Levothyroxine-treated Patients Research Articles

Thyroid Hormone Homeostasis in Levothyroxine-treated Patients: Findings From ELSA-Brasil.

The effectiveness of levothyroxine (LT4) in restoring thyroid hormone (TH) homeostasis, particularly serum thyroxine (T4) and triiodothyronine (T3) levels, remains debatable. This work aimed to assess TH homeostasis in LT4-treated individuals using data from the Longitudinal Study of Adult Health in Brazil (ELSA-Brasil) study. The ELSA-Brasil study follows 15 105 adult Brazilians (aged 35-74 years) over 8.2 years (2008-2019) with 3 observation points assessing health parameters including serum thyrotropin (TSH), free T4 (FT4), and free T3 (FT3) levels. We analyzed 186 participants that initiated treatment with LT4 during the study, and 243 individuals continuously treated with LT4 therapy. Initiation of therapy with LT4 resulted in an 11% to 19% decrease in TSH, an approximately 19% increase in FT4, and a 7% reduction in FT3 serum levels (FT3 dropped >10% in ∼40% of the LT4-treated patients). This was associated with an increase in triglyceride levels and utilization of hypolipidemic and antidiabetic medications. Participants continuously treated with LT4 exhibited a stable elevation in serum FT4 and a reduction in serum FT3 and TSH levels. While 115 participants (47.3%) had at least 1 serum FT4 levels above the control reference range (>1.52 ng/dL), 38 participants (15.6%) had at least 1 serum FT3 below the reference range (<0.23 ng/dL). The present results challenge the dogma that treatment with LT4 for hypothyroidism restores TH homeostasis in all patients. A substantial number of LT4-treated patients exhibit repeated FT4 and FT3 levels outside the normal reference range, despite normal TSH levels. Further studies are needed to define the clinical implications of these findings.

The Association Between Hypothyroidism Treatment and Mortality in Patients Hospitalized in Surgical Wards

ABSTRACT Limited data are available regarding the association between pre-admission thyroid-stimulating hormone (TSH) levels and prognosis in hospitalized surgical patients treated for hypothyroidism. We retrospectively evaluated a cohort of 1,451 levothyroxine-treated patients, hospitalized to general surgery wards. The 30-day mortality risk was 2-fold higher for patients with TSH of 5.0–10.0 mIU/L (adjusted OR, 2.3; 95% CI 1.1–5.1), and 3-fold higher for those with TSH > 10.0 mIU/L (3.4; 95% CI 1.3–8.7). Long-term mortality risk was higher in patients with TSH of 5.0–10.0 and above 10.0 mIU/L (adjusted HR, 1.2; 95% CI, 1.0–1.6, and 1.7; 95% CI 1.2–2.4, respectively). We found that in levothyroxine-treated adults hospitalized to surgical wards, increased pre-admission TSH levels are associated with increased short- and long-term mortality.

Effect of morning versus night-time administration of proton pump inhibitor (pantoprazole) on thyroid function test in levothyroxine-treated primary hypothyroidism: a prospective cross-over study

BackgroundOne of the common causes of suboptimal control of thyroid stimulating hormone (TSH) in levothyroxine-treated hypothyroidism is coadministration of proton pump inhibitors (PPIs). Morning administration of pantoprazole has been shown to suppress intragastric pH to a greater extent. We therefore aimed to determine the effect of pantoprazole at different time points of the day on thyroid function test (TFT) in levothyroxine-treated overt primary hypothyroidism.MethodsIn this single centre, hospital based, prospective, two arm cross-over study (AB, BA), participants were randomized into 2 groups based on morning (6:00 am – 7:00 am simultaneously with the scheduled levothyroxine tablet) (group M) and evening (30 min before dinner) intake of 40 mg pantoprazole tablet (group N). After the initial 6 weeks (period 1), a washout period of 1 week for pantoprazole was given, and then both the groups crossed over for another 6 weeks (period 2). Patients were instructed to continue the same brand of levothyroxine tablet at empty stomach 1-hour before breakfast. Serum TSH was measured at baseline, week 6, and week 13.ResultsData from 30 patients, who completed the study with 100% compliance, were analysed. Mean TSH values of the study participants were significantly higher both at week 6 and week 13 compared to the baseline. Mean baseline serum TSH concentrations for groups M and N were 2.70 (± 1.36), and 2.20 (± 1.06) µlU/mL, respectively. Mean serum TSH concentrations at the end periods 1 and 2 for group M were 3.78 (± 4.29), and 3.76 (± 2.77) while the levels in group N were 3.30 (± 1.90), and 4.53 (± 4.590) µlU/mL, respectively. There was a significant rise in serum TSH concentration across periods 1 and 2 in both the groups (F2, 58 = 3.87, p = 0.03). Within group changes in TSH across periods 1 and 2 were not statistically significant. Similarly difference in TSH between the groups, either at 6 weeks or at 13 weeks, were also not statistically significant.ConclusionsConcomitant use of pantoprazole, even for 6 weeks, leads to significant elevation in serum TSH in levothyroxine-treated patients who are biochemically euthyroid, irrespective of timing of pantoprazole intake. Early morning and night-time administration of pantoprazole have similar effect on TFT in these patients.

Hypothyroidism: The difficulty in attributing symptoms to their underlying cause.

Common symptoms of overt hypothyroidism are non-specific and include fatigue, lethargy, and dry skin. Although the diagnosis is considered to be straightforward, no single symptom can be used to identify patients with overt hypothyroidism, while many patients with subclinical hypothyroidism are asymptomatic. A large population-based study on the spectrum of symptoms in subclinical hypothyroidism showed similar rates of thyroid disease-related symptoms compared with euthyroid subjects, while the TSH concentration had no impact on symptom score. Together, these findings make it challenging to attribute symptoms to their underlying cause. This is also true in the case of unexplained persistent symptoms in levothyroxine-treated patients. Although generally considered a life-long replacement therapy, successful thyroid hormone discontinuation resulting in euthyroidism has been reported in approximately one third of patients. Thus, we overtreat patients with (subclinical) hypothyroidism, highlighting the importance of reliable diagnostic criteria. The diagnostic process, including the implementation of robust TSH and FT4 reference intervals, is especially challenging in specific situations including aging, pregnancy, non-thyroidal illness, and central hypothyroidism. There is a clear need for improved adherence to current guidelines from scientific societies and for willingness to manage symptoms without a clear pathological correlate, especially in the case of mild TSH elevations. This review will highlight recent literature on this topic and offers some practice points.

Free triiodothyronine levels and age influences the metabolic profile and COVID-19 severity parameters in euthyroid and levothyroxine-treated patients.

Metabolic reprogramming is required to fight infections and thyroid hormones are key regulators of metabolism. We have analyzed in hospitalized COVID-19 patients: 40 euthyroid and 39 levothyroxine (LT4)-treated patients in the ward and 29 euthyroid and 9 LT4-treated patients in the intensive care unit (ICU), the baseline characteristics, laboratory data, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), the FT3/FT4 ratio, 11 antiviral cytokines and 74 metabolomic parameters. No evidence for significant differences between euthyroid and LT4-treated patients were found in the biochemical, metabolomic and cytokines parameters analyzed. Only TSH (p=0.009) and ferritin (p=0.031) showed significant differences between euthyroid and LT4-treated patients in the ward, and TSH (p=0.044) and FT4 (p=0.012) in the ICU. Accordingly, severity and mortality were similar in euthyroid and LT4-treated patients. On the other hand, FT3 was negatively related to age (p=0.012), independently of sex and body mass index in hospitalized COVID-19 patients. Patients with low FT3 and older age showed a worse prognosis and higher levels of the COVID-19 severity markers IL-6 and IL-10 than patients with high FT3. IL-6 negatively correlated with FT3 (p=0.023) independently of age, body mass index and sex, whereas IL-10 positively associated with age (p=0.035) independently of FT3, body mass index and sex. A metabolomic cluster of 6 parameters defined low FT3 ward patients. Two parameters, esterified cholesterol (p=4.1x10-4) and small HDL particles (p=6.0x10-5) correlated with FT3 independently of age, body mass index and sex, whereas 3-hydroxybutyrate (p=0.010), acetone (p=0.076), creatinine (p=0.017) and high-density-lipoprotein (HDL) diameter (p=8.3x10-3) were associated to FT3 and also to age, with p-values of 0.030, 0.026, 0.017 and 8.3x10-3, respectively. In conclusion, no significant differences in FT3, cytokines, and metabolomic profile, or in severity and outcome of COVID-19, were found during hospitalization between euthyroid patients and hypothyroid patients treated with LT4. In addition, FT3 and age negatively correlate in COVID-19 patients and parameters that predict poor prognosis were associated with low FT3, and/or with age. A metabolomic cluster indicative of a high ketogenic profile defines non-critical hospitalized patients with low FT3 levels.

B cells from anti-thyroid antibody positive, infertile women show hyper-reactivity to BCR stimulation.

Anti-thyroid antibody (ATA) positivity affects 1 out of 9 women in childbearing age and presents a significant risk for infertility. Emerging evidence indicates that alterations in the B cell receptor induced calcium (Ca2+) signaling could be key in the development of autoimmunity. We aimed to investigate the Ca2+ flux response of B lymphocyte subsets to BCR stimulation in Hashimoto's thyroiditis and related infertility. We collected peripheral blood samples from ATA+, infertile, euthyroid patients (HIE), hypothyroid, ATA+ patients before (H1) and after levothyroxine treatment (H2), and age-matched healthy controls (HC). All B cell subsets of ATA+, infertile, euthyroid patients showed elevated basal Ca2+ level and hyper-responsivity to BCR ligation compared to the other groups, which could reflect altered systemic immune function. The Ca2+ flux of hypothyroid patients was similar to healthy controls. The levothyroxine-treated patients had decreased prevalence of CD25+ B cells and lower basal Ca2+ level compared to pre-treatment. Our results support the role of altered Ca2+ flux of B cells in the early phase of thyroid autoimmunity and infertility.

Use of thyroid hormones in hypothyroid and euthyroid patients: A THESIS questionnaire survey of UK endocrinologists.

Management of hypothyroidism is controversial because of medication cost pressures and scientific uncertainty on how to address treatment dissatisfaction experienced by some patients. The objective was to investigate the experience and preferences of UK endocrinologists in use of thyroid hormones. Web-based survey. UK endocrinologists were invited to participate. Responses to questionnaire. The response rate was 21% (272/1295). While levothyroxine monotherapy is regarded as the treatment of choice for hypothyroidism, 51% of respondents stated that combined treatment with levothyroxine and liothyronine could be considered for levothyroxine-treated patients whose symptoms persist despite normalisation of serum thyroid stimulating hormone (TSH) concentration. However, only 40% are currently prescribing such treatment, and just 23% would consider taking it themselves. A small minority prescribe desiccated thyroid extract, and those most likely to do so are aged over 60 years. Most respondents stated that they have no influence over brand or formulation of levothyroxine dispensed to their patients and expect no major differences in efficacy between different formulations. A total of 9% would prescribe levothyroxine for euthyroid enlarging goitre, and 29% for euthyroid female infertility with high titre thyroid peroxidase antibodies, despite recent trials finding no benefit. UK endocrine practice in management of hypothyroidism is broadly in line with international guidance. However, a minority of respondents would consider thyroid hormone supplementation in euthyroid individuals for female infertility, enlarging goitre, and other indications in which evidence of efficacy is lacking. Willingness to consider prescribing combined levothyroxine and liothyronine, for hypothyroid symptoms which persist despite normalised TSH, has increased in comparison to previous international surveys, despite inconsistent evidence of benefit.

Relatively Lower FT3 Levels Are Associated with Impaired Quality of Life in Levothyroxine-Treated Patients with Hashimoto Thyroiditis.

Objective Patients with Hashimoto thyroiditis (HT) frequently have some complaints despite achieving euthyroidism after levothyroxine (LT4) treatment. This study aimed to investigate the relevant factors affecting the quality of life (QoL) in euthyroid HT patients after LT4 treatment. Methods In this case-control study, 133 participants with HT were included. They were divided into two groups: 64 euthyroid HT subjects (control group) and 69 HT patients were rendered euthyroid by LT4 treatment (well-controlled group). QoL was measured with the Thyroid-Related Patient-Reported Outcome (ThyPRO-39) questionnaire. Results Both study groups were well matched with respect to gender, age, BMI, euthyroidism, and thyroid antibodies (TPOAb and TGAb). Compared with the control group, the well-controlled group had lower FT3 (P < 0.01) levels. Of note, QoL was impaired on all scales in the well-controlled group. Moreover, ThyPRO-39 scores among the well-controlled group were significantly higher (worse) than the control group in all scales. Regarding the composite scale, its score was related to FT3 (r = −0.176, P=0.043) but not to FT4 and TSH levels. Further logistic regression analysis revealed FT3 was significantly associated with elevated composite QoL [0.128 (0.029–0.577), P < 0.01] after adjustment of potential confounders. Conclusion Relatively lower FT3 concentrations, even within the normal reference range, were related to impaired QoL in HT patients treated with LT4. This finding supports the great value of FT3 in clinical decision-making on dose adequacy.

Liothyronine for hypothyroidism: a candidate for disinvestment or in need of further research? A value of information analysis

ObjectiveMedicines with limited evidence of effectiveness are prime candidates for disinvestment. However, investment in further research may be preferable to deimplementation, given that the absence of evidence is not evidence...

Trends in costs and prescribing for liothyronine and levothyroxine in England and wales 2011-2020.

Recent prescribing policies in England and Wales have imposed significant restrictions on liothyronine prescribing in general practice driven by the prohibitive costs and uncertain benefits of liothyronine in the management of hypothyroidism. However, the impact of these policies on liothyronine usage and costs is still unclear. Data were downloaded from the NHS monthly General Practice Prescribing Data in England and from the Comparative Analysis System for Prescribing Audit (CASPA) in Wales for 2011-2020. Trends over the period in amount and costs of levothyroxine and liothyronine prescribing were analysed. The total medication costs per year for England Wales for hypothyroidism rose from £60.8 million to £129.8 million in 2015-16 and have since reduced to £88.4 million. Levothyroxine prescriptions have been growing above the population growth rate at 0.7%/annum in England and 1.1% in Wales. The costs/patient/year for liothyronine rose from £550 to £3000 in 2015-16 and has since fallen to £2500. Use of liothyronine as a percentage of levothyroxine started to fall in 2015-16 at 7%/annum in England and 3% in Wales. Nevertheless, 0.5% of levothyroxine-treated patients continue to receive liothyronine. All Clinical Commission Groups (CCGs) in England continue to have at least one liothyronine prescribing practice and 48.5% of English general practices prescribed liothyronine in 2019-20. In spite of strenuous attempts to limit prescribing of liothyronine in general practice, a significant number of patients continue to receive this therapy. The price differential of liothyronine vs levothyroxine should be examined again in light of the continuing use of liothyronine.

Recent evidence sets therapeutic targets for levothyroxine-treated patients with primary hypothyroidism based on risk of death.

Since the introduction of sensitive assays for serum thyroid-stimulating hormone (TSH) clinicians have advised hypothyroid patients to adjust the dose of levothyroxine (L-T4) in order to achieve a normal serum TSH. A minority of patients are dissatisfied with this treatment strategy and experience symptoms. Some indirect evidence suggests that a normal serum TSH may not necessarily reflect euthyroidism at the tissue level in patients treated with L-T4. Increasingly hypothyroid patients demand higher doses of L-T4 or liothyronine (L-T3) or animal thyroid extract, often purchased online, and titrate the dose against symptoms, although ample evidence suggests that combination treatment (L-T4 with L-T3) is no more effective than L-T4 alone. Community surveys show that up to 53% of treated hypothyroid patients at any time have a serum TSH outside the normal range. The recommendation by guidelines that the upper limit of the normal range for serum TSH should not be exceeded is supported by robust evidence and is generally accepted by clinicians and patients. However, until recently the lower limit of serum TSH for optimal L-T4 replacement has been controversial. New evidence obtained by two independent large population studies over the past two years has shown that mortality of hypothyroid patients treated with levothyroxine is increased when the serum TSH exceeds or is reduced outside the normal reference range. It is estimated that the implementation of a policy of normalising serum TSH in hypothyroid patients will reduce the risk of death of 28.3 million people in the USA and Europe alone.

Different effects of metformin on hypothalamic-pituitary-thyroid axis activity in levothyroxine-treated and levothyroxine-naïve women with non-autoimmune hypothyroidism.

Metformin was found to reduce thyrotrophin levels in subjects with hypothyroidism. This case-control study was aimed at comparing metformin action on hypothalamic-pituitary-thyroid axis activity between levothyroxine-treated and levothyroxine-naïve women with non-autoimmune thyroid hypofunction. The study included two groups of thyroid antibody-negative women with thyrotrophin levels in the range between 4.5 and 10mIU/L and untreated prediabetes, matched for age, body mass index, thyrotrophin levels and glucose homeostasis markers. The first group had been treated for at least 6months with levothyroxine, whereas the second group had not received thyroid hormones. All these women were then managed with metformin (3g daily). Circulating levels of glucose, insulin, glycated haemoglobin, thyrotrophin, total and free thyroid hormones and prolactin were assessed at baseline and 6months later. Thirty-two women (16 in each treatment arm) completed the study. At baseline, both groups differed only in free and total thyroxine levels. Metformin reduced glucose levels and glycated haemoglobin, improved insulin sensitivity and decreased thyrotrophin levels. The impact on insulin sensitivity and thyrotrophin was stronger in women simultaneously treated with levothyroxine than in women not receiving this hormone. In levothyroxine-treated patients, metformin slightly reduced prolactin levels. In both study groups, metformin treatment exerted a neutral effect on freeand total thyroxine and triiodothyronine. The thyrotrophin-lowering effect of metformin correlated with the improvement in insulin sensitivity and in levothyroxine-treated women with the changes in prolactin levels. The obtained results suggest that metformin/levothyroxine combination therapy may be an interesting treatment option in women with non-autoimmune hypothyroidism poorly tolerating high-dose levothyroxine treatment.

Impact of Lifestyle Changes During Ramadan on Thyroid Function Tests in Hypothyroid Patients Taking Levothyroxine

The holy month of Ramadan poses a challenge for levothyroxine-treated patients due to altered eating habits and time restrictions. The aim of this study was to examine the impact of lifestyle changes during Ramadan on thyroid function tests in hypothyroid patients taking levothyroxine in the United Arab Emirates. Retrospective design whereby levothyroxine-treated hypothyroid patients who had thyroid function tests within 3 months pre-Ramadan and within 2 months post-Ramadan were included. We looked at adherence to levothyroxine, eating pattern, and levothyroxine administration in relation to meal times during Ramadan. Pre- and post-Ramadan thyroid function tests and the potential impact of independent variables using a random-intercept mixed effects linear model were examined. A total of 112 patients (89 females) were recruited in the study, with a mean age ± standard error (SE) of 44.70±1.36 years (range, 19.0 to 79.0 years). The mean thyroid-stimulating hormone (TSH) within 3 months before Ramadan was 1.809±0.094 mIU/L (median, 41.5 days; interquartile range &lsqb;IQR], 25.0 to 73.0 days), while the mean TSH within 2 months post-Ramadan was higher at 3.072±0.312 mIU/L (median, 27.5 days; IQR, 14.0 to 42.0 days). Post-Ramadan, 36 out of 112 patients had a plasma TSH outside of the normal reference range. The independent variable outcomes model showed that older patients and males were more likely to have an increased plasma TSH post-Ramadan. There was no relationship between the time of levothyroxine administration and change in TSH level. Levothyroxine-treated hypothyroid patients showed a significant increase in plasma TSH post-Ramadan, amounting to 2.525 standard deviations, with older patients and males more likely to be affected. IQR = interquartile range; T4 = thyroxine; TSH = thyroid-stimulating hormone.

Achieving euthyroidism in hypothyroid patients using levothyroxine improves depressivity and impaired daily life scores using ThyPRO questionnaire

BackgroundLevothyroxine is the recommended treatment to achieve euthyroidism in hypothyroid patients. Achieving euthyroidism was found to improve quality of life in some studies but failed to do so in other studies. Thyroid patient reported outcomes (ThyPRO) is a thyroid-specific health-related quality of life measure. This study aims to assess patient-reported outcomes in levothyroxine-treated hypothyroid patients using ThyPRO.Patients and methodsThe study included 194 patients, divided into two groups: group 1 included 141 hypothyroid patients with benign thyroid disease treated with l-thyroxine, stable in euthyroidism for at least 6 months, and group 2 included 53 patients with euthyroid benign thyroid disease. All patients completed a professionally translated, carefully revised version of the ThyPRO questionnaire into Arabic language. All patients had their Thyroid stimulating hormone (TSH) measured at inclusion. Anti-thyroperoxidase and/or anti-thyroglobulin antibodies were recorded for each patient where available.ResultsThere were no significant differences between the two studied groups regarding age, sex, and TSH. Anti-thyroperoxidase antibodies were significantly higher in treatment group versus group 2, but anti-thyroglobulin antibodies did not differ among the two studied groups. Group 1, l-thyroxine treatment group, showed significantly lower scores in the goiter symptoms, depressivity, impaired daily life, and hyperthyroid symptom scales compared with group 2. No significant differences were found regarding the remaining symptom scales.ConclusionHypothyroid patients of different etiologies rendered euthyroid for at least 6 months compared with euthyroid patients with benign thyroid disease have significantly better depression, goiter, impaired daily life scores using a thyroid-specific questionnaire, the ThyPRO, compared with euthyroid benign thyroid disease.

Hypothyroid Symptoms in Levothyroxine-Treated Patients.

Approximately 15% of patients with hypothyroidism are dissatisfied with their treatment due to persistence of residual symptoms associated with hypothyroidism. The purpose of this study was to compare thyroid symptoms using the hypothyroid symptom scale (HSS) in patients receiving stable thyroid therapy for 6 months to patients without hypothyroidism. The HSS was used to identify the percentage of levothyroxine-treated hypothyroid patients with residual or persistent hypothyroid symptoms. Patients included in the study had hypothyroidism and were receiving a stable/maintenance dose of levothyroxine sodium therapy, unchanged for at least 6 months. A control group of patients were included if they did not have an active prescription for thyroid hormone therapy. The HSS was administered via phone or face-to-face interactions. Patients were asked to score 10 symptoms over the past month on a scale of 0 to 4 (e.g., 0, absence of, to 4, severe symptoms). Results were analyzed using descriptive and inferential statistics. T-tests and chi-squared analysis were used to assess differences in continuous and categorical variables. A total of 68% of the contacted patients responded to the survey. A total of 302 patients were in the intervention group and 273 were in the control group. The mean total HSS scores between groups were significantly higher in the treatment compared to the control group (13.92 ± 10.91 vs.10.07 ± 7.85; P < 0.001). Significantly more patients receiving thyroid hormone therapy experienced residual thyroid symptoms compared to control patients. Attempts should be made to offer alternatives for hypothyroid patients with persistent symptoms.

MON-623 Higher FT4 Results in Levothyroxine-Treated Patients with Normal TSH Compared to Patients without Thyroid Disease

Background: Patients being treated for hypothyroidism with levothyroxine are typically monitored by measuring serum thyroid stimulating hormone (TSH) and if needed, free thyroxine (FT4) concentrations. However, FT4 reference intervals (RIs) established using healthy subjects may not be applicable to patients taking synthetic thyroid hormone. Establishing method-specific FT4 RIs for patients on thyroxine replacement would be valuable. Objective: The objectives were to: 1) Compare central 95th percentile (%) ranges for serum FT4 concentrations in patients with no thyroid disease and normal TSH with ranges in patients prescribed levothyroxine with normal TSH and 2) Determine if there are differences in serum FT4 concentrations between patients taking levothyroxine with normal TSH who have had Hashimoto’s disease, thyroid lobectomy, or thyroidectomy. Methods: One year of TSH and FT4 results reported on the same day for individual patients were extracted from the electronic medical record (10/1/2017-10/1/2018, n=27,534 unique patients). Patients with TSH results outside of the RI (n=7,082), hospitalized patients (n=4,833) and pregnant patients (n=223) were excluded. Results from patients without documented thyroid disease for whom thyroid testing was ordered due to symptoms suggestive of thyroid dysfunction (no thyroid disease (NTD) patients, n=6,774; male=39% and female=61%) and those from patients taking levothyroxine for established thyroid disease (levothyroxine-treated (LT) patients, n=4,294; male=21% and female=79%) were analyzed. The LT group was subsequently divided into patients with: Hashimoto’s disease (n=150), thyroid lobectomy (n=128) and thyroidectomy (n=381). TSH (RI: 0.3-4.2 mIU/L) and FT4 (RI: 0.9-1.7 ng/dL) tests were performed on Roche Cobas 8000 immunoassays. Central 95th percentile (%) was determined using non-parametric analysis. Results: FT4 values for the NTD and LT patients had a median(interquartile range) of 1.2(1.1-1.3) ng/dL and 1.4(1.2-1.6) ng/dL, respectively. The central 95th % for FT4 was 0.9-1.6 ng/dL for NTD and 0.9-2.0 ng/dL for LT patients using the Roche FT4 assay. In LT patients with Hashimoto’s disease, thyroid lobectomy, or thyroidectomy, the median (interquartile range) FT4 values were 1.4(1.2-1.6) ng/dL, 1.5(1.3-1.7) ng/dL, and 1.6(1.4-1.8) ng/dL, respectively. The central 95th % for FT4 in LT patients was 0.8-1.9 ng/dL for Hashimoto’s disease, 0.8-2.3 ng/dL for thyroid lobectomy and 1.0-2.1 ng/dL for thyroidectomy patients. Conclusion: In levothyroxine-treated patients with normal TSH, the FT4 results are shifted higher compared to the population without thyroid disease. Awareness of this finding should prevent inadvertent changes in levothyroxine dose in patients whose TSH is at goal.

Symptomatic Relief is Related to Serum Free Triiodothyronine Concentrations during Follow-up in Levothyroxine-Treated Patients with Differentiated Thyroid Cancer

Patients on levothyroxine-treatment frequently have complaints although TSH is within the reference range. Moreover, FT3 is often low in these patients. The clinical significance of this disequilibrium is studied here. We conducted a retrospective longitudinal study including 319 patients with differentiated thyroid carcinoma on LT4-medication (1.8 [1.6,2.1] µg/kg body weight). Patients were followed at 2309 visits for at median 63 [46,81] months. Association of reported complaints during follow-up with changes in thyroid parameters were analysed using a generalised linear mixed model accounting for within-variability and intra-subject correlations. 26% of patients expressed hypothyroid and 9.7% hyperthyroid complaints at any one visit, rates per visit being 6.5% and 2%, respectively. During follow-up, median changes in spans were as follows, LT4-dose 0.49 [IQR 0.29,0.72] µg/kg, FT3 1.77 [1.25,2.32] pmol/l, FT4 9.80 [6.70,12.8] pmol/l and TSH 1.25 [0.42,2.36] mIU/l. While rates of both hypothyroid or hyperthyroid symptoms were significantly related to all three thyroid parameters, the relationship of hypothyroid symptoms with FT3 extended to a below reference TSH range. Hypothyroid symptom relief was associated with both a T4 dose giving TSH-suppression below the lower reference limit and FT3 elevated further into the upper half of its reference range. In multivariable analysis, relationships between complaints and FT3 concentrations remained significant after adjusting for gender, age and BMI. Residual hypothyroid complaints in LT4-treated patients are specifically related to low FT3 concentrations. This supports an important role of FT3 for clinical decision making on dose adequacy, particularly in symptomatic athyreotic patients.

Pre-admission TSH levels predict long-term mortality in adults treated for hypothyroidism.

Limited data is available regarding the association between pre-admission thyroid function and prognosis of hospitalized patients treated for hypothyroidism. Evaluate an association between thyroid stimulating hormone (TSH) levels and mortality in hospitalized levothyroxine-treated patients. Observational data of patients admitted to medical wards between 2011 and 2013. TSH levels obtained up to 180 days prior to admission were stratified as follows: low (≤0.5 mIU/L), normal (0.5-5 mIU/L), high (>5 mIU/L). Patients aged 60-80 years with available thyroid function tests were matched with controls without hypothyroidism. All-cause mortality up to 66-months following discharge. One thousand and fifty seven patients (73% females, mean (SD) age 71 ± 6 years) were matched with controls without hypothyroidism. Mean hospital stay and in-hospital mortality were not different between groups. Mortality risk at the end-of-follow-up was 41% (438/1057) and 37% (392/1057) for patients with and without hypothyroidism (p < 0.05). TSH levels were classified as follows: low, 84 patients (8%); normal, 667 patients (63%); high, 306 patients (29%). Length of hospitalization and in-hospital mortality were not different between TSH categories. Mortality risk at the end-of-follow-up was 30, 39, and 50% with low, normal and elevated TSH, respectively. Adjusted hazard ratio (95% CI) of mortality at the end-of-follow-up was of 2.2 (1.2-3.8) for high vs. low TSH levels, and 1.4 (1.1-1.9) for high vs. normal TSH levels. In treated hypothyroid adult patients, increased TSH up to 6 months prior to admission is associated with increased mortality. Treatment should aim at achieving euthyroidism to improve survival.

A Deiodinase 2 Polymorphism May Lower Serum T3 and Tissue T3 in Levothyroxine-Treated Patients

Clinical ThyroidologyVol. 29, No. 9 SummariesA Deiodinase 2 Polymorphism May Lower Serum T3 and Tissue T3 in Levothyroxine-Treated PatientsJerome M. HershmanJerome M. HershmanSearch for more papers by this authorPublished Online:1 Sep 2017https://doi.org/10.1089/ct.2017;29.338-340AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited byThyroid Hormone Replacement – a Counterblast to Guidelines*1 December 2017 | Journal of the Royal College of Physicians of Edinburgh, Vol. 47, No. 4 Volume 29Issue 9Sep 2017 InformationCopyright 2017 American Thyroid Association, Inc.To cite this article:Jerome M. Hershman.A Deiodinase 2 Polymorphism May Lower Serum T3 and Tissue T3 in Levothyroxine-Treated Patients.Clinical Thyroidology.Sep 2017.338-340.http://doi.org/10.1089/ct.2017;29.338-340Published in Volume: 29 Issue 9: September 1, 2017PDF download

Long-Term Outcome in Levothyroxine Treated Patients With Subclinical Hypothyroidism and Concomitant Heart Disease.

Subclinical hypothyroidism is a common condition that may lead to impaired cardiac function. This study sought to examine the effects of levothyroxine treatment in patients with subclinical hypothyroidism and heart disease. This was a register-based historical cohort study. The study was composed of Danish primary care patients and hospital outpatients age 18 years and older with established heart disease who were diagnosed with subclinical hypothyroidism in 1997-2011. Patients were stratified according to whether they claimed a subsequent prescription of levothyroxine. Event rates and incidence rate ratios (IRR) were calculated by use of time-dependent multivariable Poisson regression models. Measures included all-cause mortality and major adverse cardiac events (MACEs), defined as cardiovascular death, fatal or nonfatal myocardial infaction and stroke, and all-cause hospital admissions. Of 61 611 patients with a diagnosis of cardiac disease having their first time thyroid function testing, 1192 patients with subclinical hypothyroidism (mean age 73.6 [SD ± 13.3] y, 63.8% female) were included, of whom 136 (11.4%) were treated with levothyroxine. During a median follow-up time of 5.6 y (interquartile range, 6.5 y), 694 (58.2%) patients died. Patients treated with levothyroxine displayed no significantly increased risk of all-cause mortality (adjusted IRR, 1.17; 95% confidence interval [CI], 0.90-1.52), MACE (adjusted IRR, 1.08; 95% CI, 0.80-1.45), or hospital admission (adjusted IRR, 0.94; 95% CI, 0.71-1.24), when compared with patients not treated with levothyroxine. Levothyroxine treatment in patients with subclinical hypothyroidism and heart disease was not associated with a significant benefit nor risk of all-cause mortality, MACE, or hospital admission in this large real-world cohort study.