The Journal of clinical endocrinology and metabolism, Volume 109, Issue 3, 1 1 2024, Pages e1167-e1174 Incidence and Determinants of Spontaneous Normalization of Subclinical Hypothyroidism in Older Adults. van der Spoel E, van Vliet NA, Poortvliet RKE, Du Puy RS, den Elzen WPJ, Quinn TJ, Stott DJ, Sattar N, Kearney PM, Blum MR, Alwan H, Rodondi N, Collet TH, Westendorp RGJ, Ballieux BE, Jukema JW, Dekkers OM, Gussekloo J, Mooijaart SP, van Heemst D
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.
