Continuing Education Activity

Although the consequences of iodine deficiency have been recognized for years, the prevalence or the consequences of iodine excess are understated. Acute iodine toxicity is rare and difficult to identify. The acute toxicity is typically caused by overconsumption of supplements containing iodine. The presenting symptoms can vary from mild to severe, including nausea, vomiting, and diarrhea, but can progress to delirium, stupor, and shock. As these symptoms overlap with many drug toxicities, clinicians should institute a full toxicology workup when iodine toxicity is on the differential diagnosis. Initial diagnosis requires a broad assessment, and while the history aids, a definitive diagnosis may need specialist consultation. Interprofessional teams collaborate to triage undifferentiated patients with signs of iodine toxicity.

This activity reviews the diagnosis and evaluation of iodine toxicity and explains the role of the healthcare team in managing patients with this condition. Participating clinicians are equipped to work with emergency clinicians, primary care teams, and clinicians from internal medicine in the care of patients with iodine toxicity.

Objectives:

• Identify the sources of iodine that may cause short- and long-term effects in patients if consumed in excess.
• Apply the stepwise evaluation of iodine toxicity in patients presenting with symptoms and signs of toxic ingestion.
• Determine the management options for iodine toxicity depending on when the ingestion occurred.
• Implement interprofessional team strategies for improving care coordination in treating patients with iodine toxicity.

Introduction

Iodine is an essential micronutrient that has a crucial role in metabolism. The micronutrient is oxidized to produce iodine-containing thyroid hormones. Thyroid hormones are necessary for regulating growth, metabolism, and many other body functions, especially during fetal and neonatal brain development.[1] Iodine deficiency has long been a recognized global problem and remains a leading cause of preventable fetal brain damage.[2] Iodine deficiency in pregnancy leads to hypothyroidism and impaired infant neurobehavioral development.[3]

Although the consequences of iodine deficiency have been recognized for years, the prevalence or the consequences of iodine excess have not been highlighted. Iodine is not synthesized in the human body and must be obtained from food, dietary supplements, medications, and iodinated contrast media.[4] The recommended dietary allowance varies: 150 μg/d for adults, 220 to 250 μg/d for pregnant women, and 250 to 290 μg/d for breastfeeding women.[5][6] Up to 1 mg/d is considered safe for most individuals.[7] The sources of excess iodine can be from overconsumption of iodized salt, foods containing excess iodine, and dietary supplements containing iodine, in many cases being the treatment of overtreated iodine deficiency.[8][9] Ingestion of over 1.1 mg/d of iodine may be harmful and can lead to acute or chronic toxicity.

Iodine excess can cause subclinical or overt thyroid dysfunction in patients with specific risk factors, including those with preexisting thyroid disease, older patients, fetuses, and neonates. The effect of excess iodine varies among individuals and is closely related to underlying thyroid function.[10] Iodine toxicity may lead to thyroiditis, hypothyroidism, hyperthyroidism, and thyroid papillary cancer.[11] Clinical features of iodine toxicity from oral ingestion can range from mild to severe. Mild symptoms consist of gastrointestinal upset, nausea, vomiting, and diarrhea, which may progress to more severe manifestations such as delirium, confusion, lethargy, and shock. The condition is rarely fatal.[12]

Etiology

Iodine toxicity most commonly results from overconsumption of dietary supplements. Generally, a large amount of iodine must be ingested to cause toxicity. Foods containing iodine include iodized salt (1 g contains about 77 µg of iodine), drinking water, milk, certain types of seafood, and seaweed. In addition, some oral medications may contain iodine, such as amiodarone and potassium supplements. Topical antiseptics such as tinctures of iodine and betadine can cause skin rash or blistering when used topically. However, if ingested, they can lead to severe toxicity.[13] During the COVID-19 pandemic, nasal sprays containing iodine were used for prophylaxis against the virus or infection with positive results. However, no reports of thyroid problems were documented in different studies.[14][15]

Epidemiology

The 2018 annual report of the American Association of Poison Control Center's National Poison Data System documented 1537 single exposures to dietary supplements with 58 adverse events but no deaths. The report documented 853 single exposures to topical iodine with 51 adverse events and no deaths. Electrolytes and minerals were listed as the top 25 substances most frequently involved in human exposures, with 30,046 exposures.[16]

Pathophysiology

Individual variabilities exist in the thyroid response to excess iodine intake due to the unmasking of underlying thyroid disease. Iodine excess can cause subclinical or overt thyroid dysfunction.[17] The normal thyroid gland has defense mechanisms to block the stimulation of the thyroid hormone production after a load of iodine, inciting the Wolff–Chaikoff effect that is typically temporary. Depending on the underlying thyroid status and the presence of autoimmunity, the thyroid function can be altered, and either hypothyroidism or hyperthyroidism may prevail.[18]

History and Physical

The initial assessment of patients with an accidental or intentional overdose should include obtaining a detailed history whenever possible, stabilizing the patient's condition, and performing a thorough physical examination with close attention to airway, breathing, and circulation. Acute iodine poisoning may manifest with symptoms such as burning of the mouth, fever, nausea, and vomiting. Vital signs and mental status require continuous monitoring. Decontamination should be implemented when appropriate. Consultation with a poison control center may prove helpful when managing overdoses. If the patient's history is limited or unavailable, information can be obtained from bystanders, family, or emergency medical services. The five W's should be remembered when obtaining a history: who, what, when, where, and why. Timing, quantity, and type of ingestion are of crucial importance.[19]

Evaluation

After initial stabilization and assessment, the clinician should conduct a comprehensive evaluation. Laboratory tests should include, but are not limited to, a complete blood count (CBC), electrolyte levels, liver and renal function tests, thyroid panel, coagulation studies, pregnancy test for age-appropriate women, serum and urine toxicology screens, and drug levels when available. An electrocardiogram (ECG) is necessary to evaluate for any dysrhythmias or concerns about QT prolongation. ECG findings should be compared to the patient's previous ECGs whenever available. Radiographic studies are helpful in identifying complicating underlying conditions, such as aspiration pneumonia or trauma.

Treatment / Management

The approach to management should start with supporting the airway, breathing, and circulation. If the patient is unstable, they should immediately be placed on a cardiac monitor with supplemental oxygen, with 2 large-bore intravenous catheters placed. Endotracheal intubation is necessary if the patient is unable to protect their airway due to depressed mental status. Currently, there is no specific antidote available for iodine poisoning, and the management primarily involves providing supportive care. If the patient is stable, alert, and protecting their airway, activated charcoal should be administered to decontaminate the gastrointestinal tract.[20] The patient may require hospitalization or prolonged observation in the emergency department until deemed medically stable.  

Differential Diagnosis

The differential diagnosis is broad when a patient presents with mild symptoms such as gastrointestinal upset, nausea, vomiting, and diarrhea. Obtaining a detailed and accurate history is crucial for narrowing the differential diagnosis. Underlying medical conditions should merit consideration, as should medications, dietary supplements, and possible co-ingestants. Stabilization is the priority in treatment, followed by supportive care of the patient. The differential diagnosis can be narrowed with further evaluation and testing.

Prognosis

According to the 2018 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 36th Annual Report, no deaths were documented due to iodine toxicity in 2018.[16] Iodine-induced hyperthyroidism occurs in iodine-deficient populations after the implementation of iodine supplementation programs. Due to the preexisting iodine deficiency, the thyroid may have developed nodules that are resistant to the regulatory effects of thyroid-stimulating hormones. These nodules overproduce thyroid hormones in response to sudden iodine supply. This condition results in symptoms of hyperthyroidism such as weight loss, tachycardia, and muscle weakness. Iodine-induced hyperthyroidism may be dangerous in patients with underlying heart disease.

In iodine-sufficient individuals, iodine excess causes elevated thyroid-stimulating hormone levels, which inhibits thyroid hormone production and leads to hypothyroidism and goiter. Patients with iodine deficiency and preexisting thyroid disease may be sensitive to iodine levels that otherwise appear safe for the general population.[18] Neonates, older, and pregnant women may be more susceptible to iodine excess.[21]

Complications

Thyroid cancer is the most common and steadily increasing endocrine malignancy. The increased incidence is due in part to improved diagnosis and screening. A hypothesis exists suggesting that the increased incidence may also be related to iodine excess. Changes in iodine intake appear to affect the histological type of thyroid cancer. However, whether iodine deficiency or iodine excess increases the overall risk of thyroid cancer is unclear.[22]

Iodine excess during pregnancy may cause problems for both mother and fetus. Pregnant women may experience subclinical hypothyroidism, with the fetus being affected in different ways. Several case reports in the literature describe problems in the neurological development of the fetus and increased incidence of preterm births.[23][24]

Consultations

When high suspicion of iodine toxicity is present, as in other situations of suspected poisoning, toxicology and poison control centers should be contacted to provide more focused instructions on the initial management steps. Depending on the presenting symptoms and the affected organ systems, more specialists might need to be involved in treating these patients, including but not limited to endocrinologists with special attention to thyroid function.

Deterrence and Patient Education

The Agency for Toxic Substances and Disease Registry (ATSDR) provides information on patient education. The general public has low exposure levels to iodine. Food (iodized salt) is the primary source of exposure. The general public is rarely exposed to radioactive iodine unless they have specific tests or treatment for thyroid disease. Iodine is both potentially beneficial and harmful. The thyroid requires iodine to produce thyroid hormones. Conversely, exposure to high levels of iodine can damage the thyroid.[25]

Pearls and Other Issues

Although the initial effect of iodine in achieving pregnancy was first discovered in the 1950s, some more recent studies have revisited this effect with the use of a specific iodine-containing contrast material oil-based used for hysterosalpingograms in women with unexplained infertility problems. This material has been shown to improve infertility, resulting in up to a 10.7% increase in the pregnancy rate that leads to live births.[26][27][28] 

Enhancing Healthcare Team Outcomes

Iodine toxicity is a rare condition that requires a broad initial diagnosis and heightened suspicion. These patients may exhibit very vague signs and symptoms such as nausea, vomiting, and diarrhea, but they can also progress to more serious reactions with delirium, stupor, and shock. Although obtaining a detailed history may reveal the toxicity, determining the underlying cause often requires further evaluation.

Although emergency clinicians are almost always involved in the initial care of toxicology patients, consulting an interprofessional team comprising specialists such as intensivists, toxicologists, and endocrinologists is crucial. Nurses are also a vital part of the interprofessional team, as they monitor the patient's vital signs and assist with educating the patient and family. The outcomes of iodine toxicity depend on the cause and severity. However, prompt consultation with interprofessional specialists is recommended to improve outcomes.

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Disclosure: Alison Southern declares no relevant financial relationships with ineligible companies.

Disclosure: Catherine Anastasopoulou declares no relevant financial relationships with ineligible companies.

Disclosure: Sharhabeel Jwayyed declares no relevant financial relationships with ineligible companies.