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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)e1167-e1174
JournalJournal of Clinical Endocrinology and Metabolism
Volume109
Issue number3
DOIs
Publication statusPublished - 1 Mar 2024

Keywords

  • follow-up studies
  • older adults
  • subclinical hypothyroidism
  • thyrotropin

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