Carmen Floriani1, Martin Feller1,2, Carole E Aubert1, Khadija M'Rabet-Bensalah1, Tinh-Hai Collet3, Wendy P J den Elzen4, Douglas C Bauer5, Anne Angelillo-Scherrer6,7, Drahomir Aujesky1, Nicolas Rodondi1,2. 1. 1 Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern , Bern, Switzerland . 2. 2 Institute of Primary Health Care (BIHAM), University of Bern , Bern, Switzerland . 3. 3 Service of Endocrinology, Diabetes and Metabolism, University Hospital of Lausanne , Lausanne, Switzerland . 4. 4 Leiden University Medical Center , Department of Clinical Chemistry and Laboratory Medicine, Leiden, the Netherlands . 5. 5 Departments of Medicine and Epidemiology and Biostatistics, University of California , San Francisco, California. 6. 6 Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern , Bern, Switzerland . 7. 7 Department of Clinical Research, University of Bern , Bern, Switzerland .
Abstract
BACKGROUND: Even though the association between thyroid dysfunction and anemia is commonly described, it is not known whether it is clinically relevant. This study set out to quantify the association of thyroid dysfunction on hemoglobin (Hb) concentration and risk of anemia. A systematic review (MEDLINE and EMBASE, from inception until May 15, 2017) was conducted to interpret the findings in context. METHODS: Participants from the EPIC-Norfolk cohort with available baseline thyrotropin (TSH), free thyroxine (fT4), and Hb were included. Euthyroidism was defined as TSH 0.45-4.49 mIU/L (reference category), hypothyroidism as TSH ≥4.50 mIU/L (subclinical [SHypo] with normal fT4 or overt [OHypo] with low fT4), and hyperthyroidism as TSH ≤0.44 mIU/L (subclinical [SHyper] with normal fT4 or overt [OHyper] with elevated fT4). Anemia was defined as Hb <12 g/dL in women and Hb <13 g/dL in men. In the cross-sectional analyses, multiple linear regression was used to compare Hb across TSH categories. In the prospective analysis, participants with OHypo/OHyper at baseline were excluded, as it was assumed that they were treated for overt thyroid disease. A covariance model was used to determine change in Hb concentration from baseline to last follow-up, and multivariable Cox regression was used to analyze anemia risk. RESULTS: In the cross-sectional population (n = 12,337), the adjusted Hb was 0.22 g/dL lower [confidence interval (CI) 0.07-0.38] in OHypo compared to euthyroids, and 0.08 g/dL lower [CI -0.23 to 0.38] in OHyper. In the prospective analysis, 460/7031 participants developed anemia over a median follow-up of 4.7 years. The adjusted mean Hb change over time was -0.04 g/dL in SHypo [CI -0.14 to 0.06] and 0.05 g/dL in SHyper [CI -0.10 to 0.20]. The adjusted hazard ratio for anemia was 0.99 [CI 0.67-1.48] in SHypo, and 0.52 [CI 0.23-1.16] in SHyper. The systematic review returned no other prospective studies on this association, but cross-sectional and case-control studies showed comparable results. CONCLUSION: In this first prospective population-based cohort, subclinical thyroid dysfunction was not associated with a change in Hb concentration during follow-up and was not an independent risk factor for developing anemia; variations in Hb concentration in patients with overt thyroid dysfunction were not clinically relevant.
BACKGROUND: Even though the association between thyroid dysfunction and anemia is commonly described, it is not known whether it is clinically relevant. This study set out to quantify the association of thyroid dysfunction on hemoglobin (Hb) concentration and risk of anemia. A systematic review (MEDLINE and EMBASE, from inception until May 15, 2017) was conducted to interpret the findings in context. METHODS:Participants from the EPIC-Norfolk cohort with available baseline thyrotropin (TSH), free thyroxine (fT4), and Hb were included. Euthyroidism was defined as TSH 0.45-4.49 mIU/L (reference category), hypothyroidism as TSH ≥4.50 mIU/L (subclinical [SHypo] with normal fT4 or overt [OHypo] with low fT4), and hyperthyroidism as TSH ≤0.44 mIU/L (subclinical [SHyper] with normal fT4 or overt [OHyper] with elevated fT4). Anemia was defined as Hb <12 g/dL in women and Hb <13 g/dL in men. In the cross-sectional analyses, multiple linear regression was used to compare Hb across TSH categories. In the prospective analysis, participants with OHypo/OHyper at baseline were excluded, as it was assumed that they were treated for overt thyroid disease. A covariance model was used to determine change in Hb concentration from baseline to last follow-up, and multivariable Cox regression was used to analyze anemia risk. RESULTS: In the cross-sectional population (n = 12,337), the adjusted Hb was 0.22 g/dL lower [confidence interval (CI) 0.07-0.38] in OHypo compared to euthyroids, and 0.08 g/dL lower [CI -0.23 to 0.38] in OHyper. In the prospective analysis, 460/7031 participants developed anemia over a median follow-up of 4.7 years. The adjusted mean Hb change over time was -0.04 g/dL in SHypo [CI -0.14 to 0.06] and 0.05 g/dL in SHyper [CI -0.10 to 0.20]. The adjusted hazard ratio for anemia was 0.99 [CI 0.67-1.48] in SHypo, and 0.52 [CI 0.23-1.16] in SHyper. The systematic review returned no other prospective studies on this association, but cross-sectional and case-control studies showed comparable results. CONCLUSION: In this first prospective population-based cohort, subclinical thyroid dysfunction was not associated with a change in Hb concentration during follow-up and was not an independent risk factor for developing anemia; variations in Hb concentration in patients with overt thyroid dysfunction were not clinically relevant.
Authors: Daisy M Wopereis; Robert S Du Puy; Diana van Heemst; John P Walsh; Alexandra Bremner; Stephan J L Bakker; Douglas C Bauer; Anne R Cappola; Graziano Ceresini; Jean Degryse; Robin P F Dullaart; Martin Feller; Luigi Ferrucci; Carmen Floriani; Oscar H Franco; Massimo Iacoviello; Georgio Iervasi; Misa Imaizumi; J Wouter Jukema; Kay-Tee Khaw; Robert N Luben; Sabrina Molinaro; Matthias Nauck; Kushang V Patel; Robin P Peeters; Bruce M Psaty; Salman Razvi; Roger K Schindhelm; Natasja M van Schoor; David J Stott; Bert Vaes; Mark P J Vanderpump; Henry Völzke; Rudi G J Westendorp; Nicolas Rodondi; Christa M Cobbaert; Jacobijn Gussekloo; Wendy P J den Elzen Journal: J Clin Endocrinol Metab Date: 2018-10-01 Impact factor: 5.958
Authors: Robert S Du Puy; Rosalinde K E Poortvliet; Simon P Mooijaart; David J Stott; Terry Quinn; Naveed Sattar; Rudi G J Westendorp; Patricia M Kearney; Vera J C McCarthy; Stephen Byrne; Nicolas Rodondi; Oliver Baretella; Tinh-Hai Collet; Diana van Heemst; Olaf M Dekkers; J Wouter Jukema; Johannes W A Smit; Jacobijn Gussekloo; Wendy P J den Elzen Journal: J Clin Endocrinol Metab Date: 2022-05-17 Impact factor: 6.134
Authors: Nicolien A van Vliet; Annelies E P Kamphuis; Wendy P J den Elzen; Gerard J Blauw; Jacobijn Gussekloo; Raymond Noordam; Diana van Heemst Journal: J Clin Endocrinol Metab Date: 2022-01-18 Impact factor: 5.958