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      Non-invasive assessment of tissue sodium content in patients with primary adrenal insufficiency

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          Abstract

          Objective

          Replacement therapy in primary adrenal insufficiency (PAI) with corticosteroids modulates sodium homeostasis. Serum sodium is, however, prone to osmotic shifts induced by several additional factors besides corticosteroids and does not always reliably reflect treatment quality. Non-osmotic tissue storage can be visualized by sodium MRI ( 23Na-MRI) and might better reflect corticosteroid activity.

          Design

          Longitudinal study of 8 patients with newly diagnosed PAI and cross-sectional study in 22 patients with chronic PAI is reported here. Comparison was made with matched healthy controls.

          Methods

          Using a 23Na-MRI protocol on a 3T scanner, relative sodium signal intensities (rSSI) to signal intensities of the reference vial with 100 mmol/L of sodium were determined in the muscle and skin of the lower calf.

          Results

          In newly diagnosed patients, tissue rSSI (median, range) were reduced and significantly increased after treatment initiation reaching levels similar to healthy controls (muscle: from 0.15 (0.08, 0.18) to 0.18 (0.14, 0.27), P = 0.02; skin: from 0.12 (0.09, 0.18) to 0.18 (0.14, 0.28), P < 0.01). Muscle rSSI was significantly higher in patients with chronic PAI compared to controls (0.19 (0.14, 0.27) vs 0.16 (0.12, 0.20), P < 0.01). In chronic PAI, skin rSSI significantly correlated with plasma renin concentration.

          Conclusion

          23Na-MRI provides an additional insight into sodium homeostasis, and thus the quality of replacement therapy in PAI, as tissue sodium significantly changes once therapy is initiated. The increased tissue sodium in patients with chronic PAI might be an indication of over-replacement.

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          Most cited references37

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          Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline.

          This clinical practice guideline addresses the diagnosis and treatment of primary adrenal insufficiency.
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            (23)Na magnetic resonance imaging of tissue sodium.

            Hypertension is linked to disturbed total-body sodium (Na(+)) regulation; however, measuring Na(+) disposition in the body is difficult. We implemented (23)Na magnetic resonance spectroscopy ((23)Na-MR) and imaging technique ((23)Na-MRI) at 9.4T for animals and 3T for humans to quantify Na(+) content in skeletal muscle and skin. We compared (23)Na-MRI data with actual tissue Na(+) content measured by chemical analysis in animal and human tissue. We then quantified tissue Na(+) content in normal humans and in patients with primary aldosteronism. We found a 29% increase in muscle Na(+) content in patients with aldosteronism compared with normal women and men. This tissue Na(+) was mobilized after successful treatment without accompanying weight loss. We suggest that, after further refinements, this tool could facilitate understanding the relationships between Na(+) accumulation and hypertension. Furthermore, with additional technical advances, a future clinical use may be possible.
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              23Na magnetic resonance imaging-determined tissue sodium in healthy subjects and hypertensive patients.

              High dietary salt intake is associated with hypertension; the prevalence of salt-sensitive hypertension increases with age. We hypothesized that tissue Na(+) might accumulate in hypertensive patients and that aging might be accompanied by Na(+) deposition in tissue. We implemented (23)Na magnetic resonance imaging to measure Na(+) content of soft tissues in vivo earlier, but had not studied essential hypertension. We report on a cohort of 56 healthy control men and women, and 57 men and women with essential hypertension. The ages ranged from 22 to 90 years. (23)Na magnetic resonance imaging measurements were made at the level of the calf. We observed age-dependent increases in Na(+) content in muscle in men, whereas muscle Na(+) content did not change with age in women. We estimated water content with conventional MRI and found no age-related increases in muscle water in men, despite remarkable Na(+) accumulation, indicating water-free Na(+) storage in muscle. With increasing age, there was Na(+) deposition in the skin in both women and men; however, skin Na(+) content remained lower in women. Similarly, this sex difference was found in skin water content, which was lower in women than in men. In contrast to muscle, increasing Na(+) content was paralleled with increasing skin water content. When controlled for age, we found that patients with refractory hypertension had increased tissue Na(+) content, compared with normotensive controls. These observations suggest that (23)Na magnetic resonance imaging could have utility in assessing the role of tissue Na(+) storage for cardiovascular morbidity and mortality in longitudinal studies.

                Author and article information

                Journal
                Eur J Endocrinol
                Eur J Endocrinol
                EJE
                European Journal of Endocrinology
                Bioscientifica Ltd (Bristol )
                0804-4643
                1479-683X
                04 July 2022
                01 September 2022
                : 187
                : 3
                : 383-390
                Affiliations
                [1 ]Division of Endocrinology and Diabetology , Department of Internal Medicine I, University Hospital of Würzburg, University of Würzburg, Würzburg, Germany
                [2 ]Department of Diagnostic and Interventional Radiology , University Hospital Würzburg, Würzburg, Germany
                [3 ]Comprehensive Heart Failure Center , University and University Hospital Würzburg, Würzburg, Germany
                [4 ]Department of Internal Medicine I , University Hospital Würzburg, Würzburg, Germany
                Author notes
                Correspondence should be addressed to I Chifu; Email: chifu_i@ 123456ukw.de

                *(I Chifu and A M Weng contributed equally to this work)

                Author information
                http://orcid.org/0000-0002-6741-2689
                http://orcid.org/0000-0002-8703-7644
                Article
                EJE-22-0396
                10.1530/EJE-22-0396
                9346263
                35895687
                ad02dffb-9277-47a1-b06d-3e23920c8877
                © The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 29 April 2022
                : 04 July 2022
                Categories
                Original Research

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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