Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism

David J. Stott; Nicolas Rodondi; Patricia M. Kearney; Ian Ford; Rudi G. J. Westendorp; Simon P. Mooijaart; Naveed Sattar; Carole E. Aubert; Drahomir Aujesky; Douglas C. Bauer; Christine Baumgartner; Manuel R. Blum; John P. Browne; Stephen L. Byrne; Tinh-Hai Collet; Olaf M. Dekkers; Wendy P. J. den Elzen; Robert S. Du Puy; Graham Ellis; Martin Feller; Carmen Floriani; Kirsty Hendry; Caroline Hurley; J. Wouter Jukema; Sharon Kean; Maria Kelly; Danielle Krebs; Peter Langhorne; Gemma McCarthy; Vera McCarthy; Alex McConnachie; Mairi McDade; Martina Messow; Annemarie O’Flynn; David O’Riordan; Rosalinde K. E. Poortvliet; Terence J. Quinn; Audrey Russell; Carol Sinnott; Jan W. A. Smit; H. Anette Van Dorland; Kieran A. Walsh; Elaine K. Walsh; Torquil Watt; Robbie Wilson; Jacobijn Gussekloo; the TRUST Study Group

doi:10.1056/nejmoa1603825

Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism

David J. Stott, Nicolas Rodondi, Patricia M. Kearney, Ian Ford, Rudi G. J. Westendorp, Simon P. Mooijaart, Naveed Sattar, Carole E. Aubert, Drahomir Aujesky, Douglas C. Bauer, Christine Baumgartner, Manuel R. Blum, John P. Browne, Stephen L. Byrne, Tinh-Hai Collet, Olaf M. Dekkers, Wendy P. J. den Elzen, Robert S. Du Puy, Graham Ellis, Martin FellerCarmen Floriani, Kirsty Hendry, Caroline Hurley, J. Wouter Jukema, Sharon Kean, Maria Kelly, Danielle Krebs, Peter Langhorne, Gemma McCarthy, Vera McCarthy, Alex McConnachie, Mairi McDade, Martina Messow, Annemarie O’Flynn, David O’Riordan, Rosalinde K. E. Poortvliet, Terence J. Quinn, Audrey Russell, Carol Sinnott, Jan W. A. Smit, H. Anette Van Dorland, Kieran A. Walsh, Elaine K. Walsh, Torquil Watt, Robbie Wilson, Jacobijn Gussekloo, the TRUST Study Group

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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.

Original language	English
Journal	New England Journal of Medicine
Volume	376
Issue number	26
Pages (from-to)	2534-2544
Number of pages	11
ISSN	0028-4793
DOIs	https://doi.org/10.1056/nejmoa1603825
Publication status	Published - 29 Jun 2017

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Stott, D. J., Rodondi, N., Kearney, P. M., Ford, I., Westendorp, R. G. J., Mooijaart, S. P., Sattar, N., Aubert, C. E., Aujesky, D., Bauer, D. C., Baumgartner, C., Blum, M. R., Browne, J. P., Byrne, S. L., Collet, T-H., Dekkers, O. M., den Elzen, W. P. J., Du Puy, R. S., Ellis, G., ... the TRUST Study Group (2017). Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism. New England Journal of Medicine, 376(26), 2534-2544. https://doi.org/10.1056/nejmoa1603825

Stott, DJ, Rodondi, N, Kearney, PM, Ford, I, Westendorp, RGJ, Mooijaart, SP, Sattar, N, Aubert, CE, Aujesky, D, Bauer, DC, Baumgartner, C, Blum, MR, Browne, JP, Byrne, SL, Collet, T-H, Dekkers, OM, den Elzen, WPJ, Du Puy, RS, Ellis, G, Feller, M, Floriani, C, Hendry, K, Hurley, C, Jukema, JW, Kean, S, Kelly, M, Krebs, D, Langhorne, P, McCarthy, G, McCarthy, V, McConnachie, A, McDade, M, Messow, M, O’Flynn, A, O’Riordan, D, Poortvliet, RKE, Quinn, TJ, Russell, A, Sinnott, C, Smit, JWA, Van Dorland, HA, Walsh, KA, Walsh, EK, Watt, T, Wilson, R, Gussekloo, J & the TRUST Study Group 2017, 'Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism', New England Journal of Medicine, vol. 376, no. 26, pp. 2534-2544. https://doi.org/10.1056/nejmoa1603825

@article{b42969ed26d148c5acc8daaded42514d,

title = "Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism",

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.",

author = "Stott, {David J.} and Nicolas Rodondi and Kearney, {Patricia M.} and Ian Ford and Westendorp, {Rudi G. J.} and Mooijaart, {Simon P.} and Naveed Sattar and Aubert, {Carole E.} and Drahomir Aujesky and Bauer, {Douglas C.} and Christine Baumgartner and Blum, {Manuel R.} and Browne, {John P.} and Byrne, {Stephen L.} and Tinh-Hai Collet and Dekkers, {Olaf M.} and {den Elzen}, {Wendy P. J.} and {Du Puy}, {Robert S.} and Graham Ellis and Martin Feller and Carmen Floriani and Kirsty Hendry and Caroline Hurley and Jukema, {J. Wouter} and Sharon Kean and Maria Kelly and Danielle Krebs and Peter Langhorne and Gemma McCarthy and Vera McCarthy and Alex McConnachie and Mairi McDade and Martina Messow and Annemarie O{\textquoteright}Flynn and David O{\textquoteright}Riordan and Poortvliet, {Rosalinde K. E.} and Quinn, {Terence J.} and Audrey Russell and Carol Sinnott and Smit, {Jan W. A.} and {Van Dorland}, {H. Anette} and Walsh, {Kieran A.} and Walsh, {Elaine K.} and Torquil Watt and Robbie Wilson and Jacobijn Gussekloo and {the TRUST Study Group}",

year = "2017",

month = jun,

day = "29",

doi = "10.1056/nejmoa1603825",

language = "English",

volume = "376",

pages = "2534--2544",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "26",

}

TY - JOUR

T1 - Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism

AU - Stott, David J.

AU - Rodondi, Nicolas

AU - Kearney, Patricia M.

AU - Ford, Ian

AU - Westendorp, Rudi G. J.

AU - Mooijaart, Simon P.

AU - Sattar, Naveed

AU - Aubert, Carole E.

AU - Aujesky, Drahomir

AU - Bauer, Douglas C.

AU - Baumgartner, Christine

AU - Blum, Manuel R.

AU - Browne, John P.

AU - Byrne, Stephen L.

AU - Collet, Tinh-Hai

AU - Dekkers, Olaf M.

AU - den Elzen, Wendy P. J.

AU - Du Puy, Robert S.

AU - Ellis, Graham

AU - Feller, Martin

AU - Floriani, Carmen

AU - Hendry, Kirsty

AU - Hurley, Caroline

AU - Jukema, J. Wouter

AU - Kean, Sharon

AU - Kelly, Maria

AU - Krebs, Danielle

AU - Langhorne, Peter

AU - McCarthy, Gemma

AU - McCarthy, Vera

AU - McConnachie, Alex

AU - McDade, Mairi

AU - Messow, Martina

AU - O’Flynn, Annemarie

AU - O’Riordan, David

AU - Poortvliet, Rosalinde K. E.

AU - Quinn, Terence J.

AU - Russell, Audrey

AU - Sinnott, Carol

AU - Smit, Jan W. A.

AU - Van Dorland, H. Anette

AU - Walsh, Kieran A.

AU - Walsh, Elaine K.

AU - Watt, Torquil

AU - Wilson, Robbie

AU - Gussekloo, Jacobijn

AU - the TRUST Study Group

PY - 2017/6/29

Y1 - 2017/6/29

N2 - 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.

AB - 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.

U2 - 10.1056/nejmoa1603825

DO - 10.1056/nejmoa1603825

M3 - Journal article

C2 - 28402245

SN - 0028-4793

VL - 376

SP - 2534

EP - 2544

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 26

ER -

Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism

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