scholarly journals Interlaboratory Agreement of Insulin-like Growth Factor 1 Concentrations Measured by Mass Spectrometry

2014 ◽  
Vol 60 (3) ◽  
pp. 541-548 ◽  
Author(s):  
Holly D Cox ◽  
Filipe Lopes ◽  
Getachew A Woldemariam ◽  
Jessica O Becker ◽  
Mark C Parkin ◽  
...  

Abstract BACKGROUND Insulin-like growth factor 1 (IGF-1)7 is a key mediator of growth hormone (GH) action and a well-characterized biomarker of GH abuse. Current immunoassays for IGF-1 suffer from poor concordance between platforms, which makes comparison of results between laboratories difficult. Although previous work has demonstrated good interlaboratory imprecision of LC-MS/MS methods when plasma is supplemented with purified proteins, the interlaboratory imprecision of an endogenous protein in the nanogram-per-milliliter concentration range has not been reported. METHODS We deployed an LC-MS/MS method to quantify serum IGF-1 in 5 laboratories using 5 different instruments and analyzed 130 healthy human samples and 22 samples from patients with acromegaly. We determined measurement imprecision (CV) for differences due to instrumentation, calibration curve construction, method of calibration, and reference material. RESULTS Instrument-dependent variation, exclusive of digestion, across 5 different instrument platforms was determined to be 5.6%. Interlaboratory variation was strongly dependent on calibration. Calibration materials from a single laboratory resulted in less variation than materials made in individual laboratories (CV 5.2% vs 12.8%, respectively). The mean imprecision for 152 samples between the 5 laboratories was 16.0% when a calibration curve was made in each laboratory and 11.1% when a single-point calibration approach was used. CONCLUSIONS The interlaboratory imprecision of serum IGF-1 concentrations is acceptable for use of the assay in antidoping laboratories and in standardizing results across clinical laboratories. The primary source of variability is not derived from the sample preparation but from the method of calibration.

2011 ◽  
Vol 64 (7-8) ◽  
pp. 362-367
Author(s):  
Lidija Banjac

Introduction. Chronic lung disease in the newborn is a complication of mechanical ventilation. The diagnosis of chronic lung disease is made in children of over 36 post-conceptual weeks? age who still require additional oxygen and who have abnormal chest x-ray findings. This study was aimed at triaging newborns at risk of developing chronic lung disease. The operating study hypothesis was that the values of insulin-like growth factor I below 30 ?g/L in the 33rd post-conceptual week were associated with the development of chronic lung disease. Material and Methods. The above hypothesis was verified by a cohort, prospective study, which included preterm newborns of 33 gestational weeks? age or less who were hospitalised at the Department of Neonatology of the Clinical Centre of Montenegro from Aril 2008 to July 2009. The blood sample was taken in the 33rd post-conceptual week and the insulin-like growth factor value was determined by the method of enzyme immunoassay. Results. Our study results confirmed the theory of statistically significant correlation of the length of pregnancy and birth body weight with insulin-like growth factor serum level. Discussion. We did not find any statistically significant correlation between the insulin-like growth factor serum value and chronic lung disease in the newborn. It is possible that the insulin-like growth factor has a different role at various stages of pathogenesis of diseases of prematurity. Conclusion. We believe that by correcting the term for determining the levels we can get a significant correlation between low values of insulin- like growth factor -1 and chronic lung disease.


2020 ◽  
Vol 66 (4) ◽  
pp. 579-586 ◽  
Author(s):  
Danielle Moncrieffe ◽  
Holly D Cox ◽  
Samantha Carletta ◽  
Jessica O Becker ◽  
Andreas Thomas ◽  
...  

Abstract Background Insulin-like growth factor-I (IGF-1) is measured mainly by immunoassay for the diagnosis and treatment of growth hormone (GH) disorders, and to detect misuse of GH in sport. Immunoassays often have insufficient inter-laboratory agreement, especially between commercial kits. Over the expected range of IGF-1 in blood (∼50–500 ng/mL), in an inter-laboratory study we previously established a measurement imprecision of 11% (%CV) for the digested protein analyzed by LC-MS. Measuring intact IGF-1 by LC-MS should be simpler. However, no inter-laboratory agreement has been published. Methods Intact and trypsin-digested IGF-1 in 32 serum samples from healthy volunteers and human growth hormone administration studies were analyzed by LC-MS using different instruments in five laboratories, as well as by immunoassay in a single laboratory. Another 100 samples were analyzed for IGF-1, both intact and after trypsin-digestion, in each laboratory by LC-MS. The statistical relationship between measurements and the imprecision of each assay group was assessed. Results An intra-laboratory variability of 2-4% CV was obtained. Inter-laboratory variability was greater at 14.5% CV. Orthogonal regression of intact versus trypsin-digestion methods (n = 646) gave a slope of 1.01 and intercept of 2.05 ng/mL. Conclusions LC-MS measurements of IGF-1 by intact and trypsin-digestion methods are not statistically different and each is similar to immunoassay. The two LC-MS approaches may be used interchangeably or together to eliminate concerns regarding an immunoassay IGF-1 measurement. Because intact and digested IGF-1 measurements generally agreed within 20% of each other, we propose this as a criterion of assay acceptability.


2021 ◽  
Author(s):  
Rita E Roberts ◽  
Jacqueline Cavalcante Silva ◽  
Rhonda D Kineman ◽  
Timothy J Koh

Insulin-like growth factor (IGF)-1 plays important roles in tissue repair through its ability to stimulate wound cell activity. While IGF-1 is expressed locally by wound cells, liver-derived IGF-1 is also present at high levels in the circulation, and the contributions of local versus circulating IGF-1 to wound levels remain undefined. The hypothesis of this study was that liver is a primary source of IGF-1 during skin wound healing. To test this hypothesis, we utilized a model that allows inducible ablation of IGF-1 specifically in liver of adult mice. We demonstrate that ablation of liver IGF-1 leads to >85% loss of circulating IGF-1 and ~60% decrease in wound IGF-1 during the proliferative phase of healing in both male and female mice. This reduction of liver-derived IGF-1 did not alter local mRNA expression of IGF-1 in wounds. Knockdown of liver IGF-1 significantly delayed wound re-epithelialization, and reduced granulation tissue formation and collagen deposition. Knockdown of liver IGF-1 also significantly reduced angiogenesis and resulted in persistent macrophage accumulation. In summary, liver is a primary source of IGF-1 in skin wounds, and contributes to many aspects of both epithelial and dermal healing.


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