Effect Of Levothyroxine Treatment Research Articles

Increased frequency of microalbuminuria in patients with type 3 autoimmune polyglandular syndrome (APS) compared to isolated autoimmune type 1 diabetes mellitus: A real-life study

Aim of the studyThe primary aim of the study was to evaluate the differences in metabolic control and chronic microvascular complications in patients with type 3 autoimmune polyglandular syndrome (APS3), compared to type 1 diabetes mellitus (T1DM) alone. Secondary aims were to evaluate the age of autoimmune thyroid disease (AIT) onset and the effects of levothyroxine treatment on metabolic control in patients with APS3. Material and methodsWe retrospectively reviewed 276 patients with T1DM alone and 214 patients with APS3 and evaluated clinical and metabolic parameters and microvascular complications. ResultsPatients with T1DM showed a longer duration of diabetes (p = 0.001) and lower age of diabetes onset (p = 0.020) compared to patients with APS3. Female gender (p = 0.001) and microalbuminuria (p = 0.006) were significantly more frequent in patients with APS3 compared to T1DM. In addition, patients with APS3 showed higher AIT onset frequency in the 16–30 quartile age-range. Furthermore, APS3 patients treated with levothyroxine showed significantly better HbA1c values than non-treated patients (p = 0.001). ConclusionsWe found that patients with APS3 showed positive microalbuminuria, earlier than T1DM. Patients with APS3 showed higher frequency of AIT age of onset in the 16–30 age-range and those treated with levothyroxine had better metabolic control, than untreated ones.

Effects of levothyroxine treatment on serum thyroid hormone levels in euthyroid patients with papillary thyroid microcarcinoma

We recently reported that lowering serum thyroid stimulating hormone (TSH) levels with levothyroxine (LT4) may be associated with decreased tumor growth during active surveillance (AS) of papillary thyroid microcarcinoma (PTMC). Most clinicians might believe that low serum TSH levels following LT4 therapy indicate subclinical thyrotoxicosis. This study aimed to evaluate the effects of TSH-lowering therapy using small doses of LT4 on serum thyroid hormone levels in euthyroid patients with PTMC. We retrospectively analyzed data from 28 patients with low-risk PTMC who had undergone measurement of both FT4 and FT3 consecutively and received LT4 to achieve serum TSH levels of < 0.5 μIU/mL and > 0.05 μIU/mL between January 2012 and May 2018 at Kuma Hospital. There were 24 females and 4 males (aged 55 ± 12 years [mean ± standard deviation {SD}]). We compared their serum FT4 and FT3 levels at diagnosis with those following TSH-lowering therapy with LT4. Following LT4 therapy, the patients’ serum FT4 levels were significantly increased (P < 0.001). Serum FT3 levels, however, remained unchanged (P = 0.10). The proportions of patients whose FT3 levels increased by more than 1 SD, remained unchanged, and decreased by more than 1 SD were 11 %, 57 %, and 32 %, respectively. Our study indicated that mild TSH-lowering doses of LT4 for euthyroid patients with PTMC increased serum FT4 levels but did not increase serum FT3 levels in most cases, suggesting that a mild TSH-lowering therapy for euthyroid patients may not necessarily cause thyrotoxicosis.

Effects of Levothyroxine Treatment on Fertility and Pregnancy Outcomes in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Subclinical hypothyroidism, defined by elevated thyrotropin (TSH) and normal free thyroxine levels, is associated with adverse pregnancy outcomes, including preterm birth, pre-eclampsia, and small for gestational age. Despite the uncertainty regarding the effectiveness of levothyroxine (LT4) treatment on pregnancy outcomes in subclinical hypothyroidism, LT4 is widely administered with a pre-treatment threshold TSH level of 2.5 mU/L. The aim of this study is to investigate the efficacy of periconceptional LT4 treatment for subclinical hypothyroidism, including TSH levels >2.5 mU/L, and identify the characteristics of subclinical hypothyroidism that can benefit from LT4 treatment. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials from inception to February 2023. We analyzed the pooled effects of LT4 on subclinical hypothyroidism before and during pregnancy. The main outcomes before pregnancy were live birth, pregnancy, and miscarriage. The main outcomes during pregnancy were live birth, miscarriage, and preterm birth. We conducted subgroup analyses to compare the effects of LT4 on subclinical hypothyroidism with TSH levels of 2.5-4.0 and >4.0 mU/L. Results: Of the 888 studies identified, 27 full-text articles were screened for eligibility. Five studies on pre-conception treatment with 768 participants and eight studies on treatment during early pregnancy with 2622 participants were analyzed. One of the two studies on pre-conception treatment in subclinical hypothyroidism with TSH >4.0 mU/L had high risk of bias and the other was composed of 64 participants. Pre-conception LT4 treatment had no significant effect in improving rates of live births and pregnancies, or reducing miscarriages (risk ratio [RR], 95% confidence interval): 1.41 (0.84-2.36), 1.73 (0.88-3.39), and 0.46 (0.11-2.00), respectively. LT4 treatment during pregnancy was not significantly associated with higher rates of live births (RR 1.03, 0.98-1.09) nor decreased miscarriage rates (RR 1.01, 0.66-1.53). The effect of LT4 treatment on preterm birth during pregnancy was significantly different depending on the TSH values (p = 0.04); a positive effect was shown in the subclinical hypothyroidism subgroup with TSH >4.0 mU/L (RR 0.47, 0.20-1.10), while no significant effect was observed in the subgroup with TSH 2.5-4.0 mU/L (RR 1.35, 0.79-2.31). Conclusions: Pre-conceptional LT4 treatment for subclinical hypothyroidism does not improve fertility or decrease the incidence of miscarriages. However, further well-designed studies are needed for pre-conceptional treatment, especially in TSH >4.0 mU/L. LT4 treatment during pregnancy had a positive effect on preterm birth; nevertheless, this was only applicable to subclinical hypothyroidism with TSH >4.0 mU/L.

Effect of levothyroxine treatment on depression among newly diagnosed cases of hypothyroidism in adolescents at a tertiary care center

Effect of levothyroxine treatment on depression among newly diagnosed cases of hypothyroidism in adolescents at a tertiary care center

Effect of levothyroxine treatment on fetal growth among women with mild subclinical hypothyroidism and thyroid peroxidase antibody negative: a cohort study

BackgroundSome clinicians used levothyroxine (LT4) treatment for mild subclinical hypothyroidism (SCH) pregnant women (2.5 < thyroid-stimulating hormone (TSH) ≤ the pregnancy-specific reference range with normal free thyroxine (FT4) level) with thyroid peroxidase antibody negative (TPOAb−), although the recent clinical guideline did not recommend it. It is unknown whether LT4 treatment for pregnant women with mild SCH and TPOAb− have impact on fetal growth. Therefore, the aim of the study was to investigate the effect of LT4 treatment on fetal growth and birth weight among mild SCH pregnant women with TPOAb−.MethodsThis was a birth cohort study including 14,609 pregnant women between 2016 and 2019 in Tongzhou Maternal and Child Health Hospital of Beijing, China. Pregnant women were divided into 3 groups as follows: Euthyroid (n = 14,285, 0.03 ≤ TSH ≤ 2.5mIU/L, normal FT4), TPOAb−; Untreated mild SCH with TPOAb− (n = 248, 2.5 < TSH ≤ 2.9mIU/L, normal FT4, without LT4 treatment); Treated mild SCH with TPOAb− (n = 76, 2.5 < TSH ≤ 2.9mIU/L, normal FT4, with LT4 treatment). The main outcome measures were Z-scores of fetal growth indicators (abdominal circumference (AC), biparietal diameter (BPD), femur length (FL), head circumference (HC), estimated fetal weight (EFW)), fetal growth restriction (FGR) and birth weight.ResultsThere was no difference in fetal growth indicators and birth weight between the untreated mild SCH women with TPOAb− and the euthyroid pregnant women. But the HC Z-score was lower in the LT4 treated mild SCH women with TPOAb−, compared with the euthyroid pregnant women (β = -0.223, 95%CI: -0.422, -0.023). The LT4 treated mild SCH women with TPOAb− had lower fetal HC Z-score (β = -0.236, 95%CI: -0.457, -0.015), compared with the untreated mild SCH women with TPOAb−.ConclusionsWe observed that LT4 treatment for mild SCH with TPOAb− was associated with decreased fetal HC, which was not observed for untreated mild SCH women with TPOAb−. The adverse effect of LT4 treatment for mild SCH with TPOAb− provided new evidence for the recent clinical guideline.

SYSTEMATIC ANALYSIS OF THE ASSOCIATION BETWEEN HYPOTHYROIDISM AND DEPRESSION: A META-ANALYSIS OF OBSERVATIONAL STUDIES

The association among depression and subclinical hypothyroidism (SCH) is far from being obviously true, regardless of the way that changes in the hypothalamic-pituitary-thyroid hub are connected with depression. There is right now a deciency of data on how levothyroxine treatment inuences burdensome side effects in individuals with existing together SCH. To evaluate the connection among SCH and depression, we played out a metaexamination that saw three variables: 1) the pervasiveness of depression in SCH (with a sub-investigation of the geriatric partner), 2) the degree of thyroid invigorating chemical (TSH) among discouraged patients, and 3) the effect of levothyroxine treatment among patients with SCH and coinciding depression. There is an expanded possibility securing mind-set issues over the span of one's life among individuals with various immune system sicknesses, including immune system hypothyroidism (AHT).

Serum lipid profile in relation to free thyroxine and the effect of levothyroxine treatment on lipids in patients with isolated hypothyroxinemia during pregnancy: a single-center retrospective study

BackgroundThyroid function is widely considered a lipid metabolism regulator. However, studies on lipid metabolism in pregnant women with low free thyroxine (FT4) levels are limited and inconclusive. Furthermore, the association between maternal FT4 deficiency and adverse lipid metabolic parameters is unknown. Therefore, we aimed to investigate this association and the effects of levothyroxine (L-T4) treatment on these metabolic indicators.MethodsThis retrospective study included 164 patients with isolated hypothyroidism (IH) (FT4 levels below the 5th percentile with normal thyroid stimulating hormone levels according to the gestational-specific reference range) and 407 euthyroidism patients (control group who had regular antenatal examinations at Zhejiang Provincial People's Hospital, Hangzhou, China) between January 1, 2019, and December 31, 2020. Patients with IH were divided into levothyroxine (L-treatment group, n = 77) and dietary iodine supplement treatment groups (dietary treatment group, n=87) according to the hospital’s treatment policy and clinical experience. The intervention lasted for at least 8 weeks. Metabolic indicators, including thyroid function and lipid parameters, were collected at least twice before and after the intervention. Other data collected included maternal age, history of abortion, prepregnancy BMI, and gestational weight gain (Fig. 1).ResultsCompared with the control group, Patients with IH had a higher degree of dyslipidemia, reflected in elevated total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo B) levels. In IH patients, an inverse correlation was found between FT4 and TG levels, which remained after adjusting for prepregnancy BMI. The L-treatment group demonstrated a significantly slower rate of hypercholesterolemia progression during pregnancy than the dietary treatment group. In addition, there was a relationship between the therapeutic effect and the degree of disease, with the main factors being FT4, TSH and TG levels prior to starting treatment.ConclusionsLow FT4 levels were associated with elevated blood lipid levels. Serum FT4 and lipid levels in patients could be improved by medical intervention.

Analysis of the Effect of Levothyroxine Treatment in Elderly Patients with Subclinical Hypothyroidism

Analysis of the Effect of Levothyroxine Treatment in Elderly Patients with Subclinical Hypothyroidism

Effects of Levothyroxine Treatment on Cardiac Functions in Infants with Compensated Hypothyroidism

Effects of Levothyroxine Treatment on Cardiac Functions in Infants with Compensated Hypothyroidism

Subclinical Hypothyroidism: Prevalence, Health Impact, and Treatment Landscape.

Subclinical hypothyroidism (sHypo) is defined as normal serum free thyroid hormone levels coexisting with elevated serum thyroid-stimulating hormone (TSH) levels. sHypo is a common condition observed in clinical practice with several unique features. Its diagnosis should be based on an understanding of geographic and demographic differences in biochemical criteria versus a global reference range for TSH that is based on the 95% confidence interval of a healthy population. During the differential diagnosis, it is important to remember that a considerable proportion of sHypo cases are transient and reversible in nature; the focus is better placed on persistent or progressive forms, which mainly result from chronic autoimmune thyroiditis. Despite significant evidence documenting the health impacts of sHypo, the effects of levothyroxine treatment (LT4-Tx) in patients with sHypo remains controversial, especially in patients with grade 1 sHypo and older adults. Existing evidence suggests that it is reasonable to refrain from immediate LT4-Tx in most patients if they are closely monitored, except in women who are pregnant or in progressive cases. Future research is needed to further characterize the risks and benefits of LT4-Tx in different patient cohorts.

Effect of Levothyroxine Treatment on the Outcome of IVF-ET/ICSI in Patients with Hypothyroidism

Effect of Levothyroxine Treatment on the Outcome of IVF-ET/ICSI in Patients with Hypothyroidism

Effect of levothyroxine treatment on pregnancy outcomes in euthyroid women with thyroid autoantibody positive: a Meta-analysis

Objective: To conduct a systematic review of the association of levothyroxine treatment with pregnancy outcomes in euthyroid women who are thyroid autoantibody positive. Methods: Medline, Excerpta Medica (EMBASE), Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Wanfang data and VIP database were searched from inception until Jan. 28, 2020. All published randomized controlled trials assessing the association of levothyroxine treatment with pregnancy outcomes in euthyroid women with thyroid autoantibody-positive were included. STATA 11.0 and RevMan 5.3 softwares were used to perform this Meta-analysis. Results: A total of 6 studies met the inclusion criteria, with 2 188 women randomized. Meta-analysis showed that there was no significantly association between miscarriage (OR=0.85, 95%CI: 0.65-1.11, P=0.234) and preterm birth (OR=0.79, 95%CI: 0.54-1.16, P=0.224) with levothyroxine treatment. Conclusions: Levothyroxine therapy could not reduce the risk of miscarriage and preterm birth in euthyroid women with thyroid autoantibody-positive. Therefore, levothyroxine should be used with caution for these pregnant women.

Cholesterol Levels in Subclinical Hypothyroidism and the Effect of Levothyroxine Treatment on Cholesterol Levels

Cholesterol Levels in Subclinical Hypothyroidism and the Effect of Levothyroxine Treatment on Cholesterol Levels

Subclinical hypothyroidism in pregnancy: controversies on diagnosis and treatment.

The negative impact of even subtle maternal thyroid hormone deficiency on the pregnancy outcome and intellectual development of the progeny has been known for many years, but unfortunately the diagnosis and treatment of subclinical hypothyroidism in pregnant women still evokes controversies. Due to physiological changes in thyroid function and thyroid hormones metabolism during pregnancy, the trimester‑specific reference ranges for thyroid‑stimulating hormone (TSH) and free thyroid hormones should be established. However, because of interassay variability and other confounders including ethnicity and iodine intake, such norms are reliable only for local populations and a specific laboratory method. In turn, the fixed reference ranges suggested by endocrine societies may carry a risk of misclassificating some healthy pregnant women to be hypothyroid. The effect of levothyroxine treatment on pregnancy and children's cognitive outcomes remains unclear. Therapeutic benefits in decreasing miscarriage and preterm delivery rates were observed when intervention was held in the first trimester in women with a TSH level between 2.5 to 10 mU/l, mainly higher than or equal to 4 mU/l. The possible harmful effect of treatment includes preterm delivery, gestational diabetes, hypertension, and pre‑eclampsia. The only 3 prospective, randomized, placebo‑controlled trials evaluating the efficacy of levothyroxine therapy on children's intelligence quotient were started in the second trimester, which may be too late to demonstrate differences between treatment and placebo groups. Awaiting the results of future trials, clinicians should be aware of the fact that low‑dose levothyroxine at a daily dose of 25 to 50 µg is probably not harmful and may be beneficial, but the routine implementation of the therapy in each pregnant women with a TSH level exceeding 2.5 mU/l seems too premature.

The role of echocardiography in monitoring the therapeutic effect of levothyroxine replacement therapy in subclinical hypothyroidism

Paper description: • Clarification of the effects of levothyroxine treatment on cardiovascular risk present in subclinical hypothyroidism may contribute to the strategy in planning cardiovascular preventive treatments. • We examined whether treatment of subclinical hypothyroidism by levothyroxine has any effect on cardiac morphology and function estimated by standard electrocardiographic and echocardiographic indicators. • Our results suggest a subtle improvement of cardiac structure and function. • The study supports electrocardiographic and echocardiographic evaluation for monitoring the therapeutic effect of levothyroxine. This could also be an objective approach when deciding whether a patient should be treated permanently after the trial period. Abstract: Current controversies related to the treatment of subclinical hypothyroidism (SCH) with thyrotropin (TSH) < than 10 mU/L are based on the lack of evidence that levothyroxine therapy has beneficial effects. The aim of our study is to estimate the effect of levothyroxine treatment on cardiac morphology and function in subclinical hypothyroidism. Body mass index, waist circumference, blood pressure, electrocardiographic and standard echocardiographic parameters were measured before levothyroxine therapy and 3 months after TSH normalization. Significant reduction in systolic and diastolic blood pressure, PR, QT and QT corrected intervals, as well as increase in heart rate were recorded in the group on levothyroxine therapy. The following parameters of the left and right ventricle were significantly decreased in the treatment group: left ventricular mass index and volume, systolic and diastolic time intervals, and mitral annular plane systolic excursion (MAPSE). The increase was recorded as fractional shortening and pressure rise in early systole (dP/dt), right atrial wall thickness and diameters. Our study did not confirm differences in basic echocardiographic parameters between the treated and control groups, apart from an echocardiographic improvement of cardiac structure and function in treated individuals. The findings suggest electrocardiographic and echocardiographic screening in monitoring the therapeutic effect. https://doi.org/10.2298/ABS191029007P Received: October 29, 2019; Revised: January 5, 2020; Accepted: February 11, 2020; Published online: February 19, 2020 How to cite this article: Pandrc MS, Ristic A, Kostovski V, Milin-Lazovic J, Milic N, Ciric J. The role of echocardiography in monitoring the therapeutic effect of levothyroxine replacement therapy in subclinical hypothyroidism. Arch Biol Sci. 2020;72(1):137-46.

Prevalence of thyroid autoimmunity and effect of levothyroxine treatment in a cohort of 1064 patients with recurrent pregnancy loss.

Does initiating levothyroxine treatment based on thyroid-stimulating hormone (TSH) >2.5mIU/l or thyroid autoimmunity improve pregnancy continuation rates in recurrent pregnancy loss (RPL) patients? A retrospective cohort study of 1064 RPL patients, in which subjects were classified as either euthyroid (TSH 0.1 to ≤2.5mIU/l), borderline-subclinical hypothyroid (borderline-SCH, TSH 2.5 to ≤4mIU/l) or subclinical hypothyroid (SCH, TSH 4 to ≤10mIU/l). For subjects with ≥2 pregnancy losses and a subsequent pregnancy with known outcome, a comparison was done of the pregnancy continuation rate past 10 weeks of treated and untreated borderline-SCH (n = 98) and untreated euthyroid (n = 279) subjects, and between subjects with positive (n = 18) and negative (n = 206) thyroid peroxidase (TPOAb tests) within the borderline-SCH and euthyroid groups. 72.7% were euthyroid (721/992), 19.4% (192/992) were borderline-SCH, and 5.4% (54/992) were subclinically hypothyroid (SCH). Of 401 women with a subsequent pregnancy of known outcome at 10 gestational weeks, 21% received treatment with levothyroxine. 57.7% of subjects had a TPOAb test, which was positive in 9.25% (37/400) in euthyroid, 16.5% (22/133) in borderline-SCH subjects and 35.3% (12/34) in SCH subjects. Treatment did not improve pregnancy continuation rates in borderline-SCH subjects (P = 0.392). There was no difference in pregnancy outcomes based on TPOAb status and treatment for borderline-SCH subjects (P = 0.4214), or based on TPOAb status for euthyroid subjects (P = 0.2668). Treatment of hypothyroidism in pregnancy should be initiated based on a TSH >4mIU/l. Treatment initiation based on thyroid autoimmunity or a TSH >2.5mIU/l may result in overtreatment.

Levothyroxine treatment and pregnancy outcomes in women with subclinical hypothyroidism: a systematic review and meta-analysis.

To evaluate the benefits of LT4 treatment on pregnancy outcomes in SCH women. PubMed [including Medline], Web of Science, Wiley, Google Scholar, Science direct and Scopus were searched for identifying and retrieving all English articles published up to May 2018 on the effects of levothyroxine treatment on pregnancy outcomes in pregnant women with SCH compared to untreated or healthy controls. In this systematic review and meta-analysis, both fixed and random effect models were applied to estimate the pooled effect size. Heterogeneity and publication bias were evaluated using the I-squared (I2) and Begg's statistics, respectively. We also explored heterogeneity sources using meta-regression models and sensitivity analysis. Data of 13 cohort studies and randomized controlled trials with a total of 11,503 participants were analyzed. This meta-analysis showed that pregnant women with SCH treated with levothyroxine had lower chances of pregnancy loss (OR 0.78, 95% CI 0.66-0.94; I2 = 0%) and higher chances for live birth rates (OR 2.72, 95% CI 1.44-5.11; I2 = 25%) than the placebo group. Compared to euthyroid women, SCH patients treated with levothyroxine had higher odds ratio for preterm labor (OR 1.82, 95% CI 1.14-2.91; I2 = 0%). Results of this study showed that the effects of treatment with levothyroxine in SCH pregnant women are not the same for all pregnancy outcomes. Levothyroxine treatment in these patients can reduce pregnancy loss. Considering the limited number of studies available, further studies are warranted to document more precise data on other consequences.

The effect of levothyroxine treatment on serum lipid levels in women with subclinical hypothyroidism

The effect of levothyroxine treatment on serum lipid levels in women with subclinical hypothyroidism

Study protocol: a randomised controlled trial on the clinical effects of levothyroxine treatment for subclinical hypothyroidism in people aged 80\xa0years and over

BackgroundSubclinical hypothyroidism is common in older people and its contribution to health and disease needs to be elucidated further. Observational and clinical trial data on the clinical effects of subclinical hypothyroidism in persons aged 80 years and over is inconclusive, with some studies suggesting harm and some suggesting benefits, translating into equipoise whether levothyroxine therapy provides clinical benefits. This manuscript describes the study protocol for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial to generate the necessary evidence base.MethodsThe IEMO 80-plus thyroid trial was explicitly designed as an ancillary experiment to the Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism randomised placebo controlled Trial (TRUST) with a near identical protocol and shared research infrastructure. Outcomes will be presented separately for the IEMO and TRUST 80-plus groups, as well as a pre-planned combined analysis of the 145 participants included in the IEMO trial and the 146 participants from the TRUST thyroid trial aged 80 years and over.The IEMO 80-plus thyroid trial is a multi-centre randomised double-blind placebo-controlled parallel group trial of levothyroxine treatment in community-dwelling participants aged 80 years and over with persistent subclinical hypothyroidism (TSH ≥4.6 and ≤ 19.9 mU/L and fT4 within laboratory reference ranges). Participants are randomised to levothyroxine 25 or 50 micrograms daily or matching placebo with dose titrations according to TSH levels, for a minimum follow-up of one and a maximum of three years.Primary study endpoints: hypothyroid physical symptoms and tiredness on the thyroid-related quality of life patient-reported outcome (ThyPRO) at one year. Secondary endpoints: generic quality of life, executive cognitive function, handgrip strength, functional ability, blood pressure, weight, body mass index, and mortality. Adverse events will be recorded with specific interest on cardiovascular endpoints such as atrial fibrillation and heart failure.DiscussionThe combined analysis of participants in the IEMO 80-plus thyroid trial with the participants aged over 80 in the TRUST trial will provide the largest experimental evidence base on multimodal effects of levothyroxine treatment in 80-plus persons to date.Trial registrationNederlands (Dutch) Trial Register: NTR3851 (12–02-2013), EudraCT: 2012–004160-22 (17–02-2013), ABR-41259.058.13 (12–02-2013).

Resistance to Thyroid Hormone due to Heterozygous Mutations in Thyroid Hormone Receptor Alpha.

Thyroid hormone (TH) acts via nuclear thyroid hormone receptors (TRs). TR isoforms (TRα1, TRα2, TRβ1, TRβ2) are encoded by distinct genes (THRA and THRB) and show differing tissue distributions. Patients with mutations in THRB, exhibiting resistance within the hypothalamic-pituitary-thyroid axis with elevated TH and nonsuppressed thyroid-stimulating hormone (TSH) levels, were first described decades ago. In 2012, the first patients with mutations in THRA were identified. Scope of this review: This review describes the clinical and biochemical characteristics of patients with resistance to thyroid hormone alpha (RTHα) due to heterozygous mutations in THRA. The genetic basis and molecular pathogenesis of the disorder together with effects of levothyroxine treatment are discussed. The severity of the clinical phenotype of RTHα patients seems to be associated with the location and type of mutation in THRA. The most frequent abnormalities observed include anemia, constipation, and growth and developmental delay. In addition, serum (F)T3 levels can be high-normal to high, (F)T4 and rT3 levels normal to low, while TSH is normal or mildly raised. Despite heterogeneous consequences of mutations in THRA, RTHα should be suspected in subjects with even mild clinical features of hypothyroidism together with high/high-normal (F)T3, low/low-normal (F)T4, and normal TSH.