Table 3.

Longitudinal studies evaluating the associations between MetS and thyroid function (from 2009 to July 2019).

Author (region)	Follow-up	n	Population	Main results
Marzullo et al.28 (Italy)	4 months	100	Obese submitted to diet	A = weight loss was associated with reduction in TSH and FT3; also, with increase in FT4 levels
Ferrannini et al.82 (Italy)	3 years	940	Euthyroid subjects	G = baseline FT3 and FT4 were positively associated with increases in FPG and decrease in insulin sensitivity measured by euglycemic clamp (CLAMP)
Nada106 (Saudi Arabia)	Post-normalization	42	Women with OH	G = after LT4 replacement, there was no significant change in FBG or HOMA-IR as compared with before starting treatment, while fasting insulin significantly increased
Amouzegar et al.95 (Iran)	9 years	1938	Population-based cohort study	A = increment in FT4 levels was accompanied by decreased risk of metabolically healthy obesity and metabolically healthy, normal-weight phenotypic development TSH increment was positively associated with metabolically unhealthy, normal-weight phenotypic development
Mehran et al.76 (Iran)	3 years	2393	Frameworks of a community-based study	BP = FT4 was associated with higher odds of high BP after adjusting for age, sex, smoking, BMI, and HOMA-IR; no significant associations between TSH and BP
Langén et al.107 (Finland)	11 years	2486	Population-based cohort	L = no association with TSH
Langén et al.108 (Finland)	11 years	3453	Population-based cohort	BP = TSH did not predict incident hypertension and was inversely associated with change in SBP and DBP in men
Volzke et al.18 (Germany)	5 × years	2910	Population-based cohort	A = NE G = NE L = NE BP = SC hyper was not associated with changes in BP or incident hypertension in multivariate analysis
De Vries et al.99 (Europe)	7.6–5.9 years	5542	Metanalysis of population surveys	G = no more risk for incident DM
Itterman et al.109 (Europe)	5 years	10,048	Population survey	BP = High TSH was not associated with incident HBP
Liu et al.110 (USA)	2 years	811	Obese and overweight submitted to diet protocols	A = Baseline FT3 and FT4 predicted weight loss; FT3 and TT3 were positively associated with changes in body weight, BP, G, insulin, and TG; without associations with FT4 or TSH
Eray et al.111 (Turkey)	6 months	129	Obese before and after pharmacological treatment	No effects on TSH, FT3 and FT4
Teixeira et al.17 (Brazil)	1 year	103	Ambulatory from a tertiary hospital (EU, SCH, OH)	A = no significant changes in BMI and BF% G = no significant changes in HOMA-IR L = reduction in TG with OH treatment BP = NE
Park et al.34 (Korea)	3 years	5998	EU, SCH, SC hyper	Changes in TSH was positively associated with MetS development A = WC was not associated with changes in TSH or FT4 G = glucose and HOMA-IR were positively associated with changes in TSH L = TG was positively associated with changes in TSH and negative with FT4 BP = positively associated with changes on FT4 and TSH
Chen et al.112 (Taiwan)	11 years	38,200	Hypo-, hyperthyroid participants and controls	G = there was significantly higher occurrence of T2D in the hypothyroidism and also hyperthyroidism groups than in the control group
Lee et al.68 (USA)	6.1	2912	EU participants	A = NA with TSH or FT4 G = NA with TSH or FT4 L = NA with TSH or FT4 BP = NA with TSH or FT4
Tiller et al.74 (Europe)	5 years	2912 (713 for body composition)	Population-based cohort studies	A = serum TSH at baseline was inversely associated with anthropometric changes (WC, BMI); however, with a positive association with TSH changes G = NE L = NE BP = NE
Chang et al.113 (Taiwan)	4.2 years	66,822	EU at baseline	Higher risk for SCH development in MetS (HR = 1.12) A = NA G = NA L = higher risk for SCH development when high TG BP = an increased risk of SCH was associated with high BP
Caixàs et al.114 (Spain)	Post-normalization	51	Hyper- and hypothyroid patients (pre- and post-treatment)	G = Patients with hyperthyroidism showed higher glucose, insulin concentrations and HOMA-IR than their controls; after normalization of thyroid function, glucose and HOMA-IR decreased to the normal range
Chaker et al.115 (Netherlands)	7.9 years	8452	Population survey	G = risk for developing diabetes 1.09 times higher for every doubling of TSH levels; higher FT4 levels within the normal range were associated with a decreased risk of diabetes; In participants with pre-diabetes, the associated risk of developing diabetes was 1.13 times higher for every doubling of TSH levels The risk of progression from pre-diabetes to diabetes was higher with low–normal thyroid function (HR 1.32; 95% CI, 1.06–1.64 for TSH and HR 0.91; 95% CI, 0.86–0.97 for FT4) Absolute risk of developing T2D in participants with pre-diabetes decreased from 35% to almost 15% with higher FT4 levels within the normal range
Bjergved et al.116 (Denmark)	11 years	1577	Population survey	A = positive association between BMI changes and TSH changes
Soriguer et al.117 (Spain)	6 years	479	784	A = obesity development was related to higher concentrations of FT3 and FT4; weight gain with FT3

A, adiposity; BMI, body mass index; BP, blood pressure; BF, body fat; CI, confidence interval; DBP, diastolic blood pressure; DM, diabetes mellitus; EU, euthyroid; FPG, fasting plasmatic glycaemia; FT3, free triiodothyronine; FT4, free thyroxine; G, glucose metabolism; HBP, high blood pressure; HDL-c, high-density-lipoprotein cholesterol; HOMA-IR, Homeostatic Model Assessment of Insulin Resistance index; HR, hazard ratio; IR, insulin resistance; L, lipid profile; MetS, metabolic syndrome; NA, no association; NE, not evaluated; OH, overt hypothyroidism; SBP, systolic blood pressure; SCH, sub-clinical hypothyroidism; SC hyper, sub-clinical hyperthyroidism; T2D, type 2 diabetes; TG, triglycerides; TSH, thyrotropin; TT3, total triiodothyronine; WC, waist circumference; QUICKI, quantitative insulin sensitivity check index; TPO-Ab+, positive antibodies against thyroperoxidasis on serum; VFA, visceral fat area; HSC, is the same as SCH (subclinical hypothyroidism); T4L, is the same as FT4 (Free Thyroxine); LT4: levothyroxine.