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      Evaluation of renal function in subclinical hypothyroidism

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          Abstract

          INTRODUCTION:

          Patients with subclinical hypothyroidism (SCH) have a few or no symptoms or signs of thyroid dysfunction and thus by its very nature, SCH is a laboratory diagnosis. Serum creatinine is elevated and glomerular filtration rate (GFR) values are reversibly reduced in overt hypothyroid patients. We hypothesize that SCH also may be associated with low GFR.

          AIMS AND OBJECTIVES:

          The objective of this study was (1) to know the effect of SCH on kidney function, (2) to find the correlation between the renal function parameter creatinine, estimated GFR (eGFR), and thyroid-stimulating hormone (TSH), and (3) to know if creatinine values can be predicted by TSH values in SCH cases.

          MATERIALS AND METHODS:

          This is a hospital-based cross-sectional study for 1 year. A total of 608 subjects of either sex were included in the study and were divided into 3 groups: (1) SCH, (2) overt hypothyroidism (OHT), and (3) euthyroidism (ET). TSH, free triiodothyronine, free thyroxine, and serum creatinine were estimated and eGFR was calculated using modification of diet in renal disease study equation and the chronic kidney disease epidemiology collaboration equations.

          RESULTS:

          Serum creatinine levels were higher and eGFR was lower significantly in the subclinical hypothyroid group when compared to the control ET group ( P < 0.001). The overtly hypothyroid group had significantly higher levels of serum creatinine and lower eGFR when compared to both the groups ( P < 0.001). Significant correlation between TSH, creatinine, and eGFR was found in OHT group only. Linear regression analysis showed the regression in creatinine upon TSH is attributable to 44.5% among OHT group, 48.2% in SCH group.

          CONCLUSION:

          It can be concluded that the SCH group behaves biochemically similar to OHT group and changes in serum creatinine reflect tissue hypothyroidism in SCH cases.

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          Most cited references18

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          Subclinical thyroid disease: scientific review and guidelines for diagnosis and management.

          Patients with serum thyroid-stimulating hormone (TSH) levels outside the reference range and levels of free thyroxine (FT4) and triiodothyronine (T3) within the reference range are common in clinical practice. The necessity for further evaluation, possible treatment, and the urgency of treatment have not been clearly established. To define subclinical thyroid disease, review its epidemiology, recommend an appropriate evaluation, explore the risks and benefits of treatment and consequences of nontreatment, and determine whether population-based screening is warranted. MEDLINE, EMBASE, Biosis, the Agency for Healthcare Research and Quality, National Guideline Clearing House, the Cochrane Database of Systematic Reviews and Controlled Trials Register, and several National Health Services (UK) databases were searched for articles on subclinical thyroid disease published between 1995 and 2002. Articles published before 1995 were recommended by expert consultants. A total of 195 English-language or translated papers were reviewed. Editorials, individual case studies, studies enrolling fewer than 10 patients, and nonsystematic reviews were excluded. Information related to authorship, year of publication, number of subjects, study design, and results were extracted and formed the basis for an evidence report, consisting of tables and summaries of each subject area. The strength of the evidence that untreated subclinical thyroid disease is associated with clinical symptoms and adverse clinical outcomes was assessed and recommendations for clinical practice developed. Data relating the progression of subclinical to overt hypothyroidism were rated as good, but data relating treatment to prevention of progression were inadequate to determine a treatment benefit. Data relating a serum TSH level higher than 10 mIU/L to elevations in serum cholesterol were rated as fair but data relating to benefits of treatment were rated as insufficient. All other associations of symptoms and benefit of treatment were rated as insufficient or absent. Data relating a serum TSH concentration lower than 0.1 mIU/L to the presence of atrial fibrillation and progression to overt hyperthyroidism were rated as good, but no data supported treatment to prevent these outcomes. Data relating restoration of the TSH level to within the reference range with improvements in bone mineral density were rated as fair. Data addressing all other associations of subclinical hyperthyroid disease and adverse clinical outcomes or treatment benefits were rated as insufficient or absent. Subclinical hypothyroid disease in pregnancy is a special case and aggressive case finding and treatment in pregnant women can be justified. Data supporting associations of subclinical thyroid disease with symptoms or adverse clinical outcomes or benefits of treatment are few. The consequences of subclinical thyroid disease (serum TSH 0.1-0.45 mIU/L or 4.5-10.0 mIU/L) are minimal and we recommend against routine treatment of patients with TSH levels in these ranges. There is insufficient evidence to support population-based screening. Aggressive case finding is appropriate in pregnant women, women older than 60 years, and others at high risk for thyroid dysfunction.
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            Thyroid dysfunction and kidney disease.

            Thyroid hormones (TH) are essential for an adequate growth and development of the kidney. Conversely, the kidney is not only an organ for metabolism and elimination of TH, but also a target organ of some of the iodothyronines' actions. Thyroid dysfunction causes remarkable changes in glomerular and tubular functions and electrolyte and water homeostasis. Hypothyroidism is accompanied by a decrease in glomerular filtration, hyponatremia, and an alteration of the ability for water excretion. Excessive levels of TH generate an increase in glomerular filtration rate and renal plasma flow. Renal disease, in turn, leads to significant changes in thyroid function. The association of different types of glomerulopathies with both hyper- and hypofunction of the thyroid has been reported. Less frequently, tubulointerstitial disease has been associated with functional thyroid disorders. Nephrotic syndrome is accompanied by changes in the concentrations of TH due primarily to loss of protein in the urine. Acute kidney injury and chronic kidney disease are accompanied by notable effects on the hypothalamus-pituitary-thyroid axis. The secretion of pituitary thyrotropin (TSH) is impaired in uremia. Contrary to other non-thyroidal chronic disease, in uraemic patients it is not unusual to observe the sick euthyroid syndrome with low serum triodothyronine (T(3)) without elevation of reverse T(3) (rT(3)). Some authors have reported associations between thyroid cancer and kidney tumors and each of these organs can develop metastases into the other. Finally, data from recent research suggest that TH, especially T(3), can be considered as a marker for survival in patients with kidney disease.
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              Thyroid dysfunction and kidney disease: An update.

              Thyroid hormones influence renal development, kidney hemodynamics, glomerular filtration rate and sodium and water homeostasis. Hypothyroidism and hyperthyroidism affect renal function by direct renal effects as well as systemic hemodynamic, metabolic and cardiovascular effects. Hypothyroidism has been associated with increased serum creatinine and decreased glomerular filtration rate. The reverse effects have been reported in thyrotoxicosis. Most of renal manifestations of thyroid dysfunction are reversible with treatment. Kidney disease may also cause thyroid dysfunction by several mechanisms. Nephrotic syndrome has been associated to changes in serum thyroid hormone concentrations. Different forms of glomerulonephritis and tubulointerstitial disease may be linked to thyroid derangements. A high prevalence of thyroid hormone alteration has been reported in acute kidney injury. Thyroid dysfunction is highly prevalent in chronic kidney disease patients. Subclinical hypothyroidism and low triiodothyronine syndrome are common features in patients with chronic kidney disease. Patients treated by both hemodialysis and peritoneal dialysis, and renal transplantation recipients, exhibit thyroid hormone alterations and thyroid disease with higher frequency than that found in the general population. Drugs used in the therapy of thyroid disease may lead to renal complications and, similarly, drugs used in kidney disorders may be associated to thyroid alterations. Lastly, low thyroid hormones, especially low triiodothyronine levels, in patients with chronic kidney disease have been related to a higher risk of cardiovascular disease and all-cause mortality. Interpretation of the interactions between thyroid and renal function is a challenge for clinicians involved in the treatment of patients with thyroid and kidney disease.
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                Author and article information

                Journal
                J Lab Physicians
                J Lab Physicians
                JLP
                Journal of Laboratory Physicians
                Medknow Publications & Media Pvt Ltd (India )
                0974-2727
                0974-7826
                Jan-Mar 2018
                : 10
                : 1
                : 50-55
                Affiliations
                [1] Department of Biochemistry, SDM College of Medical Sciences and Hospital, Dharwad, Karnataka, India
                [1 ] Department of Community Medicine, SDM College of Medical Sciences and Hospital, Dharwad, Karnataka, India
                Author notes
                Address for correspondence: Dr. Vijayetha P. Patil, Department of Biochemistry, SDM College of Medical Sciences and Hospital, Sattur, Dharwad, Karnataka, India. E-mail: drvijayetha@ 123456gmail.com
                Article
                JLP-10-50
                10.4103/JLP.JLP_67_17
                5784293
                a4ebb3a8-1e6c-436d-8d16-986e82831ab7
                Copyright: © 2018 Journal of Laboratory Physicians

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 10 April 2017
                : 28 July 2017
                Categories
                Original Article

                Clinical chemistry
                creatinine,estimated glomerular filtration rate,renal dysfunction,subclinical hypothyroidism,thyroid-stimulating hormone,tissue hypothyroidism

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