Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults

Evie van der Spoel; Nicolien A van Vliet; Rosalinde K E Poortvliet; Robert S Du Puy; Wendy P J den Elzen; Terence J Quinn; David J Stott; Naveed Sattar; Patricia M Kearney; Manuel R Blum; Heba Alwan; Nicolas Rodondi; Tinh-Hai Collet; Rudi G J Westendorp; Bart E Ballieux; J Wouter Jukema; Olaf M Dekkers; Jacobijn Gussekloo; Simon P Mooijaart; Diana van Heemst

doi:10.1210/clinem/dgad623

Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults

Evie van der Spoel, Nicolien A van Vliet, Rosalinde K E Poortvliet, Robert S Du Puy, Wendy P J den Elzen, Terence J Quinn, David J Stott, Naveed Sattar, Patricia M Kearney, Manuel R Blum, Heba Alwan, Nicolas Rodondi, Tinh-Hai Collet, Rudi G J Westendorp, Bart E Ballieux, J Wouter Jukema, Olaf M Dekkers, Jacobijn Gussekloo, Simon P Mooijaart, Diana van Heemst

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Abstract

CONTEXT: With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown.

OBJECTIVE: To investigate incidence and determinants of spontaneous normalization of thyroid-stimulating hormone (TSH) levels in older adults with subclinical hypothyroidism.

DESIGN: Pooled data were used from the (i) pre-trial population, and (ii) in-trial placebo group from two randomized, double-blind, placebo-controlled trials (TRUST and IEMO thyroid 80-plus thyroid trial).

SETTING: Community-dwelling 65 + adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom.

PARTICIPANTS: The pre-trial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free thyroxine (fT4) within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included.

MAIN OUTCOME MEASURES: Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization.

RESULTS: In the pre-trial phase, TSH levels normalized in 60.8% of participants in a median follow-up of one year. In the in-trial phase, levels normalized in 39.9% of participants after one year follow-up. Younger age, female sex, lower initial TSH level, higher initial fT4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization.

CONCLUSIONS: Since TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment.

Original language	English
Journal	The Journal of clinical endocrinology and metabolism
Volume	109
Issue number	3
Pages (from-to)	e1167–e1174
Number of pages	8
ISSN	0021-972X
DOIs	https://doi.org/10.1210/clinem/dgad623
Publication status	Published - 2024

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van der Spoel, E., van Vliet, N. A., Poortvliet, R. K. E., Du Puy, R. S., den Elzen, W. P. J., Quinn, T. J., Stott, D. J., Sattar, N., Kearney, P. M., Blum, M. R., Alwan, H., Rodondi, N., Collet, T-H., Westendorp, R. G. J., Ballieux, B. E., Jukema, J. W., Dekkers, O. M., Gussekloo, J., Mooijaart, S. P., & van Heemst, D. (2024). Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults. The Journal of clinical endocrinology and metabolism, 109(3), e1167–e1174. https://doi.org/10.1210/clinem/dgad623

Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults. / van der Spoel, Evie; van Vliet, Nicolien A; Poortvliet, Rosalinde K E; Du Puy, Robert S; den Elzen, Wendy P J; Quinn, Terence J; Stott, David J; Sattar, Naveed; Kearney, Patricia M; Blum, Manuel R; Alwan, Heba; Rodondi, Nicolas; Collet, Tinh-Hai; Westendorp, Rudi G J; Ballieux, Bart E; Jukema, J Wouter; Dekkers, Olaf M; Gussekloo, Jacobijn; Mooijaart, Simon P; van Heemst, Diana.

In: The Journal of clinical endocrinology and metabolism, Vol. 109, No. 3, 2024, p. e1167–e1174.

Research output: Contribution to journal › Journal article › Research › peer-review

van der Spoel, E, van Vliet, NA, Poortvliet, RKE, Du Puy, RS, den Elzen, WPJ, Quinn, TJ, Stott, DJ, Sattar, N, Kearney, PM, Blum, MR, Alwan, H, Rodondi, N, Collet, T-H, Westendorp, RGJ, Ballieux, BE, Jukema, JW, Dekkers, OM, Gussekloo, J, Mooijaart, SP & van Heemst, D 2024, 'Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults', The Journal of clinical endocrinology and metabolism, vol. 109, no. 3, pp. e1167–e1174. https://doi.org/10.1210/clinem/dgad623

van der Spoel, Evie ; van Vliet, Nicolien A ; Poortvliet, Rosalinde K E ; Du Puy, Robert S ; den Elzen, Wendy P J ; Quinn, Terence J ; Stott, David J ; Sattar, Naveed ; Kearney, Patricia M ; Blum, Manuel R ; Alwan, Heba ; Rodondi, Nicolas ; Collet, Tinh-Hai ; Westendorp, Rudi G J ; Ballieux, Bart E ; Jukema, J Wouter ; Dekkers, Olaf M ; Gussekloo, Jacobijn ; Mooijaart, Simon P ; van Heemst, Diana. / Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults. In: The Journal of clinical endocrinology and metabolism. 2024 ; Vol. 109, No. 3. pp. e1167–e1174.

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title = "Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults",

abstract = "CONTEXT: With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown.OBJECTIVE: To investigate incidence and determinants of spontaneous normalization of thyroid-stimulating hormone (TSH) levels in older adults with subclinical hypothyroidism.DESIGN: Pooled data were used from the (i) pre-trial population, and (ii) in-trial placebo group from two randomized, double-blind, placebo-controlled trials (TRUST and IEMO thyroid 80-plus thyroid trial).SETTING: Community-dwelling 65 + adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom.PARTICIPANTS: The pre-trial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free thyroxine (fT4) within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included.MAIN OUTCOME MEASURES: Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization.RESULTS: In the pre-trial phase, TSH levels normalized in 60.8% of participants in a median follow-up of one year. In the in-trial phase, levels normalized in 39.9% of participants after one year follow-up. Younger age, female sex, lower initial TSH level, higher initial fT4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization.CONCLUSIONS: Since TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment.",

author = "{van der Spoel}, Evie and {van Vliet}, {Nicolien A} and Poortvliet, {Rosalinde K E} and {Du Puy}, {Robert S} and {den Elzen}, {Wendy P J} and Quinn, {Terence J} and Stott, {David J} and Naveed Sattar and Kearney, {Patricia M} and Blum, {Manuel R} and Heba Alwan and Nicolas Rodondi and Tinh-Hai Collet and Westendorp, {Rudi G J} and Ballieux, {Bart E} and Jukema, {J Wouter} and Dekkers, {Olaf M} and Jacobijn Gussekloo and Mooijaart, {Simon P} and {van Heemst}, Diana",

note = "{\textcopyright} The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.",

year = "2024",

doi = "10.1210/clinem/dgad623",

language = "English",

volume = "109",

pages = "e1167–e1174",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

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TY - JOUR

T1 - Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults

AU - van der Spoel, Evie

AU - van Vliet, Nicolien A

AU - Poortvliet, Rosalinde K E

AU - Du Puy, Robert S

AU - den Elzen, Wendy P J

AU - Quinn, Terence J

AU - Stott, David J

AU - Sattar, Naveed

AU - Kearney, Patricia M

AU - Blum, Manuel R

AU - Alwan, Heba

AU - Rodondi, Nicolas

AU - Collet, Tinh-Hai

AU - Westendorp, Rudi G J

AU - Ballieux, Bart E

AU - Jukema, J Wouter

AU - Dekkers, Olaf M

AU - Gussekloo, Jacobijn

AU - Mooijaart, Simon P

AU - van Heemst, Diana

PY - 2024

Y1 - 2024

N2 - CONTEXT: With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown.OBJECTIVE: To investigate incidence and determinants of spontaneous normalization of thyroid-stimulating hormone (TSH) levels in older adults with subclinical hypothyroidism.DESIGN: Pooled data were used from the (i) pre-trial population, and (ii) in-trial placebo group from two randomized, double-blind, placebo-controlled trials (TRUST and IEMO thyroid 80-plus thyroid trial).SETTING: Community-dwelling 65 + adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom.PARTICIPANTS: The pre-trial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free thyroxine (fT4) within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included.MAIN OUTCOME MEASURES: Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization.RESULTS: In the pre-trial phase, TSH levels normalized in 60.8% of participants in a median follow-up of one year. In the in-trial phase, levels normalized in 39.9% of participants after one year follow-up. Younger age, female sex, lower initial TSH level, higher initial fT4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization.CONCLUSIONS: Since TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment.

AB - CONTEXT: With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown.OBJECTIVE: To investigate incidence and determinants of spontaneous normalization of thyroid-stimulating hormone (TSH) levels in older adults with subclinical hypothyroidism.DESIGN: Pooled data were used from the (i) pre-trial population, and (ii) in-trial placebo group from two randomized, double-blind, placebo-controlled trials (TRUST and IEMO thyroid 80-plus thyroid trial).SETTING: Community-dwelling 65 + adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom.PARTICIPANTS: The pre-trial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free thyroxine (fT4) within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included.MAIN OUTCOME MEASURES: Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization.RESULTS: In the pre-trial phase, TSH levels normalized in 60.8% of participants in a median follow-up of one year. In the in-trial phase, levels normalized in 39.9% of participants after one year follow-up. Younger age, female sex, lower initial TSH level, higher initial fT4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization.CONCLUSIONS: Since TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment.

U2 - 10.1210/clinem/dgad623

DO - 10.1210/clinem/dgad623

M3 - Journal article

C2 - 37862463

VL - 109

SP - e1167–e1174

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

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