David J Stott1, Nicolas Rodondi1, Patricia M Kearney1, Ian Ford1, Rudi G J Westendorp1, Simon P Mooijaart1, Naveed Sattar1, Carole E Aubert1, Drahomir Aujesky1, Douglas C Bauer1, Christine Baumgartner1, Manuel R Blum1, John P Browne1, Stephen Byrne1, Tinh-Hai Collet1, Olaf M Dekkers1, Wendy P J den Elzen1, Robert S Du Puy1, Graham Ellis1, Martin Feller1, Carmen Floriani1, Kirsty Hendry1, Caroline Hurley1, J Wouter Jukema1, Sharon Kean1, Maria Kelly1, Danielle Krebs1, Peter Langhorne1, Gemma McCarthy1, Vera McCarthy1, Alex McConnachie1, Mairi McDade1, Martina Messow1, Annemarie O'Flynn1, David O'Riordan1, Rosalinde K E Poortvliet1, Terence J Quinn1, Audrey Russell1, Carol Sinnott1, Jan W A Smit1, H Anette Van Dorland1, Kieran A Walsh1, Elaine K Walsh1, Torquil Watt1, Robbie Wilson1, Jacobijn Gussekloo1. 1. From the Academic Section of Geriatric Medicine, Institute of Cardiovascular and Medical Sciences (D.J.S., K.H., P.L., M. McDade, T.J.Q.), the Robertson Centre for Biostatistics, Institute of Health and Wellbeing (I.F., S.K., A.M., M. Messow, R.W.), and the Institute of Cardiovascular and Medical Sciences (N.S.), University of Glasgow, Glasgow, and Care of the Elderly-Rehabilitation, Monklands Hospital, NHS Lanarkshire, Airdrie (G.E.) - all in the United Kingdom; the Department of General Internal Medicine, Inselspital, Bern University Hospital (N.R., C.E.A., D.A., C.B., M.R.B., M.F., C.F., D.K., H.A.V.D.), and the Institute of Primary Health Care (N.R., M.F.), University of Bern, Bern, and the Service of Endocrinology, Diabetes, and Metabolism, University Hospital of Lausanne, Lausanne (T.-H.C.) - all in Switzerland; the Department of Epidemiology and Public Health (P.M.K., J.P.B., C.H., G.M., A.O., D.O., C.S., K.A.W., E.K.W.), the Pharmaceutical Care Research Group, School of Pharmacy (S.B., M.K., K.A.W.), the School of Nursing and Midwifery (V.M.), and the Department of General Practice (A.R., E.K.W.), University College Cork, and the Health Research Board Clinical Research Facility, Mercy University Hospital (M.K.) - all in Cork, Ireland; the Department of Public Health and Center for Healthy Aging, University of Copenhagen (R.G.J.W.), and the Department of Medical Endocrinology, Copenhagen University Hospital Rigshospitalet (T.W.), Copenhagen, and the Department of Internal Medicine, Copenhagen University Hospital Herlev, Herlev (T.W.) - all in Denmark; the Departments of Gerontology and Geriatrics (S.P.M.), Internal Medicine (O.M.D.), Clinical Epidemiology (O.M.D.), Clinical Chemistry and Laboratory Medicine (W.P.J.E.), Public Health and Primary Care (R.S.D.P., R.K.E.P., J.G.), and Cardiology (J.W.J.), Leiden University Medical Center, and the Institute for Evidence-based Medicine in Old Age (S.P.M.), Leiden, and Radboud University Medical Center, Nijmegen (J.W.A.S.) - all in the Netherlands; and the Departments of Medicine, Epidemiology, and Biostatistics, University of California, San Francisco, San Francisco (D.C.B.).
Abstract
BACKGROUND: The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. METHODS: We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 μg daily, or 25 μg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points). RESULTS: The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 μg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval [CI], -2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest. CONCLUSIONS:Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126 .).
RCT Entities:
BACKGROUND: The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. METHODS: We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 μg daily, or 25 μg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points). RESULTS: The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 μg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval [CI], -2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest. CONCLUSIONS:Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126 .).
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