van der Spoel, Evie; van Vliet, Nicolien A; Poortvliet, Rosalinde K E; Du Puy, Robert S; den Elzen, Wendy P J; Quinn, Terence J; Stott, David J; Sattar, Naveed; Kearney, Patricia M; Blum, Manuel R; Alwan, Heba; Rodondi, Nicolas; Collet, Tinh-Hai; Westendorp, Rudi G J; Ballieux, Bart E; Jukema, J Wouter; Dekkers, Olaf M; Gussekloo, Jacobijn; Mooijaart, Simon P and van Heemst, Diana (2024). Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults. The journal of clinical endocrinology and metabolism, 109(3), e1167-e1174. Oxford University Press 10.1210/clinem/dgad623
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vanderSpoel_JClinEndocrinolMetab_2024.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (474kB) | Preview |
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dgad623.pdf - Accepted Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (577kB) | Preview |
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.
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