Simon P Mooijaart1,2, Robert S Du Puy3, David J Stott4, Patricia M Kearney5, Nicolas Rodondi6,7, Rudi G J Westendorp8,9, Wendy P J den Elzen10, Iris Postmus1,2, Rosalinde K E Poortvliet3, Diana van Heemst1, Barbara C van Munster11, Robin P Peeters12, Ian Ford13, Sharon Kean13, Claudia-Martina Messow13, Manuel R Blum6,14, Tinh-Hai Collet15, Torquil Watt16, Olaf M Dekkers17, J Wouter Jukema18, Johannes W A Smit19, Peter Langhorne20, Jacobijn Gussekloo1,3. 1. Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands. 2. Institute for Evidence-Based Medicine in Old Age, Leiden, the Netherlands. 3. Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands. 4. Geriatric Medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom. 5. School of Public Health, University College Cork, Cork, Ireland. 6. Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 7. Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland. 8. Department of Public Health, University of Copenhagen, Copenhagen, Denmark. 9. Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark. 10. Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands. 11. Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands. 12. Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, the Netherlands. 13. Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom. 14. Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California. 15. Service of Endocrinology, Diabetes and Metabolism, Lausanne University Hospital, Lausanne, Switzerland. 16. Department of Internal Medicine, Copenhagen University Hospital Herlev, Gentofte, Denmark. 17. Department of Endocrinology and Metabolic Disorders, Leiden University Medical Center, Leiden, the Netherlands. 18. Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands. 19. Radboud University Medical Center, Nijmegen, the Netherlands. 20. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
Abstract
IMPORTANCE: It is unclear whether levothyroxine treatment provides clinically important benefits in adults aged 80 years and older with subclinical hypothyroidism. OBJECTIVE: To determine the association of levothyroxine treatment for subclinical hypothyroidism with thyroid-related quality of life in adults aged 80 years and older. DESIGN, SETTING, AND PARTICIPANTS: Prospectively planned combined analysis of data involving community-dwelling adults aged 80 years and older with subclinical hypothyroidism. Data from a randomized clinical trial were combined with a subgroup of participants aged 80 years and older from a second clinical trial. The trials were conducted between April 2013 and May 2018. Final follow-up was May 4, 2018. EXPOSURES: Participants were randomly assigned to receive levothyroxine (n = 112; 52 participants from the first trial and 60 from the second trial) or placebo (n = 139; 53 participants from the first trial and 86 from the second trial). MAIN OUTCOMES AND MEASURES: Co-primary outcomes were Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire scores for the domains of hypothyroid symptoms and tiredness at 1 year (range, 0-100; higher scores indicate worse quality of life; minimal clinically important difference, 9). RESULTS: Of 251 participants (mean age, 85 years; 118 [47%] women), 105 were included from the first clinical trial and 146 were included from the second clinical trial. A total of 212 participants (84%) completed the study. The hypothyroid symptoms score decreased from 21.7 at baseline to 19.3 at 12 months in the levothyroxine group vs from 19.8 at baseline to 17.4 at 12 months in the placebo group (adjusted between-group difference, 1.3 [95% CI, -2.7 to 5.2]; P = .53). The tiredness score increased from 25.5 at baseline to 28.2 at 12 months in the levothyroxine group vs from 25.1 at baseline to 28.7 at 12 months in the placebo group (adjusted between-group difference, -0.1 [95% CI, -4.5 to 4.3]; P = .96). At least 1 adverse event occurred in 33 participants (29.5%) in the levothyroxine group (the most common adverse event was cerebrovascular accident, which occurred in 3 participants [2.2%]) and 40 participants (28.8%) in the placebo group (the most common adverse event was pneumonia, which occurred in 4 [3.6%] participants). CONCLUSIONS AND RELEVANCE: In this prospectively planned analysis of data from 2 clinical trials involving adults aged 80 years and older with subclinical hypothyroidism, treatment with levothyroxine, compared with placebo, was not significantly associated with improvement in hypothyroid symptoms or fatigue. These findings do not support routine use of levothyroxine for treatment of subclinical hypothyroidism in adults aged 80 years and older. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01660126; Netherlands Trial Register: NTR3851.
IMPORTANCE: It is unclear whether levothyroxine treatment provides clinically important benefits in adults aged 80 years and older with subclinical hypothyroidism. OBJECTIVE: To determine the association of levothyroxine treatment for subclinical hypothyroidism with thyroid-related quality of life in adults aged 80 years and older. DESIGN, SETTING, AND PARTICIPANTS: Prospectively planned combined analysis of data involving community-dwelling adults aged 80 years and older with subclinical hypothyroidism. Data from a randomized clinical trial were combined with a subgroup of participants aged 80 years and older from a second clinical trial. The trials were conducted between April 2013 and May 2018. Final follow-up was May 4, 2018. EXPOSURES: Participants were randomly assigned to receive levothyroxine (n = 112; 52 participants from the first trial and 60 from the second trial) or placebo (n = 139; 53 participants from the first trial and 86 from the second trial). MAIN OUTCOMES AND MEASURES: Co-primary outcomes were Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire scores for the domains of hypothyroid symptoms and tiredness at 1 year (range, 0-100; higher scores indicate worse quality of life; minimal clinically important difference, 9). RESULTS: Of 251 participants (mean age, 85 years; 118 [47%] women), 105 were included from the first clinical trial and 146 were included from the second clinical trial. A total of 212 participants (84%) completed the study. The hypothyroid symptoms score decreased from 21.7 at baseline to 19.3 at 12 months in the levothyroxine group vs from 19.8 at baseline to 17.4 at 12 months in the placebo group (adjusted between-group difference, 1.3 [95% CI, -2.7 to 5.2]; P = .53). The tiredness score increased from 25.5 at baseline to 28.2 at 12 months in the levothyroxine group vs from 25.1 at baseline to 28.7 at 12 months in the placebo group (adjusted between-group difference, -0.1 [95% CI, -4.5 to 4.3]; P = .96). At least 1 adverse event occurred in 33 participants (29.5%) in the levothyroxine group (the most common adverse event was cerebrovascular accident, which occurred in 3 participants [2.2%]) and 40 participants (28.8%) in the placebo group (the most common adverse event was pneumonia, which occurred in 4 [3.6%] participants). CONCLUSIONS AND RELEVANCE: In this prospectively planned analysis of data from 2 clinical trials involving adults aged 80 years and older with subclinical hypothyroidism, treatment with levothyroxine, compared with placebo, was not significantly associated with improvement in hypothyroid symptoms or fatigue. These findings do not support routine use of levothyroxine for treatment of subclinical hypothyroidism in adults aged 80 years and older. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01660126; Netherlands Trial Register: NTR3851.
Authors: Nydia Burgos; Freddy J K Toloza; Naykky M Singh Ospina; Juan P Brito; Ramzi G Salloum; Leslie C Hassett; Spyridoula Maraka Journal: Thyroid Date: 2020-12-29 Impact factor: 6.568
Authors: Laurien E Zijlstra; J Wouter Jukema; Rudi G J Westendorp; Robert S Du Puy; Rosalinde K E Poortvliet; Patricia M Kearney; Linda O'Keeffe; Olaf M Dekkers; Manuel R Blum; Nicolas Rodondi; Tinh-Hai Collet; Terence J Quinn; Naveed Sattar; David J Stott; Stella Trompet; Wendy P J den Elzen; Jacobijn Gussekloo; Simon P Mooijaart Journal: Front Endocrinol (Lausanne) Date: 2021-05-20 Impact factor: 5.555