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.

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