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Incidence and Determinants of Spontaneous Normalization of Subclinical Hypothyroidism in Older Adults
Evie van der Spoel1, Nicolien A van Vliet1, Rosalinde K E Poortvliet2
1Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
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.
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