Incidence of Thyroid Dysfunction in Children < 3 Years of Age After Exposure to Iodine-Containing Contrast Agents During Cardiac Catheterization

Incidence of Thyroid Dysfunction in Children < 3 Years of Age After Exposure to Iodine-Containing Contrast Agents During Cardiac Catheterization | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Incidence of Thyroid Dysfunction in Children < 3 Years of Age After Exposure to Iodine-Containing Contrast Agents During Cardiac Catheterization Ashley Molloy, Jason N. Johnson, Neil Tailor, Sarah Parkerson, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7303976/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: In March 2022, the U.S. Food and Drug Administration (FDA) issued a drug safety communication recommending evaluation for thyroid dysfunction in all patients under three years of age, three weeks after exposure to iodinated contrast media (ICM). The purpose of this study was to describe the incidence of thyroid dysfunction following ICM exposure during cardiac catheterizations in children < 3 years of age. Study Design: Thyroid function tests (TFT), including serum thyroid-stimulating hormone (TSH) and free thyroxine (free T4) levels, were measured in children < 3 years of age exposed to ICM during cardiac catheterization, both pre-procedure and 3-weeks post-procedure, between May 2022 and April 2023. Clinical hypothyroidism was defined as a low free T4 level and high TSH level compared to reference standards. Results: Eighty patients were included in the analysis, undergoing 99 cardiac catheterization procedures with exposure to ICM. The median age and weight were 5 months (20 minutes – 35 months) and 6 kg (0.62-15.7 kg), respectively. The median dose of ICM per procedure was 3.9mL/kg (0.1 – 20.4mL/kg). The median time of follow-up TFT was 23 days (9-143 days). On follow-up, only one infant with Trisomy-21 developed new-onset hypothyroidism requiring treatment with levothyroxine (incidence rate of 1.0%). However, whether this was an association or causation could not be established. Conclusions: The risk of thyroid dysfunction after exposure to ICM during cardiac catheterization is low. It is likely unnecessary to routinely screen all patients for hypothyroidism post ICM exposure and can be limited to high-risk groups candidates. Thyroid dysfunction hypothyroidism iodinated contrast media cardiac catheterization angiography pediatric cardiac catheterization Figures Figure 1 Background Cardiac catheterization is often utilized for both diagnostic and therapeutic purposes in children with congenital heart diseases (CHD). With the advent of newer techniques and smaller equipment, cardiac catheterization has increasingly become a therapeutic option for percutaneous interventions in smaller patients, including infants and neonates [ 1 – 3 ]. It typically involves using iodinated contrast media (ICM) to visualize cardiovascular anatomy. Some studies indicate an increased risk of hypothyroidism in young children linked to the excess iodine dose present in ICM [ 4 – 7 ]. After exposure to an excess iodine load, thyroid hormone synthesis is paradoxically inhibited by a phenomenon known as the Wolff-Chaikoff effect [ 8 ]. In most patients with normal, mature thyroid glands, there is an escape from this inhibition after a period, allowing thyroid hormone synthesis to resume and levels to normalize, typically around 6 days [ 9 ]. However, it is speculated that infants and neonates, particularly premature ones, have immature thyroid glands whose escape mechanism is not well developed, leaving them at risk for persistent inhibition of thyroid hormone synthesis and consequently, for developing acquired hypothyroidism [ 10 ]. Therefore, it has been suggested that exposure to ICM during various diagnostic procedures may disrupt the thyroid hormone synthesis process in young children, including during cardiac procedures catheterizations. In November 2015, the U.S. Food and Drug Administration (FDA) issued a drug safety communication (DSC) alerting the public about rare cases of underactive thyroid in infants following the administration of ICM [ 11 ]. This action was prompted by the FDA's efforts to petition the manufacturers of ICM to investigate the phenomenon thoroughly. However, these companies showed no urgency or initiative in response. Consequently, in May 2022, the FDA recommended that all patients under three years of age be evaluated for thyroid dysfunction three weeks after exposure to ICM [ 12 ]. The DSC further indicated that infants and young children with congenital heart disease (CHD) are particularly at higher risk for hypothyroidism after exposure to ICM during cardiac catheterizations, which often occur more than once in the first three years of life for certain congenital heart lesions. Nonetheless, research on the true incidence of thyroid dysfunction following exposure to ICM is limited. Most studies conducted so far have small sample sizes and/or report only rare instances of hypothyroidism [ 7 , 13 , 14 ] For many pediatric patients entering the cardiac catheterization lab, exposure to ICM at these ages is common, while new-onset thyroid dysfunction requiring replacement therapy is rare. The incidence of thyroid dysfunction following exposure to ICM is unknown. The DSC issued by the FDA provided us with an opportunity to heed its recommendations, thereby allowing us to study the incidence of hypothyroidism in this high-risk group. In this study, we report the findings of the changes in practice brought about by the DSC. Methods After the FDA released the safety communication in 2022, we established a standard practice at our institution to obtain baseline thyroid-stimulating hormone (TSH) and free thyroxine (T4) levels prior to the procedure in all patients < 3 years of age undergoing cardiac catheterization with an anticipated need for ICM to assess for pre-existing thyroid dysfunction. In those patients who received ICM during their catheterization procedure, in line with the FDA safety communication, serum TSH and free T4 levels were measured 3-weeks post-procedure to evaluate for potential iodine-induced complications hypothyroidism. This is a retrospective cohort study involving all cardiac catheterizations using ICM that were performed on euthyroid patients under the age of 3 years at our institution from May 2022 to April 2023. The study received approval from the Institutional Review Board of the University of Tennessee Health Science Center, and the requirement for consent was waived. Patients with pre-existing thyroid conditions were excluded from this study. Data was collected for each individual cardiac catheterization; therefore, if patients underwent multiple catheterizations during this period, each procedure was recorded separately. Demographics such as age, weight at the time of the procedure, gender, race, genetic diagnoses, and ventricular physiology (including single ventricle physiology, 1.5 ventricle, and biventricular physiology) were gathered. Since prematurity is linked to a higher risk of thyroid dysfunction, gestational age at birth and birth weight were also recorded. The iodine-containing contrast used in our cardiac catheterization lab is Isovue-300 (iopamidol, Bracco, Milan, Italy), which contains 300 mg I/mL. The contrast dose received by each patient during their cardiac catheterization was documented. If any patient had additional imaging studies involving extra ICM exposure, specifically computed tomography angiography (CTA) with Isovue-370 (iopamidol, Bracco, Milan, Italy), between their cardiac catheterization and follow-up thyroid labs, that data was also collected, including the weight and age at the time of the CTA and the additional dose of contrast administered. Patients diagnosed with pre-existing thyroid disease, such as clinical hypothyroidism or hyperthyroidism, were excluded from this cohort; however, follow-up thyroid function tests (TFT) were still conducted according to our institutional protocol. Clinical hypothyroidism was defined as having a TSH > 10 mcIU/mL, while subclinical hypothyroidism was defined as a TSH concentration of ≥ 4.5 and < 10 mcIU/mL. Patients with pre-existing subclinical hypothyroidism were not excluded from the study. Patients with TFT indicative of clinical hypothyroidism (either at baseline or during follow-up) were promptly referred to the pediatric endocrinology team for evaluation and treatment. If the patient’s lab results indicated subclinical hypothyroidism, the TFT was repeated 2-weeks later. Should the hormone levels remain abnormal, the patient would then be referred to the pediatric endocrinology team for further evaluation and/or treatment. Statistical Methods: This is a descriptive study. Categorical data are reported as counts and percentages. Continuous data are reported as medians unless otherwise specified, and the range is provided to show the minimum and maximum values. Results Between May 2022 and April 2023, 276 cardiac catheterizations were performed on 217 patients < 3 years of age (Fig. 1 ). ICM was utilized in 116 of these procedures involving 92 individual patients. Seven cardiac catheterizations were performed on patients with pre-existing thyroid dysfunction; consequently, these cases were excluded from this study. Ten patients who underwent a total of 10 catheterizations were lost to follow-up, and post-procedure serum TSH and free T4 levels could not be obtained; thus, these patients were excluded from the study. Nine patients had two separate encounters for cardiac catheterizations during this timeframe, four patients had three catheterizations, and one patient had four catheterizations. Overall, 99 cardiac catheterization procedures were performed on 80 individual patients included in this study. The demographics of these patients are detailed in Table 1 . The median age at the time of exposure to ICM was 5 months, ranging from 20 minutes of life to 35 months. Our cohort included 55.6% Black, 32.3% White, 8.1% Hispanic, and 4.0% of other ethnicities. 31% of our patients had abnormal genetic evaluations, which included genetic diagnoses such as Trisomy 21 (4.0%), DiGeorge Syndrome (4.0%), Trisomy 18 (1.0%), Turner’s Syndrome (1.0%), Soto Syndrome (1.0%), GATA4 mutations (2.0%), CHARGE Syndrome (1.0%), and others listed in Table 1 . A total of 42.4% of the procedures were performed on patients with single ventricle physiology, 2.0% on patients with 1.5 ventricle physiology, and 55.6% on patients with biventricular physiology (Table 1 ). Additionally, 34% of the procedures were performed on premature infants, with 9.1% born under 28 weeks gestation, 7.0% born between 28 and 31 6/7 weeks gestation, and 18.2% born between 32 and 36 6/7 weeks gestation. The median birth weight was 2.72 kg, ranging from 0.45 to 4.42 kg. Table 2 presents the procedural details along with the results from the baseline and follow-up thyroid function tests of this patient cohort. The median procedural weight was 6 kg, with a range of 0.62 kg to 15.7 kg. The median dose of ICM exposure per procedure was 3.9 mL/kg (0.1–20.4 mL/kg). The median interval from the procedure to the follow-up lab evaluation was 23 days (9–143 days). Ten patients did not have their pre-procedure TSH and free T4 levels measured, but all of these patients had normal newborn screening results, which in the United States includes baseline TSH values. Additionally, none of these patients exhibited thyroid dysfunction upon follow-up screening lab tests after cardiac catheterization After cardiac catheterization, 15 of the 80 patients were evaluated by our endocrinology team, either in an inpatient setting during hospital admission or in the outpatient setting. Of these 15 patients, only 3 were referred for thyroid evaluation, while the other 12 were monitored for other endocrinological diseases. Among the 3 who underwent thyroid evaluation, only one was diagnosed with hypothyroidism and treated with levothyroxine. This patient also had a diagnosis of Trisomy 21. Prior to the procedure, the patient's TSH level was 3.03 mcIU/mL, and the free T4 level was 2.14 ng/dL. At the time of the procedure, the patient was 4 months old, weighed 6.3 kg, and received 1.6 mL/kg of Iopamidol. Thirty-five days later, the patient’s TSH level rose to 10.1 mcIU/mL, while the free T4 was 8.2 ng/dL. The endocrinology team evaluated and treated this patient, who has since been weaned off therapy with normal TFT results. Eighteen patients met the criteria for subclinical hypothyroidism based on pre-procedure testing; however, 16 of them showed improvement in their TFT on follow-up testing post-procedure, with 13 achieving complete normalization of their TFT. Based on the post-procedure TSH levels, 15 patients met the definition of subclinical hypothyroidism, with a median TSH value of 5.61 mcIU/mL, ranging from 4.81 to 7.94 mcIU/mL. Two of these patients had persistent abnormalities in their TFT on follow-up testing and were referred to the endocrinology team for further thyroid evaluation. None of these patients developed clinical hypothyroidism upon follow-up testing, and none required hormone replacement therapy. In this cohort, the overall prevalence of pre-existing thyroid dysfunction prior to cardiac catheterization was 6.5% (6 out of 92 patients), while the incidence of acquired thyroid dysfunction following ICM exposure via cardiac catheterization was 1.3% (1 out of 80 euthyroid patients). Additionally, the 6 patients with baseline thyroid dysfunction who were excluded did not require any changes in their medication doses or modifications to their ongoing therapy. It is also noteworthy that 10 of our patients received additional ICM exposures outside of the cardiac catheterization lab via computed tomography angiography (CTA) performed between their cardiac catheterization and their follow-up TFT 3 weeks later (Table 3). The patients who received a CTA had a median age of 3 months (range 0 to 12 months) and weighed 4.1 kg (range 2.6 to 8.4 kg) at the time of the CTA. The median dose of contrast used for these patients was 6 mL (range 5 to 40 mL), or 1.5 mL/kg (range 0.4 to 6.7 mL/kg). Despite the additional dose of ICM, none of these patients developed clinical hypothyroidism. Discussion The use of ICM in infants and young children is often necessary for diagnostic imaging, such as CT angiography, and serves as an integral part of many radiological procedures, including cardiac catheterization. There are concerns about its effects on thyroid function that have been described [ 4 , 5 , 15 ]. The relationship between ICM exposure and thyroid dysfunction in infants and young children is not fully understood, and limited data have been presented to support routine monitoring of thyroid function after exposure. Among the 11 studies cited by the FDA during the DSC, several suggest a possible correlation between ICM exposure and thyroid dysfunction, although all reveal an overall low incidence. In fact, one study showed no significant difference in thyroid function among very low birth weight premature infants exposed to ICM compared to age- and weight-matched controls [ 16 ]. The studies that describe significant changes in thyroid hormone levels also report that these changes in lab values are typically transient and have uncertain clinical significance, as most patients did not require the initiation of hormone replacement therapy [ 5 , 14 , 15 , 17 , 18 ]. In response to the FDA’s safety communication, the pediatric medical community formed specialized task forces among various national societies, including the Pediatric Endocrine Society (PES) and the American College of Radiology (ACR), and subsequently released additional statements to guide practitioners [ 19 , 20 ]. Due to the limited evidence available, these societies did not recommend routine thyroid testing for this patient population but suggested a more individualized approach based on patient-specific risk factors. More evidence is needed to help determine which patients are at highest risk for thyroid dysfunction and the associated clinical consequences In this cohort, we analyzed thyroid function both before and after incidents of ICM exposure in the cardiac catheterization lab. As is often observed in patients with CHD, several individuals in our cohort underwent multiple cardiac catheterizations before the age of 3 years which involved repeated episodes of ICM exposure. Despite this, only one patient, who had a single cardiac catheterization using a relatively low dose of ICM (1.6 mL/kg), was diagnosed with new-onset thyroid dysfunction post-procedure. This patient was 4 months old at the time of the cardiac catheterization and had Trisomy 21, a condition known to increase the risk of congenital hypothyroidism. Calcaterra et al. report an incidence of congenital hypothyroidism of 16.4% among patients with Trisomy 21, with 13.3% of these patients diagnosed within the first 6 months of life after a normal newborn screen [ 21 ]. It is reasonable to suspect that this patient’s thyroid dysfunction could have been incidental to the ICM exposure or at least multifactorial. Nevertheless, it is impossible to establish association versus causation in this case. Other risk factors for thyroid dysfunction in this patient population have been proposed, such as prematurity, impaired renal function, concurrent use of thyroid-disrupting medications (i.e., amiodarone), and illness acuity [ 13 , 22 ]. We are reporting a separate cohort of very young, premature infants exposed to ICM in a separate report. There has been no consensus on the dosing threshold of ICM at which thyroid dysfunction becomes more evident [ 17 ]. Kubicki et al. showed no significant correlation between thyroid dysfunction and the cumulative dose of iodine contrast in patients with congenital heart disease [ 13 ]. If a direct correlation existed between ICM exposure and hypothyroidism, one would expect that higher doses of ICM would lead to greater disruption of the thyroid hormone synthesis process. However, in our study, the dose of contrast varied from 0.1mL/kg to 20.4mL/kg, yet there was no correlation with the development of clinical or subclinical hypothyroidism at any dose range. In fact, the only patient who developed hypothyroidism was on the lower end of this spectrum, receiving just 1.6mL/kg of ICM. Furthermore, patients who had additional exposures to ICM through other methods such as contrast-enhanced CTA did not show a higher incidence of thyroid dysfunction, suggesting that the cumulative dose of ICM does not correlate with the development of hypothyroidism. It is also important to recognize the prevalence of thyroid dysfunction in our cohort before cardiac catheterization. The overall rate of pre-existing thyroid dysfunction in this population prior to cardiac catheterization was 6.5%, diagnosed incidentally due to the pre-procedure screening TFT, whereas the rate of thyroid dysfunction after ICM exposure via cardiac catheterization was only 1.3%. This aligns with a study conducted by Gilligan et al., which demonstrated a similar presence of TSH abnormalities in children ≤ 24 months who received ICM compared to propensity score-matched controls who were not exposed to ICM [ 23 ]. This suggests that thyroid dysfunction in this patient population may simply be an incidental finding related to ICM exposure. Because our practice was adjusted to monitor each patient’s thyroid function post-procedure, it was also found that none of the patients with pre-existing hypothyroidism or hyperthyroidism experienced further exacerbation of their thyroid dysfunction post-procedure or required changes to their therapies, regardless of the dose of ICM. The implications of transient changes in TSH/free T4 levels remain poorly understood and carry uncertain clinical significance. Subclinical hypothyroidism is generally not treated with medication, as it is often considered benign and typically transient. The effects of subclinical hypothyroidism on neurological outcomes in children < 3 years of age are not entirely understood. In a 2-year prospective case-control study, infants and children with untreated subclinical hypothyroidism showed no impairment in neurocognitive function compared to those who received levothyroxine therapy [ 25 ]. Among patients diagnosed with subclinical hypothyroidism prior to the procedure, 89% (i.e., 16 out of 18 patients) exhibited improvement or even complete normalization of their thyroid function on follow-up testing after ICM exposure without receiving therapy. This highlights the complexity of thyroid function in this patient population, which is unrelated to ICM exposure. This study is constrained by its retrospective nature and a relatively small sample size of only 99 ICM exposures through cardiac catheterizations. Follow-up labs were intended to be collected within the 3-week window as per institutional protocol; however, some labs were drawn outside this timeframe. This may have caused some transient changes in lab values to be overlooked in some patients, but ultimately, none of these patients developed sustained thyroid dysfunction. While we attempted to account for all extraneous exposures to ICM outside of the cardiac catheterization lab, we are limited to the data available at our institution. We cannot account for all ICM studies conducted at outside institutions; however, it is unlikely that a significant number of our patients are involved. Some reports suggest that iodine-containing skin disinfectants may also affect thyroid function; however, we are unable to determine which of our patients may have been exposed in this manner. Conclusion Clinical hypothyroidism is rarely solely due to ICM and is more likely multifactorial. More long-term research is needed to clarify the clinical significance of transient changes in thyroid lab results on neurological outcomes. Based on the findings of this study, it is not possible to make definitive recommendations. Nonetheless, it remains true that the incidence of thyroid dysfunction after ICM exposure in infants and children is low. Routine screening of every patient for transient changes in thyroid function following ICM exposure is probably unnecessary and can be confined to specific high-risk individuals. After several discussions with various societies, including the Society for Cardiovascular Angiography and Interventions, the FDA updated its statement on April 26, 2023, recommending that decisions regarding thyroid monitoring after contrast administration for children aged 3 years and younger should be tailored based on each child’s risk factors. These risk factors may include prematurity, very low birth weight, and underlying medical conditions that affect thyroid function [Reference]. This study supports the recent FDA statement that thyroid monitoring after ICM exposure during cardiac catheterization should be determined individually after assessing each child’s risk factors. Declarations Conflicts of Interest Statement: None of the authors have any relevant conflict of interests with the source material. Author Contribution AM and Shyam S. wrote the main manuscript text. JJ, NT, and KH reviewed the manuscript and assisted with literature review. AM, SP and AW collected data and helped with data review. Shiva S. assisted with data analysis and statistics. References Kogure, T. and S.A. Qureshi, The Future of Paediatric Heart Interventions: Where Will We Be in 2030? Curr Cardiol Rep, 2020. 22 (12): p. 158. Kiene, A.M., et al., Percutaneous Stage 1 Palliation for Hypoplastic Left Heart Syndrome. Ann Thorac Surg, 2021. 112 (5): p. e341-e343. Sathanandam, S.K., et al., Amplatzer Piccolo Occluder clinical trial for percutaneous closure of the patent ductus arteriosus in patients >/=700 grams. Catheter Cardiovasc Interv, 2020. 96 (6): p. 1266-1276. Barr, M.L., et al., Thyroid Dysfunction in Children Exposed to Iodinated Contrast Media. J Clin Endocrinol Metab, 2016. 101 (6): p. 2366-70. Parravicini, E., et al., Iodine, thyroid function, and very low birth weight infants. Pediatrics, 1996. 98 (4 Pt 1): p. 730-4. Ahmet, A., et al., Hypothyroidism in neonates post-iodinated contrast media: a systematic review. Acta Paediatr, 2009. 98 (10): p. 1568-74. Jick, S.S., et al., Iodinated Contrast Agents and Risk of Hypothyroidism in Young Children in the United States. Invest Radiol, 2019. 54 (5): p. 296-301. Wolff J, Chaikoff IL. The inhibitory action of excessive iodide upon the synthesis of diiodotyrosine and of thyroxine in the thyroid gland of the normal rat. Endocrinology. 1948;43(3):174–179. Eng PH, Cardona GR, Fang SL, Previti M, Alex S, Carrasco N, Chin WW, Braverman LE. Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. Endocrinology. 1999 Aug;140(8):3404-10. doi: 10.1210/endo.140.8.6893. PMID: 10433193. Putnins, R., et al., Risk of Hypothyroidism After Administration of Iodinated Contrast Material in Neonates: Are You Aware? Can Assoc Radiol J, 2021. 72 (2): p. 192-193. Administration, U.S.F.a.D. FDA Drug Safety Communication: FDA advises of rare cases of underactive thyroid in infants given iodine-containing contrast agents for medical imaging . 2015; Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-advises-rare-cases-underactive-thyroid-infants-given-iodine. Administration, U.S.F.a.D. FDA recommends thyroid monitoring in babies and young children who receive injections of iodine-containing contrast media for medical imaging . 2022; Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-recommends-thyroid-monitoring-babies-and-young-children-who-receive-injections-iodine-containing. Kubicki, R., et al., Frequency of thyroid dysfunction in pediatric patients with congenital heart disease exposed to iodinated contrast media - a long-term observational study. J Pediatr Endocrinol Metab, 2020. 33 (11): p. 1409-1415. Dechant, M.J., et al., Thyroidal response following iodine excess for cardiac catheterisation and intervention in early infancy. Int J Cardiol, 2016. 223 : p. 1014-1018. Rosenberg, V., et al., Hypothyroidism in Young Children Following Exposure to Iodinated Contrast Media: An Observational Study and a Review of the Literature. Pediatr Endocrinol Rev, 2018. 16 (2): p. 256-265. Dembinski, J., et al., Thyroid function in very low birthweight infants after intravenous administration of the iodinated contrast medium iopromide. Arch Dis Child Fetal Neonatal Ed, 2000. 82 (3): p. F215-7. Belloni, E., et al., Effect of iodinated contrast medium on thyroid function: a study in children undergoing cardiac computed tomography. Pediatr Radiol, 2018. 48 (10): p. 1417-1422. Ares, S., et al., Thyroid complications, including overt hypothyroidism, related to the use of non-radiopaque silastic catheters for parenteral feeding in prematures requiring injection of small amounts of an iodinated contrast medium. Acta Paediatr, 1995. 84 (5): p. 579-81. Society, P.E. PES Statement on Thyroid Monitoring in Infants and Young Children Receiving Iodine-Containing Contrast Media . 2022 May 10, 2022; Available from: https://pedsendo.org/news-announcements/pes-statement-on-thyroid-monitoring-in-infants-and-young-children-receiving-iodine-containing-contrast-media/. Radiology, A.C.o. ACR Statement on Use of Iodinated Contrast Material for Medical Imaging in Young Children and Need for Thyroid Monitoring . 2022 May 18, 2022; Available from: https://www.acr.org/Advocacy-and-Economics/ACR-Position-Statements/Use-of-Iodinated-Contrast-Material-for-Medical-Imaging-in-Young-Children Calcaterra, V., et al., Timing, prevalence, and dynamics of thyroid disorders in children and adolescents affected with Down syndrome. J Pediatr Endocrinol Metab, 2020. 33 (7): p. 885-891. Thaker, V.V., et al., Hypothyroidism in Infants With Congenital Heart Disease Exposed to Excess Iodine. J Endocr Soc, 2017. 1 (8): p. 1067-1078. Gilligan, L.A., et al., Primary thyroid dysfunction after single intravenous iodinated contrast exposure in young children: a propensity score matched analysis. Pediatr Radiol, 2021. 51 (4): p. 640-648. Salerno, M., N. Improda, and D. Capalbo, MANAGEMENT OF ENDOCRINE DISEASE Subclinical hypothyroidism in children. Eur J Endocrinol, 2020. 183 (2): p. R13-R28. 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Tables Table 1: Patient demographics, VUS: variant of unknown significance Median (range) N = 99 cardiac catheterizations Age (months) 5 (20 min – 35 months) Gender (female) 67 (68%) Birth weight (kg) 2.72 (0.45 – 4.42 kg) Prematurity 37 weeks 66 (66.7%) Race Black 55 (55.6%) White 32 (32.3%) Hispanic 8 (8.1%) Other 4 (4.0%) Genetic diagnosis Normal genetic evaluation 68 (68.7%) Trisomy 21 4 (4.0%) DiGeorge Syndrome (22q11.1 deletion) 4 (4.0%) Trisomy 18 1 (1.0%) Turner’s Syndrome (45, X) 1 (1.0%) Soto Syndrome (NSD1 gene mutation) 1 (1.0%) GATA4 deletion 2 (2.0%) CHARGE Syndrome (CDH7) 1 (1.0%) JAG1 variant 1 (1.0%) COL27A1 mutation 1 (1.0%) Biotinidase deficiency 1 (1.0%) Trisomy 22 mosaicism 1 (1.0%) Chromosome 8 duplication 1 (1.0%) Duplication on DMD gene 1 (1.0%) VUS 11 (11.1%) Ventricle Physiology Single Ventricle 42 (42.4%) 1.5 Ventricle 2 (2.0%) Biventricular 55 (55.6%) Table 2. Procedure Details and Thyroid Function Tests Median (range) N = 99 Cardiac Catheterizations Procedure weight (kg) 6.0 (0.62 - 15.7) Contrast Dose (mL) 26.5 (0.1 – 140) Contrast Dose (mL/kg) 3.9 (0.1 – 20.4) Baseline Serum TSH (mcIU/mL) 2.7 (0.4 – 9.5) Baseline Serum Free T4 (ng/dL) 1.7 (0.7 – 3.6) Follow Up Serum TSH (mcIU/mL) 2.7 (0.02 – 10.1) Follow Up Serum Free T4 (ng/dL) 1.6 (0.8 – 8.7) Median time from procedure to follow up lab evaluation 23 days (9 - 143 days) Endocrine Referral/Evaluation Need for continued thyroid monitoring 1 patient Followed for other endocrinological issues 12 patients Discharged from endocrine service without treatment 2 patients Table 3. Additional ICM Exposures via CTA with Isovue-370 Additional ICM Exposure via CTA with Isovue-370 (n=10) Age (months) 3 (0 – 12) Gender (female) 6 (60%) Weight (kg) 4.1 (2.6 – 8.4) CTA contrast dose (mL) 6 (5 – 40) CTA contrast dose (mL/kg) 1.5 (0.4 – 6.7) Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7303976","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":500163972,"identity":"2dc595c4-b261-4426-b362-e7a97c740e04","order_by":0,"name":"Ashley Molloy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwUlEQVRIiWNgGAWjYDACHsYGIGnDwCAB5jITrSWNgYcELWDyMAla+HsONz4uqDifuF+6/eEHhgrrxAZCWiTONjYbzzhzO7FH5oyxBMOZdMJaGM4ztknztgG1SOSwMTC2HSasRf48Y/tv3n/ngFrSnzEw/iNCi8HZxjZm3oYDQC0JZgyMDURoMTxzsFma51iycc+NHGOJhGPpxgS1yJ1Jf/iZp8ZOtn1G+sMPH2qsZQlqQQUJpCkfBaNgFIyCUYALAACx7z4aS3SFlwAAAABJRU5ErkJggg==","orcid":"","institution":"University of Tennessee Health Science Center Le Bonheur Children’s Hospital","correspondingAuthor":true,"prefix":"","firstName":"Ashley","middleName":"","lastName":"Molloy","suffix":""},{"id":500163973,"identity":"f5a2b520-fc0d-41a1-8269-30f295f39ca3","order_by":1,"name":"Jason N. Johnson","email":"","orcid":"","institution":"University of Tennessee Health Science Center Le Bonheur Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jason","middleName":"N.","lastName":"Johnson","suffix":""},{"id":500163974,"identity":"e6cc4ce5-a17e-4455-ac1a-15ecec4cf453","order_by":2,"name":"Neil Tailor","email":"","orcid":"","institution":"University of Tennessee Health Science Center Le Bonheur Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Neil","middleName":"","lastName":"Tailor","suffix":""},{"id":500163975,"identity":"8e93bd86-6c34-475c-9a41-cffa71be436d","order_by":3,"name":"Sarah Parkerson","email":"","orcid":"","institution":"University of Tennessee Health Science Center Le Bonheur Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"","lastName":"Parkerson","suffix":""},{"id":500163976,"identity":"092e5ef9-e4a6-4c89-965a-d9cc43852e3f","order_by":4,"name":"Aaron Walsh","email":"","orcid":"","institution":"University of Tennessee Health Science Center Le Bonheur Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Aaron","middleName":"","lastName":"Walsh","suffix":""},{"id":500163977,"identity":"cc6dc1d3-ce3a-4bb0-8d99-32dca4ced916","order_by":5,"name":"Shiva Sathanandam","email":"","orcid":"","institution":"James Cook University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shiva","middleName":"","lastName":"Sathanandam","suffix":""},{"id":500163979,"identity":"d9a7d5c0-059e-4cbe-b8be-c377b8e71cbe","order_by":6,"name":"Katherine Hunter","email":"","orcid":"","institution":"University of Tennessee Health Science Center Le Bonheur Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Katherine","middleName":"","lastName":"Hunter","suffix":""},{"id":500163981,"identity":"29751761-80db-4c9c-9c1b-514ac9409df5","order_by":7,"name":"Shyam Sathanandam","email":"","orcid":"","institution":"Nicklaus Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shyam","middleName":"","lastName":"Sathanandam","suffix":""}],"badges":[],"createdAt":"2025-08-05 21:08:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7303976/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7303976/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89402063,"identity":"3a783672-8d1a-4305-9824-0a5ccc5ca3bd","added_by":"auto","created_at":"2025-08-19 14:24:35","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":380081,"visible":true,"origin":"","legend":"\u003cp\u003eInclusion/Exclusion criteria\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7303976/v1/4e59f61686f3ac4f585516a3.jpeg"},{"id":89606556,"identity":"11e39b10-c669-4efb-bd67-1579286ff2e8","added_by":"auto","created_at":"2025-08-21 20:16:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":866947,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7303976/v1/c65648d5-0caf-41b7-b2a9-9c2182f71d4b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Incidence of Thyroid Dysfunction in Children \u003c 3 Years of Age After Exposure to Iodine-Containing Contrast Agents During Cardiac Catheterization","fulltext":[{"header":"Background","content":"\u003cp\u003eCardiac catheterization is often utilized for both diagnostic and therapeutic purposes in children with congenital heart diseases (CHD). With the advent of newer techniques and smaller equipment, cardiac catheterization has increasingly become a therapeutic option for percutaneous interventions in smaller patients, including infants and neonates [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. It typically involves using iodinated contrast media (ICM) to visualize cardiovascular anatomy. Some studies indicate an increased risk of hypothyroidism in young children linked to the excess iodine dose present in ICM [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e–\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. After exposure to an excess iodine load, thyroid hormone synthesis is paradoxically inhibited by a phenomenon known as the Wolff-Chaikoff effect [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In most patients with normal, mature thyroid glands, there is an escape from this inhibition after a period, allowing thyroid hormone synthesis to resume and levels to normalize, typically around 6 days [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, it is speculated that infants and neonates, particularly premature ones, have immature thyroid glands whose escape mechanism is not well developed, leaving them at risk for persistent inhibition of thyroid hormone synthesis and consequently, for developing acquired hypothyroidism [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Therefore, it has been suggested that exposure to ICM during various diagnostic procedures may disrupt the thyroid hormone synthesis process in young children, including during cardiac procedures catheterizations.\u003c/p\u003e\u003cp\u003eIn November 2015, the U.S. Food and Drug Administration (FDA) issued a drug safety communication (DSC) alerting the public about rare cases of underactive thyroid in infants following the administration of ICM [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This action was prompted by the FDA's efforts to petition the manufacturers of ICM to investigate the phenomenon thoroughly. However, these companies showed no urgency or initiative in response. Consequently, in May 2022, the FDA recommended that all patients under three years of age be evaluated for thyroid dysfunction three weeks after exposure to ICM [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The DSC further indicated that infants and young children with congenital heart disease (CHD) are particularly at higher risk for hypothyroidism after exposure to ICM during cardiac catheterizations, which often occur more than once in the first three years of life for certain congenital heart lesions. Nonetheless, research on the true incidence of thyroid dysfunction following exposure to ICM is limited. Most studies conducted so far have small sample sizes and/or report only rare instances of hypothyroidism [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eFor many pediatric patients entering the cardiac catheterization lab, exposure to ICM at these ages is common, while new-onset thyroid dysfunction requiring replacement therapy is rare. The incidence of thyroid dysfunction following exposure to ICM is unknown. The DSC issued by the FDA provided us with an opportunity to heed its recommendations, thereby allowing us to study the incidence of hypothyroidism in this high-risk group. In this study, we report the findings of the changes in practice brought about by the DSC.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eAfter the FDA released the safety communication in 2022, we established a standard practice at our institution to obtain baseline thyroid-stimulating hormone (TSH) and free thyroxine (T4) levels prior to the procedure in all patients \u0026lt; 3 years of age undergoing cardiac catheterization with an anticipated need for ICM to assess for pre-existing thyroid dysfunction. In those patients who received ICM during their catheterization procedure, in line with the FDA safety communication, serum TSH and free T4 levels were measured 3-weeks post-procedure to evaluate for potential iodine-induced complications hypothyroidism.\u003c/p\u003e\u003cp\u003eThis is a retrospective cohort study involving all cardiac catheterizations using ICM that were performed on euthyroid patients under the age of 3 years at our institution from May 2022 to April 2023. The study received approval from the Institutional Review Board of the University of Tennessee Health Science Center, and the requirement for consent was waived. Patients with pre-existing thyroid conditions were excluded from this study. Data was collected for each individual cardiac catheterization; therefore, if patients underwent multiple catheterizations during this period, each procedure was recorded separately. Demographics such as age, weight at the time of the procedure, gender, race, genetic diagnoses, and ventricular physiology (including single ventricle physiology, 1.5 ventricle, and biventricular physiology) were gathered. Since prematurity is linked to a higher risk of thyroid dysfunction, gestational age at birth and birth weight were also recorded.\u003c/p\u003e\u003cp\u003eThe iodine-containing contrast used in our cardiac catheterization lab is Isovue-300 (iopamidol, Bracco, Milan, Italy), which contains 300 mg I/mL. The contrast dose received by each patient during their cardiac catheterization was documented. If any patient had additional imaging studies involving extra ICM exposure, specifically computed tomography angiography (CTA) with Isovue-370 (iopamidol, Bracco, Milan, Italy), between their cardiac catheterization and follow-up thyroid labs, that data was also collected, including the weight and age at the time of the CTA and the additional dose of contrast administered.\u003c/p\u003e\u003cp\u003ePatients diagnosed with pre-existing thyroid disease, such as clinical hypothyroidism or hyperthyroidism, were excluded from this cohort; however, follow-up thyroid function tests (TFT) were still conducted according to our institutional protocol. Clinical hypothyroidism was defined as having a TSH \u0026gt; 10 mcIU/mL, while subclinical hypothyroidism was defined as a TSH concentration of ≥ 4.5 and \u0026lt; 10 mcIU/mL. Patients with pre-existing subclinical hypothyroidism were not excluded from the study.\u003c/p\u003e\u003cp\u003ePatients with TFT indicative of clinical hypothyroidism (either at baseline or during follow-up) were promptly referred to the pediatric endocrinology team for evaluation and treatment. If the patient’s lab results indicated subclinical hypothyroidism, the TFT was repeated 2-weeks later. Should the hormone levels remain abnormal, the patient would then be referred to the pediatric endocrinology team for further evaluation and/or treatment.\u003c/p\u003e\u003cp\u003eStatistical Methods: This is a descriptive study. Categorical data are reported as counts and percentages. Continuous data are reported as medians unless otherwise specified, and the range is provided to show the minimum and maximum values.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eBetween May 2022 and April 2023, 276 cardiac catheterizations were performed on 217 patients\u0026thinsp;\u0026lt;\u0026thinsp;3 years of age (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). ICM was utilized in 116 of these procedures involving 92 individual patients. Seven cardiac catheterizations were performed on patients with pre-existing thyroid dysfunction; consequently, these cases were excluded from this study. Ten patients who underwent a total of 10 catheterizations were lost to follow-up, and post-procedure serum TSH and free T4 levels could not be obtained; thus, these patients were excluded from the study. Nine patients had two separate encounters for cardiac catheterizations during this timeframe, four patients had three catheterizations, and one patient had four catheterizations. Overall, 99 cardiac catheterization procedures were performed on 80 individual patients included in this study. The demographics of these patients are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age at the time of exposure to ICM was 5 months, ranging from 20 minutes of life to 35 months. Our cohort included 55.6% Black, 32.3% White, 8.1% Hispanic, and 4.0% of other ethnicities. 31% of our patients had abnormal genetic evaluations, which included genetic diagnoses such as Trisomy 21 (4.0%), DiGeorge Syndrome (4.0%), Trisomy 18 (1.0%), Turner\u0026rsquo;s Syndrome (1.0%), Soto Syndrome (1.0%), GATA4 mutations (2.0%), CHARGE Syndrome (1.0%), and others listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A total of 42.4% of the procedures were performed on patients with single ventricle physiology, 2.0% on patients with 1.5 ventricle physiology, and 55.6% on patients with biventricular physiology (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Additionally, 34% of the procedures were performed on premature infants, with 9.1% born under 28 weeks gestation, 7.0% born between 28 and 31 6/7 weeks gestation, and 18.2% born between 32 and 36 6/7 weeks gestation. The median birth weight was 2.72 kg, ranging from 0.45 to 4.42 kg.\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents the procedural details along with the results from the baseline and follow-up thyroid function tests of this patient cohort. The median procedural weight was 6 kg, with a range of 0.62 kg to 15.7 kg. The median dose of ICM exposure per procedure was 3.9 mL/kg (0.1\u0026ndash;20.4 mL/kg). The median interval from the procedure to the follow-up lab evaluation was 23 days (9\u0026ndash;143 days). Ten patients did not have their pre-procedure TSH and free T4 levels measured, but all of these patients had normal newborn screening results, which in the United States includes baseline TSH values. Additionally, none of these patients exhibited thyroid dysfunction upon follow-up screening lab tests after cardiac catheterization\u003c/p\u003e\u003cp\u003eAfter cardiac catheterization, 15 of the 80 patients were evaluated by our endocrinology team, either in an inpatient setting during hospital admission or in the outpatient setting. Of these 15 patients, only 3 were referred for thyroid evaluation, while the other 12 were monitored for other endocrinological diseases. Among the 3 who underwent thyroid evaluation, only one was diagnosed with hypothyroidism and treated with levothyroxine. This patient also had a diagnosis of Trisomy 21. Prior to the procedure, the patient's TSH level was 3.03 mcIU/mL, and the free T4 level was 2.14 ng/dL. At the time of the procedure, the patient was 4 months old, weighed 6.3 kg, and received 1.6 mL/kg of Iopamidol. Thirty-five days later, the patient\u0026rsquo;s TSH level rose to 10.1 mcIU/mL, while the free T4 was 8.2 ng/dL. The endocrinology team evaluated and treated this patient, who has since been weaned off therapy with normal TFT results.\u003c/p\u003e\u003cp\u003eEighteen patients met the criteria for subclinical hypothyroidism based on pre-procedure testing; however, 16 of them showed improvement in their TFT on follow-up testing post-procedure, with 13 achieving complete normalization of their TFT. Based on the post-procedure TSH levels, 15 patients met the definition of subclinical hypothyroidism, with a median TSH value of 5.61 mcIU/mL, ranging from 4.81 to 7.94 mcIU/mL. Two of these patients had persistent abnormalities in their TFT on follow-up testing and were referred to the endocrinology team for further thyroid evaluation. None of these patients developed clinical hypothyroidism upon follow-up testing, and none required hormone replacement therapy.\u003c/p\u003e\u003cp\u003eIn this cohort, the overall prevalence of pre-existing thyroid dysfunction prior to cardiac catheterization was 6.5% (6 out of 92 patients), while the incidence of acquired thyroid dysfunction following ICM exposure via cardiac catheterization was 1.3% (1 out of 80 euthyroid patients). Additionally, the 6 patients with baseline thyroid dysfunction who were excluded did not require any changes in their medication doses or modifications to their ongoing therapy.\u003c/p\u003e\u003cp\u003eIt is also noteworthy that 10 of our patients received additional ICM exposures outside of the cardiac catheterization lab via computed tomography angiography (CTA) performed between their cardiac catheterization and their follow-up TFT 3 weeks later (Table\u0026nbsp;3). The patients who received a CTA had a median age of 3 months (range 0 to 12 months) and weighed 4.1 kg (range 2.6 to 8.4 kg) at the time of the CTA. The median dose of contrast used for these patients was 6 mL (range 5 to 40 mL), or 1.5 mL/kg (range 0.4 to 6.7 mL/kg). Despite the additional dose of ICM, none of these patients developed clinical hypothyroidism.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe use of ICM in infants and young children is often necessary for diagnostic imaging, such as CT angiography, and serves as an integral part of many radiological procedures, including cardiac catheterization. There are concerns about its effects on thyroid function that have been described [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The relationship between ICM exposure and thyroid dysfunction in infants and young children is not fully understood, and limited data have been presented to support routine monitoring of thyroid function after exposure. Among the 11 studies cited by the FDA during the DSC, several suggest a possible correlation between ICM exposure and thyroid dysfunction, although all reveal an overall low incidence. In fact, one study showed no significant difference in thyroid function among very low birth weight premature infants exposed to ICM compared to age- and weight-matched controls [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The studies that describe significant changes in thyroid hormone levels also report that these changes in lab values are typically transient and have uncertain clinical significance, as most patients did not require the initiation of hormone replacement therapy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn response to the FDA\u0026rsquo;s safety communication, the pediatric medical community formed specialized task forces among various national societies, including the Pediatric Endocrine Society (PES) and the American College of Radiology (ACR), and subsequently released additional statements to guide practitioners [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Due to the limited evidence available, these societies did not recommend routine thyroid testing for this patient population but suggested a more individualized approach based on patient-specific risk factors. More evidence is needed to help determine which patients are at highest risk for thyroid dysfunction and the associated clinical consequences\u003c/p\u003e\u003cp\u003eIn this cohort, we analyzed thyroid function both before and after incidents of ICM exposure in the cardiac catheterization lab. As is often observed in patients with CHD, several individuals in our cohort underwent multiple cardiac catheterizations before the age of 3 years which involved repeated episodes of ICM exposure. Despite this, only one patient, who had a single cardiac catheterization using a relatively low dose of ICM (1.6 mL/kg), was diagnosed with new-onset thyroid dysfunction post-procedure. This patient was 4 months old at the time of the cardiac catheterization and had Trisomy 21, a condition known to increase the risk of congenital hypothyroidism. Calcaterra et al. report an incidence of congenital hypothyroidism of 16.4% among patients with Trisomy 21, with 13.3% of these patients diagnosed within the first 6 months of life after a normal newborn screen [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. It is reasonable to suspect that this patient\u0026rsquo;s thyroid dysfunction could have been incidental to the ICM exposure or at least multifactorial. Nevertheless, it is impossible to establish association versus causation in this case. Other risk factors for thyroid dysfunction in this patient population have been proposed, such as prematurity, impaired renal function, concurrent use of thyroid-disrupting medications (i.e., amiodarone), and illness acuity [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. We are reporting a separate cohort of very young, premature infants exposed to ICM in a separate report.\u003c/p\u003e\u003cp\u003eThere has been no consensus on the dosing threshold of ICM at which thyroid dysfunction becomes more evident [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Kubicki et al. showed no significant correlation between thyroid dysfunction and the cumulative dose of iodine contrast in patients with congenital heart disease [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. If a direct correlation existed between ICM exposure and hypothyroidism, one would expect that higher doses of ICM would lead to greater disruption of the thyroid hormone synthesis process. However, in our study, the dose of contrast varied from 0.1mL/kg to 20.4mL/kg, yet there was no correlation with the development of clinical or subclinical hypothyroidism at any dose range. In fact, the only patient who developed hypothyroidism was on the lower end of this spectrum, receiving just 1.6mL/kg of ICM. Furthermore, patients who had additional exposures to ICM through other methods such as contrast-enhanced CTA did not show a higher incidence of thyroid dysfunction, suggesting that the cumulative dose of ICM does not correlate with the development of hypothyroidism.\u003c/p\u003e\u003cp\u003eIt is also important to recognize the prevalence of thyroid dysfunction in our cohort before cardiac catheterization. The overall rate of pre-existing thyroid dysfunction in this population prior to cardiac catheterization was 6.5%, diagnosed incidentally due to the pre-procedure screening TFT, whereas the rate of thyroid dysfunction after ICM exposure via cardiac catheterization was only 1.3%. This aligns with a study conducted by Gilligan et al., which demonstrated a similar presence of TSH abnormalities in children\u0026thinsp;\u0026le;\u0026thinsp;24 months who received ICM compared to propensity score-matched controls who were not exposed to ICM [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. This suggests that thyroid dysfunction in this patient population may simply be an incidental finding related to ICM exposure. Because our practice was adjusted to monitor each patient\u0026rsquo;s thyroid function post-procedure, it was also found that none of the patients with pre-existing hypothyroidism or hyperthyroidism experienced further exacerbation of their thyroid dysfunction post-procedure or required changes to their therapies, regardless of the dose of ICM.\u003c/p\u003e\u003cp\u003eThe implications of transient changes in TSH/free T4 levels remain poorly understood and carry uncertain clinical significance. Subclinical hypothyroidism is generally not treated with medication, as it is often considered benign and typically transient. The effects of subclinical hypothyroidism on neurological outcomes in children\u0026thinsp;\u0026lt;\u0026thinsp;3 years of age are not entirely understood. In a 2-year prospective case-control study, infants and children with untreated subclinical hypothyroidism showed no impairment in neurocognitive function compared to those who received levothyroxine therapy [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Among patients diagnosed with subclinical hypothyroidism prior to the procedure, 89% (i.e., 16 out of 18 patients) exhibited improvement or even complete normalization of their thyroid function on follow-up testing after ICM exposure without receiving therapy. This highlights the complexity of thyroid function in this patient population, which is unrelated to ICM exposure.\u003c/p\u003e\u003cp\u003eThis study is constrained by its retrospective nature and a relatively small sample size of only 99 ICM exposures through cardiac catheterizations. Follow-up labs were intended to be collected within the 3-week window as per institutional protocol; however, some labs were drawn outside this timeframe. This may have caused some transient changes in lab values to be overlooked in some patients, but ultimately, none of these patients developed sustained thyroid dysfunction. While we attempted to account for all extraneous exposures to ICM outside of the cardiac catheterization lab, we are limited to the data available at our institution. We cannot account for all ICM studies conducted at outside institutions; however, it is unlikely that a significant number of our patients are involved. Some reports suggest that iodine-containing skin disinfectants may also affect thyroid function; however, we are unable to determine which of our patients may have been exposed in this manner.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eClinical hypothyroidism is rarely solely due to ICM and is more likely multifactorial. More long-term research is needed to clarify the clinical significance of transient changes in thyroid lab results on neurological outcomes. Based on the findings of this study, it is not possible to make definitive recommendations. Nonetheless, it remains true that the incidence of thyroid dysfunction after ICM exposure in infants and children is low. Routine screening of every patient for transient changes in thyroid function following ICM exposure is probably unnecessary and can be confined to specific high-risk individuals. After several discussions with various societies, including the Society for Cardiovascular Angiography and Interventions, the FDA updated its statement on April 26, 2023, recommending that decisions regarding thyroid monitoring after contrast administration for children aged 3 years and younger should be tailored based on each child\u0026rsquo;s risk factors. These risk factors may include prematurity, very low birth weight, and underlying medical conditions that affect thyroid function [Reference]. This study supports the recent FDA statement that thyroid monitoring after ICM exposure during cardiac catheterization should be determined individually after assessing each child\u0026rsquo;s risk factors.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eConflicts of Interest\u003c/h2\u003e\u003cp\u003eStatement: None of the authors have any relevant conflict of interests with the source material.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAM and Shyam S. wrote the main manuscript text. JJ, NT, and KH reviewed the manuscript and assisted with literature review. AM, SP and AW collected data and helped with data review. Shiva S. assisted with data analysis and statistics.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKogure, T. and S.A. Qureshi, \u003cem\u003eThe Future of Paediatric Heart Interventions: Where Will We Be in 2030?\u003c/em\u003e Curr Cardiol Rep, 2020. \u003cstrong\u003e22\u003c/strong\u003e(12): p. 158.\u003c/li\u003e\n\u003cli\u003eKiene, A.M., et al., \u003cem\u003ePercutaneous Stage 1 Palliation for Hypoplastic Left Heart Syndrome.\u003c/em\u003e Ann Thorac Surg, 2021. \u003cstrong\u003e112\u003c/strong\u003e(5): p. e341-e343.\u003c/li\u003e\n\u003cli\u003eSathanandam, S.K., et al., \u003cem\u003eAmplatzer Piccolo Occluder clinical trial for percutaneous closure of the patent ductus arteriosus in patients \u0026gt;/=700 grams.\u003c/em\u003e Catheter Cardiovasc Interv, 2020. \u003cstrong\u003e96\u003c/strong\u003e(6): p. 1266-1276.\u003c/li\u003e\n\u003cli\u003eBarr, M.L., et al., \u003cem\u003eThyroid Dysfunction in Children Exposed to Iodinated Contrast Media.\u003c/em\u003e J Clin Endocrinol Metab, 2016. \u003cstrong\u003e101\u003c/strong\u003e(6): p. 2366-70.\u003c/li\u003e\n\u003cli\u003eParravicini, E., et al., \u003cem\u003eIodine, thyroid function, and very low birth weight infants.\u003c/em\u003e Pediatrics, 1996. \u003cstrong\u003e98\u003c/strong\u003e(4 Pt 1): p. 730-4.\u003c/li\u003e\n\u003cli\u003eAhmet, A., et al., \u003cem\u003eHypothyroidism in neonates post-iodinated contrast media: a systematic review.\u003c/em\u003e Acta Paediatr, 2009. \u003cstrong\u003e98\u003c/strong\u003e(10): p. 1568-74.\u003c/li\u003e\n\u003cli\u003eJick, S.S., et al., \u003cem\u003eIodinated Contrast Agents and Risk of Hypothyroidism in Young Children in the United States.\u003c/em\u003e Invest Radiol, 2019. \u003cstrong\u003e54\u003c/strong\u003e(5): p. 296-301.\u003c/li\u003e\n\u003cli\u003eWolff J, Chaikoff IL. The inhibitory action of excessive iodide upon the synthesis of diiodotyrosine and of thyroxine in the thyroid gland of the normal rat. Endocrinology. 1948;43(3):174\u0026ndash;179.\u003c/li\u003e\n\u003cli\u003eEng PH, Cardona GR, Fang SL, Previti M, Alex S, Carrasco N, Chin WW, Braverman LE. Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. Endocrinology. 1999 Aug;140(8):3404-10. doi: 10.1210/endo.140.8.6893. PMID: 10433193.\u003c/li\u003e\n\u003cli\u003ePutnins, R., et al., \u003cem\u003eRisk of Hypothyroidism After Administration of Iodinated Contrast Material in Neonates: Are You Aware?\u003c/em\u003e Can Assoc Radiol J, 2021. \u003cstrong\u003e72\u003c/strong\u003e(2): p. 192-193.\u003c/li\u003e\n\u003cli\u003eAdministration, U.S.F.a.D. \u003cem\u003eFDA Drug Safety Communication: FDA advises of rare cases of underactive thyroid in infants given iodine-containing contrast agents for medical imaging\u003c/em\u003e. 2015; Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-advises-rare-cases-underactive-thyroid-infants-given-iodine.\u003c/li\u003e\n\u003cli\u003eAdministration, U.S.F.a.D. \u003cem\u003eFDA recommends thyroid monitoring in babies and young children who receive injections of iodine-containing contrast media for medical imaging\u003c/em\u003e. 2022; Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-recommends-thyroid-monitoring-babies-and-young-children-who-receive-injections-iodine-containing.\u003c/li\u003e\n\u003cli\u003eKubicki, R., et al., \u003cem\u003eFrequency of thyroid dysfunction in pediatric patients with congenital heart disease exposed to iodinated contrast media - a long-term observational study.\u003c/em\u003e J Pediatr Endocrinol Metab, 2020. \u003cstrong\u003e33\u003c/strong\u003e(11): p. 1409-1415.\u003c/li\u003e\n\u003cli\u003eDechant, M.J., et al., \u003cem\u003eThyroidal response following iodine excess for cardiac catheterisation and intervention in early infancy.\u003c/em\u003e Int J Cardiol, 2016. \u003cstrong\u003e223\u003c/strong\u003e: p. 1014-1018.\u003c/li\u003e\n\u003cli\u003eRosenberg, V., et al., \u003cem\u003eHypothyroidism in Young Children Following Exposure to Iodinated Contrast Media: An Observational Study and a Review of the Literature.\u003c/em\u003e Pediatr Endocrinol Rev, 2018. \u003cstrong\u003e16\u003c/strong\u003e(2): p. 256-265.\u003c/li\u003e\n\u003cli\u003eDembinski, J., et al., \u003cem\u003eThyroid function in very low birthweight infants after intravenous administration of the iodinated contrast medium iopromide.\u003c/em\u003e Arch Dis Child Fetal Neonatal Ed, 2000. \u003cstrong\u003e82\u003c/strong\u003e(3): p. F215-7.\u003c/li\u003e\n\u003cli\u003eBelloni, E., et al., \u003cem\u003eEffect of iodinated contrast medium on thyroid function: a study in children undergoing cardiac computed tomography.\u003c/em\u003e Pediatr Radiol, 2018. \u003cstrong\u003e48\u003c/strong\u003e(10): p. 1417-1422.\u003c/li\u003e\n\u003cli\u003eAres, S., et al., \u003cem\u003eThyroid complications, including overt hypothyroidism, related to the use of non-radiopaque silastic catheters for parenteral feeding in prematures requiring injection of small amounts of an iodinated contrast medium.\u003c/em\u003e Acta Paediatr, 1995. \u003cstrong\u003e84\u003c/strong\u003e(5): p. 579-81.\u003c/li\u003e\n\u003cli\u003eSociety, P.E. \u003cem\u003ePES Statement on Thyroid Monitoring in Infants and Young Children Receiving Iodine-Containing Contrast Media\u003c/em\u003e. 2022 May 10, 2022; Available from: https://pedsendo.org/news-announcements/pes-statement-on-thyroid-monitoring-in-infants-and-young-children-receiving-iodine-containing-contrast-media/.\u003c/li\u003e\n\u003cli\u003eRadiology, A.C.o. \u003cem\u003eACR Statement on Use of Iodinated Contrast Material for Medical Imaging in Young Children and Need for Thyroid Monitoring\u003c/em\u003e. 2022 May 18, 2022; Available from: https://www.acr.org/Advocacy-and-Economics/ACR-Position-Statements/Use-of-Iodinated-Contrast-Material-for-Medical-Imaging-in-Young-Children\u003c/li\u003e\n\u003cli\u003eCalcaterra, V., et al., \u003cem\u003eTiming, prevalence, and dynamics of thyroid disorders in children and adolescents affected with Down syndrome.\u003c/em\u003e J Pediatr Endocrinol Metab, 2020. \u003cstrong\u003e33\u003c/strong\u003e(7): p. 885-891.\u003c/li\u003e\n\u003cli\u003eThaker, V.V., et al., \u003cem\u003eHypothyroidism in Infants With Congenital Heart Disease Exposed to Excess Iodine.\u003c/em\u003e J Endocr Soc, 2017. \u003cstrong\u003e1\u003c/strong\u003e(8): p. 1067-1078.\u003c/li\u003e\n\u003cli\u003eGilligan, L.A., et al., \u003cem\u003ePrimary thyroid dysfunction after single intravenous iodinated contrast exposure in young children: a propensity score matched analysis.\u003c/em\u003e Pediatr Radiol, 2021. \u003cstrong\u003e51\u003c/strong\u003e(4): p. 640-648.\u003c/li\u003e\n\u003cli\u003eSalerno, M., N. Improda, and D. Capalbo, \u003cem\u003eMANAGEMENT OF ENDOCRINE DISEASE Subclinical hypothyroidism in children.\u003c/em\u003e Eur J Endocrinol, 2020. \u003cstrong\u003e183\u003c/strong\u003e(2): p. R13-R28.\u003c/li\u003e\n\u003cli\u003eCapalbo, D., et al., \u003cem\u003eCognitive Function in Children With Idiopathic Subclinical Hypothyroidism: Effects of 2 Years of Levothyroxine Therapy.\u003c/em\u003e J Clin Endocrinol Metab, 2020. \u003cstrong\u003e105\u003c/strong\u003e(3).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1: Patient demographics, VUS: variant of unknown significance\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"582\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 396px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003cp\u003eN = 99 cardiac catheterizations\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003eAge (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 396px;\"\u003e\n \u003cp\u003e5 (20 min \u0026ndash; 35 months)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003eGender (female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 396px;\"\u003e\n \u003cp\u003e67 (68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003eBirth weight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 396px;\"\u003e\n \u003cp\u003e2.72 (0.45 \u0026ndash; 4.42 kg)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003ePrematurity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003e\u0026lt;28 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e9 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003e28 \u0026ndash; 31 6/7 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e7 (7.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003e32 \u0026ndash; 36 6/7 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e18 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003e\u0026gt;37 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e66 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003eRace\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eBlack\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e55 (55.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eWhite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e32 (32.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eHispanic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e8 (8.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e4 (4.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"15\" valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003eGenetic diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eNormal genetic evaluation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e68 (68.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eTrisomy 21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e4 (4.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eDiGeorge Syndrome (22q11.1 deletion)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e4 (4.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eTrisomy 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eTurner\u0026rsquo;s Syndrome (45, X)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eSoto Syndrome (NSD1 gene mutation)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eGATA4 deletion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e2 (2.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eCHARGE Syndrome (CDH7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eJAG1 variant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eCOL27A1 mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eBiotinidase deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eTrisomy 22 mosaicism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eChromosome 8 duplication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eDuplication on DMD gene\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eVUS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e11 (11.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003eVentricle Physiology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eSingle Ventricle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e42 (42.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003e1.5 Ventricle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e2 (2.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 276px;\"\u003e\n \u003cp\u003eBiventricular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e55 (55.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2. Procedure Details and Thyroid Function Tests\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 258px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 366px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003cp\u003eN = 99 Cardiac Catheterizations\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 258px;\"\u003e\n \u003cp\u003eProcedure weight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 366px;\"\u003e\n \u003cp\u003e6.0 (0.62 - 15.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 258px;\"\u003e\n \u003cp\u003eContrast Dose (mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 366px;\"\u003e\n \u003cp\u003e26.5 (0.1 \u0026ndash; 140)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 258px;\"\u003e\n \u003cp\u003eContrast Dose (mL/kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 366px;\"\u003e\n \u003cp\u003e3.9 (0.1 \u0026ndash; 20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 258px;\"\u003e\n \u003cp\u003eBaseline Serum TSH (mcIU/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 366px;\"\u003e\n \u003cp\u003e2.7 (0.4 \u0026ndash; 9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 258px;\"\u003e\n \u003cp\u003eBaseline Serum Free T4 (ng/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 366px;\"\u003e\n \u003cp\u003e1.7 (0.7 \u0026ndash; 3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 258px;\"\u003e\n \u003cp\u003eFollow Up Serum TSH (mcIU/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 366px;\"\u003e\n \u003cp\u003e2.7 (0.02 \u0026ndash; 10.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 258px;\"\u003e\n \u003cp\u003eFollow Up Serum Free T4 (ng/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 366px;\"\u003e\n \u003cp\u003e1.6 (0.8 \u0026ndash; 8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 258px;\"\u003e\n \u003cp\u003eMedian time from procedure to follow up lab evaluation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 366px;\"\u003e\n \u003cp\u003e23 days (9 - 143 days)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 258px;\"\u003e\n \u003cp\u003eEndocrine Referral/Evaluation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003eNeed for continued thyroid monitoring\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e1 patient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003eFollowed for other endocrinological issues\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e12 patients\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003eDischarged from endocrine service without treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e2 patients\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 3. \u0026nbsp;Additional ICM Exposures via CTA with Isovue-370\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 623px;\"\u003e\n \u003cp\u003eAdditional ICM Exposure via CTA with Isovue-370 (n=10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eAge (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e3 (0 \u0026ndash; 12)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eGender (female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e6 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eWeight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e4.1 (2.6 \u0026ndash; 8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eCTA contrast dose (mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e6 (5 \u0026ndash; 40)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eCTA contrast dose (mL/kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e1.5 (0.4 \u0026ndash; 6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Thyroid dysfunction, hypothyroidism, iodinated contrast media, cardiac catheterization, angiography, pediatric cardiac catheterization","lastPublishedDoi":"10.21203/rs.3.rs-7303976/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7303976/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e In March 2022, the U.S. Food and Drug Administration (FDA) issued a drug safety communication recommending evaluation for thyroid dysfunction in all patients under three years of age, three weeks after exposure to iodinated contrast media (ICM). The purpose of this study was to describe the incidence of thyroid dysfunction following ICM exposure during cardiac catheterizations in children \u0026lt; 3 years of age.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Design:\u003c/strong\u003e Thyroid function tests (TFT), including serum thyroid-stimulating hormone (TSH) and free thyroxine (free T4) levels, were measured in children \u0026lt; 3 years of age exposed to ICM during cardiac catheterization, both pre-procedure and 3-weeks post-procedure, between May 2022 and April 2023. Clinical hypothyroidism was defined as a low free T4 level and high TSH level compared to reference standards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Eighty patients were included in the analysis, undergoing 99 cardiac catheterization procedures with exposure to ICM. The median age and weight were 5 months (20 minutes – 35 months) and 6 kg (0.62-15.7 kg), respectively. The median dose of ICM per procedure was 3.9mL/kg (0.1 – 20.4mL/kg). The median time of follow-up TFT was 23 days (9-143 days). On follow-up, only one infant with Trisomy-21 developed new-onset hypothyroidism requiring treatment with levothyroxine (incidence rate of 1.0%). However, whether this was an association or causation could not be established.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e The risk of thyroid dysfunction after exposure to ICM during cardiac catheterization is low. It is likely unnecessary to routinely screen all patients for hypothyroidism post ICM exposure and can be limited to high-risk groups candidates.\u003c/p\u003e","manuscriptTitle":"Incidence of Thyroid Dysfunction in Children \u0026lt; 3 Years of Age After Exposure to Iodine-Containing Contrast Agents During Cardiac Catheterization","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-19 14:24:31","doi":"10.21203/rs.3.rs-7303976/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8d6f6c00-c6e7-4d70-a789-c8be919addd7","owner":[],"postedDate":"August 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-21T20:08:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-19 14:24:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7303976","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7303976","identity":"rs-7303976","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}