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

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  • 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
  • Westendorp, Rudi GJ
  • Bart E Ballieux
  • J Wouter Jukema
  • Olaf M Dekkers
  • Jacobijn Gussekloo
  • Simon P Mooijaart
  • Diana van Heemst

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 languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Issue number3
Pages (from-to)e1167–e1174
Number of pages8
Publication statusPublished - 2024

Bibliographical note

© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.

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