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Automated Requests for Thyroid-Stimulating Hormone and Ferretin Tests in Young Primary Care Patients with Anorexia as an Intervention to Improve Detection of Underlying Conditions.
Salinas, M, López-Garrigós, M, Flores, E, Leiva-Salinas, C
Laboratory medicine. 2019;(3):268-272
Abstract
OBJECTIVE To improve clinical laboratory contribution to the treatment of primary care patients with anorexia through automated computerized strategies. METHODS We recorded the number of laboratory requests due to anorexia; the demographic data, laboratory values, and presence of pathological values for the applicable patients. In a prospective study, the laboratory information management system (LIMS) automatically added thyroid-stimulating hormone (TSH) and/or ferritin testing when it was not requested by general practitioners for all primary care patients with anorexia who were younger than 16 years. RESULTS A total of 3562 patients underwent laboratory testing due to anorexia, of whom 47% were younger than 16 years. The tests in which the results most frequently were abnormal were hemoglobin, ferritin, and TSH. TSH results were abnormal in 20% of patients younger than 16 years. Through the intervention, we detected 3 low ferritin values and 7 cases of pathological TSH levels. CONCLUSIONS The LIMS required TSH and ferritin testing in young patients even when not requested, potentially avoiding the adverse effects of iron deficiency and thyroid disorders on neurological development and cognition in those patients.
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Slightly elevated thyrotropin levels in pregnancy in our clinical practice.
Alcázar Lázaro, V, López Del Val, T, García Lacalle, C, Torres Moreno, B, Castillo Carvajal, G, Vergara Fernández, L, Benfdil, L, Torre Carrera, C, Orizales Lago, MC, Ramos Zuñiga, L
Endocrinologia, diabetes y nutricion. 2019;(10):620-627
Abstract
OBJECTIVE The aim of this study was to assess the incidence of obstetric and neonatal complications in pregnant women with "normal" thyroid-stimulating hormone (TSH) levels in the first trimester (group A) and to compare them with those with "slightly elevated" TSH (SET) levels treated with levothyroxine (group B2) or not treated (group B1). METHODS A total of 2375 women who had been performed laboratory tests in their first trimester of pregnancy were detected at our hospital between April 2015 and August 2017. Of these, 469 patients with SET were prospectively detected and randomized to groups B1 (227) and B2 (242). They were monitored prospectively until 6 months after delivery. Data of the control group (n=1906, group A) were retrospectively reviewed. A total of 1745 women were analyzed. Variables assessed included demographic and clinical characteristics and complications of pregnancy and delivery. RESULTS A, B1, and B2 had similar clinical characteristics. There were no statistically significant differences in complications between the three groups during pregnancy, except in that natural deliveries were more common in group A as compared to group B1 (76.8% vs. 68.7%, p 0.017) and group B2 (66.3%), p<0.002). There were more induced deliveries in groups B1 (35.8%), and B2 (36.2%) than in group A (18.4%), p<0.01. Although the recommended TSH level was achieved in the second and third trimesters, no benefit could be found of treatment of SET. CONCLUSION Although there were less natural deliveries and more induced deliveries in patients with SET, treatment with levothyroxine could not reverse this situation, despite achievement of levels considered appropriate in the second and third trimester.
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Association of Thyroid Function Genetic Predictors With Atrial Fibrillation: A Phenome-Wide Association Study and Inverse-Variance Weighted Average Meta-analysis.
Salem, JE, Shoemaker, MB, Bastarache, L, Shaffer, CM, Glazer, AM, Kroncke, B, Wells, QS, Shi, M, Straub, P, Jarvik, GP, et al
JAMA cardiology. 2019;(2):136-143
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Abstract
IMPORTANCE Thyroid hormone levels are tightly regulated through feedback inhibition by thyrotropin, produced by the pituitary gland. Hyperthyroidism is overwhelmingly due to thyroid disorders and is well recognized to contribute to a wide spectrum of cardiovascular morbidity, particularly the increasingly common arrhythmia atrial fibrillation (AF). OBJECTIVE To determine the association between genetically determined thyrotropin levels and AF. DESIGN, SETTING, AND PARTICIPANTS This phenome-wide association study scanned 1318 phenotypes associated with a polygenic predictor of thyrotropin levels identified by a previously published genome-wide association study that included participants of European ancestry. North American individuals of European ancestry with longitudinal electronic health records were analyzed from May 2008 to November 2016. Analysis began March 2018. MAIN OUTCOMES AND MEASURES Clinical diagnoses associated with a polygenic predictor of thyrotropin levels. EXPOSURES Genetically determined thyrotropin levels. RESULTS Of 37 154 individuals, 19 330 (52%) were men. The thyrotropin polygenic predictor was positively associated with hypothyroidism (odds ratio [OR], 1.10; 95% CI, 1.07-1.14; P = 5 × 10-11) and inversely associated with diagnoses related to hyperthyroidism (OR, 0.64; 95% CI, 0.54-0.74; P = 2 × 10-8 for toxic multinodular goiter). Among nonthyroid associations, the top association was AF/flutter (OR, 0.93; 95% CI, 0.9-0.95; P = 9 × 10-7). When the analyses were repeated excluding 9801 individuals with any diagnoses of a thyroid-related disease, the AF association persisted (OR, 0.91; 95% CI, 0.88-0.95; P = 2.9 × 10-6). To replicate this association, we conducted an inverse-variance weighted average meta-analysis using AF single-nucleotide variant weights from a genome-wide association study of 17 931 AF cases and 115 142 controls. As in the discovery analyses, each SD increase in predicted thyrotropin was associated with a decreased risk of AF (OR, 0.86; 95% CI, 0.79-0.93; P = 4.7 × 10-4). In a set of AF cases (n = 745) and controls (n = 1680) older than 55 years, directly measured thyrotropin levels that fell within the normal range were inversely associated with AF risk (OR, 0.91; 95% CI, 0.83-0.99; P = .04). CONCLUSIONS AND RELEVANCE This study suggests a role for genetically determined variation in thyroid function within a physiologically accepted normal range as a risk factor for AF. The clinical decision to treat subclinical thyroid disease should incorporate the risk for AF as antithyroid medications to treat hyperthyroidism may reduce AF risk and thyroid hormone replacement for hypothyroidism may increase AF risk.
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Thyroid-stimulating hormone levels in the normal range and incident type 2 diabetes mellitus.
de Vries, TI, Kappelle, LJ, van der Graaf, Y, de Valk, HW, de Borst, GJ, Nathoe, HM, Visseren, FLJ, Westerink, J, ,
Acta diabetologica. 2019;(4):431-440
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AIM: To evaluate the relationship between thyroid-stimulating hormone (TSH) levels within the normal range and the risk of type 2 diabetes mellitus (T2DM) in a cohort of patients at high cardiovascular risk, and to perform a systematic review and meta-analysis of previous studies. METHODS We included 5542 patients without T2DM from the prospective Secondary Manifestations of ARTerial disease study with TSH levels between 0.35 and 5.0 mIU/L without anti-thyroid medication or thyroid-hormone replacement therapy. Cox regression was used to investigate the relationship between baseline plasma TSH levels and incident T2DM. MEDLINE, EMBASE, and Cochrane were searched for prospective cohorts assessing TSH and incident T2DM. Hazard ratios (HR) from included prospective cohort studies were pooled using a random-effects model. RESULTS In patients at high cardiovascular risk, higher plasma TSH levels in the normal range were not associated [HR 1.07 per mIU/L increase in TSH (95% confidence interval (95% CI) 0.95-1.22)] with an increased risk of T2DM, adjusted for age, sex, smoking, total and HDL cholesterol, and triglycerides. In the meta-analysis involving three prospective cohort studies, including the present study, including 29,791 participants with 1930 incident events, there was no relation between plasma TSH levels in the normal range and incident T2DM [pooled HR 1.06 (95% CI 0.99-1.14)]. CONCLUSION There is no apparent relation between plasma TSH levels in the normal range and incident T2DM in patients at high cardiovascular risk.
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Effect of metformin on thyroid function tests in patients with subclinical hypothyroidism: an open-label randomised controlled trial.
Palui, R, Sahoo, J, Kamalanathan, S, Kar, SS, Sridharan, K, Durgia, H, Raj, H, Patil, M
Journal of endocrinological investigation. 2019;(12):1451-1458
Abstract
PURPOSE Though most of the observational studies have shown that metformin can reduce serum thyroid stimulating hormone (TSH) level in patients of hypothyroidism with diabetes or polycystic ovarian disease, randomised controlled trials are sparse. The primary objective of this study was to evaluate the effect of metformin on thyroid function tests (TSH, free T4, and free T3) in patients with subclinical hypothyroidism (SCH). METHODOLOGY In this open label, parallel arm, randomised controlled trial, 60 patients of SCH (TSH 5.5-10 mIU/L) were randomised to either metformin group (1500 mg/day) or control group. RESULT A total of 46 patients (23 in each group) completed the study and no significant difference in serum TSH, free T4 or free T3 was found in between the 2 groups. Neither there was any significant change in serum TSH, free T4 or free T3 (pre and post 6 months) within the individual groups. However, the rate of normalisation of serum TSH in patients with negative thyroid antibody was significantly higher than patients with positive thyroid antibody (71.4% vs. 18.8%; P = 0.026) in metformin group in post hoc analysis. Fasting plasma glucose, serum high-density lipoprotein and indices of insulin sensitivity significantly improved in metformin group. Four patients (17%) had mild gastrointestinal adverse effects in the metformin group. CONCLUSION We did not find any significant change in thyroid function test in patients with SCH with metformin therapy.
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Agreement between markers of population iodine status in classifying iodine status of populations: a systematic review.
Wassie, MM, Middleton, P, Zhou, SJ
The American journal of clinical nutrition. 2019;(4):949-958
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BACKGROUND Population iodine deficiency is indicated by >3% of the population with newborn thyroid-stimulating hormone (TSH) concentration >5 mIU/L, median urinary iodine concentration (MUIC) <100 µg/L, or >5% prevalence of goiter in school-age children. However, the agreement between these population markers has not been systematically investigated. OBJECTIVE To assess the agreement between TSH, MUIC, and goiter as markers of population iodine status. METHODS We performed a systematic search for studies published on PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, and PsycINFO up to 29 October, 2018. Studies assessing iodine status in the population using the TSH marker and either MUIC or goiter prevalence in school-age children were included. The agreement between markers in classifying iodine status of the population was assessed. The sensitivity and specificity of the TSH marker was determined against MUIC and goiter prevalence as the reference markers. RESULTS Of 17,435 records identified by the search strategy, 57 eligible studies were included in the review. The agreement between markers in classifying the iodine status of populations into the same category was 65% for TSH and MUIC, and 83% for TSH and goiter prevalence. The TSH marker had a sensitivity of 0.75 and specificity of 0.53 when compared with MUIC, and 0.86 and 0.50 when compared with goiter prevalence. CONCLUSIONS The TSH marker has a better agreement with goiter prevalence than MUIC when classifying the iodine status of populations. Re-evaluation of the current criteria for classifying the iodine status of populations using the TSH marker is warranted. This systematic review was registered at PROSPERO (http://www.crd.york.ac.uk/prospero/) as CRD42018091247.
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Changes in TSH levels in athyreotic patients with differentiated thyroid cancer during levothyroxine therapy: influence on dose adjustments.
Grani, G, Tumino, D, Ramundo, V, Ciotti, L, Lomonaco, C, Armillotta, M, Falcone, R, Lucia, P, Maranghi, M, Filetti, S, et al
Journal of endocrinological investigation. 2019;(12):1485-1490
Abstract
PURPOSE The aim of the study was to describe the spontaneous TSH level variations and levothyroxine dose adjustments in athyreotic patients with differentiated thyroid cancer (DTC) in real-life practice. METHODS Patients with DTC were retrospectively evaluated at a tertiary referral center between October 2006 and November 2013. Hormone measurements (TSH and FT4 serum levels), L-T4 prescription information (dose per kg per day) and other medications were recorded at 1 month and 3, 12, 24, 36 and 48 months after primary treatment (surgery ± radioiodine therapy). RESULTS The cohort was composed of 452 patients; about 20% of patients with stable levothyroxine dose have clinically meaningful spontaneous TSH variations (defined as ΔTSH > 2 mcUI/mL) at yearly follow-up visit. Furthermore, about 25% of athyreotic DTC patients with stable dose have a ΔTSH > 1.5 mcUI/mL and about 40% a ΔTSH > 1 mcUI/mL during each follow-up visit. We further investigated whether this TSH variation would lead to subsequent dose changes. About 19.9-37.7% of DTC patients on stable LT4 dose on the previous visit had their levothyroxine dose reduced, while 7.8-14.9% increased due to TSH variations. We further evaluated the decision to change the dose in relation with the age-specific TSH range. Up to 77.2% of patients had their dose adjusted due to TSH falling below the age-specific range. CONCLUSIONS Spontaneous serum TSH variations determine levothyroxine replacement therapy in athyreotic patients with DTC, requiring multiple dose changes.
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In thyroxine-replaced hypothyroid postmenopausal women under simultaneous calcium supplementation, switch to oral liquid or softgel capsule L-thyroxine ensures lower serum TSH levels and favorable effects on blood pressure, total cholesterolemia and glycemia.
Morini, E, Catalano, A, Lasco, A, Morabito, N, Benvenga, S
Endocrine. 2019;(3):569-579
Abstract
PURPOSE In postmenopausal women under L-T4 therapy, which was subsequently accompanied by calcium carbonate (CC) supplementation taken 6-8 h after tablet L-T4, TSH levels were greater than prior to adding CC. Total cholesterolemia [CHOL], fasting glycemia [FG], systolic and diastolic blood pressure [SBP, DBP] were also greater than baseline. Our aim was to explore the effects of either liquid or softgel capsule L-T4, while maintaining CC ingestion 6-8 h, later on TSH levels, CHOL, FG, SBP, and DBP. METHODS We proposed to 50 hypothyroid postmenopausal women under tablet L-T4 therapy, to switch to either liquid or softgel capsule L-T4 at the same daily dose while maintaining CC ingestion 6-8 h later. Sixteen women accepted [group I; liquid (n = 9), capsule (n = 7)], while 34 continued tablet L-T4 [group II, (n = 34)]. RESULTS After 3 months, in group I, TSH decreased significantly (1.23 ± 0.49 vs. 1.80 ± 0.37 mU/L, P < 0.01), as did FG (80.7 ± 7.9 vs. 83.4 ± 6.3 mg/dL, P < 0.05); CHOL, SBP, and DBP decreased, though insignificantly. In contrast, in group II, TSH, FG, CHOL, SBP increased insignificantly, and DBP increased borderline significantly (69.7 ± 9 vs. 66.3 ± 6.5, P < 0.10). Compared to baseline (before adding CC), in group I, TSH was significantly lower (P < 0.01) and the other indices similar; in group II, TSH, FG, and SBP were significantly higher (P < 0.05), DBP borderline significantly higher (P < 0.10) and CHOL insignificantly higher. Performance of liquid L-T4 and capsule L-T4 was similar. CONCLUSION Delaying CC ingestion even by 6-8 h after taking tablet L-T4 is not entirely satisfactory, unlike liquid or softgel L-T4.
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Does the use of an iodine-containing contrast agent to visualise the PICC tip in preterm babies cause hypothyroidism? A randomised controlled trial.
Rath, CP, Thomas, M, Sullivan, D, Kluckow, M
Archives of disease in childhood. Fetal and neonatal edition. 2019;(2):F212-F214
Abstract
AIM: To compare thyroid function tests in preterm neonates (<30 weeks and >48 hour old) exposed to iodine-based contrast with controls and ascertain the certainty of peripherally inserted central catheter (PICC) tip position. METHODS Infants requiring a PICC were randomised to receive 0.3 mL of iodine-containing contrast or normal saline. The primary outcome was the difference in thyroid-stimulating hormone (TSH) levels on day 14 post PICC insertion and on day 28 of life. RESULTS 41 infants were randomised with no significant differences in TSH level (mIU/L) at day 14 post PICC insertion (3.1 vs 2) or on day 28 of life (2.2 vs 1.7). The PICC tip was more easily localised in the contrast group (85% vs 55%). Urinary iodine levels were significantly increased in the contrast-exposed group. CONCLUSION Use of contrast did not suppress subsequent thyroid function and helped visualise the PICC tip with more certainty. CLINICAL TRIAL REGISTRATION NUMBER ACTRN12614000560695, pre-result.
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TSH suppression aggravates arterial inflammation - an 18F-FDG PET study in thyroid carcinoma patients.
Boswijk, E, Sanders, KJC, Broeders, EPM, de Ligt, M, Vijgen, GHEJ, Havekes, B, Mingels, AMA, Wierts, R, van Marken Lichtenbelt, WD, Schrauwen, P, et al
European journal of nuclear medicine and molecular imaging. 2019;(7):1428-1438
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PURPOSE We aimed to investigate the influence of both hypothyroidism and thyroid-stimulating hormone (TSH) suppression on vascular inflammation, as assessed with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT). METHODS Ten thyroid carcinoma patients underwent an 18F-FDG PET/CT during post-thyroidectomy hypothyroidism and during thyrotropin (TSH) suppression after 131I (radioiodine) ablation therapy. We analysed the 18F-FDG uptake in the carotids, aortic arch, ascending, descending, and abdominal aorta to investigate the effects of thyroid hormone status on arterial inflammation. Target-to-background ratios (TBRs) corrected for blood pool activity were established for all arterial territories. Results were further compared to euthyroid historic control subjects. RESULTS In general, there was a trend towards higher vascular TBRs during TSH suppression than during hypothyroidism (TBRmax all vessels = 1.6 and 1.8, respectively, p = 0.058), suggesting a higher degree of arterial inflammation. In concurrence with this, we found increased C-reactive protein (CRP) levels after levothyroxine treatment (CRP = 2.9 mg/l and 4.8 mg/l, p = 0.005). An exploratory comparison with euthyroid controls showed significant higher TBRs during TSH suppression for the carotids, aortic arch, thoracic descending aorta, and when all vascular territories were combined (TBRmaxp = 0.013, p = 0.016, p = 0.030 and p = 0.018 respectively). CONCLUSIONS Arterial inflammation is increased during TSH suppression. This finding sheds new light on the underlying mechanism of the suspected increased risk of cardiovascular disease in patients with TSH suppression.