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

J Clin Endocrinol Metab. 2024 Feb 20;109(3):e1167-e1174. doi: 10.1210/clinem/dgad623.

Authors

Evie van der Spoel¹, Nicolien A van Vliet¹, Rosalinde K E Poortvliet², Robert S Du Puy², Wendy P J den Elzen³, Terence J Quinn⁴, David J Stott⁴, Naveed Sattar⁵, Patricia M Kearney⁶, Manuel R Blum^{7

8}, Heba Alwan^{8

9}, Nicolas Rodondi^{8

9}, Tinh-Hai Collet^{10

11}, Rudi G J Westendorp^{12

13}, Bart E Ballieux¹⁴, J Wouter Jukema^{15

16}, Olaf M Dekkers^{17

18}, Jacobijn Gussekloo^{1

2}, Simon P Mooijaart¹, Diana van Heemst¹

Affiliations

¹ Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
² Department of Public Health and Primary Care, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
³ Amsterdam UMC, University of Amsterdam, Department of Clinical Chemistry, Amsterdam Public Health Research Institute, 1081 HV Amsterdam, The Netherlands.
⁴ Department of Geriatric Medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G4 0SF, UK.
⁵ Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK.
⁶ School of Public Health, University College Cork, Cork T12 K8AF, Ireland.
⁷ Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, Switzerland.
⁸ Institute of Primary Health Care (BIHAM), University of Bern, 3012 Bern, Switzerland.
⁹ Graduate School for Health Sciences, University of Bern, Mittelstrasse 43, 3012 Bern, Switzerland.
¹⁰ Service of Endocrinology, Diabetes, Nutrition and Therapeutic Education, Department of Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland.
¹¹ Diabetes Centre, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland.
¹² Department of Public Health, University of Copenhagen, 1353 Copenhagen, Denmark.
¹³ Center for Healthy Aging, University of Copenhagen, 2200 Copenhagen, Denmark.
¹⁴ Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
¹⁵ Department of Cardiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
¹⁶ Netherlands Heart Institute, 3511 EP Utrecht, The Netherlands.
¹⁷ Department of Internal Medicine, Section of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
¹⁸ Department Clinical Epidemiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

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 TSH levels in older adults with subclinical hypothyroidism.

Design: Pooled data were used from the (1) pretrial population and (2) in-trial placebo group from 2 randomized, double-blind, placebo-controlled trials (Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism Trial and Institute for Evidence-Based Medicine in Old Age thyroid 80-plus thyroid trial).

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

Participants: The pretrial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free T4 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 pretrial phase, TSH levels normalized in 60.8% of participants in a median follow-up of 1 year. In the in-trial phase, levels normalized in 39.9% of participants after 1 year of follow-up. Younger age, female sex, lower initial TSH level, higher initial free T4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization.

Conclusion: Because 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.

Trial registration: ClinicalTrials.gov, NCT01660126 and Netherlands Trial Register, NTR3851.

Keywords: follow-up studies; older adults; subclinical hypothyroidism; thyrotropin.

Publication types

Randomized Controlled Trial

MeSH terms

Aged
Female
Humans
Hypothyroidism* / drug therapy
Hypothyroidism* / epidemiology
Incidence
Thyrotropin* / therapeutic use
Thyroxine / therapeutic use

Substances

Thyrotropin
Thyroxine

Associated data

ClinicalTrials.gov/NCT01660126

Grants and funding

SNSF_/Swiss National Science Foundation/Switzerland