Continuing Education Activity

Although the consequences of iodine deficiency have been recognized for years, there has not been much emphasis on the prevalence or the consequences of iodine excess. Acute iodine toxicity is rare and is often difficult to recognize. Clinical manifestations may range from nausea, vomiting, and diarrhea to delirium, stupor, and shock. This activity reviews the diagnosis and evaluation of iodine toxicity and explains the role of the healthcare team in managing patients with this condition.

Objectives:

• Summarize the epidemiology of iodine toxicity.
• Review the steps for the evaluation of iodine toxicity.
• Outline the management options available for iodine toxicity.
• Discuss interprofessional team strategies for improving care coordination and communication to advance and improve outcomes.

Introduction

Iodine is an essential micronutrient that has a crucial role in metabolism.  It is oxidized to produce iodine-containing thyroid hormones. Thyroid hormones are necessary for controlling growth, metabolism, and many other body functions. They are crucial for 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, there was not much much emphasis on the prevalence or the consequences of iodine excess. Iodine is not synthesized in the human body and must be obtained from food, dietary supplements, medications, and iodinated contrast media. The recommended dietary allowance (RDA) for adults is 150 micrograms/day, 220 to 250 micrograms/day for pregnant women, and 250 to 290 micrograms/day for breastfeeding women.[4] It is felt that up to 1 mg/day is safe for most people.[5] The sources of excess iodine can be from overconsumption of iodized salt, drinking water, milk rich in iodine, certain seaweeds, and dietary supplements containing iodine.[6]  Ingestion of over 1.1 milligrams/day of iodine may be harmful and can lead to acute and/or chronic toxicity.  

Iodine excess can cause subclinical or overt thyroid dysfunction in patients with specific risk factors, including those with pre-existing thyroid disease, the elderly, fetuses, and neonates. The effects of excess iodine are variable among individuals and relate to the individuals underlying thyroid function.[7] Iodine toxicity may lead to thyroiditis, hypothyroidism, hyperthyroidism, and thyroid papillary cancer.[8] Clinical features of iodine toxicity from oral ingestion can range from mild to severe. Mild symptoms consist of GI upset, nausea, vomiting, and diarrhea, which may progress to delirium, stupor, and shock. It is rarely fatal.[9]

Etiology

Iodine toxicity most commonly results from over-consumption of dietary supplements. Generally, many grams of iodine must be ingested to cause toxicity. Foods containing iodine include iodized salt ( one gram contains about 77ug of iodine), drinking water, milk, certain seafood, and seaweeds. Some oral medications may also contain iodine, such as amiodarone and potassium supplements. Tincture of iodine and betadine are topical medications used as antiseptics and can cause a rash or blistering when applied topically and will lead to more severe toxicity if accidentally ingested.

Epidemiology

The 2018 annual report of the American Association of Poison Control Center's National Poison Data System reported 1537 single exposures to dietary supplements with 58 adverse events and no deaths. It also lists 853 single exposures to topical iodine with 51 adverse events and no deaths. The report lists electrolytes and minerals in the top 25 categories of substances most frequently involved in human exposures with 30,046 exposures.[10]

Pathophysiology

There appear to be individual variabilities 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.

History and Physical

The initial assessment of patients with an accidental or intentional overdose should include a comprehensive history whenever possible, stabilization of the patient's condition, a thorough physical examination with close attention to airway, breathing, and circulation. Acute iodine poisoning can result in the 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 history is limited or unavailable from the patient, it is essential to obtain as much information as possible from bystanders, family, and/or EMS.  It can be useful to remember the "Five W's" when taking a history: who, what, when, where, and why. Timing, quantity, and type of ingestion are of crucial importance.[11] 

Evaluation

After initial stabilization and assessment, the practitioner should proceed with a thorough evaluation. Laboratory tests should include but are not be limited to, a CBC, electrolytes, liver and renal function, thyroid panel, coagulation studies, pregnancy test for age-appropriate females, serum and urine toxicology screens, and drug levels when available. EKG is necessary to evaluate any dysrhythmias or concern for QT prolongation. EKG should be compared to the previous EKG when available. Radiographic studies are helpful when appropriate to assess for complicating underlying conditions, such as aspiration pneumonia or trauma.

Treatment / Management

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 two large-bore IVs placed. Endotracheal intubation is necessary if the patient is unable to protect their airway due to depressed mental status.

There is no specific antidote to iodine poisoning; therefore, management is largely supportive. If the patient is stable, alert, and protecting their airway, activated charcoal should be given to decontaminate the gastrointestinal tract.[12] The patient may require hospitalization or prolonged observation in the emergency department until deemed medically stable.  

Differential Diagnosis

When a patient presents with mild symptoms of GI upset, nausea, vomiting, and diarrhea, the differential diagnosis is broad. Complete and accurate history taking is of crucial importance to narrowing the differential diagnosis.  Underlying medical conditions should merit consideration as well as medications, dietary supplements, and possible coingestants. Stabilization is the-priority followed by supportive care of the patient. The differential diagnosis can be narrowed with further evaluation and testing.

Prognosis

There were no reported deaths due to iodine toxicity in 2018, according to the 2018 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 36th Annual Report.[10] Iodine induced hyperthyroidism occurs in iodine-deficient populations after the implementation of iodine supplementation programs. Their pre-existing Iodine deficiency leads to the development of TSH resistant thyroid nodules. These nodules then overproduce thyroid hormones in response to sudden iodine supply. This condition results in symptoms of hyperthyroidism: 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 leading to hypothyroidism and goiter.

Patients with iodine deficiency and patients with pre-existing thyroid disease may be sensitive to iodine levels, which appear to be safe for the general population.  Neonates, elderly, and pregnant women may also be more susceptible to iodine excess.[13]

Complications

Thyroid cancer is the most common and steadily increasing endocrine malignancy. The increased incidence is due in part to improved diagnosis and screening. There has been a hypothesis that the increased incidence may also be related to iodine excess. Changes in iodine intake appear to affect the histologic type of thyroid cancer, and it is unclear whether iodine deficiency or iodine excess increases the overall risk of thyroid cancer.[14]

Deterrence and Patient Education

The agency for toxic substances and disease registry (ATSDR) provides the following patient education information. 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 of thyroid disease. Iodine is both potentially beneficial and harmful. The thyroid requires iodine to produce thyroid hormones. Conversely, exposure to unnecessarily high levels of iodine can result in damage to the thyroid.[15]

Enhancing Healthcare Team Outcomes

Iodine toxicity is a rare condition that requires a broad initial diagnosis and heightened suspicion.  These patients may exhibit vague signs and symptoms such as nausea, vomiting, and diarrhea. While history taking may reveal the toxicity, the cause is difficult to determine without further evaluation. 

While the emergency physician is almost always involved in the initial care of toxicology patients, it is important to consult with an interprofessional team of specialists that include an intensivist, toxicologist, and endocrinologist. The nurses are also a vital part of the interprofessional team as they will monitor the patient's vital signs and assist with the education of the patient and family. 

The outcomes of iodine toxicity depend on the cause and severity. However, to improve outcomes, prompt consultation with an interprofessional group of specialists is recommended.