Levothyroxine Therapy Research Articles

Trace elements in hypothyroidism in relation to L-thyroxine therapy

Hypothyroidism is a common disorder in the population with a female predominance. Most hypothyroidism cases were found in the age group range of 30–35 in both the sexes of individuals but women were more prone to develop it. Disturbance or imbalance in the thyroid hormone levels is the underlying cause of resultant hypothyroidism. A comparative study of serum T3 (triiodothyronine), T4 (thyroxine), TSH (thyroid stimulating hormone), copper, zinc, magnesium and iron was done in 100 normal individuals as controls (Group I). 100 Hypothyroid patients showing Good Response to Levothyroxine Therapy – GRLT as (Group II A) and 100 Hypothyroid patients showing Poor Response to Levothyroxine Therapy – PRLT as (Group II B) over a period of 1 and half year in the age group of 20 to 45 years. The levels of TSH were found to be elevated in hypothyroid patients with relatively lower levels of serum T3 and T4 as per our study conducted in hypothyroid patients with PRLT when compared with the healthy subjects and patients in GRLT group. A study of implementation of levothyroxine therapy in hypothyroid subjects showed improvement in the patients with all the hormone levels returning back to the pre – hypothyroid state in majority of the hypothyroid patients with GRLT in comparison with the controls. Results of the study indicate a significant decreased levels of serum copper, zinc and iron in hypothyroid patients showing poor response to levothyroxine therapy whereas the magnesium levels in the serum of hypothyroid individuals with poor response to levothyroxine was found elevated. The serum levels of all the trace elements studied i.e., copper, zinc, magnesium, and iron in GRLT hypothyroid individuals and controls were within the normal ranges. Further studies are however needed on these parameters for establishing serum levels of trace elements in hypothyroidism in relation to response to levothyroxine therapy.

Effect of Suppressive Levothyroxine Therapy on Bone Mineral Density in Young Patients with Differentiated Thyroid Carcinoma.

Suppressive levothyroxine therapy (sT4) is a cornerstone in the management of differentiated thyroid cancer (DTC). Long-term sT4 may affect bone mineral density (BMD). We evaluated the effect of sT4 on the bone mass of young DTC patients. In this cross-sectional study, BMD was evaluated via dual-energy X-ray absorptiometry in DTC patients younger than 25 years at diagnosis and undergoing sT4 for ≥1 year. The two control groups comprised patients matched for sex, age, and body-mass-index who were thyroidectomized for indications other than DTC and undergoing L-T4-replacement therapy, and healthy individuals with no prior known thyroid disease. Ninety-three participants were included (thirty-one in each group). There were no differences in the mean age, female sex (77.4% in all groups), or BMI between the sT4 group and each control group. The median TSH level was lower (0.4 [0.04–6.5] vs. 2.7 [0.8–8.5] mIU/mL, p = 0.01) and the mean L-T4 mcg/Kg levels were higher (2.4 ± 0.6 vs. 1.6 ± 0.3, p = 0.01) in the sT4 group compared to the L-T4-replacement therapy group. Lumbar spine, femoral neck, and total femur BMD were all similar among the groups. sT4 does not impact BMD in young DTC patients after a median time of suppression of 8 years. These findings may help in the decision-making and risk/benefit evaluation of sT4 for this population.

Association Between Blood Pressure, Glomerular Filtration Rate, and Serum Thyroid-Stimulating Hormone Levels in Hypothyroid Patients: A Retrospective Single-Center Study.

Background: Thyroid hormones have substantial effects on blood pressure (BP) and renal function as they influence the glomerular filtration rate (GFR). Maintaining healthy BP and preventing premature development of nephropathy necessitates taking steps.Objectives: The aim of this study was to explore the association between BP, GFR, and thyroid-stimulating hormone (TSH) levels in hypothyroid patients at King Abdulaziz University Hospital, Jeddah, Saudi Arabia.Methods: A retrospective record review study of all hypothyroid patients from June 1, 2010 to June 6, 2020. The medical records of 1,181 adult patients were reviewed, and 157 met the criteria. All patients aged >18 years who were diagnosed with hypothyroidism and were on levothyroxine therapy, were included in this study.Results: More than half of the participants were female (83.4%). There was no significant correlation between TSH and systolic BP (P= 0.6), or TSH and diastolic BP (P=0.8), while there was a positive correlation between TSH and creatinine (r=0.4, P=0.001) and a negative correlation between TSH and GFR (r=−0.2, P=0.01).Conclusions: We found no association between BP and TSH, while creatinine correlated directly and GFR inversely with TSH. Follow-up renal function should be a target for physicians in hypothyroid patients to prevent premature complications.

Screening for thyroid dysfunction with free T4 instead of thyroid stimulating hormone (TSH) improves efficiency in older adults in primary care.

Subclinical hypothyroidism (SCHT) is defined as a consistently elevated thyroid stimulating hormone (TSH) with a free T4 (fT4) within the reference range. This diagnosis may lead to additional monitoring, levothyroxine therapy and increased patient concerns, despite lack of evidence of treatment benefit in older adults. In order to avoid this diagnosis, we evaluated the efficiency of fT4-based screening for thyroid dysfunction, in older adults in primary care and compared it with TSH-based screening.Individuals aged >65years in primary care were selected for this retrospective study when both TSH and fT4 were individually requested irrespective of the TSH value. Exclusion criteria were C-reactive protein > 10 mg/l or a history of thyroid hormone monitoring in the previous year.Screening based on fT4 instead of TSH decreased reflex testing from 23.8% to 11.2%. The positive predictive value (PPV) for clinical hypothyroidism increased from 17.3% to 52.2%. The negative predictive value was 96.1% with TSH-based screening versus 97.8% with fT4-based screening. Elevation of the TSH cutoff value from 4.2 to 6.5 mU/l resulted in a reflex test percentage of 12.5% and a PPV of 31.0%.Our results suggest that screening for thyroid dysfunction in older individuals in primary care can be improved by screening based on fT4 instead of TSH or by adjusting the TSH cutoff value. Adjustment of the screening strategy may be of interest to health policy makers because of potential cost reduction. From a patient perspective, medical concerns and unnecessary biochemical follow-up might be reduced by circumventing the diagnosis SCHT.

Brain effects of combined levothyroxine (T4) and 3-iodothyronamine (T1AM) replacement therapy in a murine model of hypothyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

No Adverse Effect of Levothyroxine Therapy on Bone Density during the Treatment of Subclinical Hypothyroidism

No Adverse Effect of Levothyroxine Therapy on Bone Density during the Treatment of Subclinical Hypothyroidism

Subclinical Hypothyroidism in Pediatric Age: How Important Is Autoimmunity?

BackgroundThe natural history of subclinical hypothyroidism (SHT) is influenced by the underlying etiology, being the most common Hashimoto's thyroiditis (HT) and isolated hyperthyrotropinemia (IH). Additionally, controversy exists surrounding the need for pharmacological treatment.MethodsA retrospective observational study that included patients diagnosed with SHT caused by HT or IH at pediatric age, under levothyroxine therapy and with follow-up at Centro Hospitalar Baixo Vouga between January/2014 and July/2019. Patients with follow-up time <12 months or missing records were excluded. This study aims to compare clinical, analytical and echographic parameters and levothyroxine dose between patients with SHT caused by HT or IH.ResultsSample of 39 patients with 16.5 ± 3.4 years, 22 (56.4%) females. There was a preponderance of females in the HT group and males in the IH (p=0.001). Changes in thyroid ultrasound were more prevalent in the HT group (85.7% vs 16.7%, p<0.001). The median initial and final doses of levothyroxine were higher in the HT group (p=0.016, p=0.011). There was a trend towards a higher levothyroxine discontinuation rate in the IH group (22.2% vs 4.8%, p=0.162).Two positive and statistically significant correlations were found between the level of anti-thyroid peroxidase antibodies (TPOAbs) and both the final levothyroxine dose (ρ=0.544; p=0.004) and the final weight-adjusted levothyroxine dose (ρ=0.434; p=0.027).ConclusionsHT was more common in females and was associated with higher levothyroxine requirements and less likelihood of treatment discontinuation, especially if high TPOAbs levels. These results can be useful in the difficult daily decision of starting therapy, especially in milder forms of SHT.

Hypothyroidism and Depression: A Narrative Review.

There has been an established relationship between hypothyroidism and depression. Studies have demonstrated that somatostatin and serotonin influence the hypothalamus-pituitary-thyroid axis, which links hypothyroidism to depression. Multiple studies concluded that undiagnosed, untreated, undertreated patients with hypothyroidism are at increased risk of developing depression. Autoimmune thyroiditis is also associated with an increased risk of depression. Elevated thyroid-stimulating hormone (TSH), antithyroglobulin (TgAb), and thyroid peroxidase antibodies (TPOAb) levels have all been linked to depression and an increased risk of suicide. Moreover, hypothyroidism is known to be one of the leading causes of treatment-resistant depression. Treating underlying hypothyroidism with thyroid replacement therapy could significantly improve mood disorders such as depression. Levothyroxine therapy is also used as adjunctive therapy to antidepressants in the management of depression, and it is known to improve the symptoms of depression rapidly when compared to antidepressants alone. This review strengthens the link between hypothyroidism and depression, and it also demonstrates how treating the underlying hypothyroidism in people who have been diagnosed with depression will be very beneficial.

The impact of levothyroxine therapy on the pregnancy, neonatal and childhood outcomes of subclinical hypothyroidism during pregnancy: An updated systematic review, meta-analysis and trial sequential analysis.

BackgroundSeveral systematic reviews and meta-analyses have investigated the effect of levothyroxine (LT4) therapy in pregnant women with subclinical hypothyroidism (SCH). However, all these studies have clinical or methodological problems (such as adopting the old 2011 American Thyroid Association [ATA] diagnostic criteria, directly combining randomized controlled trials [RCTs] and cohort studies for meta-analysis, and so on), and cannot provide accurate and satisfactory results. Thus, we performed this updated systematic review, meta-analysis and trial sequential analysis (TSA) to assess the effect of LT4 therapy in pregnant women with SCH, with the goal of providing more accurate and reliable evidence for clinical practice.MethodsWe searched nine databases from inception to February 2022. The search strategy targeted the RCTs and cohort studies on pregnancy, neonatal and childhood outcomes following LT4 treatment in pregnant women with SCH based on the new 2017 ATA diagnostic criteria. We performed meta-analyses of RCTs and cohort studies separately, and further performed meta-analyses by excluding studies with high risk of bias. TSA was performed to test whether the current evidence was sufficient, and the quality of evidence was evaluated using the GRADE method.ResultsA total of 9 RCTs and 13 cohort studies comprising 11273 pregnant women with SCH were included. There were no statistically significant differences between LT4 group and control group in all primary and secondary outcomes, such as preterm delivery (RR=0.46, 95%CI: 0.19-1.09, P=0.08, I2 = 65%), miscarriage (RR=0.36, 95%CI: 0.13-1.03, P=0.06, I2 = 38%), gestational hypertension (RR=0.91, 95%CI: 0.58-1.43, P=0.69, I2 = 0%), preeclampsia (RR=1.10, 95%CI: 0.61-1.97, P=0.76, I2 = 0%), gestational diabetes (RR=0.80, 95%CI: 0.51-1.25, P=0.32, I2 = 34%), and so on. TSA showed that the results for all outcomes were insufficient and inconclusive. According to GRADE, the evidences for four outcomes (miscarriage, gestational hypertension, gestational diabetes, and small for gestational age) were rated as moderate quality, while the evidences for the other outcomes were rated as low or very low quality.ConclusionUnlike previous systematic reviews and meta-analyses, our study found no evidence of benefit of LT4 therapy on pregnancy, neonatal and childhood outcomes in pregnant women with SCH.Systematic Review RegistrationPROSPERO, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022321937, identifier CRD42022321937.

Bone geometry in older adults with subclinical hypothyroidism upon levothyroxine therapy: A nested study within a randomized placebo controlled trial.

The effect of levothyroxine (LT4) therapy for subclinical hypothyroidism (SHypo) on appendicular bone geometry and volumetric density has so far not been studied. In a nested study within the randomized, placebo-controlled Thyroid Hormone Replacement for Subclinical Hypothyroidism (TRUST) trial, we assessed the effect of LT4 therapy on bone geometry as measured by peripheral quantitative computed tomography (pQCT). In the TRUST trial, community-dwelling adults aged ≥65years with SHypo were randomized to LT4 with dose titration vs. placebo with mock titration. We analyzed data from participants enrolled at the TRUST site in Bern, Switzerland who had bone pQCT measured at baseline and at 1 to 2years follow-up. The primary outcomes were the annual percentage changes of radius and tibia epi- and diaphysis bone geometry (total and cortical cross-sectional area (CSA) and cortical thickness), and of volumetric bone mineral density (bone mineral content (BMC) and total, trabecular and cortical volumetric bone mineral density (vBMD)). We performed linear regression of the annual percentage changes adjusted for sex, LT4 dose at randomization and muscle cross-sectional area. The 98 included participants had a mean age of 73.9 (±SD 5.4) years, 45.9% were women, and 12% had osteoporosis. They were randomized to placebo (n=48) or LT4 (n=50). Annual changes in BMC and vBMD were similar between placebo and LT4-treated groups, without significant difference in bone geometry or volumetric bone mineral density changes, neither at the diaphysis, nor at the epiphysis. For example, in the placebo group, epiphyseal BMC (radius) decreased by a mean 0.2% per year, with a similar decrease of 0.5% per year in the LT4 group (between-group difference in %ΔBMC 0.3, 95% CI -0.70 to 1.21, p=0.91). Compared to placebo, LT4 therapy for an average 14months had no significant effect on bone mass, bone geometry and volumetric density in older adults with subclinical hypothyroidism. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov numbers NCT01660126 (TRUST Thyroid trial) and NCT02491008 (Skeletal outcomes).

Effects of Levothyroxine Therapy on Pregnancy and Neonatal Outcomes in Subclinical Hypothyroidism.

PurposeTo assess the effects of levothyroxine (LT4) therapy on pregnancy and neonatal outcomes in pregnant women with subclinical hypothyroidism (SCH) who had different thyroid peroxidase antibody (TPOAb) status.MethodsThe data of pregnant women from the Chengdu Hospital of Integrated Traditional Chinese and Western Medicine between January 2017 and August 2019 were collected. SCH was defined as 11.88 < free thyroxine (FT4) < 20.06pmol/L in conjunction with thyroid-stimulating hormone (TSH) >4.00 mU/L. Some clinical characteristics have been collected, including body mass index (BMI) before pregnancy, number of pregnancies, number of miscarriages (spontaneous abortion), parity, family history of diabetes, history of smoking, history of drinking, TSH, FT4, and TPOAb levels. The prevalence of pregnancy and neonatal outcomes in the LT4 and non-LT4 groups, and in the LT4 and euthyroid control groups were compared, respectively. Univariate and multivariate logistic regression analyses were used to assess the effects of LT4 therapy on pregnancy and neonatal outcomes in SCH pregnant women with TPOAb.ResultsA total of 985 subjects were enrolled and divided into LT4 group with 478 patients, non-LT4 group with 156 patients and euthyroid control group with 351 patients. The prevalence of amniotic fluid abnormalities and premature delivery in the LT4 group was lower than that in the non-LT4 group in participants with TPOAb-positive (TPOAb+). After adjusting age, BMI prior to pregnancy, number of pregnancies, number of miscarriages, parity, TSH and FT4 level, the SCH pregnant women with TPOAb+ in the LT4 group had a lower risk of amniotic fluid abnormalities and premature delivery than that in the non-LT4 group.ConclusionLT4 therapy could reduce the risk of premature delivery and amniotic fluid abnormalities in the SCH pregnant women with TPOAb+. However, more randomized trials are required to confirm this association before the unequivocal advocacy of LT4 therapy in pregnant women with SCH.

MECHANISMS IN ENDOCRINOLOGY: The pathophysiology of transient congenital hypothyroidism

Transient congenital hypothyroidism (TCH) refers to congenital hypothyroidism which spontaneously resolves in the first few months or years of life. Currently, there is a paucity of reliable markers predicting TCH at diagnosis, and the diagnosis is established following the withdrawal of levothyroxine therapy around 3 years of age. The incidence of TCH is increasing, and it is a major contributor to the overall increase in the incidence of CH in recent studies. Both genetic factors, in particular mutations affecting DUOX2 and DUOXA2, and environmental factors, for example, iodine deficiency and excess, anti- TSHR antibodies and exposure to antithyroid or iodine-rich medications, may cause TCH. Resolution of TCH in childhood may reflect both normal thyroid physiology (decreased thyroid hormone biosynthesis requirements after the neonatal period) and clearance or cessation of environmental precipitants. The relative contributions and interactions of genetic and environmental factors to TCH, and the extent to which TCH may be prevented, require evaluation in future population-based studies.

Levothyroxine supplementation among individuals with Subclinical Hypothyroidism and Depression | a review

IntroductionDepression is known to be associated with changes in the hypothalamic-pituitary-thyroid axis and the brain is a major target organ for thyroid hormone. Overt hypothyroidism can cause symptoms compatible with depression. However, its relationship with subclinical hypothyroidism (SCH) is not well established.ObjectivesTo review the literature regarding the effect of levothyroxine therapy among patients with SCH and coexistent depression.MethodsWe conducted a MEDLINE search using depression, subclinical hypothyroidism and levothyroxine as keywords, selecting studies written in English.ResultsSCH is defined as an elevated thyroid stimulating hormone with normal peripheric hormone levels. The association between SCH and depression is controversial. Some studies indicate that SCH had the same propensity with overt hypothyroidism, while others report that major affective symptoms are not associated with SCH, but are likely due to independent psychiatric diagnoses, which are common in the general population and occur with similar frequency in patients with SCH. Individuals with SCH are recommended to initiate levothyroxine replacement therapy only when their TSH level is above 10 mIU/L or if symptoms are present. There is a lack of evidence supporting the use of levothyroxine therapy to improve mental health outcomes and the majority of meta-analysis do not show relief of affective symptoms after levothyroxine therapy, among individuals with SCH.ConclusionsRoutine screening for depressive symptoms among individuals with SCH is important to prevent morbidity. Nevertheless, there is no evidence enduring levothyroxine supplementation in these cases. Further studies, with larger sample sizes and longer follow-up periods are needed to enlighten the potential benefit of this therapy.DisclosureNo significant relationships.

Immune checkpoint inhibitor-related endocrinopathies: A nationwide population-based study.

2653 Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, unleashing the body’s immune system against cancer is not without consequences and may trigger immune-related adverse events (irAEs), such as endocrinopathies. Real-world data of these endocrinopathies is lacking. This study aims to obtain the prevalence of endocrine irAEs and identify possible underlying demographic risk factors or disparities. Methods: A cross-sectional study was performed using a US-based population database (Explorys) that aggregates records from 26 healthcare systems and includes over 79 million patients. Our sample included all patients on an ICI, and we further identified patients who developed endocrinopathies while on different ICI regimens. The demographic data extracted was categorical, hence presented as counts and percentages. The odds ratio (OR), standard error, and 95% confidence interval were calculated with the use of SPSS software version 28.0 (IBM). Results: There were 20,950 patients on an ICI; 58% males, 83% Caucasians, 10% African-Americans (AA), 38% aged between 18-65, and 63% were over 65 years. The prevalence of the studied endocrinopathies is listed in the table. The most prevalent ICI-induced endocrinopathy was hypothyroidism (7.9-13%). Combination therapy with ipilimumab and nivolumab showed the highest prevalence of ICI-induced endocrinopathies, followed by durvalumab. The odds of developing ICI-induced endocrinopathy were significantly higher with combination therapy than nivolumab monotherapy (OR 1.6; 95% CI 1.4-1.9). There was no statistically significant difference in endocrinopathy prevalence when comparing Caucasians to AA and adults18-65 years to seniors over 65 years. Conclusions: This is the largest epidemiological study of ICI-related endocrinopathies. We find an intriguing divergence from endocrinopathy prevalence reported in the literature and real-world data we are presenting here. Over diagnosis of overt hypothyroidism, as opposed to subclinical hypothyroidism, is concerning as the former necessitates levothyroxine therapy. More alarming is the under diagnosis of hypopituitarism and PAI, in which delay in treatment can be fatal. The diagnosis of these conditions can be challenging. Raising awareness, setting protocols for testing, and involving endocrinologists are crucial. Further studies are needed to clarify our findings. [Table: see text]

Changes in Thyroid Metabolites after Liothyronine Administration: A Secondary Analysis of Two Clinical Trials That Incorporated Pharmacokinetic Data.

We examined relationships between thyroid hormone (TH) metabolites in humans by measuring 3,5-diiodothyronine (3,5-T2) and 3-iodothyronamine (3-T1AM) levels after liothyronine administration. In secondary analyses, we measured 3,5-T2 and 3-T1AM concentrations in stored samples from two clinical trials. In 12 healthy volunteers, THs and metabolites were documented for 96 h after a single dose of 50 mcg liothyronine. In 18 patients treated for hypothyroidism, levothyroxine therapy was replaced by daily dosing of 30–45 mcg liothyronine. Analytes were measured prior to the administration of liothyronine weekly for 6 weeks, and then hourly for 8 h after the last liothyronine dose of the study. In the weekly samples from the hypothyroid patients, 3,5-T2 was higher by 0.033 nmol/L with each mcg/dL increase in T4 and 0.24 nmol/L higher with each ng/dL increase in FT4 (p-values = 0.007, 0.0365). In hourly samples after the last study dose of liothyronine, patients with T3 values higher by one ng/dL had 3-T1AM values that were lower by 0.004 nmol/L (p-value = 0.0473); patients with 3,5-T2 higher by one nmol/L had 3-T1AM values higher by 2.45 nmol/L (p-value = 0.0044). The positive correlations between weekly trough levels of 3,5-T2 and T4/FT4 during liothyronine therapy may provide insight into 3,5-T2 production, possibly supporting some production of 3,5-T2 from endogenous T4, but not from exogenous liothyronine. In hourly sampling after liothyronine administration, the negative correlation between T3 levels and 3-T1AM, but positive correlation between 3,5-T2 levels and 3-T1AM could support the hypothesis that 3-T1AM production occurs via 3,5-T2 with negative regulation by T3.

Outcomes With Levothyroxine Treatment in Early Pregnancy With Subclinical Hypothyroidism.

IntroductionAdverse pregnancy outcomes in women with subclinical hypothyroidism (SCH) are well documented, whereas data regarding the risk and benefit of levothyroxine treatment in such cases are insufficient and inconsistent. Our study aimed to evaluate the effects of levothyroxine treatment on pregnancy outcomes in these women.Materials and methodsHealthy women with a singleton pregnancy were screened before 12 weeks of gestation for subclinical hypothyroidism using 2017 American Thyroid Association guidelines. They were treated with an initial dose of 50 mcg of levothyroxine and the dose was adjusted at six-week intervals to achieve a normal thyrotropin level. All the participants were followed up with thyroid function tests and ultrasonography till delivery. Pregnancy outcomes were compared with those of healthy pregnant women with normal thyroid function.Results A total of 1058 women were screened and 5.1% (n=54) were found to have subclinical hypothyroidism, out of which 57.4% (n=31) were thyroid peroxidase antibody positive. The median gestational age at the initiation of levothyroxine treatment was nine weeks. The risks for miscarriage (odds ratio (OR): 1.284, p=0.811), gestational hypertension (OR: 1.993, p=0.365), intra-uterine growth restriction (OR: 1.688, p=0.488), low birth weight (OR: 1.591, p=0.392), and preterm birth (OR: 1.606, p=0.529) were not significantly higher in women with subclinical hypothyroidism as compared to euthyroid women. However, the risk of gestational diabetes mellitus was significantly higher in women with SCH (OR: 3.432, 95% confidence interval (95% CI): 1.115-10.562).ConclusionLevothyroxine therapy initiated in the first trimester of pregnancy has possible beneficial effects in subclinical hypothyroidism but with a higher risk for gestational diabetes.

Compare the effects of levothyroxine therapy vs liothyronine/levothyroxine combination therapy on cardiac biomarkers in 364 patients with hypothyroidism

Compare the effects of levothyroxine therapy vs liothyronine/levothyroxine combination therapy on cardiac biomarkers in 364 patients with hypothyroidism

Thyroid Signaling Biomarkers in Female Symptomatic Hypothyroid Patients on Liothyronine versus Levothyroxine Monotherapy: A Randomized Crossover Trial.

Background Levels of thyroid-stimulating hormone (TSH) are believed to reflect degree of disease in patients with hypothyroidism, and normalization of levels is the treatment goal. However, despite adequate levels of TSH after starting levothyroxine (LT4) therapy, 5–10% of hypothyroid patients complain of persisting symptoms with a significant negative impact on quality of life. This indicates that TSH is not an optimal indicator of intracellular thyroid hormone effects in all patients. Our aim was to investigate different effects of LT3 and LT4 monotherapy on other biomarkers of the thyroid signaling pathway, in addition to adverse effects, in patients with residual hypothyroid symptoms. Methods Fifty-nine female hypothyroid patients, with residual symptoms on LT4 monotherapy or LT4/liothyronine (LT3) combination therapy, were randomly assigned in a non-blinded crossover study and received LT4 or LT3 monotherapy for 12 weeks each. Measurements, including serum analysis of a number of biochemical and hormonal parameters, were obtained at the baseline visit and after both treatment periods. Results Free thyroxine (FT4) was higher in the LT4 group, while free triiodothyronine (FT3) was higher in the LT3 group. The levels of reverse triiodothyronine (rT3) decreased after LT3 treatment compared with LT4 treatment. Both low-density lipoprotein (LDL) and total cholesterol levels were reduced, while sex hormone-binding globulin (SHBG) increased after LT3 treatment compared with LT4 treatment. The median TSH levels for both treatment groups were within the reference range, however, lower in the LT4 group than in the LT3 group. We did not find any differences in pro-B-type natriuretic peptide (NT pro-BNP), handgrip strength, bone turnover markers, or adverse events between the two treatment groups. Conclusion We have demonstrated that FT4, FT3, rT3, cholesterol, and SHBG show significantly different values on LT4 treatment compared with LT3 treatment in women with hypothyroidism and residual symptoms despite normal TSH levels. No differences in general or bone-specific adverse effects were demonstrated. This trial is registered with NCT03627611 in May 2018.

Efficacy and safety of supraphysiologic doses of levothyroxine for patients with bipolar depression in adults: A systematic review.

In bipolar disorder (BD), depression is the most difficult-to-treat dimension and available evidence suggests that add-on supraphysiological doses of levothyroxine may be an effective augmenting agent. This systematic review has been conducted to evaluate the efficacy and safety of supraphysiologic doses of levothyroxine in bipolar depression in adults. After a comprehensive literature search on MEDLINE/PubMed, Scopus, Cochrane databases and International Clinical Trial Registry Platform (ICTRP), reviewers extracted data from eight relevant articles. PRISMA guidelines were followed in the selection, analysis and reporting of findings. Quality assessment was done using the risk of bias assessment and a random effects model was used to estimate effect size. Meta-analysis could not be done due to the lack of randomized, placebo-controlled trials and adequate data. A systematic review was done on eight studies and analysis on the pre-post change in Hamilton depression rating scale score (HDRS) was done for six studies. The random model analysis of pooled effects showed a standardized mean difference of HDRS score by 2.62 (95% CI: 2.21-3.04; p < 0.0001). The responder and remission rates were not significant as reported in one study. Markov chain analysis performed in one study revealed that patients in the levothyroxine group had a significantly greater increase in time in the euthymic state and a decrease in the mixed state. In most of the studies, levothyroxine therapy was well tolerated, with no serious adverse events. Add-on supraphysiological dose of levothyroxine has a potential role in attenuating depressive symptoms in bipolar depression, especially in therapy-resistant BD. CRD42020218456.

Levothyroxine Therapy for Pregnant Women with Negative Thyroid Peroxidase Antibody and Subclinical Hypothyroidism May Be Associated with Improved Intellectual Development of the Offspring

Levothyroxine Therapy for Pregnant Women with Negative Thyroid Peroxidase Antibody and Subclinical Hypothyroidism May Be Associated with Improved Intellectual Development of the Offspring