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      Assessing treatment adherence is crucial to determine adequacy of mineralocorticoid therapy


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          There is no consensus strategy for mineralocorticoid (MC) therapy titration in patients with primary adrenal insufficiency (PAI). We aim to measure serum fludrocortisone (sFC) and urine fludrocortisone (uFC) levels and to determine their utility, alongside clinical/biochemical variables and treatment adherence to guide MC replacement dose titration.


          Multi-centre, observational, cross-sectional study on 41 patients with PAI on MC replacement therapy. sFC and uFC levels (measured by liquid chromatography-tandem mass spectrometry), plasma renin concentration (PRC), electrolytes (Na +, K +), mean arterial blood pressure (MAP), total daily glucocorticoid (dGC) and MC (dMC) dose, and assessment of treatment adherence were incorporated into statistical models.


          We observed a close relationship between sFC and uFC ( r = 0.434, P = 0.005) and between sFC and the time from the last fludrocortisone dose ( r = −0.355, P = 0.023). Total dMC dose was related to dGC dose ( r = 0.556, P < 0.001), K + ( r = −0.388, P = 0.013) as well as sFC ( r = 0.356, P = 0.022) and uFC ( r = 0.531, P < 0.001). PRC was related to Na + ( r = 0.517, P < 0.001) and MAP ( r = −0.427, P = 0.006), but not to MC dose, sFC or uFC. Regression analyses did not support a role for sFC, uFC or PRC measurements and confirmed K + ( B = −44.593, P = 0.005) as the most important variable to guide dMC titration. Of the patients, 32% were non-adherent with replacement therapy. When adherence was inserted into the regression model, it was the only factor affecting dMC.


          sFC and uFC levels are not helpful in guiding dMC titration. Treatment adherence impacts on clinical variables used to assess MC replacement and should be included as part of routine care in patients with PAI.

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          Most cited references53

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          Adherence to Medication

          New England Journal of Medicine, 353(5), 487-497
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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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              Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline.

              Our objective was to develop clinical practice guidelines for the diagnosis and treatment of patients with primary aldosteronism. The Task Force comprised a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, six additional experts, one methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. Systematic reviews of available evidence were used to formulate the key treatment and prevention recommendations. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) group criteria to describe both the quality of evidence and the strength of recommendations. We used "recommend" for strong recommendations and "suggest" for weak recommendations. Consensus was guided by systematic reviews of evidence and discussions during one group meeting, several conference calls, and multiple e-mail communications. The drafts prepared by the task force with the help of a medical writer were reviewed successively by The Endocrine Society's CGS, Clinical Affairs Core Committee (CACC), and Council. The version approved by the CGS and CACC was placed on The Endocrine Society's Web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes. We recommend case detection of primary aldosteronism be sought in higher risk groups of hypertensive patients and those with hypokalemia by determining the aldosterone-renin ratio under standard conditions and that the condition be confirmed/excluded by one of four commonly used confirmatory tests. We recommend that all patients with primary aldosteronism undergo adrenal computed tomography as the initial study in subtype testing and to exclude adrenocortical carcinoma. We recommend the presence of a unilateral form of primary aldosteronism should be established/excluded by bilateral adrenal venous sampling by an experienced radiologist and, where present, optimally treated by laparoscopic adrenalectomy. We recommend that patients with bilateral adrenal hyperplasia, or those unsuitable for surgery, optimally be treated medically by mineralocorticoid receptor antagonists.

                Author and article information

                Endocr Connect
                Endocr Connect
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                03 July 2023
                15 June 2023
                01 September 2023
                : 12
                : 9
                : e230059
                [1 ]Department of Endocrinology , Oxford Centre for Diabetes, Endocrinology and Metabolism and NIHR Oxford Biomedical Research Centre, Churchill Hospital, University of Oxford, Oxford, UK
                [2 ]Department of Experimental Medicine , Sapienza University of Rome, Viale Regina Elena, Rome, Italy
                [3 ]Department of Clinical Chemistry and Immunology , Heartlands Hospital, Birmingham, UK
                [4 ]Department of Clinical Biochemistry , Oxford University Hospitals NHS Foundation Trust, Oxford, UK
                Author notes
                Correspondence should be addressed to J W Tomlinson: jeremy.tomlinson@ 123456ocdem.ox.ac.uk
                Author information
                © the author(s)

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

                : 17 February 2023
                : 03 July 2023

                mineralocorticoids,glucocorticoids,congenital adrenal hyperplasia,addison’s disease,renin


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