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      Effect of GH Deficiency Caused by Nonfunctioning Pituitary Masses on Serum C-reactive Protein Levels

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          Abstract

          Context

          GH supplementation for GH deficiency (GHD) has been reported to decrease high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker; however, the association between GHD and hs-CRP remains unclear.

          Objective

          We aimed to clarify the impact of impaired GH secretion due to pituitary masses on hs-CRP levels.

          Methods

          We retrospectively examined the association between GH secretion, assessed using GH-releasing peptide-2, and serum hs-CRP levels before and a year after the pituitary surgery in patients with nonfunctioning pituitary neuroendocrine tumor or Rathke cleft cyst.

          Results

          Among 171 patients, 55 (32%) presented with severe GHD (peak GH response to GH-releasing peptide-2 < 9 ng/mL). Serum hs-CRP levels were significantly higher in patients with severe GHD than in those without ( P < .001) and significantly correlated with the peak GH ( r = −0.50, P < .001). Multiple regression analyses showed that the peak GH significantly and negatively predicted hs-CRP levels (β = −0.345; 95% CI, −0.533 to −0.158) and the lowest quartile of the peak GH (<5.04 ng/mL) were significantly associated with increase in hs-CRP levels (exp [β] = 1.840; 95% CI, 1.209 to 2.801), after controlling for other anterior hormones and metabolic parameters. Postoperative change in the peak GH (N = 60) significantly predicted change in hs-CRP levels (β = −0.391; 95% CI, −0.675 to −0.108), independent of alterations in other anterior hormones and metabolic parameters.

          Conclusion

          The inverse association between GH secretion and hs-CRP levels highlights the protective role of GH in the increase in hs-CRP.

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          Most cited references39

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          Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.

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            Revised equations for estimated GFR from serum creatinine in Japan.

            Estimation of glomerular filtration rate (GFR) is limited by differences in creatinine generation among ethnicities. Our previously reported GFR-estimating equations for Japanese had limitations because all participants had a GFR less than 90 mL/min/1.73 m2 and serum creatinine was assayed in different laboratories. Diagnostic test study using a prospective cross-sectional design. New equations were developed in 413 participants and validated in 350 participants. All samples were assayed in a central laboratory. Hospitalized Japanese patients in 80 medical centers. Patients had not participated in the previous study. Measured GFR (mGFR) computed from inulin clearance. Estimated GFR (eGFR) by using the modified isotope dilution mass spectrometry (IDMS)-traceable 4-variable Modification of Diet in Renal Disease (MDRD) Study equation using the previous Japanese Society of Nephrology Chronic Kidney Disease Initiative (JSN-CKDI) coefficient of 0.741 (equation 1), the previous JSN-CKDI equation (equation 2), and new equations derived in the development data set: modified MDRD Study using a new Japanese coefficient (equation 3), and a 3-variable Japanese equation (equation 4). Performance of equations was assessed by means of bias (eGFR - mGFR), accuracy (percentage of estimates within 15% or 30% of mGFR), root mean squared error, and correlation coefficient. In the development data set, the new Japanese coefficient was 0.808 (95% confidence interval, 0.728 to 0.829) for the IDMS-MDRD Study equation (equation 3), and the 3-variable Japanese equation (equation 4) was eGFR (mL/min/1.73 m2) = 194 x Serum creatinine(-1.094) x Age(-0.287) x 0.739 (if female). In the validation data set, bias was -1.3 +/- 19.4 versus -5.9 +/- 19.0 mL/min/1.73 m2 (P = 0.002), and accuracy within 30% of mGFR was 73% versus 72% (P = 0.6) for equation 3 versus equation 1 and -2.1 +/- 19.0 versus -7.9 +/- 18.7 mL/min/1.73 m(2) (P < 0.001) and 75% versus 73% (P = 0.06) for equation 4 versus equation 2 (P = 0.06), respectively. Most study participants had chronic kidney disease, and some may have had changing GFRs. The new Japanese coefficient for the modified IDMS-MDRD Study equation and the new Japanese equation are more accurate for the Japanese population than the previously reported equations.
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              Role of C-Reactive Protein at Sites of Inflammation and Infection

              C-reactive protein (CRP) is an acute inflammatory protein that increases up to 1,000-fold at sites of infection or inflammation. CRP is produced as a homopentameric protein, termed native CRP (nCRP), which can irreversibly dissociate at sites of inflammation and infection into five separate monomers, termed monomeric CRP (mCRP). CRP is synthesized primarily in liver hepatocytes but also by smooth muscle cells, macrophages, endothelial cells, lymphocytes, and adipocytes. Evidence suggests that estrogen in the form of hormone replacement therapy influences CRP levels in the elderly. Having been traditionally utilized as a marker of infection and cardiovascular events, there is now growing evidence that CRP plays important roles in inflammatory processes and host responses to infection including the complement pathway, apoptosis, phagocytosis, nitric oxide (NO) release, and the production of cytokines, particularly interleukin-6 and tumor necrosis factor-α. Unlike more recent publications, the findings of early work on CRP can seem somewhat unclear and at times conflicting since it was often not specified which particular CRP isoform was measured or utilized in experiments and whether responses attributed to nCRP were in fact possibly due to dissociation into mCRP or lipopolysaccharide contamination. In addition, since antibodies for mCRP are not commercially available, few laboratories are able to conduct studies investigating the mCRP isoform. Despite these issues and the fact that most CRP research to date has focused on vascular disorders, there is mounting evidence that CRP isoforms have distinct biological properties, with nCRP often exhibiting more anti-inflammatory activities compared to mCRP. The nCRP isoform activates the classical complement pathway, induces phagocytosis, and promotes apoptosis. On the other hand, mCRP promotes the chemotaxis and recruitment of circulating leukocytes to areas of inflammation and can delay apoptosis. The nCRP and mCRP isoforms work in opposing directions to inhibit and induce NO production, respectively. In terms of pro-inflammatory cytokine production, mCRP increases interleukin-8 and monocyte chemoattractant protein-1 production, whereas nCRP has no detectable effect on their levels. Further studies are needed to expand on these emerging findings and to fully characterize the differential roles that each CRP isoform plays at sites of local inflammation and infection.
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                Author and article information

                Contributors
                Journal
                J Endocr Soc
                J Endocr Soc
                jes
                Journal of the Endocrine Society
                Oxford University Press (US )
                2472-1972
                02 November 2023
                04 November 2023
                04 November 2023
                : 7
                : 12
                : bvad137
                Affiliations
                Department of Internal Medicine, Tokyo Women's Medical University , Tokyo, 162-8666, Japan
                Department of Internal Medicine, Tokyo Women's Medical University , Tokyo, 162-8666, Japan
                Department of Internal Medicine, Tokyo Women's Medical University , Tokyo, 162-8666, Japan
                Department of Internal Medicine, Tokyo Women's Medical University , Tokyo, 162-8666, Japan
                Department of Internal Medicine, Tokyo Women's Medical University , Tokyo, 162-8666, Japan
                Department of Internal Medicine, Tokyo Women's Medical University , Tokyo, 162-8666, Japan
                Department of Neurosurgery, Tokyo Women's Medical University , Tokyo, 162-8666, Japan
                Department of Neurosurgery, Tokyo Women's Medical University , Tokyo, 162-8666, Japan
                Department of Internal Medicine, Tokyo Women's Medical University , Tokyo, 162-8666, Japan
                Author notes
                Correspondence: Yasufumi Seki, MD, PhD, Department of Internal Medicine, Tokyo Women’s Medical University, 8-1 Kawada-cho Shinjuku-ku, Tokyo, 162-8666, Japan. Email: seki.yasufumi@ 123456twmu.ac.jp .
                Author information
                https://orcid.org/0000-0002-1950-7704
                https://orcid.org/0000-0002-2292-2319
                https://orcid.org/0000-0003-0597-8406
                https://orcid.org/0000-0002-6526-829X
                https://orcid.org/0000-0001-7922-8275
                https://orcid.org/0000-0002-6076-7065
                https://orcid.org/0000-0002-3872-9767
                Article
                bvad137
                10.1210/jendso/bvad137
                10661662
                38024646
                0a1594a4-af6a-4ed4-b7cc-6575af7b44d5
                © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 September 2023
                : 01 November 2023
                : 21 November 2023
                Page count
                Pages: 10
                Funding
                Funded by: Japan Society for the Promotion of Science, DOI 10.13039/501100001691;
                Funded by: KAKENHI, DOI 10.13039/501100001691;
                Award ID: JP23K15169
                Categories
                Clinical Research Article
                AcademicSubjects/MED00250

                hypopituitarism,inflammation,pituitary neuroendocrine tumor,rathke's cleft cyst

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