and Serum Thyroid Function in Adults after Iodinated Contrast Administration CREST Seminar Presentation March 10 2015 Sun Y Lee MD 2 nd year Crest Fellow Overview Excess iodine exposure from iodinated contrast media and its implications ID: 911604
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Slide1
Urinary Iodine Excretion and Serum Thyroid Function in Adults after Iodinated Contrast Administration
CREST Seminar PresentationMarch 10, 2015Sun Y. Lee, MD2nd year Crest Fellow
Slide2OverviewExcess iodine exposure from iodinated contrast media and its implicationsLiterature on urinary iodine clearance after iodinated media exposure
Study DesignResultsConclusion
Slide3OverviewExcess iodine exposure from iodinated contrast media and its implicationsLiterature on urinary iodine clearance after iodinated media exposure
Study DesignResultsConclusion
Slide4EpidemiologyThere has been a nearly 3-fold increase in CT examinations from 1996 to 2010, with approximately 70 million CT scans being performed annually in 2007.
With increased use of CT scans, exposure to huge amounts of iodine from radiographic contrast media is also increasing.Iodine content in radiographic contrast media = 320 mg/ml to 370 mg/ml, while RDA of iodine is 150 mcg.
Smith-
Bindman
, R. et al.
JAMA
2012;307(22):2400-2409
Slide5Why are We Interested in the Urinary Iodine Clearance after ICM Administration?
Timing of radioactive iodine ablation after thyroidectomy for thyroid cancerTiming of radioactive iodine treatment and/or diagnostic uptakes and scans for hyperthyroidism (Graves’ disease or toxic multinodular goiter)Potential for development of thyroid dysfunction from exposure to excess iodine.
Slide6OverviewExcess iodine exposure from iodinated contrast media and its implicationsLiterature on urinary iodine clearance after iodinated media exposure
Study DesignResultsConclusion
Slide7Urinary Iodine Excretion after ICM Exposure in Patients s/p Total ThyroidectomyProspective study25 patients s/p total thyroidectomy for thyroid cancer
UIC back to baseline by one month
Padovani
, R. et al.
Thyroid
. 2012;22(9):926-930
Slide8Urinary Iodine Excretion after ICM Exposure in Patients s/p Total Thyroidectomy
Retrospective study of 1023 patients with differentiated thyroid cancer.Five different time intervals between preoperative CT scan and spot urinary iodine measurements.No significant difference between UIC one month and 6 months after CT scan.
Comparison of urinary iodine concentration according to time interval between CT scan and urine iodine measurements.
Sohn
, et al.
Thyroid
2014; 24(5): 872-877.
Slide9Urinary Iodine Excretion after ICM Exposure in Patients without Thyroid DiseaseProspective study21 patients without reported
hx of thyroid diseaseUIC measured every 2 weeks after ICM exposure for 12 weeksThyroid function not assessed.
Nimmons
, GL. et al.
JAMA
Otolaryngol
Head Neck Surg
. 2013;139(5):479-482
Slide10Comparison of Urinary Iodine Clearance between Athyreotic Patients and Patients with Intact Thyroid Glands
Prospective study6 patients with thyroid cancer s/p total thyroidectomy vs. to 7 euthyroid controls.UIC assessed every 2 weeks up to 2 months, then monthly up to 6 months after CT scan.No difference in time to normalization of UIC between the two groups.
No thyroid function tests.
Ho, et al.
Journal of Thyroid Research,
2014;article ID 580569
Slide11OverviewExcess iodine exposure from iodinated contrast media and its implicationsLiterature on urinary iodine clearance after iodinated media exposure
Study DesignResultsConclusion
Slide12Study ObjectivesTo determine the time required for UIC to normalize following iodinated contrast media (ICM) exposure in clinically euthyroid
adults.To assess any potential changes in serum thyroid function following ICM exposure.To assess for any potential predictors of time to normalization of UIC and serum thyroid dysfunction following ICM exposure
Slide13Study SubjectsInclusion criteriaAge ≥ 18 yr undergoing elective CT scan with iodinated contrast agent
Exclusion criteriaICM exposure ≤ 6 monthsKnown thyroid dysfunction or use of thyroid medicationsAmiodarone ≤ 2 yearsLithium ≤ 6 monthsCurrent pregnancy or lactationUnable to give informed consent
Slide14Methods
Measurements
Spot UIC and TFTs at every visit
Thyroid ultrasound within the first 4 weeks
of
follow-up.
Baseline
Follow-up
Extended Follow-up
Slide15Outcomes of InterestPrimary outcomesMedian time for UIC to peakMedian time for UIC to return to 1.5 x baseline or below 164 mcg/L (national median), whichever comes first
Secondary outcomesPredictors of primary outcomesPattern of changes in thyroid function over study periodPredictors for developing incident thyroid dysfunction
Slide16Statistical AnalysesPearson’s rank correlation and binomial analyses to determine univariate associations between various predictors and peak UIC, duration to peak or normalization of UIC, and development of incident thyroid dysfunction.
Mixed effects models to assess potential changes in serum thyroid function tests during the study period for each subject.Multivariate linear regression models to assess potential predictors of peak UIC, duration to peak UIC, and duration to normalization of UIC.Multivariate logistic regression model to asses predictors for the development of incident thyroid dysfunction.
Slide17Statistical AnalysesPotential predictors assessed were:
Age, gender, race, smoking status, place of birth, personal or family history of autoimmune disease, family history of thyroid diseasePresence of thyroid nodules ≥ 1cm and thyroid volumeBaseline UICBaseline serum TSH, free T4 (FT4), total T3 (TT3), and TPO antibody.Subjects with abnormal serum thyroid function at baseline were excluded from analyses assessing development of incident thyroid dysfunction and change in thyroid function over time.
Slide18OverviewExcess iodine exposure from iodinated contrast media and its implicationsLiterature on urinary iodine clearance after iodinated media exposure
Study DesignResultsConclusion
Slide19Baseline Characteristics of Subjects
Mean±SD or Median (Range)Age (years)
50.8±12.4
Amount of iodine administered (grams)
34.5±6.1
UIC at baseline (µg/L)
105.6 (10.0-866.1)
TSH at baseline (mIU/L)*
1.26 (0.5-11.2)
FT4 at baseline (ng/
dL
)*
0.83 (0.47-1.34)
TT3 at baseline (ng/mL)*
1.40 (0.71-2.34)
57% Men, 48% White, 37% Black, and 11% Hispanic.
15% with thyroid nodule ≥ 1cm.
One subject with positive Thyroid Peroxidase antibody titer.
n=54, except *n=51
Slide20Descriptive statisticsMean ± SD time to achieve peak UIC =
1.1 ± 0.5 weeks.Median (range) peak UIC = 3,519 (233-157,500) µg/L.Mean ± SD time to normalization of UIC =
5.2 ± 4.0 weeks.
Slide21Median Urinary Iodine Concentrations following ICM Administration
Slide22Development of Incident Thyroid Dysfunction after ICM Administration
11 subjects (22%) developed abnormal serum TSH concentrations within 1-4 weeks after ICM administrationFive with suppressed TSHOne with T3 thyrotoxicosisFour with subclinical hyperthyroidismSix with elevated TSHFour with overt hypothyroidism (with low free T4)Two with subclinical hypothyroidism
Slide23Univariate Correlations between Covariates and Duration to Normalization of UIC after ICM Administration
CovariatesCorrelation CoefficientP-value
Age (years)
0.024
0.87
Amount of iodine received (grams)
-0.207
0.137
Thyroid volume (cm
3
)
0.017
0.90
Baseline UIC (mcg/L)
-0.219
0.116
Peak UIC (mcg/L)
-0.047
0.74
Duration to peak UIC (weeks)
0.026
0.86
Baseline TSH (µIU/L)*
0.075
0.61
Slide24Univariate Correlations between CovariatesModerate positive correlation between amount of iodine received and peak UIC (r=0.649; p<0.001).
Moderate inverse correlation between baseline TSH and time to achieve peak UIC (r=-0.283; p=0.049).The lower the baseline TSH, the longer it took to achieve peak UIC.
Slide25Univariate Correlations between Covariates and Development of Incident Thyroid Dysfunction after ICM Administration
CovariatesCorrelation Coefficient
P-valueAge (years)
0.047
0.75
Amount of iodine received (grams)
0.096
0.51
Thyroid volume (cm
3
)
-0.091
0.53
Baseline UIC (mcg/L)
-0.143
0.33
Peak UIC (mcg/L)
-0.056
0.70
Duration to peak UIC (weeks)
-0.056
0.70
Duration to normalization of UIC (weeks)
0.076
0.60
Baseline TSH (µIU/L)
0.194
0.18
Slide26Multivariate Linear Regression Model Predicting Peak UIC after ICM Administration
PredictorsBeta-coefficient
p-value
Age (years)
695.45
0.024*
Amount of iodine received (grams)
2866.31
<0.001*
Thyroid volume (cm
3
)
-215.29
0.77
Presence of nodules ≥ 1cm
2899.08
0.67
Gender
N/A
0.34
Race/ethnicity
N/A
0.77
Smoking status
N/A
0.98
Place of birth
N/A
0.76
History of autoimmune disease
N/A
0.40
Family history of thyroid disease
N/A
0.47
Family history of autoimmune disease
N/A
0.05
Baseline UIC (mcg/L)
-3.97
0.83
Baseline TSH
(
mIU
/L
)
-471.90
0.76
Baseline FT4 (ng/dL)
-2890.39
0.90
Baseline TT3 (ng/mL)
-2877.18
0.57
Overall model p-value = 0.035
Slide27Multivariate Regression ModelsNo significant predictors of
Duration to achieve peak UIC (p=0.55)Duration to normalization of UIC (p=0.44)Development of incident thyroid dysfunction (p=0.29)
Slide28OverviewExcess iodine exposure from iodinated contrast media and its implicationsLiterature on urinary iodine clearance after iodinated media exposure
Study DesignResultsConclusion
Slide29ConclusionIt would be prudent to wait at least 2 months after CT with ICM
before radioactive iodine is given for thyroid scans or therapy.Monitoring of thyroid function should be considered in at-risk patients, as 22% of subjects developed abnormal thyroid function after a single ICM dose.
Slide30AcknowledgementDr. Lewis BravermanDr. Elizabeth PearceDr. Angela LeungDr. Donny ChangDr. Xuemei He
Boston University Medical Center General Clinical Research Unit staffEast Newton Campus Radiology StaffNIH T32 grantCREST fellowship grant
Slide31Questions?
Slide32Baseline Serum Thyroid Function AbnormalitiesThree subjects with both elevated TSH and total T3 levels: presumably from either heterophlic antibodies interfering with assay or recovery from non-thyroidal illness.
Two subjects with elevated baseline TSH levels with normal free T4 and total T3 concentrations.Subsequently, data from 49 subjects were used in analyses of serum thyroid function.Data from the whole cohort (54 subjects) were used in analyses of urinary iodine concentrations.
Slide33Summary of FindingsThe largest prospective study assessing urinary iodine clearance after ICM administration (n=54).
Baseline UIC 105.6 µg/L (national median 164 µg/L).Median peak UIC was 3519 µg/L, but highest peak UIC was 157,500 µg/L after single dose of ICM.UIC peaked at a mean of 1.1 weeks and normalized by a mean of 5.2 weeks after administration of a single dose ICM for routine CT scans in clinically euthyroid patients with intact thyroid glands.No significant predictors of time to normalization of UIC.
22% (11 subjects) developed incident thyroid dysfunction.
Slide34Strength of Our StudyThe largest prospective study to date assessing urinary iodine excretion after iodinated contrast media administration.Assessment of thyroid function in patients with intact thyroid glands.Assessment of
thyroid morphology (size of the gland and presence of thyroid nodules)
Slide35Limitations of Our StudyLack of data on subjects’ thyroid radioactive iodine uptakeRadioactive iodine uptake data would have added information on the status of iodine saturation in thyroid gland.