of acromegaly, normal pituitary imaging, and spontaneous IGF-1 improvement, it was decided to postpone GH measurements with oral glucose tolerance test but repeat IGF-1 in 6 months. Patient was able to follow up 11 months after initial visit at which patient denied any worsening symptoms. At that time, repeat laboratory study showed normal IGF-1 of 231. Given spontaneous normalization of IGF-1 levels, no further laboratory testing or imaging studies were recommended, and patient was instructed to follow up in 11-12 months. Discussion Prompt diagnosis of acromegaly is crucial. However, it is important to note IGF-1 could be falsely elevated. A retrospective review by Erickson et. al of 2747 unique patients with IGF-1 elevation, 117 (4%) were found to have false-positive results following a review of the clinical data. In addition to acromegaly, other causes of elevated IGF-1 levels include high protein and high glycemic-index diet, pregnancy, hyperthyroidism, IGF-1 assay problems, and some rare tumors (carcinoids) secreting IGF-1. Discovery of "falsely" elevated IGF-1 may lead to unnecessary testing and physician visits. Therefore, clinicians should consider retesting patients after some time interval if spurious IGF-1 is suspected, before aggressively pursuing more extensive investigations. Presentation: No date and time listed

Low-Plasma Insulin-Like Growth Factor-1 Associates With Increased Mortality in Chronic Kidney Disease Patients With Reduced Muscle Strength

Chronic kidney disease (CKD) leads to metabolic and nutritional abnormalities including resistance to insulin-like growth factor-1 (IGF-1) action, and reduced muscle mass and strength. Low IGF-1 as well as low hand-grip muscle strength (HGS) are independent predictors of increased mortality in CKD patients. In 685 patients (CKD Stage 3-5, median age 58years; 62% men), baseline measurements of IGF-1, HGS, subjective global assessment (SGA), lean body mass index (LBMI), and metabolic and inflammatory biomarkers potentially linked to IGF-1 were analyzed in relation to mortality during 5years of follow-up. We compared survival in 4 groups with high or low (cut-offs defined by receiver operating characteristic curve analysis) levels of IGF-1 and HGS. Patients with low IGF-1 were older; had lower BMI, HGS, and LBMI, were more likely to have diabetes, cardiovascular disease (CVD), and malnutrition (SGA >1); and had high-sensitivity C-reactive protein levels. During 5years of follow-up, 208 patients died. The mortality rate was highest among patients with Low IGF-1+Low HGS. In competing-risk regression analysis, Low IGF-1+Low HGS was independently associated with 2.8 times higher all-cause mortality risk than Low IGF-1+High HGS, after adjusting for Framingham's CVD risk score, presence of CVD, SGA, dialysis status, high-sensitivity C-reactive protein, albumin, LBMI, and sample time in freezer. Low IGF-1 was associated with increased all-cause mortality in patients who also had low HGS but not in those with high HGS, suggesting that the association of IGF-1 with survival in CKD patients depends on nutritional status.

Vocal Characteristics of Children With Short Stature Before and After Growth Hormone Treatment.

To evaluate the vocal characteristics of children with short stature before and 12 months after growth hormone treatment. This analytical, observational cohort study included 23 children (age 5-11 years) diagnosed with short stature. Children in the short stature group (SSG) were matched (1:1) for age and sex with children with normal growth (normal stature group; NSG). Participants in the SSG underwent assessments before and 12 months after growth hormone treatment, while those in the NSG underwent the same assessments at baseline and 12 months. The assessments included evaluation of (A) vocal characteristics (history, vocal self-assessment, auditory-perceptual evaluation, and acoustic analysis), (B) anthropometry, (C) bone age, and (D) measurement of insulin-like growth factor-1 (IGF-1) levels. Children in the SSG had more vocal complaints (P=0.026) than those in the NSG. The groups were similar in terms of vocal self-assessment and auditory-perceptual evaluation (P=nonsignificant). Results of acoustic analysis were also similar for fundamental frequency (F 0) and perturbation measures (P for both=nonsignificant). F 0 and speech frequency decreased significantly at 12 months in both groups. F1 values were higher at 12 months in the NSG, while F2 values were significantly higher in the baseline evaluation in boys in the SSG. Children in the SSG compared with those in the NSG presented a greater increase in height measurements at 12 months, although the anthropometric means were lower in both evaluations (P < 0.001). Vocal characteristics in children with short stature before and after treatment with growth hormone are comparable to those in children with normal growth.

Association between circulating insulin-like growth factor 1 and risk of all-cause and cause-specific mortality.

Insulin-like growth factor 1 (IGF1) is an important growth factor modulating development, homeostasis, and aging. However, whether and how circulating IGF1 concentrations influence early death risk in the general population remains largely unknown. We included 380 997 participants who had serum IGF1 measurement and no history of cancer, cardiovascular disease (CVD), or diabetes at baseline from UK Biobank, a prospective cohort study initiated in 2006-2010. Restricted cubic splines and Cox proportional hazards regression models were used to assess the association between baseline IGF-1 concentrations and all-cause and cause-specific mortality. Over a median follow-up of 8.8 years, 10 753 of the participants died, including 6110 from cancer and 1949 from CVD. Dose-response analysis showed a U-shaped relationship between IGF1 levels and mortality. Compared to the fifth decile of IGF1, the lowest decile was associated with 39% (95% CI: 29-50%), 20% (95% CI: 8-34%), and 39% (95% CI: 14-68%) higher risk of all-cause, cancer, and CVD mortality, respectively, while the highest decile was associated with 17% (95% CI: 7-28%) and 38% (95% CI: 11-71%) higher risk of all-cause and CVD mortality, respectively. The results remained stable in detailed stratified and sensitivity analyses. Our findings indicate that both low and high concentrations of serum IGF1 are associated with increased risk of mortality in the general population. Our study provides a basis for future interrogation of underlying mechanisms of IGF1 in early death occurrence and possible implications for mitigating the risk.

New developments and perspectives in acromegaly

Acromegaly is a rare but severe disorder which is usually due to an excessive secretion of growth hormone (GH) by a pituitary adenoma. Screening mainly relies on the measurement of insulin-like growth factor 1, and confirmatory diagnostics includes a GH suppression test. As delayed diagnosis results in increased morbidity and mortality, we here discuss recently published suggestions regarding the biochemical work-up of suspected cases and the follow-up of co-morbidities. Moreover, new analytical tools (such as automatic identification of typical facial changes using artificial intelligence) are presented, hopefully allowing for an earlier diagnosis in the future. So far, surgery is still regarded as therapy of first choice. In cases without postoperative remission, a new imaging approach (combining sellar magnetic resonance imaging and position emission tomography) may improve the results of repeated surgery. The pharmaceutical arsenal now includes the first orally available somatostatin analogue, and recent data on possible drug combinations and the outcome of radiotherapy are presented. Finally, special attention is paid to older and pregnant patients, as well as certain considerations during the COVID-19 pandemic (where appropriate diagnosis and management of acromegaly is particularly challenging).

The utility of serum inhibin B, anti-Müllerian hormone and insulin growth factor-1 in predicting a positive response to GnRH analogs for diagnosing central precocious puberty in girls

Abstract Objectives The use of inhibin B (INHB), anti-Müllerian hormone (AMH) and insulin-like growth factor-1 (IGF-1) in differentiating central precocious puberty (CPP) from non-CPP was evaluated. Methods In total, 115 Chinese girls were recruited (CPP: 44, non-CPP: 71). The diagnostic performance of INHB, AMH and IGF-1 in differentiating CPP from non-CPP was analyzed using receiver operating characteristic (ROC) curves. Results INHB levels were higher in the CPP group than in the non-CPP group (55.56 ± 22.42 vs. 32.97 ± 15.59 pg/mL; p&lt;0.001). AMH levels were similar in the CPP and non-CPP groups (6.63 ± 3.74 vs. 5.70 ± 3.15 pg/mL; p=0.158), and IGF-1 levels were much higher in the CPP group than in the non-CPP group (290.75 ± 79.78 vs. 200.10 ± 54.01 pg/mL; p&lt;0.001). The area under the ROC curve (AUC) was greatest for INHB (0.819, standard error (SE) 0.041), followed by IGF-1 (0.809, SE 0.047) and AMH (0.567, SE 0.057). Among the ROC curves including combinations of these parameters, the AUC for INHB + IGF-1 was 0.849 and that for INHB + AMH was 0.768. Conclusions Serum INHB and IGF-1 measurements could predict positive responses to gonadotropin-releasing hormone (GnRH) analog stimulation in girls with precocious puberty.

Pre-diagnostic circulating concentrations of insulin-like growth factor-1 and risk of COVID-19 mortality: results from UK Biobank.

Coronavirus disease 2019 (COVID-19) deteriorates suddenly primarily due to excessive inflammatory injury, and insulin-like growth factor-1 (IGF-1) is implicated in endocrine control of the immune system. However, the effect of IGF-1 levels on COVID-19 prognosis remains unknown. Using UK Biobank resource, we investigated the association between circulating IGF-1 concentrations and mortality risk (available death data updated on 07 Sep 2020) among COVID-19 patients who had pre-diagnostic serum IGF-1 measurements at baseline (2006–2010). Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of mortality. Among 1670 COVID-19 patients, 415 deaths occurred due to COVID-19. Compared to the lowest quartile of IGF-1 concentrations, the highest quartile was associated with a 41% lower risk of mortality (OR = 0.59, 95% CI 0.41–0.86, P-trend = 0.01). In the continuous model, per 1-standard deviation increment in log-transformed IGF-1 was associated with a 15% reduction in the risk (intraclass correlation coefficients corrected OR = 0.85, 95% CI 0.73–0.99). The association was largely consistent in the various stratified and sensitivity analyses. In conclusion, our data suggest that higher IGF-1 concentrations are associated with a lower risk of COVID-19 mortality. Further studies are required to determine whether and how targeting IGF-1 pathway might improve COVID-19 prognosis.

The Relationship between Serum Insulin-Like Growth Factor-1 Levels and Body Composition Changes after Sleeve Gastrectomy

Introduction: We previously reported that preoperative serum insulin-like growth factor-1 (IGF-1) is a predictor of total weight loss percentage (%TWL) after laparoscopic sleeve gastrectomy (LSG). IGF-1 may suppress muscle loss after surgery. IGF-1 almost accurately reflects the growth hormone (GH) secretion status, and GH has lipolytic effects. Therefore, IGF-1 may influence both the maintenance of skeletal muscle and the reduction of adipose tissue after LSG. The identification of the relationship between preoperative serum IGF-1 and body composition changes after LSG can help in understanding the pathophysiology of obesity. Methods: We retrospectively reviewed 72 patients with obesity who underwent LSG and were followed up for 12 months. We analyzed the relationship between preoperative serum IGF-1 levels and body composition changes after LSG. A multiple regression model was used. Results: LSG led to a significant reduction in body weight. Both body fat mass and skeletal muscle mass decreased after LSG. Preoperative serum IGF-1 levels significantly correlated with %TWL, changes in skeletal muscle mass, and body fat mass after LSG. The multiple regression model showed that preoperative serum IGF-1 levels were related to decreased body fat mass and maintaining skeletal muscle mass after LSG. Discussion/Conclusion: Preoperative IGF-1 measurement helps predict not only successful weight loss but also decreases body fat mass and maintains skeletal muscle mass after LSG.

Validation of an IGF1 Screening Method for Retinopathy of Pre-maturity

Retinopathy of pre-maturity (ROP) is a retinal disease that causes arrest of vascularization of the retina and can result in retinal detachment and blindness. Current screening protocols may not be sufficiently accurate to identify all at-risk patients. The aim of this study is to validate a method for improved identification of newborns at risk of ROP. We conducted a prospective clinical trial of pre-term newborns <32 weeks of gestation and/or <1,500 g birth weight during a 6-year period in a tertiary care hospital. We applied our new method based on measurement of insulin-like growth factor 1 (IGF1) levels at 3 weeks of age and the presence of sepsis during the first 3 weeks of life. Our screening protocol allowed exclusion of 121 (79.1%) patients for whom American Academy of Pediatrics (AAP) guidelines recommended screening, had a negative predictive value of 100%, and correctly identified all patients with ROP. Following retrospective assessment of our data based on these findings, we propose further restriction of the current AAP indications for screening to <1,100 g and <28 weeks of gestation in order to improve diagnostic efficacy while ensuring optimal use of restriction of human and material resources.