The thyroid gland plays a crucial role in regulating nearly all bodily processes. A particular state of thyroid function, dubbed subclinical hypothyroidism (with high thyroid-stimulating hormone ... Show moreThe thyroid gland plays a crucial role in regulating nearly all bodily processes. A particular state of thyroid function, dubbed subclinical hypothyroidism (with high thyroid-stimulating hormone [TSH] and normal free thyroid hormone [fT4] in blood tests), becomes more prevalent with advancing age and it is unclear how this condition should be interpreted in community-dwelling older people (arbitrarily 65 years and older). Whether or not the condition is associated with negative health consequences, and whether treatment with levothyroxine (artificial thyroid hormone) is warranted, are subjects of decades-long debate. This thesis aims to identify whether subclinical hypothyroidism is associated with a range of relevant outcomes, and whether levothyroxine treatment leads to benefits, in community-dwelling older persons. The results in this thesis demonstrate that subclinical hypothyroidism is not associated with clinically (e.g. physical and cognitive function, mood or mortality risk) or biologically (e.g. thyroid antibodies or anaemia) relevant outcomes. Levothyroxine treatment does not provide benefits. These results suggest that subclinical hypothyroidism in older people is a strictly biochemical diagnosis, they support more conservative diagnostic approaches and do not support routine treatment with levothyroxine. More research is needed before extrapolating to more specific subgroups and to assess whether international guidelines should be updated. Show less
Gencer, B.; Moutzouri, E.; Blum, M.R.; Feller, M.; Collet, T.H.; Delgiovane, C.; ... ; Rodondi, N. 2020
BACKGROUND: Subclinical hypothyroidism has been associated with heart failure, but only small trials assessed whether treatment with levothyroxine has an impact on cardiac function.METHODS: In a... Show moreBACKGROUND: Subclinical hypothyroidism has been associated with heart failure, but only small trials assessed whether treatment with levothyroxine has an impact on cardiac function.METHODS: In a randomized, double-blind, placebo-controlled, trial nested within the TRUST trial, Swiss participants ages >= 65 years with subclinical hypothyroidism (thyroid-stimulating hormone [TSH] 4.60-19.99 mIU/L; free thyroxine level within reference range) were randomized to levothyroxine (starting dose of 50 mu g daily) to achieve TSH normalization or placebo. The primary outcomes were the left ventricular ejection fraction for systolic function and the ratio between mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e' ratio) for diastolic function. Secondary outcomes included e' lateral/septal, left atrial volume index, and systolic pulmonary artery pressure.RESULTS: A total of 185 participants (mean age 74.1 years, 47% women) underwent echocardiography at the end of the trial. After a median treatment duration of 18.4 months, the mean TSH decreased from 6.35 mIU/L to 3.55 mIU/L with levothyroxine (n = 96), and it remained elevated at 5.29 mIU/L with placebo (n = 89). The adjusted between-group difference was not significant for the mean left ventricular ejection fraction (62.7% vs 62.5%, difference = 0.4%, 95% confidence interval -1.8% to 2.5%, P = 0.72) and the E/e' ratio (10.6 vs 10.1, difference 0.4, 95% confidence interval -0.7 to 1.4, P = 0.47). No differences were found for the secondary diastolic function parameters or for interaction according to sex, baseline TSH, preexisting heart failure, and treatment duration (P value > 0.05).CONCLUSION: Systolic and diastolic heart function did not differ after treatment with levothyroxine compared with placebo in older adults with mild subclinical hypothyroidism. (C) 2020 Elsevier Inc. All rights reserved. Show less
