Thyroid
Everything in the library studied for it, medical and holistic together. Within each kind, what was shown to help comes first, strongest evidence first. What was tested and not shown to help stays on the list.
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Medication
Weight change when treating hypothyroidism
Shown to lower weight about 1.4 to 2.2 kg after treating hypothyroidism, in overt cases only. Weight did not change in subclinical hypothyroidism.
The numbers and sources
- Effect
- Across 23 studies, weight changed by -1.39 kg (95% CI -2.56 to -0.23) after levothyroxine restored normal thyroid levels. BMI changed by -0.39 kg/m², fat mass by -0.75 kg and lean mass by -0.95 kg. Weight and BMI fell in overt hypothyroidism but not in subclinical hypothyroidism, where lean mass fell [3]. Across 35 studies, weight fell 2.15 kg in overt hypothyroidism, mostly in the first 3 months, with no change in fat mass and a small fall in lean mass. In subclinical hypothyroidism, BMI, weight, fat mass and lean mass did not change [4].
- Population
- 763 adults with hypothyroidism [3]; 1,116 adults, 672 with overt and 444 with subclinical hypothyroidism [4].
- Sources
- [3], [4]
- Caveats
- Both reviews pooled measurements taken before and after treatment, without an untreated comparison group. They disagree on fat mass [3][4].
Pregnancy outcomes with subclinical hypothyroidism or thyroid antibodies
Mixed results: fewer preterm and low birth weight births in one review, lower miscarriage in women with thyroid antibodies, and no difference in an NIH trial.
The numbers and sources
- Effect
- In randomized trials of women with subclinical hypothyroidism in pregnancy, levothyroxine was associated with less preterm birth (RR 0.56, 95% CI 0.41 to 0.77) and fewer low birth weight infants (RR 0.56, 95% CI 0.35 to 0.89). Small for gestational age and macrosomia did not differ [5]. In euthyroid pregnant women with thyroid peroxidase antibodies, miscarriage was lower (RR 0.78, 95% CI 0.63 to 0.98), while preterm birth (RR 0.78, 95% CI 0.55 to 1.13) and live birth (RR 1.05, 95% CI 0.99 to 1.12) did not differ [6]. In subclinical hypothyroidism, gestational hypertension (OR 1.03, 95% CI 0.85 to 1.25) and pre-eclampsia (OR 1.02, 95% CI 0.66 to 1.58) did not differ from controls [7].
- Population
- 30 RCTs and cohort studies with 18,568 pregnant women with subclinical hypothyroidism [5]; 8 RCTs with 1,645 women [6]; trials and observational studies in pregnant women with subclinical or overt hypothyroidism or thyroid autoimmunity [7].
- Sources
- [5], [6], [7]
- Caveats
- [5] pooled RCTs with cohort studies, and the figures above are its RCT estimates. Preterm birth fell in [5] but not in [6], which studied a different group. The NIH trial of treatment from mid-pregnancy found no difference in pregnancy outcomes [8].
Symptoms and quality of life in subclinical hypothyroidism
Not shown to improve quality of life or thyroid symptoms in adults with subclinical hypothyroidism, including those 65 or older, though it brought TSH into range.
The numbers and sources
- Effect
- Thyroid hormone lowered mean TSH into the reference range (0.5 to 3.7 mIU/L against 4.6 to 14.7 on placebo) but did not change general quality of life (SMD -0.11, 95% CI -0.25 to 0.03) or thyroid-related symptoms (SMD 0.01, 95% CI -0.12 to 0.14) [1]. In adults aged 65 or older, the change in Hypothyroid Symptoms score at 1 year was 0.2 on both levothyroxine and placebo (difference 0.0, 95% CI -2.0 to 2.1). Tiredness scores did not differ (difference 0.4, 95% CI -2.1 to 2.9), and no secondary outcome improved [2].
- Population
- 21 RCTs with 2,192 nonpregnant adults, 3 to 18 months [1]; 737 adults with mean age 74.4 and TSH 4.60 to 19.99 mIU/L [2].
- Sources
- [1], [2]
- Caveats
- Most participants had mildly raised TSH. [1] rated the evidence moderate to high quality. [2] was funded by the European Union FP7 and others.
Child IQ when treated in pregnancy
One trial found no difference in child IQ at 5 years when women with subclinical hypothyroidism or low free T4 were treated from mid-pregnancy.
The numbers and sources
- Effect
- Children of women treated for subclinical hypothyroidism had a median IQ of 97 against 94 on placebo (P = 0.71). In a parallel trial for low free T4, median IQ was 94 against 91 (P = 0.30). No other neurocognitive or pregnancy outcome differed [8].
- Population
- 677 women with subclinical hypothyroidism and 526 with low free T4, starting at a mean 16.7 to 17.8 weeks of pregnancy, with children followed for 5 years [8].
- Sources
- [8]
- Caveats
- One trial. Treatment started at 8 to 20 weeks, so it does not describe treatment from conception. Funded by the National Institutes of Health [8].
Supplements
Goiter, hypothyroidism and growth in children
Limited evidence: in single trials, iodine lowered hypothyroidism in children and deaths in infants. Effects on goiter were very uncertain, and weight did not change.
The numbers and sources
- Effect
- In the Cochrane review, iodine likely lowered hypothyroidism (RR 0.03, 95% CI 0.00 to 0.23, 1 study, 264 participants) and all-cause death in infants (RR 0.32, 95% CI 0.14 to 0.73, 1 study, 617 infants). Weight did not differ (MD -0.20 kg, 95% CI -1.92 to 1.52, 3 studies). The effect on goiter was very uncertain (RR 0.68, 95% CI 0.15 to 3.07, 2 studies, I² 97%), and removing the study at high risk of bias gave RR 0.31 (1 study, 230 participants) [2].
- Population
- Children and adolescents in 8 RCTs. One study gave 150 µg a day for 28 weeks, one gave infants under 1 year a single 100 mg dose, and the rest gave 400 to 490 mg once to children aged 6 to 17 [2].
- Sources
- [2]
- Caveats
- Each outcome rests on one to three trials. No study reported adverse events related to iodine [2].
Mild Graves' eye disease
One trial found better quality of life and slower eye disease progression over 6 months in people with mild Graves' eye disease.
The numbers and sources
- Effect
- After 6 months, 100 µg twice a day improved quality of life, reduced eye involvement and slowed progression against placebo. The Clinical Activity Score fell more on selenium. Results held at 12 months [8].
- Population
- 159 people with mild Graves' orbitopathy [8].
- Sources
- [8]
- Caveats
- One trial. The abstract gives P values without effect sizes. Funded by the University of Pisa and the Italian ministry for education and research [8].
Thyroid function in pregnancy
Mixed results: reviews agree iodine lowered maternal thyroglobulin in pregnancy, but disagree on whether TSH changed.
The numbers and sources
- Effect
- Most studies found no effect on maternal or infant TSH or free thyroxine. Most RCTs found lower maternal thyroglobulin, and 3 found less growth in thyroid volume [3]. Cochrane found no clear difference in hypothyroidism in pregnancy or postpartum and postpartum hyperthyroidism fell (RR 0.32, 95% CI 0.11 to 0.91, 3 trials, 543 women) [5]. A 2026 meta-analysis found lower TSH (SMD -0.14, 95% CI -0.23 to -0.05) and lower thyroglobulin (SMD -0.22, 95% CI -0.32 to -0.13) with supplementation, with larger TSH drops at 200 to 300 µg a day [6].
- Population
- 37 publications in mildly to moderately deficient women [3]; 14 trials, 11 contributing data from over 2,700 women [5]; iodine-deficient pregnant women in English and Chinese studies [6].
- Sources
- [3], [5], [6]
- Caveats
- Cochrane rated the evidence low or very low quality and found the data insufficient for meaningful conclusions [5]. The reviews agree on lower thyroglobulin and differ on TSH [3][6]. The 2026 abstract does not give the number of studies or women [6].
Hashimoto's thyroiditis
Mixed results: thyroid antibodies fell in people with Hashimoto's in both reviews, while reviews disagree on whether TSH changed.
The numbers and sources
- Effect
- Thyroid peroxidase antibodies fell in both reviews. In people on levothyroxine, the weighted mean difference after 3 months was -271 (95% CI -366 to -175) [5]. Across 29 cohorts, the SMD was -0.96 (95% CI -1.36 to -0.56) [6]. On TSH, sources disagree. In people not on thyroid hormone, a 2017 review found no change in TSH, quality of life or ultrasound findings [7]. A 2024 review found TSH lower (SMD -0.21, 95% CI -0.43 to -0.02, 869 people) [6].
- Population
- Adults with chronic autoimmune thyroiditis, 16 trials [5], 9 trials [7] and 35 studies [6].
- Sources
- [5], [6], [7]
- Caveats
- Antibody levels are a lab marker. The 2016 review rated evidence quality low [5], and the 2024 review moderate, with I² of 90% for antibodies [6].
Thyroid hormones
Not shown to change TSH or T3 in adults across 23 trials. T4 rose slightly, by 0.61 µg/dL.
Practices
Thyroid function in Hashimoto's hypothyroidism
One trial found people with autoimmune hypothyroidism needed a lower levothyroxine dose 9 months after 10 sessions of near-infrared laser to the thyroid than after placebo.
The numbers and sources
- Effect
- Nine months after stopping and then re-titrating levothyroxine, the mean dose needed was 38.59 µg a day in the laser group and 106.88 µg a day in the placebo group (P < 0.001). Thyroid peroxidase antibodies were lower with laser (P = 0.043), and thyroglobulin antibodies did not differ [32].
- Population
- 43 people taking levothyroxine for hypothyroidism from chronic autoimmune thyroiditis, 23 given laser and 20 placebo [32].
- Sources
- [32]
- Caveats
- One trial at one center, using a clinical 830 nm laser applied over the thyroid by clinicians.
Blood chemistry and thyroid tests
One set of small experiments found grounding during night rest lowered serum iron, free T3 and several electrolytes and raised free T4, TSH and ferritin.
Compared with a group not in contact with the earth [9]
The numbers and sources
- Effect
- Earthing during night rest lowered serum iron, ionized calcium and inorganic phosphorus, and lowered urinary calcium and phosphorus. It decreased free T3 and increased free T4 and TSH. Continuous earthing decreased blood glucose in patients with diabetes. Earthing decreased sodium, potassium, magnesium, total protein and albumin, and increased transferrin, ferritin and globulins [9].
- Population
- Five experiments of 12 to 84 people each [9].
- Sources
- [9]
- Caveats
- The abstract gives no sizes, no durations for each experiment and no clinical meaning for the changes. Nobody uses grounding to shift these tests, and the direction is neither a benefit nor a harm that the authors define. One author is a co-author of a review of grounding's proposed benefits [10].
Lab markers
Miscarriage and preterm birth
Linked to more miscarriage and preterm birth in women with normal thyroid function, with preterm birth in 6.6% of antibody-positive women against 4.9%.
The numbers and sources
- Effect
- A meta-analysis of women with normal thyroid function found an odds ratio for miscarriage with thyroid autoantibodies of 3.90 in 19 cohort studies (95% CI 2.48 to 6.12) and 1.80 in 12 case-control studies (1.25 to 2.60). The odds ratio for preterm birth was 2.07 (1.17 to 3.68) [10]. In pooled individual data on 47,045 pregnant women, preterm birth occurred in 6.6% of TPO antibody-positive women and 4.9% of antibody-negative women (odds ratio 1.33, 95% CI 1.15 to 1.56) [11]. A pooled analysis of 11,212 pregnant women found the association with premature delivery rose with the antibody concentration [6].
- Population
- 31 studies with 12,126 women for miscarriage and 5 studies with 12,566 women for preterm birth [10]. 47,045 pregnant women in 19 cohorts, of whom 7.5% were TPO antibody positive [11]. 11,212 pregnant women in Dutch birth cohorts [6].
- Sources
- [10], [11], [6]
- Caveats
- Observational. Each study applied its own assay and cutoff, so a positive result does not mean the same level across studies.
Death from any cause
Linked to more deaths at low TSH, with no rise in deaths at mildly raised TSH, across three pooled analyses of cohorts.
The numbers and sources
- Effect
- People with TSH below 0.45 mIU/L and normal free T4 had a hazard ratio for death from any cause of 1.24 (95% CI 1.06 to 1.46) against people with TSH of 0.45 to 4.49 mIU/L [17]. Total mortality was not increased in people with TSH of 4.5 to 19.9 mIU/L and normal thyroxine [16]. In 134,346 adults, the lowest risk of cardiovascular disease and death fell at the 60th to 80th percentiles of TSH, medians of 1.90 to 2.90 mIU/L. Against that band, the lowest fifth of TSH had a hazard ratio for death from any cause of 1.09 (1.05 to 1.14) [18].
- Population
- 52,674 adults in 10 cohorts, 8,527 deaths [17]. 55,287 adults in 11 cohorts, 9,664 deaths [16]. 134,346 adults in 26 cohorts, median age 59 [18].
- Sources
- [17], [16], [18]
- Caveats
- Observational. A US guideline notes that acute illness can suppress TSH [3], so reverse causation cannot be ruled out. The percentile figures are adjusted for age and sex [18].
Atrial fibrillation
Linked to more atrial fibrillation at higher free T4 inside the reference range: 45% higher risk in the top quarter than the bottom quarter in pooled cohorts.
The numbers and sources
- Effect
- Among people with a TSH of 0.45 to 4.49 mIU/L in 11 pooled cohorts, the hazard ratio for new atrial fibrillation was 1.45 (95% CI 1.26 to 1.66) for the highest quartile of free T4 against the lowest, with a significant trend across quartiles. TSH itself was not associated [7]. In older US adults whose thyroid tests were all in the reference range, higher free T4 was associated with atrial fibrillation (P below 0.001), and the top quartile had 11.0 more cases per 1,000 person-years than the bottom quartile [8].
- Population
- 30,085 adults in 11 prospective cohorts, 2,574 new cases of atrial fibrillation [7]. 2,843 older adults in the Cardiovascular Health Study not taking thyroid medication [8].
- Sources
- [7], [8]
- Caveats
- Observational. Quartiles were set within each cohort, so the finding is not tied to one ng/dL value [7].
Cardiovascular disease and death
Linked in a J shape: risk of cardiovascular disease and death was lowest at the 20th to 40th percentiles of free T4, and the top fifth had 34% more deaths.
The numbers and sources
- Effect
- In pooled data on 134,346 adults, risk was lowest at the 20th to 40th percentiles of free T4, medians of 13.5 to 14.8 pmol/L. Against that band, the top fifth had hazard ratios of 1.20 (95% CI 1.11 to 1.31) for cardiovascular events or death combined, 1.34 (1.20 to 1.49) for death from any cause, 1.57 (1.31 to 1.89) for cardiovascular death and 1.22 (1.11 to 1.33) for cardiovascular events [9]. In older US adults with thyroid tests in the reference range, the top quartile of free T4 had more coronary heart disease, heart failure and deaths than the bottom quartile, by 8.0, 7.8 and 14.3 per 1,000 person-years [8].
- Population
- 134,346 adults in 26 cohorts, median age 59 [9]. 2,843 older adults [8].
- Sources
- [9], [8]
- Caveats
- Observational, so illness that shifts free T4 before an event cannot be ruled out. The pooled figures are adjusted for age and sex, and the percentile medians are printed in pmol/L [9].
Age, body weight and thyroid status
Linked in cohort and genetic studies to age, body weight and thyroid status: higher with age in men and with an overactive thyroid, lower at a higher body mass index.
The numbers and sources
- Effect
- In pooled individual data from 21,074 men, SHBG was directly associated with age and inversely associated with body mass index [13]. In a population-based cohort, SHBG rose in a straight line with age in men and followed a U-shaped pattern with age in women, and people with more cardiovascular risk factors had lower levels. Total testosterone and triglycerides explained 46.2% of the variation in men. Total testosterone, triglycerides, body mass index and fasting insulin explained 31.8% in women [14]. Among women with thyroid disorders, mean SHBG differed between groups because of the group with an overactive thyroid, where thyroid hormone levels were the main correlates. In the other groups the main correlates were body mass index and age [15]. In a genetic analysis, each standard deviation of genetically higher thyroid stimulating hormone went with SHBG 1.332 nmol/L lower (95% CI 0.717 to 1.946). Genetic predisposition to an underactive thyroid went with lower SHBG and to an overactive thyroid with higher SHBG [16].
- Population
- 9 cohorts of community-dwelling men with individual data [13]. 3,264 men and women in a population-based cohort [14]. Women with overt or subclinical thyroid disorders [15]. Up to 194,174 women and 167,020 men in UK Biobank [16].
- Sources
- [13], [14], [15], [16]
- Caveats
- These are associations seen across people. The cohort analyses are cross-sectional and do not show that a change in weight alters a person's SHBG. The genetic analysis found no association between thyroid function and sexual function [16].
Later hypothyroidism
Linked to later hypothyroidism: over 20 years, women with thyroid antibodies alone had 8 times the odds, and 38 times with a raised TSH as well.
The numbers and sources
- Effect
- In a 20-year British follow-up, positive thyroid antibodies alone carried odds ratios for developing hypothyroidism of 8 in women (95% CI 5 to 15) and 25 in men (10 to 63). With a raised TSH as well, the odds ratios were 38 (22 to 65) and 173 (81 to 370) [7]. In an Australian cohort, hypothyroidism 13 years later was present in 12.0% of antibody-positive women whose baseline TSH was 2.5 mU/L or less, 55.2% at 2.5 to 4.0 mU/L and 85.7% above 4.0 mU/L [5]. In a 5-year Chinese survey, 14.44% of people positive for TPO or thyroglobulin antibodies developed thyroid dysfunction, against 3.31% of those without antibodies [8]. Among 82 women with subclinical hypothyroidism, overt hypothyroidism developed in 58.5% of those with microsomal antibodies and 23.2% of those without [9]. A US guideline puts progression from subclinical to overt hypothyroidism at 4.3% a year with TPO antibodies and 2.6% a year without [4].
- Population
- 2,779 adults in the Whickham Survey [7]. 1,184 adults in the Busselton Health Surveys [5]. 3,018 people in three Chinese regions with different iodine intakes [8]. 82 women followed a mean 9.2 years [9].
- Sources
- [7], [5], [8], [9], [4]
- Caveats
- Observational. The studies used different antibody assays and cutoffs, and earlier ones measured antibodies by semiquantitative methods, not automated immunoassay [5]. The US guideline also reports that about 75% of people with chronic autoimmune thyroiditis have raised antibody levels, many with normal thyroid function at the time [4].
Coronary heart disease
Linked to more coronary heart disease at TSH of 10 mIU/L or above, with no link at 4.5 to 6.9 mIU/L or inside the reference range, in pooled cohorts.
The numbers and sources
- Effect
- In pooled data on 55,287 adults, the hazard ratio for coronary heart disease events against a TSH of 0.50 to 4.49 mIU/L was 1.00 (95% CI 0.86 to 1.18) at 4.5 to 6.9 mIU/L, 1.17 (0.96 to 1.43) at 7.0 to 9.9 mIU/L and 1.89 (1.28 to 2.80) at 10 to 19.9 mIU/L. For coronary deaths the figures were 1.09 (0.91 to 1.30), 1.42 (1.03 to 1.95) and 1.58 (1.10 to 2.27) [16]. Among 55,412 people with TSH inside 0.45 to 4.49 mIU/L, each 1 mIU/L higher TSH had a hazard ratio of 0.97 (0.90 to 1.04) for coronary death and 1.00 (0.97 to 1.03) for a first coronary event [11]. In people with TSH below 0.45 mIU/L and normal free T4, the hazard ratio for coronary death was 1.29 (1.02 to 1.62) [17].
- Population
- 55,287 adults in 11 prospective cohorts, with events data from 7 [16]. 55,412 adults in 14 cohorts with no known thyroid or cardiovascular disease [11]. 52,674 adults in 10 cohorts [17].
- Sources
- [16], [11], [17]
- Caveats
- Observational. All three analyses come from one research collaboration and share cohorts. The high TSH groups had normal thyroxine, so these figures do not describe overt thyroid disease.
Atrial fibrillation
Linked to more atrial fibrillation at TSH below 0.45 mIU/L, with no link inside the reference range or at mildly raised TSH, in pooled cohorts.
The numbers and sources
- Effect
- In people with TSH below 0.45 mIU/L and normal free T4, the hazard ratio for new atrial fibrillation was 1.68 (95% CI 1.16 to 2.43), and risk was higher below 0.10 mIU/L than at 0.10 to 0.44 mIU/L [17]. In 30,085 people with TSH of 0.45 to 19.9 mIU/L, baseline TSH was not significantly associated with new atrial fibrillation, either inside the reference range or in subclinical hypothyroidism [19].
- Population
- 8,711 adults in 5 cohorts with atrial fibrillation data, 785 cases [17]. 30,085 adults in 11 cohorts, 2,574 cases [19].
- Sources
- [17], [19]
- Caveats
- Observational. In the second analysis, higher free T4 inside the reference range was tied to atrial fibrillation while TSH was not [19].
Fractures
Linked to more hip and other fractures at TSH below 0.45 mIU/L, most at TSH below 0.10, with no link at raised TSH.
The numbers and sources
- Effect
- Against a TSH of 0.45 to 4.49 mIU/L, people with TSH below 0.45 mIU/L and normal thyroxine had a hazard ratio of 1.36 for hip fracture (95% CI 1.13 to 1.64) and 1.28 for any fracture (1.06 to 1.53). At TSH below 0.10 mIU/L the hazard ratios were 1.61 for hip fracture (1.21 to 2.15), 1.98 for any fracture (1.41 to 2.78) and 3.57 for spine fracture (1.88 to 6.78). No association was found between TSH of 4.50 to 19.99 mIU/L and fracture [20].
- Population
- 70,298 adults in 13 prospective cohorts, 762,401 person-years, 2,975 hip fractures [20].
- Sources
- [20]
- Caveats
- Observational. The authors state that trials are lacking on whether treating a low TSH prevents fractures [20].
Later hypothyroidism
Linked to later hypothyroidism in a graded way, starting inside the reference range and rising further when thyroid antibodies are present.
The numbers and sources
- Effect
- In a 20-year British follow-up, a raised TSH alone carried odds ratios for developing hypothyroidism of 8 in women (95% CI 3 to 20) and 44 in men (19 to 104). With thyroid antibodies as well, the odds ratios were 38 (22 to 65) and 173 (81 to 370). Risk rose with TSH values above 2 mU/L at the first survey [21]. In an Australian cohort followed 13 years, hypothyroidism at follow-up was present in 12.0% of antibody-positive women with baseline TSH of 2.5 mU/L or less, 55.2% with TSH between 2.5 and 4.0 mU/L and 85.7% with TSH above 4.0 mU/L [22]. Among 82 women with subclinical hypothyroidism, overt hypothyroidism developed within 10 years in 0% of those starting at 4 to 6 mU/L, 42.8% at above 6 to 12 mU/L and 76.9% above 12 mU/L [23].
- Population
- 2,779 adults in the Whickham Survey, with 96% of survivors followed up at 20 years [21]. 1,184 adults in the Busselton Health Surveys of 1981 and 1994 [22]. 82 women followed a mean 9.2 years [23].
- Sources
- [21], [22], [23]
- Caveats
- Observational. The Australian study defined hypothyroidism at follow-up as TSH above 4.0 mU/L or thyroxine treatment [22]. The 10-year figures come from 82 women at one clinic [23].
Thyroid disorders in populations with high levels
Linked to more hypothyroidism in populations with excess iodine, about twice the odds of subclinical hypothyroidism in a meta-analysis of three studies.
The numbers and sources
- Effect
- In a meta-analysis of cross-sectional studies in adults, populations with excess iodine had higher odds of overt hypothyroidism (OR 2.78, 95% CI 1.47 to 5.27) and subclinical hypothyroidism (OR 2.03, 1.58 to 2.62) than populations with adequate iodine [7]. In a five-year study of three regions of China with median urinary iodine of 84, 243 and 651 µg/L, the cumulative incidence of subclinical hypothyroidism was 0.2%, 2.6% and 2.9%, and that of autoimmune thyroiditis was 0.2%, 1.0% and 1.3%. Overt hypothyroidism developed in 0.2%, 0.5% and 0.3% [8].
- Population
- Three cross-sectional studies in adults within a review of 50 articles [7]. 3,018 people in three regions of China followed from 1999 to 2004 [8].
- Sources
- [7], [8]
- Caveats
- Observational comparisons between populations defined by their median urinary iodine, not by one person's result. The meta-analysis authors describe the included studies as few and of low quality, and the source of excess iodine was mainly iodized salt or drinking water [7].
Death in people with heart disease
One cohort found more deaths within a year among heart patients with low free T3: 14.4% against 3% with normal free T3.
The numbers and sources
- Effect
- Among 573 consecutive patients with heart disease, 173 had a free T3 below 3.1 pmol/L. Over 1 year, deaths from any cause were 14.4% in that group and 3% in the group at 3.1 pmol/L or above, and cardiac deaths were 7.5% and 1.5%. In a Cox model free T3 was the strongest predictor of death from any cause (hazard ratio 3.582) [6].
- Population
- 573 consecutive cardiac patients at one center, followed for 1 year [6].
- Sources
- [6]
- Caveats
- One observational cohort of hospital patients. A US guideline states that T3 levels are low in severe illness without thyroid disease, because less T4 is converted to T3 [2], so low free T3 may mark the severity of illness.
Type 2 diabetes
One cohort found less type 2 diabetes at higher free T4, with a hazard ratio of 0.96 per 1 pmol/L, including inside the reference range.
The numbers and sources
- Effect
- In the Rotterdam Study, each 1 pmol/L higher free T4 had a hazard ratio for diabetes of 0.96 (95% CI 0.93 to 0.99), and the same within the reference range (0.96, 0.92 to 0.99). Higher TSH went with more diabetes (hazard ratio 1.13 per log unit, 1.08 to 1.18). In people with prediabetes, the hazard ratio for progression was 0.63 (0.48 to 0.82) in the highest third of free T4 against the lowest [5].
- Population
- 8,452 adults, mean follow-up 7.9 years, 798 new cases of diabetes [5].
- Sources
- [5]
- Caveats
- One observational cohort [5].
Thyroid inflammation after childbirth
Limited evidence: a guideline review reports postpartum thyroiditis in 33 to 50% of women who were thyroid antibody positive in the first trimester.
The numbers and sources
- Effect
- The American Thyroid Association reports that women who are thyroid antibody positive in the first trimester have a 33 to 50% risk of postpartum thyroiditis, and that women with the highest antibody levels have the highest risk. It reports that 10 to 20% of cases result in permanent hypothyroidism [15].
- Population
- A guideline summary of earlier studies, whose sizes it does not give [15].
- Sources
- [15]
- Caveats
- Secondhand figures from guideline text, not a primary study.
Heart function and death in trials that gave T3
Mixed results: trials giving T3 after heart surgery or in heart failure with low T3 improved measures of heart function, and deaths after surgery did not differ.
The numbers and sources
- Effect
- In a systematic review of 14 randomized trials of T3 after surgery, 13 of them cardiac surgery, intravenous T3 increased cardiac index after coronary bypass. Mortality was not significantly altered by high-dose intravenous T3 and could not be assessed for the other regimens [8]. In a meta-analysis of randomized trials in heart failure with low T3, thyroid hormone treatment raised free T3 and improved left ventricular ejection fraction (weighted mean difference 5.61, 95% CI 4.38 to 6.85) and cardiac output (0.65, 0.42 to 0.89). The abstract reports no data on deaths [9].
- Population
- 14 randomized trials of postoperative T3 in adults [8]. Randomized trials in heart failure with low T3 found in English and Chinese databases to November 2021 [9].
- Sources
- [8], [9]
- Caveats
- A marker that tracks an outcome is not always one whose correction changes it. The surgical trials were small and short, with T3 given for 6 to 24 hours in most. The heart failure analysis had high heterogeneity, with I-squared of 63% to 95% for its main outcomes [8][9].
Pregnancy and child outcomes
Mixed results: low free T4 in pregnancy was linked to lower child IQ and preterm birth, while a trial that treated low free T4 found no change in IQ.
The numbers and sources
- Effect
- In a Dutch birth cohort, maternal free T4 in early pregnancy had an inverted U-shaped association with child IQ, with both low and high concentrations corresponding to a 1.4 to 3.8 point lower mean IQ [11]. In pooled data on 47,045 pregnant women, preterm birth occurred in 7.1% of women with a low free T4 and normal TSH against 5.0% of women with normal results (odds ratio 1.46, 95% CI 1.12 to 1.90) [12]. In a trial of 526 pregnant women with free T4 below 0.86 ng/dL and normal TSH, median child IQ was 94 with levothyroxine and 91 with placebo (P = 0.30), with no significant differences in other pregnancy or neonatal outcomes [6].
- Population
- 3,839 mother and child pairs, with IQ tested at a median age of 6 [11]. 47,045 pregnant women in 19 cohorts [12]. 526 women randomized at a mean of 17.8 weeks of pregnancy [6].
- Sources
- [11], [12], [6]
- Caveats
- A marker that tracks an outcome is not always one whose correction changes it. The cohort findings are observational, and the trial began treatment between 8 and 20 weeks of pregnancy [6].
Live birth and miscarriage in trials of levothyroxine for antibody-positive women
Mixed results: two large trials of levothyroxine in antibody-positive women with normal thyroid function found no change in live births or miscarriage, after small earlier trials reported fewer miscarriages.
The numbers and sources
- Effect
- In a placebo-controlled trial of 952 women with TPO antibodies, normal thyroid function and a history of miscarriage or infertility, the live-birth rate was 37.4% with levothyroxine 50 micrograms a day and 37.9% with placebo (relative risk 0.97, 95% CI 0.83 to 1.14), with no significant differences in pregnancy loss or preterm birth [12]. In an open-label trial of 600 antibody-positive women having in vitro fertilization, miscarriage rates were 10.3% with levothyroxine and 10.6% without, and live-birth rates 31.7% and 32.3% [13]. Earlier, a pooled estimate from two small randomized studies gave a relative risk of miscarriage of 0.48 (0.25 to 0.92) [10]. In one earlier study, 115 antibody-positive pregnant women were divided into a levothyroxine group and an untreated group, with miscarriage in 3.5% and 13.8% [14].
- Population
- 952 women at 49 UK hospitals, drawn from 19,585 tested [12]. 600 women at one hospital in China [13]. 115 antibody-positive pregnant women in Italy [14].
- Sources
- [12], [13], [10], [14]
- Caveats
- These trials treated women who had the antibodies and did not set out to lower the antibody level. The largest trial started treatment before conception and the Chinese trial was open label [12][13].
Pregnancy and child outcomes
Mixed results: raised TSH in pregnancy was linked to more preterm birth, while a levothyroxine trial found no difference in child IQ or pregnancy outcomes.
The numbers and sources
- Effect
- In pooled data on 47,045 pregnant women, preterm birth occurred in 6.1% of women with a raised TSH and normal free T4 against 5.0% of women with normal results (odds ratio 1.29, 95% CI 1.01 to 1.64). Each standard deviation higher TSH had an odds ratio of 1.04 (1.00 to 1.09) [27]. In a trial of 677 pregnant women with TSH of 4.00 mU/L or more and normal free T4, the median child IQ score was 97 with levothyroxine and 94 with placebo (P = 0.71), with no significant differences in other pregnancy or neonatal outcomes [28].
- Population
- 47,045 pregnant women in 19 cohorts, median 12.9 weeks at blood sampling [27]. 677 women randomized at a mean of 16.7 weeks of pregnancy [28].
- Sources
- [27], [28]
- Caveats
- The cohort finding is observational. The trial began treatment between 8 and 20 weeks of pregnancy, so it does not describe earlier treatment [28].
Symptoms and quality of life in trials that lowered a mildly raised TSH
Not shown to improve quality of life or thyroid symptoms when levothyroxine lowered TSH into range in 21 trials of adults with subclinical hypothyroidism.
The numbers and sources
- Effect
- In a trial of 737 adults aged 65 and older with TSH of 4.60 to 19.99 mIU/L, levothyroxine left TSH at 3.63 mIU/L at 1 year against 5.48 on placebo. The Hypothyroid Symptoms score did not differ (between-group difference 0.0, 95% CI -2.0 to 2.1), nor did the Tiredness score (0.4, -2.1 to 2.9) [24]. Across 21 trials, thyroid hormone brought mean TSH to 0.5 to 3.7 mIU/L against 4.6 to 14.7 mIU/L on placebo, with no benefit for general quality of life (standardized mean difference -0.11, 95% CI -0.25 to 0.03) or thyroid-related symptoms (0.01, -0.12 to 0.14) [25]. A guideline panel that reviewed the same trials issued a strong recommendation against thyroid hormones for adults with subclinical hypothyroidism, and stated that it does not apply to women trying to become pregnant or to people with TSH above 20 mIU/L [26].
- Population
- 737 adults, mean age 74.4, mean baseline TSH 6.40 mIU/L [24]. 2,192 nonpregnant adults in 21 randomized trials lasting 3 to 18 months [25].
- Sources
- [24], [25], [26]
- Caveats
- A marker that tracks an outcome is not always one whose correction changes it. The pooled trials lasted 3 to 18 months. The guideline panel judged effects on cardiovascular events and deaths to be uncertain, measured in one trial with few events [26].
Symptoms in trials that added T3 to thyroxine for hypothyroidism
Not shown to change pain, mood, fatigue, quality of life, weight or cholesterol when T3 was added to thyroxine in 11 trials of adults with hypothyroidism.
The numbers and sources
- Effect
- A meta-analysis of 11 randomized trials found no difference between combined T4 and T3 treatment and T4 alone for bodily pain (standardized mean difference 0.00, 95% CI -0.34 to 0.35), depression (0.07, -0.20 to 0.34), anxiety (0.00, -0.12 to 0.11), fatigue (-0.12, -0.33 to 0.09) or quality of life (0.03, -0.09 to 0.15). Body weight and blood lipids did not differ, and adverse events did not differ between regimens [10].
- Population
- 1,216 adults with clinical hypothyroidism in 11 randomized trials [10].
- Sources
- [10]
- Caveats
- The trials compared treatments in people already treated for hypothyroidism, and the abstract does not report the free T3 levels reached. Searches ran to September 2005 [10].
Death in older adults with normal thyroid tests
One cohort found no link between free T3 and death over 9 years in adults aged 65 and older whose thyroid tests were all in range.
The numbers and sources
- Effect
- Among 815 adults aged 65 and older with TSH, free T3 and free T4 all in the normal range, 181 died over 9 years. Neither free T3 nor free T4 quartile was associated with death from any cause. TSH in the lowest quartile was, with a hazard ratio of 2.22 (95% CI 1.19 to 4.22) against the highest quartile [7].
- Population
- 815 community-dwelling adults aged 65 and older in the Invecchiare in Chianti study in Italy [7].
- Sources
- [7]
- Caveats
- One observational cohort with 181 deaths, limited to people whose results were inside the reference ranges [7].
Thyroid disease when only thyroglobulin antibodies are positive
One large US survey found thyroglobulin antibodies without TPO antibodies were not significantly associated with thyroid disease, while TPO antibodies were.
The numbers and sources
- Effect
- In the NHANES III survey, thyroglobulin antibodies were positive in 10.4% and TPO antibodies in 11.3% of people who reported no thyroid disease. TPO antibodies were significantly associated with hypothyroidism or hyperthyroidism and thyroglobulin antibodies were not. Thyroglobulin antibodies alone, in the absence of TPO antibodies, were not significantly associated with thyroid disease [16].
- Population
- 17,353 people aged 12 and older representing the US population from 1988 to 1994, of whom 16,533 reported no thyroid disease [16].
- Sources
- [16]
- Caveats
- One cross-sectional survey, using the assays of its time. Positive antibodies were more common in women, rose with age and were less common in Black participants (4.5%) than in white participants (12.3%) [16].