Risks of Iodine Excess.

Iodine is a micronutrient that is required for thyroid hormone synthesis. The iodide cycle in thyroid hormone synthesis consists of a series of transport, oxidation, organification, and binding/coupling steps in thyroid follicular cells. Common sources of iodine include the consumption of an iodine-rich diet or iodine fortified foods, the administration of amiodarone, iodine-containing supplements, or iodinated contrast media, and other miscellaneous sources. Methods to assess population iodine status include the measurement of urinary iodine concentrations, blood thyroglobulin levels, prevalence of elevated neonatal TSH levels, and thyroid volume. Although excessive iodine intake or exposure is generally well tolerated, an acute iodine load may result in thyroid dysfunction (hypothyroidism or hyperthyroidism) in certain susceptible individuals due to the failure to escape from the Wolff-Chaikoff effect and to the Jod-Basedow phenomenon, respectively. In this review, we discuss the associations between excessive iodine intake or exposure, with particular focus on iodinated contrast media as a common source of excess iodine in healthcare settings, and risks of incident thyroid dysfunction. We also summarize the risks of iodine excess in vulnerable populations and review current guidelines regarding the screening and monitoring of iodinated contrast-induced thyroid dysfunction. Finally, we discuss the long-term potential nonthyroidal health risks associated with iodine excess and suggest the need for more data to define safe upper limits for iodine intake, particularly in high-risk populations.

Thyroid Dysfunction Risk After Iodinated Contrast Media Administration: A Prospective Longitudinal Cohort Analysis.

CONTEXT: Iodinated contrast media (ICM) is a common source of excess iodine in medical settings, given the common use of iodinated radiologic procedures. OBJECTIVE: To determine the long-term risks of thyroid dysfunction following iodinated contrast administration in a prospective study. DESIGN, SETTING, PARTICIPANTS: A longitudinal cohort study was conducted of patients in the U.S. Veterans Affairs medical system who received ICM. MAIN OUTCOME MEASURES: Serum thyroid function, thyroid antibody, and inflammatory markers were measured at baseline. Thyroid function tests were repeated at 1 month, 3 months, and every 6 months thereafter until 36 months. Risk of thyroid dysfunction and longitudinal changes in thyroid hormone levels were assessed using mixed effect models. RESULTS: There were 122 participants (median age, 70.0 [IQR 62.2-74.0] years; 98.4% male). At baseline, six subjects had subclinical thyroid dysfunction prior to ICM receipt. During median follow-up of 18 months, iodine-induced thyroid dysfunction was observed in 11.5% (14/122); six (4.9%) developed hyperthyroidism (including one with overt hyperthyroidism) and eight (6.6%) subclinical hypothyroidism. At last follow-up, ten of 20 subjects with thyroid dysfunction (14 new-onset cases and six with preexisting thyroid dysfunction) had persistent subclinical hyperthyroidism or hypothyroidism. There were also subtle changes in thyroid hormones observed longitudinally within the reference ranges in the overall cohort. CONCLUSIONS: There is a rare long-term risk of an excess iodine load on thyroid dysfunction even among individuals from an overall iodine-sufficient region, supporting the need for targeted monitoring following iodinated contrast administration.

Overview of Thyroid and Parathyroid Disease-The Endocrinology Perspective.

Thyroid and parathyroid disorders are quite common in the population and range from benign to malignant conditions that may be hormonally active or inactive. Select disorders of the thyroid and parathyroid can be managed medically, although there are a variety of circumstances that may require definitive management with surgery. Surgical intervention may be required for hormonal control, compressive symptoms, or for the removal and/or control of malignancy. The endocrinologist's perspective of the preoperative and postoperative management regarding thyroid and parathyroid surgeries will be discussed.

Iodine-Induced Hypothyroidism and Long-Term Risks of Incident Heart Failure.

Background Although most individuals can adapt to a large iodine load and remain euthyroid, hypothyroidism can develop after iodine exposure. Hypothyroidism is associated with adverse cardiovascular consequences, including heart failure. This study was performed to investigate the relationships between iodine-induced hypothyroidism and incident heart failure. Methods and Results This cohort study of the US Veterans Health Administration (1998-2021) included adults aged ≥18 years with a serum thyroid-stimulating hormone (thyrotropin) <60 days of iodine contrast administration, and <1 year of a baseline normal serum thyroid-stimulating hormone. Cox proportional hazards regression ascertained risk of incident heart failure following iodine-induced hypothyroidism, adjusting for age, sex, race and ethnicity, body mass index, and history of coronary heart disease, dyslipidemia, diabetes, and hypertension. Of 45 470 veterans (mean±SD age, 61.1±14.1 years; 88% men), 3361 (7.4%) developed iodine-induced hypothyroidism. Heart failure developed in 5685 (12.5%) individuals over a median follow-up of 3.6 years (interquartile range, 1.9-7.2 years). Adjusted for risk factors, iodine-induced hypothyroidism was associated with increased risk of heart failure, compared with those who remained euthyroid after iodine exposure (adjusted hazard ratio [HR], 1.11 [95% CI, 1.01-1.22]). Women were at greater risk than men (adjusted HR: women, 1.65 [95% CI, 1.13-2.40]; men, 1.08 [95% CI, 0.98-1.19]; P for interaction, 0.02). Conclusions In the largest US study of this topic, hypothyroidism following iodine exposure was associated with an increased risk of incident heart failure, particularly in women. These findings support the need for further research to address the clinical significance of this issue, including the possible sex-specific risks of incident heart failure in more diverse data sets and study populations.

Per- and Polyfluoroalkyl Substances (PFAS) in Community Water Systems (CWS) and the Risk of Thyroid Cancer: An Ecological Study.

Thyroid cancer incidence has been steadily increasing over the past decade in the United States (US). A discussion exists regarding the potential contribution of exposure to endocrine-disrupting chemicals, encompassing certain per- and poly-fluoroalkyl substances (PFASs). This ecological study evaluated the potential correlation between PFAS levels in drinking water and thyroid cancer incidence in the US. Data on age-adjusted thyroid cancer incidence rate (per 100,000 persons) by county were obtained from the Centers for Disease Control and Prevention (CDC) for US counties with available data in 2015-2019. Data on PFAS concentrations in the drinking water of selected community water systems (CWSs) were obtained from the CDC National Environmental Public Health Tracking Network in 2013-2015. The correlation between PFASs in CWSs and thyroid cancer incidence was calculated using Spearman correlation. A statistically significant correlation was found between perfluorooctanoic acid (PFOA) (r = 0.031; p = 0.043), perfluorononanoic acid (PFNA) (r = 0.058; p ≤ 0.001), and thyroid cancer incidence. The results suggest a potential link between certain PFAS exposures and thyroid cancer risk. However, due to the nature of an ecological study, no conclusions can be drawn at the individual level or causality. More research is needed, particularly on an individual level to allow for more detailed exposure assessment.

Patient Preference in Physician Decision-Making for Patients With Low- to Intermediate-Risk Differentiated Thyroid Cancer.

This survey study describes the association between patient preference and physician decision-making in thyroid cancer.

Landmark Discoveries in Maternal-Fetal Thyroid Disease Over the Past Century.

There have been significant advancements in the understanding of maternal-fetal disease over the past century. This narrative review summarizes the landmark studies that have advanced the understanding of thyroid pathophysiology and thyroid disease during preconception, pregnancy, and postpartum, written to commemorate the 100th year anniversary of the founding of the American Thyroid Association.

Iodine-Induced Hyperthyroidism and Long-term Risks of Incident Atrial Fibrillation and Flutter.

CONTEXT: Although iodine-induced hyperthyroidism is a potential consequence of iodinated radiologic contrast administration, its association with long-term cardiovascular outcomes has not been previously studied. OBJECTIVE: To investigate the relationships between hyperthyroidism observed after iodine contrast administration and incident atrial fibrillation/flutter. METHODS: Retrospective cohort study of the U.S. Veterans Health Administration (1998-2021) of patients age ≥18 years with a normal baseline serum thyrotropin (TSH) concentration, subsequent TSH <1 year, and receipt of iodine contrast <60 days before the subsequent TSH. Cox proportional hazards regression was employed to ascertain the adjusted hazard ratio (HR) with 95% CI of incident atrial fibrillation/flutter following iodine-induced hyperthyroidism, compared with iodine-induced euthyroidism. RESULTS: Iodine-induced hyperthyroidism was observed in 2500 (5.6%) of 44 607 Veterans (mean ± SD age, 60.9 ± 14.1 years; 88% men) and atrial fibrillation/flutter in 10.4% over a median follow-up of 3.7 years (interquartile range 1.9-7.4). Adjusted for sociodemographic and cardiovascular risk factors, iodine-induced hyperthyroidism was associated with an increased risk of atrial fibrillation/flutter compared with those who remained euthyroid after iodine exposure (adjusted HR 1.19, 95% CI 1.06-1.33). Females were at greater risk for incident atrial fibrillation/flutter than males (females, HR 1.81, 95% CI 1.12-2.92; males, HR 1.15, 95% CI 1.03-1.30; P for interaction = .04). CONCLUSION: Hyperthyroidism following a high iodine load was associated with an increased risk of incident atrial fibrillation/flutter, particularly among females. The observed sex-based differences should be confirmed in a more sex-diverse study sample, and the cost-benefit analysis of long-term monitoring for cardiac arrhythmias following iodine-induced hyperthyroidism should be evaluated.

Iodinated Contrast Administration and Risks of Thyroid Dysfunction: A Retrospective Cohort Analysis of the U.S. Veterans Health Administration System.

Background: Iodine-induced thyroid dysfunction is a potential risk among susceptible individuals. Iodinated contrast media is a common source of an acute iodine load used in the health care setting and is frequently required for diagnostic computed tomography scans, coronary angiograms, and other radiologic studies. However, the epidemiologic risks of iodine-thyroid dysfunction have not been fully established in the United States. Methods: This population-based retrospective cohort study used the U.S. Veterans Health Administration database between 1998 and 2021 and included adults aged ≥18 years with a serum thyrotropin (TSH) measurement. Multivariable logistic regression was used to ascertain the risk of incident thyroid dysfunction (defined by repeated measurements of serum thyroid function) following iodine exposure, adjusting for age, sex, race/ethnicity, baseline serum TSH concentration, and duration between baseline and follow-up TSH concentration. Results: The cohort was composed of N = 4,253,119 veterans (mean ± SD = 63.5 ± 14.3 years; 92.9% men; 65.6% non-Hispanic Whites) with 8,729,155 corresponding pairs of serum TSH measurements, from which there were 499,897 TSH pairs with intervening iodine exposure. Thyroid dysfunction occurred in 4.8% of those pairs who had received iodine contrast and 3.6% of those without iodine exposure. Iodinated exposure was associated with an increased risk of thyroid dysfunction (odds ratio [OR] = 1.39, 95% confidence intervals [CI] = 1.37-1.41, p < 0.001) and consistent for all types of serum thyroid dysfunction (overt or subclinical hypo-/hyperthyroidism). Men were at higher risk for the development of thyroid dysfunction than women (men: OR = 1.42, 95% CI = 1.40-1.44; women: OR = 1.16, 95% CI = 1.11-1.21; p-for-interaction <0.001). Conclusions: In this largest analysis of U.S. adults to date, iodine exposure was associated with only clinically small absolute increased risks of thyroid dysfunction, particularly in men. These findings suggest that screening of thyroid function following iodinated contrast administration should be targeted to high-risk individuals.

Management of thyroid eye disease: a Consensus Statement by the American Thyroid Association and the European Thyroid Association.

Thyroid eye disease (TED) remains challenging for clinicians to evaluate and manage. Novel therapies have recently emerged, and their specific roles are still being determined. Most patients with TED develop eye manifestations while being treated for hyperthyroidism and under the care of endocrinologists. Endocrinologists, therefore, have a key role in diagnosis, initial management, and selection of patients who require referral to specialist care. Given that the need for guidance to endocrinologists charged with meeting the needs of patients with TED transcends national borders, and to maximize an international exchange of knowledge and practices, the American Thyroid Association and European Thyroid Association joined forces to produce this Consensus Statement.

Management of Thyroid Eye Disease: A Consensus Statement by the American Thyroid Association and the European Thyroid Association.

Thyroid eye disease (TED) remains challenging for clinicians to evaluate and manage. Novel therapies have recently emerged, and their specific roles are still being determined. Most patients with TED develop eye manifestations while being treated for hyperthyroidism and under the care of endocrinologists. Endocrinologists, therefore, have a key role in diagnosis, initial management, and selection of patients who require referral to specialist care. Given that the need for guidance to endocrinologists charged with meeting the needs of patients with TED transcends national borders, and to maximize an international exchange of knowledge and practices, the American Thyroid Association and European Thyroid Association joined forces to produce this consensus statement.

Excess iodine exposure acutely increases salivary iodide and antimicrobial hypoiodous acid concentrations in humans.

The lactoperoxidase (LPO)-hydrogen peroxide-halides reaction (LPO system) converts iodide and thiocyanate (SCN-) into hypoiodous acid (HOI) and hypothiocyanite (OSCN-), respectively. Since this system has been implicated in defense of the airways and oropharynx from microbial invasion, in this proof-of-concept study we measured the concentrations of these analytes in human saliva from a convenience clinical sample of 40 qualifying subjects before and after acute iodine administration via the iodinated contrast medium used in coronary angiography to test the hypothesis that an iodide load increases salivary iodide and HOI concentrations. Saliva was collected and salivary iodide, SCN-, HOI and OSCN- were measured using standard methodology. The large iodine load delivered by the angiographic dye, several 100-fold in excess of the U.S. Recommended Daily Allowance for iodine (150 µg/day), significantly increased salivary iodide and HOI levels compared with baseline levels, whereas there was no significant change in salivary SCN- and OSCN- levels. Iodine load and changes of salivary iodide and HOI levels were positively correlated, suggesting that higher iodide in the circulation increases iodide output and salivary HOI production. This first of its kind study suggests that a sufficient but safe iodide supplementation less than the Tolerable Upper Limit for iodine set by the U.S. Institute of Medicine (1,100 µg/day) may augment the generation of antimicrobial HOI by the salivary LPO system in concentrations sufficient to at least in theory protect the host against susceptible airborne microbial pathogens, including enveloped viruses such as coronaviruses and influenza viruses.

Iodine contrast exposure and incident COVID-19 infection.

Background: Iodine and particularly its oxidated forms have long been recognized for its effective antiseptic properties. Limited in vitro and in vivo data suggest that iodine exposure may rapidly inactivate, reduce transmission, and reduce infectivity of SARS-CoV-2. We hypothesized that iodine exposure may be associated with decreased incident COVID-19 infection. Methods: A retrospective population-level cohort analysis was performed of the U.S. Veterans Health Administration between 1 March 2020 and 31 December 2020, before the widespread availability of vaccines against SARS-CoV-2. Multivariable logistic regression models estimated the adjusted odds ratios (OR) and 95% confidence intervals (CI) of the associations between iodinated contrast exposure and incident COVID-19 infection, adjusting for age, sex, race/ethnicity, place of residence, socioeconomic status, and insurance status. Results: 530,942 COVID-19 tests from 333,841 Veterans (mean ± SD age, 62.7 ± 15.2 years; 90.2% men; 61.9% non-Hispanic Whites) were analyzed, of whom 9% had received iodinated contrast ≤60 days of a COVID-19 test. Iodine exposure was associated with decreased incident COVID-19 test positivity (OR, 0.75 95% CI, 0.71-0.78). In stratified analyses, the associations between iodinated contrast use and decreased COVID-19 infection risk did not differ by age, sex, and race/ethnicity. Conclusion: Iodine exposure may be protective against incident COVID-19 infection. Weighed against the risks of supraphysiologic iodine intake, dietary, and supplemental iodine nutrition not to exceed its Tolerable Upper Limit may confer an antimicrobial benefit against SARS-CoV-2. A safe but antimicrobial level of iodine supplementation may be considered in susceptible individuals, particularly in geographic regions where effective COVID-19 vaccines are not yet readily available.

Diagnostic and Treatment Considerations for Thyroid Cancer in Women of Reproductive Age and the Perinatal Period.

Thyroid cancer is one of the most common cancers diagnosed in women of reproductive age and during pregnancy. This leads to important questions about thyroid cancer prognosis and treatment, but also fertility and risk for adverse obstetric and/or fetal and neonatal outcomes. The benefits of thyroid cancer treatment should be weighed against its harms, as various options may adversely impact maternal and fetal health. In the current review, the authors focus on perinatal-specific clinical considerations related to the care of patients with thyroid cancer.

The Current Status of Preclinical Endocrine Education in U.S. Medical Schools.

OBJECTIVE: To characterize the current landscape of preclinical medical endocrine education in U.S. allopathic medical schools. METHODS: U.S. endocrine curriculum directors were asked to voluntarily complete a 16-question email survey surveying the status of endocrine preclinical education at their medical school. RESULTS: Sixty-nine of 155 (45%) endocrine block director respondents completed the online survey between July 2021 and September 2021. A larger incoming class, a longer duration of the endocrine curriculum, and the offering of a separate endocrine curriculum (ie apart from the teaching of other organ systems) were each independently associated with an increased number of faculty teaching the course. Schools that used a gland-/organ-based curriculum only and those that used a combination of gland-/organ-based curriculum with topic-based curriculum differed significantly in their use of large lectures, small groups, and several curriculum components, including point of care glucose testing, continuous glucose monitoring, and insulin pumps. CONCLUSION: This survey study reports the current landscape of preclinical endocrine education in the United States and describes opportunities to improve interest in pursuing endocrinology as a career.