Normal Thyroid-stimulating Hormone Levels Research Articles

Association between High Normal TSH Levels and Obesity in Women with Anti-Thyroid Autoantibodies (ATAs).

A positive correlation between Thyroid-Stimulating Hormone (TSH) and Body Mass Index (BMI) has been reported in many studies, but data on this topic remain controversial, especially when TSH values are in the normal range. Moreover, few studies have evaluated the co-existence of thyroid autoimmunity. This study investigated the role of thyroid autoimmunity in the interconnection between TSH, BMI, and waist circumference (WC) in euthyroid patients with overweight or obesity. We enrolled 902 patients (213 males; mean age ± SD: 45 ± 14 years; mean BMI ± SD: 35.8 ± 6.5 kg/m2), with normal serum TSH concentration; anti-thyroid autoantibodies (ATAs) were evaluated in 752 patients (186 males). Patients were divided into four BMI classes, based on WHO criteria, and the relationship between BMI, WC, and TSH was evaluated in the whole sample and compared to ATAs positivity, observed in 235 patients (44 males). No significant difference was found between TSH levels in the BMI classes. A statistically significant correlation between TSH and BMI was found only in ATAs-positive females (N = 191, Spearman rho: 0.149; p-value: 0.040). However, this finding was not confirmed when considering the WC. Our study shows a positive correlation only between TSH and BMI in obese women with positive ATAs, suggesting that in these patients, the high normal levels of TSH could be attributed to a mild thyroid failure with a possible worsening obesity-related effect, and both need a careful evaluation.

Time to Normalization and Sustainable Normal Serum Thyrotropin Concentrations in Patients with Hyperthyroidism: Comparison of Methimazole and Radioactive Iodine Treatments

ObjectiveThe aim of this study was to compare the “time to euthyroidism” and “time spent in euthyroidism” following methimazole (MMI) and radioactive iodine (RAI) treatments. MethodsThree hundred fifty-eight patients with hyperthyroidism, 178 who underwent long-term MMI treatment and 180 patients who underwent RAI treatment, were analyzed. The time to normalization of increased serum values of free thyroxine and triiodothyronine and suppressed serum thyroid-stimulating hormone (TSH) values as well as the percentage of time that the thyroid hormone levels remained within normal ranges during a mean follow-up time of 12 years were compared. ResultsThe mean time to euthyroidism was 4.59 ± 2.63 months (range, 2-16 months) in the MMI group and 15.39 ± 12.11 months (range, 2-61 months) in the RAI group (P < .001). During follow-up, the percentage of time spent in euthyroidism was 94.5% ± 7.3% and 82.5% + 11.0% in the MMI and RAI groups, respectively (P < .001). Serum TSH values above and below the normal range were observed in 5.3% and 0.2% of patients, respectively, in the MMI group and 9.8% and 7.7% of patients, respectively, in the RAI group (P < .001). The time to euthyroidism and the percentage of time spent in euthyroidism in 40 RAI-treated patients with euthyroidism were similar to those in the MMI group and significantly shorter than those in the RAI-treated hypothyroid and relapsed subgroups. In patients who continued MMI therapy for >10 years, the percentage of time spent in euthyroidism was >99%. ConclusionIn our cohort of selected patients, MMI therapy was accompanied by faster achievement of the euthyroid state and more sustained normal serum TSH levels during long-term follow-up compared with RAI therapy.

Thyroid hormone resistance syndrome due to a novel heterozygous mutation and concomitant Hashimoto's Thyroiditis: A pedigree report.

Thyroid hormone resistance syndrome (THRS) is a rare disease characterized by reduced sensitivity to thyroid hormones. Mutations in the thyroid hormone receptor beta (THRB) gene are considered as contributing to the pathogenesis. This report describes a Chinese pedigree with THRS and Hashimoto’s thyroiditis (HT) due to novel point mutation in the 11th exon of the THRB gene (c. 1378 G > A). The proband complained of goitre with increased thyroid hormone and normal thyroid stimulating hormone levels. Gene sequencing was performed to confirm the diagnosis. HT was also diagnosed based on positive thyroid autoantibodies and diffuse, grid-like changes in the thyroid on ultrasound examination. Additionally, a comprehensive examination of the proband’s pedigree was conducted. The patient’s father exhibited the same gene mutation site and was diagnosed with THRS and HT. No mutation site was detected in three patients with HT only and three healthy volunteers. Thus, gene sequencing should be considered the gold standard for diagnosing THRS. Furthermore, treatment should be individualized to control the patient’s symptoms rather than normalizing thyroid hormone levels. Further studies that determine the relationship between THRS and TH are warranted.

How to approach clinically discordant FT4 results when changing testing platforms: real-world evidence

PurposeMeasurement of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is important for assessing thyroid dysfunction. After changing assay manufacturer, high FT4 versus TSH levels were reported at Ente Ospedaliero Cantonale (EOC; Bellinzona, Switzerland).MethodsExploratory analysis used existing TSH and FT4 measurements taken at EOC during routine clinical practice (February 2018–April 2020) using Elecsys® TSH and Elecsys FT4 III immunoassays on cobas® 6000 and cobas 8000 analyzers (Roche Diagnostics). Reference intervals (RIs) were estimated using both direct and indirect (refineR algorithm) methods.ResultsIn samples with normal TSH levels, 90.9% of FT4 measurements were within the normal range provided by Roche (12–22 pmol/L). For FT4 measurements, confidence intervals (CIs) for the lower end of the RI obtained using direct and indirect methods were lower than estimated values in the method sheet; the estimated value of the upper end of the RI (UEoRI) in the method sheet was within the CI for the UEoRI using the direct method but not the indirect method. CIs for the direct and indirect methods overlapped at both ends of the RI. The most common cause of increased FT4 with normal TSH was identified in a subset of patients as use of thyroxine therapy (72.6%).ConclusionsIt is important to verify RIs for FT4 in the laboratory population when changing testing platforms; indirect methods may constitute a convenient tool for this. Applying specific RIs for selected subpopulations should be considered to avoid misinterpretations and inappropriate clinical actions.

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.

Normalization of serum TSH doesn’t represent true euthyroidism for patients on levothyroxine treatment

To evaluate whether normalisation of serum thyroid-stimulating hormonelevels with levothyroxine is related with metabolic parameters and psychologic wellbeing. The observational, case-control study was conducted from to May to July 2019 in the outpatient thyroid clinics of Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey, and comprised of hypothyroid patients in the euthyroid state with levothyroxine treatment and euthyroid controls. Psychological wellbeing was assessed using the General Health Questionnaire-12, and metabolic parameters with lipid levels and body composition were analysed for both the groups. Data was analysed using SPSS 25. Of the 159 subjects, 110(69%) were cases with a mean age of 50.1±11.7 years, and 49(31%) were controls with a mean age of 47.3±15.2 years. There was no significant difference related to thyroid-stimulating hormone levels between the groups (p=0.191). Free throxine levels were significantly higher in the cases, while free triiodothyroinine levels were higher in the controls (p<0.001). Total cholesterol and triglycerides levels were significantly higher in the cases than the controls (p<0.05). The cases had lower basal metabolic rate and fat free mass than the controls, but the difference was not significant (p>0.05). The cases scored higher in terms of wellbeing than the controls, but the difference was not significant (p>0.05). Thyroid hormone replacement needs to be adjusted to provide a satisfactory treatment for hypothyroid patients with normal thyroid-stimulating hormone levels who remain clinically and biochemically asymptomatic. In symptomatic patients, peripheral parameters of hypothyroidism, such as lipid levels, physiological symptoms and quality of life, might be useful in determining the levothyroxine dose and bringing the thyroid-stimulating hormone level within the normal range.

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.

The effect of L-thyroxine replacement on blood pressure and heart rate in children with hypothyroidism

Introduction Thyroid hormones have direct and indirect cellular effects on the cardiovascular system. Chronic administration of L-thyroxine (LT4) to children with hypothyroidism may affect cardiovascular dynamics. Aim This cross-sectional observational study measured the blood pressure (BP) and heart rate (HR) of 25 randomly selected children with hypothyroidism in relation to their serum-free thyroxine (FT4), thyroid-stimulating hormone (TSH) levels, and thyroxine dose μg/kg. Patients and methods In total, 25 randomly selected children with a mean age 9.6±4.5 years with the diagnosis of congenital or acquired hypothyroidism. They were on l-thyroxine therapy to keep serum-FT4 and TSH in the normal range for age. Their BP and HR (average of three readings), weight, height, dose of thyroxine, and their serum level of TSH and free T4 levels within 2 weeks before the clinic visit were recorded. The Z scores of the height, height standard deviation score (HSDS), body mass index standard deviation score (BMISDS), systolic (SBPSDS), and diastolic blood pressure standard deviation score (DBPSDS) were calculated (as per the 2004 guideline report on hypertension from the National Heart and Lung Institute), and HR [as per the Monitoring and Diagnosis Group at Oxford (MADOX) systematic review of 2011] was calculated for age and sex. Results The authors studied 25 children with hypothyroidism. Their dose of thyroxine was 2.11±0.7 μg/kg. Their mean serum-FT4 levels were 15.1±2.5 μg/l and TSH level was 3.9±2.8 mIU/ml. Their HtSDS (−0.57±1.4) and BMISDS (0.63±1.63) were within normal. All had normal diastolic blood pressure readings (within 2 standard deviations of the mean for age and sex). Two of the individuals had systolic BPs greater than 2SDS above the mean for age and sex, with normal BMISDS. Both had normal FT4 and TSH levels. One patient had tachycardia [HR=146/min (Z-score +3.2 for age)]. His FT4 and TSH levels were normal. There was a positive correlation between thyroxine dose/kg and serum level of FT4 (r=0.52), HR (r=0.56), SBPSDS (r=0.38), and DBPSDS (r=0.24). There was no significant correlation between the HtSDS on the one hand and FT4, TSH, or thyroxine dose on the other hand. The BMISDS was negatively correlated with TSH level (r=−0.4). Conclusion In this study on hypothyroid children on l-thyroxine therapy, 2 had high systolic BP and one had tachycardia. The significant correlation between the thyroxine dose, FT4 level, and BP and HR should alert the pediatrician to monitor BP and HR closely in relation to TSH and FT4 levels of these patients.

Effects of subclinical hypothyroidism on maternal and obstetric outcomes during pregnancy

Objectives: Subclinical hypothyroidism has been defined as normal free thyroxine (FT4) with elevated thyroid stimulating hormone (TSH) levels. The aim of this study is to examine the relationship between the first trimester subclinical hypothyroidism with adverse obstetric outcomes in pregnant women. Methods: This retrospective cohort study was conducted by examining the pregnant women who applied to the Gynecology Department of Okmeydani Training and Research Hospital at their 6th to 14th gestational weeks and had antenatal follow-ups between February 1, 2017 and December 31, 2020. Results: Fetal weight (OR: 1; 95% CI, 0.99-1.03, p = 0.023), gestational age at delivery (OR: 0.91; 95% CI, 0.83-0.99, p = 0.022), and preterm delivery (OR: 0.79; 95% CI, 0.48-1.06, p = 0.005) were found to be statistically significant parameters in univariate risk analyses performed in the group whith patients normal T4 levels and TSH levels ≥ 2.5-4 mIU/L. Lower gestational age at delivery (OR: 1; 95% CI, 0.93-1.88, p = 0.016), and higher preterm delivery rates (OR: 0.99; 95% CI, 0.96-1.01, p = 0.003) were found to be statistically significant in multivariate risk analysis. Conclusions: The rate of preterm delivery was statistically higher, and fetal weight and week of delivery were significantly lower in the group of pregnant women diagnosed with SCH having TSH values between 2.5 and 4 mIU/L.

Hysterosalpingography with Oil-Soluble Contrast Medium Does Not Increase Newborn Hypothyroidism.

Objective Hysterosalpingography (HSG) with oil-soluble contrast medium (OSCM) improves pregnancy rates in women with idiopathic infertility. However, OSCM has high iodine content and slow clearance resulting in potential iodine excess. If pregnancy occurs, this could impact fetal thyroid gland development and function. We aim to determine the effect of a preconceptional OSCM HSG on the thyroid function of the neonate. Design and Patients. This was a retrospective analysis of newborn TSH data for a cohort of neonates conceived within six months of an OSCM HSG in the Auckland region, New Zealand, from the years 2000 to 2019. Thyroid-stimulating hormone (TSH) levels of these newborns were obtained from newborn screening, which is routinely performed for all children at 48–72 hours of life. The primary outcome was the incidence of permanent or transient congenital hypothyroidism in this cohort. Results Of 146 babies included, all had normal TSH levels with values ranging from 1 to 7 mIU/L on the whole blood analysis of a capillary heel sample using the Perkin–Elmer AutoDelfia assay. Conception during the first 3 cycles following an OSCM HSG was 76%; however, TSH levels in this group were not higher than those conceived in later cycles. Conclusion Preconceptional OSCM HSG did not increase the risk of congenital hypothyroidism in the New Zealand scenario.

Suture Granuloma and Surgical Clips as a Mimic of Thyroid Cancer Recurrence

A 59-year-old White man with pT3N0M0 multifocal papillary thyroid cancer, status post total thyroidectomy followed by radioactive iodine treatment (81.3 mCi), without evidence of recurrence for 6 years, presented with a 3-month history of a palpable neck mass. Physical examination revealed bilateral palpable neck nodules. Previous laboratory values demonstrated normal thyroid-stimulating hormone (TSH) and undetectable thyroglobulin level (TSH, 0.87 μU/mL; thyroglobulin, <0.1 ng/mL). Neck ultrasound (Fig. 1) and computed tomography (CT) scan (not shown) revealed bilateral neck masses interpreted as concerning for thyroid cancer recurrence.

Thyroid Function and Low Free Triiodothyronine in Chinese Patients With Autoimmune Encephalitis.

Background and ObjectivesLow free triiodothyronine (FT3) is usually associated with worse functional outcome in critical illness; however, the information on thyroid dysfunction and autoimmune encephalitis (AE) is limited. This study aims to evaluate the clinical prognostic value of thyroid function and low-T3 syndrome in patients with multiple subtypes of AE. MethodsIn this retrospective study, we identified the hospital records of 319 candidate patients with AE admitted between January 2016 and December 2020. We then extracted the clinical features and outcomes. Modified Rankin scale (mRS) scores were used to evaluate the patients’ neurological function. The serum levels of FT3, free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured upon admission. Normal thyroid stimulating hormone level with FT3 below the lower limit of the reference interval (2.63 nmol/L) was defined as low-T3 syndrome.ResultsA total of 237 AE cases remained after screening. Among these, 57.81% (137/237) were men and the average age at onset was 41 y (interquartile range, 12–61 y). We found that 83.54% (198/237) of the patients had a good prognosis, and 16.46% (39/237) had a poor prognosis. Abnormal thyroid function was observed in 30.80% of these patients, with a relatively greater prevalence in the group with a poor prognosis (p < 0.001). The serum FT3 levels in the poor-prognosis group were significantly lower than those in the good-prognosis group (p < 0.001). Low-T3 syndrome occurred in 15.19% of AE cases and was more frequent in patients with poor prognosis (p < 0.001).ConclusionsAbnormal thyroid function in AE is frequent, and serum FT3 levels in patients with poor prognosis are significantly lower than in those with good prognosis. Low-T3 syndrome could be a potential candidate for predicting the prognosis of AE following future research.

Divergent prognostic effects of pre-existing and treatment-emergent thyroid dysfunction in patients treated with immune checkpoint inhibitors

BackgroundThyroid dysfunction is among the most common autoimmune diseases and immune checkpoint inhibitor (ICI)-induced immune-related adverse events (irAE). We determined the association between longitudinal thyroid function and clinical outcomes in patients treated with ICI.MethodsWe identified all patients treated with ICI at UT Southwestern Medical Center from January 1, 2011, through December 31, 2020. We defined normal thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels according to institutional reference range. We defined clinical thyroid dysfunction using established criteria incorporating labs and treatment. We determined the association between thyroid function and overall survival (OS) using Kaplan–Meier curves, log-rank tests, and multivariate Cox proportional hazards model.ResultsA total of 1781 patients were included in analyses, of whom 381 (21%) had abnormal baseline TSH. Patients with abnormal baseline TSH were more likely to be female, have kidney cancer, and initiate levothyroxine after ICI initiation (all P < 0.001). Patients with abnormal baseline TSH had inferior OS (median 16 vs 27 months; P < 0.001). Among patients with normal baseline TSH, those who had abnormal TSH after ICI initiation had improved OS (median 41 vs 22 months; P < 0.001). In a multivariate Cox model, abnormal baseline TSH was associated with worse OS (HR 1.62; 95% CI, 1.30–2.02; P < 0.001), while initiation of levothyroxine after ICI initiation was associated with improved OS (HR 0.62; 95% CI, 0.44–0.88; P = 0.008).ConclusionsICI-induced thyroid dysfunction is associated with improved survival, although abnormal TSH prior to ICI initiation is associated with inferior survival.PrecisThyroid abnormalities occur commonly in the general population and as immunotherapy toxicities. We found that immunotherapy-induced thyroid dysfunction is associated with better survival, but pre-existing thyroid abnormalities convey worse outcomes.

Clearing Up the Fog: Insights Into Brain Fog Experienced by Patients With Hypothyroidism

Between 4.6% and 9.5% of the population in the United States is affected by hypothyroidism.1,2 The standard of care for the treatment of hypothyroidism is daily thyroid hormone replacement at doses that render the patient euthyroid. Levothyroxine, the most common form of thyroid hormone replacement, is one of the most frequently prescribed medications in the United States.3,4 However, there remains a subset of patients on thyroid hormone replacement who exhibit persistent nonspecific symptoms, sometimes even in the setting of a normal serum thyroid-stimulating hormone level.

Efficacy of Ginger Supplementation in Relieving Persistent Hypothyroid Symptoms in Patients with Controlled Primary Hypothyroidism: A Pilot Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Primary hypothyroidism is a common disease. Some patients have persistent symptoms despite normal serum thyroid-stimulating hormone (TSH) levels. Ginger is reported to be beneficial in relieving similar symptoms. Our aim was to evaluate the efficacy of ginger supplementation in relieving persistent symptoms in these patients. In this randomized, double-blind, placebo-controlled clinical trial, 60 hypothyroid patients aged 20–60 years with normal serum TSH concentrations were randomly allocated to two equal parallel study groups of ginger (500 mg twice a day) or placebo for 30 days. Hypothyroid symptoms were evaluated as the primary outcome using the Thyroid Symptom Rating Questionnaire (ThySRQ) before and after the intervention. Anthropometric measures and laboratory indices including TSH, triglyceride (TG), total cholesterol (TChol), and fasting blood sugar (FBS) were considered as secondary outcomes. A significant lower mean total ThySRQ score (8.63 ± 5.47 vs. 15.76 ± 6.09, P < 0.001) was observed in the ginger group compared to the control group. Ginger led to significant improvements in the mean scores of the weight gain, cold intolerance, constipation, dry skin, appetite, memory loss, concentration disturbance, and feeling giddy or dizzy domains (P < 0.001). However, no significant improvements were observed in hair loss, nail fragility, hearing, hoarseness, speech, and depression or feeling down (P > 0.05). Ginger supplementation also led to a significant decrease in body weight, body mass index, waist circumference, serum TSH, FBS, TG, and TChol levels compared to the placebo. In summary according to preliminary results of this study, ginger supplementation can help relieve persistent hypothyroid symptoms. Also, it may have beneficial effects in terms of weight reduction and regulation of the FBS and lipid profile in hypothyroid patients.

Association between levels of thyroid-stimulating hormone and prognosis of patients admitted to intensive care units: an analysis using the MIMIC-III

To explore the association between levels of thyroid-stimulating hormone (TSH) on admission and prognosis of patients admitted to intensive care unit (ICU). The data were collected from patients who were admitted to the ICU of the Beth Israel Deaconess Medical Center in the United States from 2001 to 2012 with available TSH test records within 24 hours after the ICU admission via the Medical Information Mart for Intensive Care-III v1.4 (MIMIC-III v1.4). Information including gender, age, ethnicity, type of admission, mechanical ventilation (MV) or renal replacement therapy (RRT) received on admission, comorbidities, and TSH test records within 24 hours after the ICU admission were collected. The sequential organ failure assessment (SOFA) score, simplified acute physiology score II (SAPS II) and the comorbidities index Elixhauser (SID30) score were calculated according to the parameters. The primary outcome was hospital mortality. Differences in baseline characteristics and prognosis were examined between patients with normal TSH levels and abnormal TSH levels which was determined according to a dichotomous variable provided by the data. Multivariable Logistic regression was used to analyze the association between TSH levels and prognosis after adjusting for confounding factors. A sensitivity analysis was conducted which categorized the study population as three groups (i.e., decreased, normal, and elevated TSH levels) using the range of 0.30-3.00 mU/L as the normal range of TSH. A total of 3 425 ICU patients were enrolled in the study, of which 2 692 (78.60%) were with normal TSH and 733 (21.40%) were with abnormal TSH. There was no statistically significant difference in gender, age, ethnicity, type of admission and the ratio of MV between the normal TSH and abnormal TSH groups. Compared with normal TSH group, the patients in abnormal TSH had a higher SOFA, SAPS II and SID30 scores as well as the ratio of RRT [SOFA score: 4 (2, 7) vs. 4 (2, 6), SAPS II score: 38.02±13.76 vs. 36.53±13.75, SID30 score: 11 (4, 22) vs. 11 (0, 20), RRT ratio: 5.32% (39/733) vs. 3.49% (94/2 692), all P < 0.05]. The hospital mortality of patients in normal TSH was significantly higher than that of those in abnormal TSH [9.82% (72/733) vs. 5.94% (160/2 692), P < 0.01]. After adjusting for confounding factors, abnormal TSH was significantly associated with hospital mortality [odds ratio (OR) = 1.71, 95% confidence interval (95%CI) was 1.24-2.35, P = 0.001]. In the sensitivity analysis in which the range of 0.30-3.00 mU/L was used as the normal range of TSH, compared with normal TSH, decreased TSH (OR = 2.36, 95%CI was 1.40-3.97, P = 0.001) and elevated TSH (OR = 1.44, 95%CI was 1.05-1.98, P = 0.023) were both significantly associated with increased hospital mortality. An abnormal level of TSH within 24 hours after admitted to ICU is an independent risk factor for hospital mortality among ICU patients.

Autoimmune thyroid disease and thyroid function test fluctuations in patients with resistance to thyroid hormone.

Resistance to thyroid hormone beta (RTHβ) is an inherited syndrome caused by mutations in the thyroid hormone receptor β (THRB) gene. Patients with RTHβ typically have elevated thyroid hormone levels with non-suppressed serum thyroid-stimulating hormone (TSH). We aimed to elucidate the clinical, laboratory, and imaging findings of RTHβ patients and further to explore their association with THRB gene mutations. We retrospectively reviewed the clinical charts and compared the clinical findings of 68 RTHβ patients (45 probands and 23 relatives) and 30 unaffected relatives in Kuma Hospital. Genetic testing revealed 35 heterozygous THRB gene mutations. Among all RTHβ patients, autoimmune thyroid disease (AITD) was detected in 42.1% of men and 40.9% of women, showing that the prevalence of AITD in affected males was significantly higher than in unaffected relatives (P = 0.019). During the follow-up of 44 patients, 13 patients (29.5%; 8 (42.1%) with AITD and 5 (20%) without AITD) temporarily showed thyroid function test results inconsistent with RTHβ. Two patients with the R383H mutation, which has little dominant-negative effect, temporarily showed normal thyroid hormone and TSH levels without AITD. The frequency of AITD in male RTHβ patients was significantly higher compared to unaffected relatives. More than 20% of RTHβ patients temporarily showed laboratory findings atypical of RTHβ during their follow-up, and patients with AITD and specific THRB mutations were prone to display such findings. Therefore, genetic testing should be performed even for patients with fluctuations in thyroid function test results to avoid misdiagnosis and inappropriate treatment.

Reduced pituitary size in subjects with mutations in the THRB gene and thyroid hormone resistance.

BackgroundThyroid hormone action is mediated by two forms of thyroid hormone receptors (α, β) with differential tissue distribution. Thyroid hormone receptor β (TRβ) mutations lead to resistance to thyroid hormone action in tissues predominantly expressing the β form of the receptor (pituitary, liver). This study seeks to identify the effects of mutant TRβ on pituitary size.MethodsHigh-resolution 3D T1-weighted magnetic resonance images were acquired in 19 patients with RTHβ in comparison to 19 healthy matched controls. Volumetric measurements of the pituitary gland were performed independently and blinded by four different raters (two neuroradiologists, one neurologist, one neuroscientist).ResultsPatients with mutant TRβ (resistance to thyroid hormone β, RTHβ) showed elevated free tri-iodothyronine/thyroxine levels with normal thyroid-stimulating hormone levels, whereas healthy controls showed normal thyroid hormone levels. Imaging revealed smaller pituitary size in RTHβ patients in comparison to healthy controls (F(1,35) = 7.05, P = 0.012, partial η2 = 0.17).ConclusionRTHβ subjects have impaired sensitivity to thyroid hormones, along with decreased size of the pituitary gland.

Specific impact of cardiovascular risk factors on coronary microcirculation in patients with subclinical hypothyroidism.

BackgroundAlthough thyroid hormones have significant effect on cardiovascular system, the impact of subtle thyroid dysfunction such as subclinical hypothyroidism (SCH) remains to be determined. We investigated coronary flow reserve (CFR) in patients with subclinical hypothyroidism.MethodsThirty two subjects with SCH and eighteen control subjects with normal serum thyroid hormones and thyroid-stimulating hormone (TSH) levels were included in the study. TSH, free thyroxine, free triiodothyronine, glucose, insulin, HbA1c, cholesterol, triglyceride and plasma levels of C-reactive protein were measured. Coronary diastolic peak flow velocities in left anterior descending coronary artery were measured at baseline and after adenosine infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocity.ResultsCFR values were not significantly different between the two groups (SCH 2.76±0.35 vs controls 2.76±0.42). There was a significant correlation of CFR with waist to hip ratio, hypertension, smoking habits, markers of glucose status (glucose level, HbA1c, insulin level, HOMA IR), cholesterol, LDL-cholesterol and triglyceride levels in SCH group, whereas only cholesterol level showed significant correlation with CFR in controls. There was no correlation between CFR and thyroid hormones.ConclusionsWe concluded that there is a different impact of cardiovascular risk factors on CFR in SCH patients compared to healthy control and that these two groups behave differently in the same circumstances under the same risk factors. The basis for this difference could be that the altered thyroid axis "set point" changes the sensitivity of the microvasculature in patients with SCH to known risk factors.

Abstract 10993: Prognostic Value of Low T 3 Syndrome in Patients with Acute Decompensated Heart Failure in Osaka Prefectural Acute Heart Failure Registry (OPAR)

Backgrounds: It is widely recognized that thyroid dysfunction is a potential cause of heart failure (HF). In HF, one of the alterations of thyroid functions is referred to as low T 3 syndrome marked by a reduction in serum free triiodothyronine (T 3 ) with normal levels of thyroid-stimulating hormone (TSH). However, there is little information available about the association between low T 3 syndrome and future cardiac events in patients with acute decompensated heart failure (ADHF), relating to left ventricular ejection fraction (LVEF). Methods and Results: We studied 565 patients admitted for ADHF with survival discharge in our prospective cohort study. Laboratory data including free T 3 , thyroxine and TSH were obtained at discharge. Among the patients with euthyroid (0.35 μU/mL &lt;TSH &lt;4.94 μU/mL, n=438), there was 62 patients who were diagnoses as low T 3 syndrome (free T 3 ≦1.68 pg/mL). The primary end point of this study was all-cause death (ACD). During a mean follow up period of 2.9±1.4 years, 121 patients died. Study subjects were stratified into two LVEF subgroup as follows; 239 patients had LVEF&lt;50% (HFrEF), and 199 patients had LVEF≧50% (HFpEF). While 68 HFrEF parients died, 53 HFpEF patients died. Kaplan-Meier curve analysis revealed that patients with the low free T 3 group had the greater risk of ACD than those with the normal free T 3 group in both LVEF subgroup (log-rank p=0.0233 in HFrEF and p=0.0265 in HFpEF). Multivariate Cox analysis showed that free T 3 was significantly associated with ACD after multivariable adjustment for major confounders, such as age, sex, systolic blood pressure and plasma brain natriuretic peptide level in both LVEF subgroup (p=0.0039 in HFrEF, p=0.0487 in HFpEF). Conclusion: Low T 3 syndrome was significantly associated with poor outcome in ADHF patients with both HFrEF and HFpEF.