Impact of Thyroid Hormone Therapy on Atherosclerosis in the Elderly With Subclinical Hypothyroidism: A Randomized Trial

Manuel R Blum; Baris Gencer; Luise Adam; Martin Feller; Tinh-Hai Collet; Bruno R da Costa; Elisavet Moutzouri; Jörn Dopheide; Michèle Depairon; Gerasimos P Sykiotis; Patricia Kearney; Jacobijn Gussekloo; Rudi Westendorp; David J Stott; Douglas C Bauer; Nicolas Rodondi

doi:10.1210/jc.2018-00279

Impact of Thyroid Hormone Therapy on Atherosclerosis in the Elderly With Subclinical Hypothyroidism: A Randomized Trial

Manuel R Blum, Baris Gencer, Luise Adam, Martin Feller, Tinh-Hai Collet, Bruno R da Costa, Elisavet Moutzouri, Jörn Dopheide, Michèle Depairon, Gerasimos P Sykiotis, Patricia Kearney, Jacobijn Gussekloo, Rudi Westendorp, David J Stott, Douglas C Bauer, Nicolas Rodondi

16 Citations (Scopus)

Abstract

Context: Subclinical hypothyroidism (SHypo) has been associated with atherosclerosis, but no conclusive clinical trials assessing the levothyroxine impact on carotid atherosclerosis exist. Objective: To assess the impact of treatment of SHypo with levothyroxine on carotid atherosclerosis. Design and Setting: Randomized, double-blind, placebo-controlled trial nested within the Thyroid Hormone Replacement for Subclinical Hypothyroidism trial. Participants: Participants aged ≥65 years with SHypo [thyroid-stimulating hormone (TSH), 4.60 to 19.99 mIU/L; free thyroxine level within reference range]. Intervention: Levothyroxine dose-titrated to achieve TSH normalization or placebo, including mock titrations. Main Outcome Measures: Carotid intima media thickness (CIMT), maximum plaque thickness measured with ultrasound. Results: One hundred eighty-five participants (mean age 74.1 years, 47% women, 96 randomized to levothyroxine) underwent carotid ultrasound. Overall mean TSH ± SD was 6.35 ± 1.95 mIU/L at baseline and decreased to 3.55 ± 2.14 mIU/L with levothyroxine compared with 5.29 ± 2.21 mIU/L with placebo (P < 0.001). After a median treatment of 18.4 months (interquartile range 12.2 to 30.0 months), mean CIMT was 0.85 ± 0.14 mm under levothyroxine and 0.82 ± 0.13 mm under placebo [between-group difference = 0.02 mm; 95% CI, 20.01 to 0.06; P = 0.30]. The proportion of carotid plaque was similar (n = 135; 70.8% under levothyroxine and 75.3% under placebo; P = 0.46). Maximum carotid plaque thickness was 2.38 ± 0.92 mm under levothyroxine and 2.37 ± 0.91 mm under placebo (between-group difference 20.03; 95% CI, 20.34 to 0.29; P = 0.86). There were no significant interactions between levothyroxine treatment and mean CIMT, according to sex, baseline TSH (categories 4.6 to 6.9, 7.0 to 9.9, and ≥10 mIU/L), or established cardiovascular disease (all P for interaction ≥ 0.14). Conclusion: Normalization of TSH with levothyroxine was associated with no difference in CIMT and carotid atherosclerosis in older persons with SHypo.

Original language	English
Journal	The Journal of clinical endocrinology and metabolism
Volume	103
Issue number	8
Pages (from-to)	2988-2997
Number of pages	10
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2018-00279
Publication status	Published - 2018

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Blum, M. R., Gencer, B., Adam, L., Feller, M., Collet, T-H., da Costa, B. R., Moutzouri, E., Dopheide, J., Depairon, M., Sykiotis, G. P., Kearney, P., Gussekloo, J., Westendorp, R., Stott, D. J., Bauer, D. C., & Rodondi, N. (2018). Impact of Thyroid Hormone Therapy on Atherosclerosis in the Elderly With Subclinical Hypothyroidism: A Randomized Trial. The Journal of clinical endocrinology and metabolism, 103(8), 2988-2997. https://doi.org/10.1210/jc.2018-00279

Blum, MR, Gencer, B, Adam, L, Feller, M, Collet, T-H, da Costa, BR, Moutzouri, E, Dopheide, J, Depairon, M, Sykiotis, GP, Kearney, P, Gussekloo, J, Westendorp, R, Stott, DJ, Bauer, DC & Rodondi, N 2018, 'Impact of Thyroid Hormone Therapy on Atherosclerosis in the Elderly With Subclinical Hypothyroidism: A Randomized Trial', The Journal of clinical endocrinology and metabolism, vol. 103, no. 8, pp. 2988-2997. https://doi.org/10.1210/jc.2018-00279

@article{f0c3990b379a45648a2329f29e80a27a,

title = "Impact of Thyroid Hormone Therapy on Atherosclerosis in the Elderly With Subclinical Hypothyroidism: A Randomized Trial",

abstract = "Context: Subclinical hypothyroidism (SHypo) has been associated with atherosclerosis, but no conclusive clinical trials assessing the levothyroxine impact on carotid atherosclerosis exist. Objective: To assess the impact of treatment of SHypo with levothyroxine on carotid atherosclerosis. Design and Setting: Randomized, double-blind, placebo-controlled trial nested within the Thyroid Hormone Replacement for Subclinical Hypothyroidism trial. Participants: Participants aged ≥65 years with SHypo [thyroid-stimulating hormone (TSH), 4.60 to 19.99 mIU/L; free thyroxine level within reference range]. Intervention: Levothyroxine dose-titrated to achieve TSH normalization or placebo, including mock titrations. Main Outcome Measures: Carotid intima media thickness (CIMT), maximum plaque thickness measured with ultrasound. Results: One hundred eighty-five participants (mean age 74.1 years, 47% women, 96 randomized to levothyroxine) underwent carotid ultrasound. Overall mean TSH ± SD was 6.35 ± 1.95 mIU/L at baseline and decreased to 3.55 ± 2.14 mIU/L with levothyroxine compared with 5.29 ± 2.21 mIU/L with placebo (P < 0.001). After a median treatment of 18.4 months (interquartile range 12.2 to 30.0 months), mean CIMT was 0.85 ± 0.14 mm under levothyroxine and 0.82 ± 0.13 mm under placebo [between-group difference = 0.02 mm; 95% CI, 20.01 to 0.06; P = 0.30]. The proportion of carotid plaque was similar (n = 135; 70.8% under levothyroxine and 75.3% under placebo; P = 0.46). Maximum carotid plaque thickness was 2.38 ± 0.92 mm under levothyroxine and 2.37 ± 0.91 mm under placebo (between-group difference 20.03; 95% CI, 20.34 to 0.29; P = 0.86). There were no significant interactions between levothyroxine treatment and mean CIMT, according to sex, baseline TSH (categories 4.6 to 6.9, 7.0 to 9.9, and ≥10 mIU/L), or established cardiovascular disease (all P for interaction ≥ 0.14). Conclusion: Normalization of TSH with levothyroxine was associated with no difference in CIMT and carotid atherosclerosis in older persons with SHypo.",

author = "Blum, {Manuel R} and Baris Gencer and Luise Adam and Martin Feller and Tinh-Hai Collet and {da Costa}, {Bruno R} and Elisavet Moutzouri and J{\"o}rn Dopheide and Mich{\`e}le Depairon and Sykiotis, {Gerasimos P} and Patricia Kearney and Jacobijn Gussekloo and Rudi Westendorp and Stott, {David J} and Bauer, {Douglas C} and Nicolas Rodondi",

year = "2018",

doi = "10.1210/jc.2018-00279",

language = "English",

volume = "103",

pages = "2988--2997",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "8",

}

TY - JOUR

T1 - Impact of Thyroid Hormone Therapy on Atherosclerosis in the Elderly With Subclinical Hypothyroidism

T2 - A Randomized Trial

AU - Blum, Manuel R

AU - Gencer, Baris

AU - Adam, Luise

AU - Feller, Martin

AU - Collet, Tinh-Hai

AU - da Costa, Bruno R

AU - Moutzouri, Elisavet

AU - Dopheide, Jörn

AU - Depairon, Michèle

AU - Sykiotis, Gerasimos P

AU - Kearney, Patricia

AU - Gussekloo, Jacobijn

AU - Westendorp, Rudi

AU - Stott, David J

AU - Bauer, Douglas C

AU - Rodondi, Nicolas

PY - 2018

Y1 - 2018

N2 - Context: Subclinical hypothyroidism (SHypo) has been associated with atherosclerosis, but no conclusive clinical trials assessing the levothyroxine impact on carotid atherosclerosis exist. Objective: To assess the impact of treatment of SHypo with levothyroxine on carotid atherosclerosis. Design and Setting: Randomized, double-blind, placebo-controlled trial nested within the Thyroid Hormone Replacement for Subclinical Hypothyroidism trial. Participants: Participants aged ≥65 years with SHypo [thyroid-stimulating hormone (TSH), 4.60 to 19.99 mIU/L; free thyroxine level within reference range]. Intervention: Levothyroxine dose-titrated to achieve TSH normalization or placebo, including mock titrations. Main Outcome Measures: Carotid intima media thickness (CIMT), maximum plaque thickness measured with ultrasound. Results: One hundred eighty-five participants (mean age 74.1 years, 47% women, 96 randomized to levothyroxine) underwent carotid ultrasound. Overall mean TSH ± SD was 6.35 ± 1.95 mIU/L at baseline and decreased to 3.55 ± 2.14 mIU/L with levothyroxine compared with 5.29 ± 2.21 mIU/L with placebo (P < 0.001). After a median treatment of 18.4 months (interquartile range 12.2 to 30.0 months), mean CIMT was 0.85 ± 0.14 mm under levothyroxine and 0.82 ± 0.13 mm under placebo [between-group difference = 0.02 mm; 95% CI, 20.01 to 0.06; P = 0.30]. The proportion of carotid plaque was similar (n = 135; 70.8% under levothyroxine and 75.3% under placebo; P = 0.46). Maximum carotid plaque thickness was 2.38 ± 0.92 mm under levothyroxine and 2.37 ± 0.91 mm under placebo (between-group difference 20.03; 95% CI, 20.34 to 0.29; P = 0.86). There were no significant interactions between levothyroxine treatment and mean CIMT, according to sex, baseline TSH (categories 4.6 to 6.9, 7.0 to 9.9, and ≥10 mIU/L), or established cardiovascular disease (all P for interaction ≥ 0.14). Conclusion: Normalization of TSH with levothyroxine was associated with no difference in CIMT and carotid atherosclerosis in older persons with SHypo.

AB - Context: Subclinical hypothyroidism (SHypo) has been associated with atherosclerosis, but no conclusive clinical trials assessing the levothyroxine impact on carotid atherosclerosis exist. Objective: To assess the impact of treatment of SHypo with levothyroxine on carotid atherosclerosis. Design and Setting: Randomized, double-blind, placebo-controlled trial nested within the Thyroid Hormone Replacement for Subclinical Hypothyroidism trial. Participants: Participants aged ≥65 years with SHypo [thyroid-stimulating hormone (TSH), 4.60 to 19.99 mIU/L; free thyroxine level within reference range]. Intervention: Levothyroxine dose-titrated to achieve TSH normalization or placebo, including mock titrations. Main Outcome Measures: Carotid intima media thickness (CIMT), maximum plaque thickness measured with ultrasound. Results: One hundred eighty-five participants (mean age 74.1 years, 47% women, 96 randomized to levothyroxine) underwent carotid ultrasound. Overall mean TSH ± SD was 6.35 ± 1.95 mIU/L at baseline and decreased to 3.55 ± 2.14 mIU/L with levothyroxine compared with 5.29 ± 2.21 mIU/L with placebo (P < 0.001). After a median treatment of 18.4 months (interquartile range 12.2 to 30.0 months), mean CIMT was 0.85 ± 0.14 mm under levothyroxine and 0.82 ± 0.13 mm under placebo [between-group difference = 0.02 mm; 95% CI, 20.01 to 0.06; P = 0.30]. The proportion of carotid plaque was similar (n = 135; 70.8% under levothyroxine and 75.3% under placebo; P = 0.46). Maximum carotid plaque thickness was 2.38 ± 0.92 mm under levothyroxine and 2.37 ± 0.91 mm under placebo (between-group difference 20.03; 95% CI, 20.34 to 0.29; P = 0.86). There were no significant interactions between levothyroxine treatment and mean CIMT, according to sex, baseline TSH (categories 4.6 to 6.9, 7.0 to 9.9, and ≥10 mIU/L), or established cardiovascular disease (all P for interaction ≥ 0.14). Conclusion: Normalization of TSH with levothyroxine was associated with no difference in CIMT and carotid atherosclerosis in older persons with SHypo.

U2 - 10.1210/jc.2018-00279

DO - 10.1210/jc.2018-00279

M3 - Journal article

C2 - 29846630

SN - 0021-972X

VL - 103

SP - 2988

EP - 2997

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 8

ER -

Impact of Thyroid Hormone Therapy on Atherosclerosis in the Elderly With Subclinical Hypothyroidism: A Randomized Trial

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