van der Spoel, EvieEvievan der Spoelvan Vliet, Nicolien ANicolien Avan VlietPoortvliet, Rosalinde K ERosalinde K EPoortvlietDu Puy, Robert SRobert SDu Puyden Elzen, Wendy P JWendy P Jden ElzenQuinn, Terence JTerence JQuinnStott, David JDavid JStottSattar, NaveedNaveedSattarKearney, Patricia MPatricia MKearneyBlum, ManuelManuelBlum0000-0003-4638-775XAl-Alwan, HebaHebaAl-AlwanRodondi, NicolasNicolasRodondiCollet, Tinh-HaiTinh-HaiColletWestendorp, Rudi G JRudi G JWestendorpBallieux, Bart EBart EBallieuxJukema, J WouterJ WouterJukemaDekkers, Olaf MOlaf MDekkersGussekloo, JacobijnJacobijnGusseklooMooijaart, Simon PSimon PMooijaartvan Heemst, DianaDianavan Heemst2024-10-252024-10-252024-02-20https://boris-portal.unibe.ch/handle/20.500.12422/170794CONTEXT 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.enFollow-Up Studies Older Adults Subclinical Hypothyroidism Thyrotropin600 - Technology::610 - Medicine & health300 - Social sciences, sociology & anthropology::360 - Social problems & social servicesarticle10.48350/1873443786246310.1210/clinem/dgad623