Table 5.

Results of clinical trials for treatment of subclinical hypothyroidism focusing on different outcomes

Reference	Place	Sample/follow-up	Age of participants	Results	Observations
Cooper et al45 randomized, placebo-controlled clinical trial	Boston, US	14 subjects in active group (4) and twelve in the placebo group (97% women); 1-year on LT4	Mean age 55 years	No difference between groups regarding symptoms of hypothyroidism	All patients included in the study presented subclinical hypothyroidism after treatment with Iodine-131 20 years earlier
Nyström et al67 randomized, double-blind, crossover trial	Gothenburg, Sweden	17 women; 6 months for placebo and 6 months for hormone	>50 years	No difference between groups regarding symptoms of hypothyroidism	All women diagnosed in a screening program
Jaeschke et al68 randomized, placebo-controlled clinical trial	Hamilton, Canada	32 subjects	>55 years	No difference between groups regarding symptoms of hypothyroidism	All subjects selected from an outpatient clinic in a community hospital
Meier et al69 randomized, placebo-controlled, double-blind clinical trial	Switzerland	63 women, 31 assigned to LT4 and 32 assigned to placebo; 48 weeks of follow-up	Mean age 58.6 (1.3) years	Results showed that physiological LT4 replacement in patients with subclinical hypothyroidism has a beneficial effect on low density lipoprotein cholesterol levels and clinical symptoms of hypothyroidism	Some patients included in the trial presented subclinical hypothyroidism after treatment with Iodine-131 20 years earlier. The proportion was similar in the active and the placebo group
Christ-Crain M et al70 randomized, double-blind, placebo-controlled trial	Basel, Switzerland	63 subjects with subclinical hypothyroidism (31 in the L-T4 group and 32 in the placebo group)	Mean age 57.5 ± 9.8 years	CRP values increases with progressive thyroid failure; supplementation of LT4 did not improve significantly CRP levels	Thyroid Research Unit of the Division of Endocrinology, Department of Medicine at the University Hospital, Basel
Iqbal et al71 randomized, placebo-controlled clinical trial	Norway	64 subjects with subclinical hypothyroidism; 32 assigned to LT4 and 32 assigned to placebo	62.0 (11.9) years in the LT4 group and 62.7 (12.4) years in the placebo group	Reduction in the levels of serum lipids in the group treated with LT4	Subjects with subclinical hypothyroidism selected from the 5143 subjects of the 5th Tromso Study
Razvi et al72 randomized placebo-controlled clinical trial	United Kingdom	150 subjects with subclinical hypothyroidism; 50 assigned to LT4 and 49 to placebo; 12 weeks of follow-up	Mean-age 53.8 (12.6) years	Subjects with subclinical hypothyroidism treated by LT4 presented a significant improvement in cardiovascular risk factors (Total cholesterol, LDL-cholesterol, waist to hip ratio, endothelial function) and symptoms of tiredness	Community-dwelling patients
Teixeira et al73 randomized double-blind, placebo-controlled clinical	Brazil	32 subjects: 18 in the LT4 group and 20 in the placebo group; 6 months follow-up	Mean age LT4 group 52.5 (10.1) years; mean age in the placebo group 46.6 (9.9) years	Reduction of serum lipids especially on the subgroup of subjects with antithyroid peroxidase antibodies, TSH > 8 IU/L, body mass index ≥25 kg/m2 and in menopause	Endocrinology Outpatient Clinic, University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro
Teixeira et al74 randomized placebo-controlled clinical trial	Brazil	26 subjects: eleven receiving LT4 and 15 receiving placebo; 1-year follow-up	Mean age LT4 group 54.4 (9.0) years; mean age in the placebo group 48.1 (10.0) years	A significant lipid profile improvement occurred 1 year after L-T4 replacement therapy in the active group compared to placebo group	Endocrinology Outpatient Clinic, University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro
Nagasaki et al75 randomized placebo-controlled, double-blind clinical trial	Japan	95 women: 48 assigned to LT4 and 47 assigned to placebo; 5-month follow-up	Mean age in LT4 group 64.4 (2.6) years; mean age in placebo group 66.0 (3.0) years	Sustained normalization of thyroid function during LT4 replacement therapy significantly decreases brachial-ankle pulse wave velocity in female subclinical hypothyroid patients suggesting possible prevention of cardiovascular disease	Ninety-five consecutive patients with newly detected subclinical hypothyroidism due to chronic thyroiditis with antithyroglobulin or antithyroid peroxidase antibodies of the Osaka City University Hospital
Parle et al76 randomized, placebo-controlled double-blind clinical trial	England	94 subjects: 52 assigned to LT4 and 42 assigned to placebo; 1-year follow-up	≥65 years	Performance in cognitive tests did not improve in subjects treated for subclinical hypothyroidism compared to placebo	Patients with subclinical hypothyroidism were recruited from a community-based cross-sectional study describing the prevalence of thyroid dysfunction in the elderly identified by screening of thyroid function

Abbreviation: LT4, L-thyroxine.