The sensitivity and specificity of thyroglobulin concentration using repeated measures of urinary iodine excretion

Purpose Iodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine excess. Tg is considered as a sensitive index of iodine status in groups of children and adults, but its usefulness for individuals is unknown....

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Published in:	European journal of nutrition Vol. 57; no. 4; pp. 1313 - 1320
Main Authors:	Ma, Zheng F., Venn, Bernard J., Manning, Patrick J., Cameron, Claire M., Skeaff, Sheila A.
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2018 Springer Nature B.V
Subjects:	Adolescent Adult adults Biomarkers Biomarkers - blood Biomarkers - urine blood blood sampling Chemistry Chemistry and Materials Science Children Creatinine Creatinine - urine Cross-Sectional Studies Diagnostic Tests, Routine - standards Excretion Female Health risk assessment Humans Iodides Iodine Iodine - deficiency Iodine - urine Male Medical diagnosis New Zealand Nutrition Nutritional Status Original Contribution reference standards ROC Curve Thyroglobulin Thyroglobulin - blood Thyroid Thyroid-stimulating hormone thyrotropin Thyrotropin - blood Thyroxine Urine Within-subjects design Young Adult New Zealand Diagnostic Adult Biomarker Iodine deficiency Thyroglobulin
ISSN:	1436-6207, 1436-6215, 1436-6215
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Abstract	Purpose Iodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine excess. Tg is considered as a sensitive index of iodine status in groups of children and adults, but its usefulness for individuals is unknown. The aim of this study was to determine the diagnostic performance of Tg as an index of iodine status in individual adults. Methods Adults aged 18–40 years ( n = 151) provided five spot urine samples for the measurement of urinary iodine concentration expressed as μg/L (UIC), μg/g of creatinine (I:Cre), and μg/day (estimated UIE); the mean of the five samples was used as the reference standard. Participants also provided a blood sample for the determination of Tg, thyroid-stimulating hormone (TSH), and free thyroxine (FT4). Results The median of UIC, I:Cre, estimated UIE, and Tg was 72 (range 16–350) μg/L, 90 (range 33–371) μg/g, 129 (range 41–646) μg/day, and 16.4 (range 0.8–178.9) μg/L, respectively. Using Tg cut-offs of >10, >11, >13, and >15 μg/L, the sensitivity and specificity for UIC, I:Cre, and estimated UIE ranged from 52 to 79% and 20–48%, respectively, below the acceptable value of ≥80%. Furthermore, receiver-operating characteristic (ROC) curves for Tg using the three measurements of urinary iodine were situated close to the chance line and the area under the curve ranged from 0.49 to 0.52. Conclusions The results from this cross-sectional study indicate that Tg has low sensitivity and specificity to repeated measures of urinary iodine excretion. Further studies are still needed to investigate the usefulness of Tg as a biomarker of individual iodine status.
AbstractList	Iodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine excess. Tg is considered as a sensitive index of iodine status in groups of children and adults, but its usefulness for individuals is unknown. The aim of this study was to determine the diagnostic performance of Tg as an index of iodine status in individual adults.PURPOSEIodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine excess. Tg is considered as a sensitive index of iodine status in groups of children and adults, but its usefulness for individuals is unknown. The aim of this study was to determine the diagnostic performance of Tg as an index of iodine status in individual adults.Adults aged 18-40 years (n = 151) provided five spot urine samples for the measurement of urinary iodine concentration expressed as μg/L (UIC), μg/g of creatinine (I:Cre), and μg/day (estimated UIE); the mean of the five samples was used as the reference standard. Participants also provided a blood sample for the determination of Tg, thyroid-stimulating hormone (TSH), and free thyroxine (FT4).METHODSAdults aged 18-40 years (n = 151) provided five spot urine samples for the measurement of urinary iodine concentration expressed as μg/L (UIC), μg/g of creatinine (I:Cre), and μg/day (estimated UIE); the mean of the five samples was used as the reference standard. Participants also provided a blood sample for the determination of Tg, thyroid-stimulating hormone (TSH), and free thyroxine (FT4).The median of UIC, I:Cre, estimated UIE, and Tg was 72 (range 16-350) μg/L, 90 (range 33-371) μg/g, 129 (range 41-646) μg/day, and 16.4 (range 0.8-178.9) μg/L, respectively. Using Tg cut-offs of >10, >11, >13, and >15 μg/L, the sensitivity and specificity for UIC, I:Cre, and estimated UIE ranged from 52 to 79% and 20-48%, respectively, below the acceptable value of ≥80%. Furthermore, receiver-operating characteristic (ROC) curves for Tg using the three measurements of urinary iodine were situated close to the chance line and the area under the curve ranged from 0.49 to 0.52.RESULTSThe median of UIC, I:Cre, estimated UIE, and Tg was 72 (range 16-350) μg/L, 90 (range 33-371) μg/g, 129 (range 41-646) μg/day, and 16.4 (range 0.8-178.9) μg/L, respectively. Using Tg cut-offs of >10, >11, >13, and >15 μg/L, the sensitivity and specificity for UIC, I:Cre, and estimated UIE ranged from 52 to 79% and 20-48%, respectively, below the acceptable value of ≥80%. Furthermore, receiver-operating characteristic (ROC) curves for Tg using the three measurements of urinary iodine were situated close to the chance line and the area under the curve ranged from 0.49 to 0.52.The results from this cross-sectional study indicate that Tg has low sensitivity and specificity to repeated measures of urinary iodine excretion. Further studies are still needed to investigate the usefulness of Tg as a biomarker of individual iodine status.CONCLUSIONSThe results from this cross-sectional study indicate that Tg has low sensitivity and specificity to repeated measures of urinary iodine excretion. Further studies are still needed to investigate the usefulness of Tg as a biomarker of individual iodine status. Purpose Iodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine excess. Tg is considered as a sensitive index of iodine status in groups of children and adults, but its usefulness for individuals is unknown. The aim of this study was to determine the diagnostic performance of Tg as an index of iodine status in individual adults. Methods Adults aged 18–40 years ( n = 151) provided five spot urine samples for the measurement of urinary iodine concentration expressed as μg/L (UIC), μg/g of creatinine (I:Cre), and μg/day (estimated UIE); the mean of the five samples was used as the reference standard. Participants also provided a blood sample for the determination of Tg, thyroid-stimulating hormone (TSH), and free thyroxine (FT4). Results The median of UIC, I:Cre, estimated UIE, and Tg was 72 (range 16–350) μg/L, 90 (range 33–371) μg/g, 129 (range 41–646) μg/day, and 16.4 (range 0.8–178.9) μg/L, respectively. Using Tg cut-offs of >10, >11, >13, and >15 μg/L, the sensitivity and specificity for UIC, I:Cre, and estimated UIE ranged from 52 to 79% and 20–48%, respectively, below the acceptable value of ≥80%. Furthermore, receiver-operating characteristic (ROC) curves for Tg using the three measurements of urinary iodine were situated close to the chance line and the area under the curve ranged from 0.49 to 0.52. Conclusions The results from this cross-sectional study indicate that Tg has low sensitivity and specificity to repeated measures of urinary iodine excretion. Further studies are still needed to investigate the usefulness of Tg as a biomarker of individual iodine status. Iodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine excess. Tg is considered as a sensitive index of iodine status in groups of children and adults, but its usefulness for individuals is unknown. The aim of this study was to determine the diagnostic performance of Tg as an index of iodine status in individual adults. Adults aged 18-40 years (n = 151) provided five spot urine samples for the measurement of urinary iodine concentration expressed as μg/L (UIC), μg/g of creatinine (I:Cre), and μg/day (estimated UIE); the mean of the five samples was used as the reference standard. Participants also provided a blood sample for the determination of Tg, thyroid-stimulating hormone (TSH), and free thyroxine (FT4). The median of UIC, I:Cre, estimated UIE, and Tg was 72 (range 16-350) μg/L, 90 (range 33-371) μg/g, 129 (range 41-646) μg/day, and 16.4 (range 0.8-178.9) μg/L, respectively. Using Tg cut-offs of >10, >11, >13, and >15 μg/L, the sensitivity and specificity for UIC, I:Cre, and estimated UIE ranged from 52 to 79% and 20-48%, respectively, below the acceptable value of ≥80%. Furthermore, receiver-operating characteristic (ROC) curves for Tg using the three measurements of urinary iodine were situated close to the chance line and the area under the curve ranged from 0.49 to 0.52. The results from this cross-sectional study indicate that Tg has low sensitivity and specificity to repeated measures of urinary iodine excretion. Further studies are still needed to investigate the usefulness of Tg as a biomarker of individual iodine status. PurposeIodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine excess. Tg is considered as a sensitive index of iodine status in groups of children and adults, but its usefulness for individuals is unknown. The aim of this study was to determine the diagnostic performance of Tg as an index of iodine status in individual adults.MethodsAdults aged 18–40 years (n = 151) provided five spot urine samples for the measurement of urinary iodine concentration expressed as μg/L (UIC), μg/g of creatinine (I:Cre), and μg/day (estimated UIE); the mean of the five samples was used as the reference standard. Participants also provided a blood sample for the determination of Tg, thyroid-stimulating hormone (TSH), and free thyroxine (FT4).ResultsThe median of UIC, I:Cre, estimated UIE, and Tg was 72 (range 16–350) μg/L, 90 (range 33–371) μg/g, 129 (range 41–646) μg/day, and 16.4 (range 0.8–178.9) μg/L, respectively. Using Tg cut-offs of >10, >11, >13, and >15 μg/L, the sensitivity and specificity for UIC, I:Cre, and estimated UIE ranged from 52 to 79% and 20–48%, respectively, below the acceptable value of ≥80%. Furthermore, receiver-operating characteristic (ROC) curves for Tg using the three measurements of urinary iodine were situated close to the chance line and the area under the curve ranged from 0.49 to 0.52.ConclusionsThe results from this cross-sectional study indicate that Tg has low sensitivity and specificity to repeated measures of urinary iodine excretion. Further studies are still needed to investigate the usefulness of Tg as a biomarker of individual iodine status. PURPOSE: Iodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine excess. Tg is considered as a sensitive index of iodine status in groups of children and adults, but its usefulness for individuals is unknown. The aim of this study was to determine the diagnostic performance of Tg as an index of iodine status in individual adults. METHODS: Adults aged 18–40 years (n = 151) provided five spot urine samples for the measurement of urinary iodine concentration expressed as μg/L (UIC), μg/g of creatinine (I:Cre), and μg/day (estimated UIE); the mean of the five samples was used as the reference standard. Participants also provided a blood sample for the determination of Tg, thyroid-stimulating hormone (TSH), and free thyroxine (FT4). RESULTS: The median of UIC, I:Cre, estimated UIE, and Tg was 72 (range 16–350) μg/L, 90 (range 33–371) μg/g, 129 (range 41–646) μg/day, and 16.4 (range 0.8–178.9) μg/L, respectively. Using Tg cut-offs of >10, >11, >13, and >15 μg/L, the sensitivity and specificity for UIC, I:Cre, and estimated UIE ranged from 52 to 79% and 20–48%, respectively, below the acceptable value of ≥80%. Furthermore, receiver-operating characteristic (ROC) curves for Tg using the three measurements of urinary iodine were situated close to the chance line and the area under the curve ranged from 0.49 to 0.52. CONCLUSIONS: The results from this cross-sectional study indicate that Tg has low sensitivity and specificity to repeated measures of urinary iodine excretion. Further studies are still needed to investigate the usefulness of Tg as a biomarker of individual iodine status.
Author	Ma, Zheng F. Venn, Bernard J. Cameron, Claire M. Skeaff, Sheila A. Manning, Patrick J.
Author_xml	– sequence: 1 givenname: Zheng F. surname: Ma fullname: Ma, Zheng F. organization: Department of Human Nutrition, University of Otago – sequence: 2 givenname: Bernard J. surname: Venn fullname: Venn, Bernard J. organization: Department of Human Nutrition, University of Otago – sequence: 3 givenname: Patrick J. surname: Manning fullname: Manning, Patrick J. organization: Department of Medicine, University of Otago – sequence: 4 givenname: Claire M. surname: Cameron fullname: Cameron, Claire M. organization: Department of Social and Preventive Medicine, University of Otago – sequence: 5 givenname: Sheila A. orcidid: 0000-0002-7971-5329 surname: Skeaff fullname: Skeaff, Sheila A. email: sheila.skeaff@otago.ac.nz organization: Department of Human Nutrition, University of Otago
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References_xml	– reference: ZimmermannMBAnderssonMAssessment of iodine nutrition in populations: past, present, and futureNutr Rev2012701055357010.1111/j.1753-4887.2012.00528.x23035804 – reference: EdmondsJCMcLeanRMWilliamsSMSkeaffSAUrinary iodine concentration of New Zealand adults improves with mandatory fortification of bread with iodised salt but not to predicted levelsEur J Nutr20155531201121210.1007/s00394-015-0933-y1:CAS:528:DC%2BC2MXpt1agsLk%3D26018655 – reference: XingMHaugenBRSchlumbergerMProgress in molecular-based management of differentiated thyroid cancerThe Lancet201338198711058106910.1016/S0140-6736(13)60109-91:CAS:528:DC%2BC3sXksFamsrk%3D – reference: SnozekCLChambersEPReadingCCSeboTJSistrunkJWSinghRJGrebeSKSerum thyroglobulin, high-resolution ultrasound, and lymph node thyroglobulin in diagnosis of differentiated thyroid carcinoma nodal metastasesJ Clin Endocrinol Metab200792114278428110.1210/jc.2007-10751:CAS:528:DC%2BD2sXhtlartb3L17684045 – reference: PinoSFangSLBravermanLEAmmonium persulfate: a safe alternative oxidizing reagent for measuring urinary iodineClin Chem19964222392431:CAS:528:DyaK28XhtFahtro%3D8595717 – reference: SwansonCAZimmermannMBSkeaffSPearceENDwyerJTTrumboPRZehalukCAndrewsKWCarriquiryACaldwellKLEganSKLongSEBaileyRLSullivanKMHoldenJMBetzJMPhinneyKWBrooksSPJohnsonCLHaggansCJSummary of an NIH workshop to identify research needs to improve the monitoring of iodine status in the United States and to inform the DRIJ Nutr201214261175S1185S10.3945/jn.111.1564481:CAS:528:DC%2BC38XnslWluro%3D – reference: MaZFVennBJManningPJCameronCMSkeaffSAIodine supplementation of mildly iodine-deficient adults lowers thyroglobulin: a randomized controlled trialJ Clin Endocrinol Metab201610141737174410.1210/jc.2015-359126891118 – reference: ThomsonCDCollsAJConaglenJVMacormackMStilesMMannJIodine status of New Zealand residents as assessed by urinary iodide excretion and thyroid hormonesBr J Nutr199778690191210.1079/BJN199702081:CAS:528:DyaK1cXjvFCjsg%3D%3D9497442 – reference: LiCPengSZhangXXieXWangDMaoJTengXShanZTengWThe urine iodine to creatinine as an optimal index of iodine during pregnancy in an iodine adequate area in ChinaJ Clin Endocrinol Metab201610131290129810.1210/jc.2015-35191:CAS:528:DC%2BC28XhtVCrt7jF26789777 – reference: MaximLDNieboRUtellMJScreening tests: a review with examplesInhal Toxicol2014261381182810.3109/08958378.2014.9559321:CAS:528:DC%2BC2cXhvVCls7fJ252649344389712 – reference: LazarusJHIodine status in Europe in 2014Eur Thyroid J2014313610.1159/000358873248474584005253 – reference: BjergvedLJørgensenTPerrildHCarléACerqueiraCKrejbjergALaurbergPOvesenLBulow PedersenIBankeRLKnudsenNPredictors of change in serum TSH after iodine fortification: an 11-year follow-up to the DanThyr studyJ Clin Endocrinol Metab201297114022402910.1210/jc.2012-25081:CAS:528:DC%2BC38Xhs12ku77J22962423 – reference: OhashiTYamakiMPandavCSKarmarkarMGIrieMSimple microplate method for determination of urinary iodineClin Chem20004645295361:CAS:528:DC%2BD3cXjvFGhu7c%3D10759477 – reference: GiovanellaLClarkPMChiovatoLDuntasLEliseiRFeldt-RasmussenULeenhardtLLusterMSchalin-JanttiCSchottMSeregniERimmeleHSmitJVerburgFAThyroglobulin measurement using highly sensitive assays in patients with differentiated thyroid cancer: a clinical position paperEur J Endocrinol20141712R33R4610.1530/EJE-14-01481:CAS:528:DC%2BC2cXht1ygs7bJ247434004076114 – reference: Feldt-RasmussenUHyltoft PetersenPBlaabjergOHørderMLong-term variability in serum thyroglobulin and thyroid related hormones in healthy subjectsActa Endocrinol (Copenh)19809533283341:STN:280:DyaL3M%2FlvVOnsg%3D%3D10.1530/acta.0.0950328 – reference: JensenEPetersenPHBlaabjergOHegedüsLBiological variation of thyroid autoantibodies and thyroglobulinClin Chem Lab Med20074581058106410.1515/CCLM.2007.1851:CAS:528:DC%2BD2sXhtVegtb3O17902201 – reference: RohnerFZimmermannMJoostePPandavCCaldwellKRaghavanRRaitenDJBiomarkers of nutrition for development- iodine reviewJ Nutr201414481322s1342s10.3945/jn.113.1819741:CAS:528:DC%2BC2cXht1ygsb%2FN – reference: FribergJCConsiderations for test selection: How do validity and reliability impact diagnostic decisions?Child Lang Teach Ther2010261779210.1177/0265659009349972 – reference: StincaSAnderssonMErhardtJZimmermannMBDevelopment and validation of a new low-cost enzyme-linked immunoassay for serum and dried blood spot thyroglobulinThyroid201525121297130510.1089/thy.2015.04281:CAS:528:DC%2BC2MXitVGhsr7F26528830 – reference: WHO/UNICEF/ICCIDD (1994) Indicators for assessing iodine deficiency disorders and their control through salt iodization. Document WHO/NUT, 6. WHO, Geneva, p 36 – reference: KnudsenNBülowIJørgensenTPerrildHOvesenLLaurbergPSerum Tg—a sensitive marker of thyroid abnormalities and iodine deficiency in epidemiological studiesJ Clin Endocrinol Metab2001868359936031:CAS:528:DC%2BD3MXlvFekt7w%3D10.1210/jcem.86.8.777211502784 – reference: KönigFAnderssonMHotzKAeberliIZimmermannMBTen repeat collections for urinary iodine from spot samples or 24-hour samples are needed to reliably estimate individual iodine status in womenJ Nutr2011141112049205410.3945/jn.111.1440711:CAS:528:DC%2BC3MXhsVSrurbL21918061 – reference: BalochZCarayonPConte-DevolxBDemersLMFeldt-RasmussenUHenryJFLiVosliVANiccoli-SirePJohnRRufJSmythPPSpencerCAStockigtJRLaboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid diseaseThyroid2003131312610.1089/10507250332108696212625976 – reference: WHO/UNICEF/ICCIDD (2007) Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers. 3rd edn. WHO, Geneva – reference: Hajian-TilakiKReceiver operating characteristic (ROC) curve analysis for medical diagnostic test evaluationCaspian J Intern Med20134262763537558243755824 – reference: GutekunstRSmolarekHHasenpuschUStubbePFriedrichHJWoodWGScribaPCGoitre epidemiology: thyroid volume, iodine excretion, thyroglobulin and thyrotropin in Germany and SwedenActa Endocrinol (Copenh)198611244945011:STN:280:DyaL28zhvV2itQ%3D%3D10.1530/acta.0.1120494 – reference: KeutgenXMFilicoriFCrowleyMJWangYScognamiglioTHodaRBuitragoDCooperDZeigerMAZarnegarRElementoOFaheyTJIA panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspirationClin Cancer Res20121872032203810.1158/1078-0432.CCR-11-24871:CAS:528:DC%2BC38XkvFOlsrg%3D22351693 – reference: Feldt-RasmussenUHyltoft PetersenPDateJSex and age correlated reference values of serum thyroglobulin measured by a modified radioimmunoassayActa Endocrinol (Copenh)19799034404501:CAS:528:DyaE1MXktVeis7Y%3D10.1530/acta.0.0900440 – reference: KarmisholtJLaurbergPAndersenSRecommended number of participants in iodine nutrition studies is similar before and after an iodine fortification programmeEur J Nutr201453248749210.1007/s00394-013-0551-51:CAS:528:DC%2BC2cXivFehtLw%3D23784090 – reference: ZimmermannMBAeberliIAnderssonMAsseyVYorgJAJoostePJukićTKartonoDKusićZPretellESan LuisTOJrUntoroJTimmerAThyroglobulin is a sensitive measure of both deficient and excess iodine intakes in children and indicates no adverse effects on thyroid function in the UIC range of 100–299µg/L: a UNICEF/ICCIDD study group reportJ Clin Endocrinol Metab20139831271128010.1210/jc.2012-39521:CAS:528:DC%2BC3sXksFylsrc%3D23345097 – reference: LaurbergPJørgensenTPerrildHOvesenLKnudsenNPedersenIBRasmussenLBCarléAVejbjergPThe Danish investigation on iodine intake and thyroid disease, DanThyr: status and perspectivesEur J Endocrinol2006155221922810.1530/eje.1.022101:CAS:528:DC%2BD28XovFGht7g%3D16868134 – reference: KnudsenNChristiansenEBrandt-ChristensenMNygaardBPerrildHAge- and sex-adjusted iodine/creatinine ratio. A new standard in epidemiological surveys? 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Snippet	Purpose Iodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine... Iodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine excess. Tg... PurposeIodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine... PURPOSE: Iodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine...
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SubjectTerms	Adolescent Adult adults Biomarkers Biomarkers - blood Biomarkers - urine blood blood sampling Chemistry Chemistry and Materials Science Children Creatinine Creatinine - urine Cross-Sectional Studies Diagnostic Tests, Routine - standards Excretion Female Health risk assessment Humans Iodides Iodine Iodine - deficiency Iodine - urine Male Medical diagnosis New Zealand Nutrition Nutritional Status Original Contribution reference standards ROC Curve Thyroglobulin Thyroglobulin - blood Thyroid Thyroid-stimulating hormone thyrotropin Thyrotropin - blood Thyroxine Urine Within-subjects design Young Adult
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Title	The sensitivity and specificity of thyroglobulin concentration using repeated measures of urinary iodine excretion
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