Continuing Education Activity

Jod-Basedow syndrome, also known as iodine-induced hyperthyroidism, is a rare cause of thyrotoxicosis typically seen after administering exogenous iodine. This syndrome often carries an association with iodinated contrast media (ICM) used in conjunction with computed tomography (CT) scans, angiography, and various other imaging studies. The problem is very frequently missed, and better awareness of it needs to be raised among physicians in primary care as well as in different specialties. It has been described in all ages, and although it is expected to be completely resolved, case reports describe occasional remnant thyroid dysfunction. This activity illustrates the etiology, pathophysiology, clinical symptomatology, and differential diagnosis of the Jod-Basedow syndrome and highlights the role of healthcare-provider team collaboration in managing this condition.

Objectives:

• Describe the pathophysiology of the Jod-Basedow phenomenon.
• Review the appropriate history, physical, and evaluation of the Jod-Basedow syndrome.
• Outline the treatment and management options available for the Jod-Basedow syndrome.
• Summarize interprofessional team strategies for improving care coordination and communication to advance care for Jod-Basedow syndrome, should it occur, and also highlight the roles of radiology, emergency medicine, endocrinology, and all other healthcare professionals involved in dealing with this potentially life-threatening condition.

Introduction

Jod-Basedow syndrome, also known as iodine-induced hyperthyroidism, is a rare cause of thyrotoxicosis typically seen after administering exogenous iodine. This syndrome is often associated with iodinated contrast media (ICM) used in conjunction with computed tomography (CT) scans, angiography, and various other imaging studies. The problem is very frequently missed, and better awareness of it needs to be raised among physicians in primary care as well as in different specialties. It has been described in all ages and although it is expected to be completely resolved, case reports describe occasional remnant thyroid dysfunction.

Etiology

Underlying thyroid conditions, such as Hashimoto thyroiditis, autoimmune thyroid disease, previous thyroid surgery, latent Graves disease, and nontoxic diffuse or nodular goiter, are predisposing factors for developing iodine-induced hyperthyroidism.[1] Since iodine excretion occurs via the kidneys, chronic kidney disease, and end-stage renal disease are also risk factors for iodine-induced hyperthyroidism.[2] Moreover, it merits noting that the Jod-Basedow syndrome, or iodine-induced hyperthyroidism, is typically associated with the administration of ICM; however, it may be seen secondary to using other exogenous sources containing iodine, such as iodinated antiseptic solutions and oral vitamins or nutritional supplements.[3] Thyrotoxicosis, seen secondary to amiodarone, which is a medication containing iodine, is a recognized separate entity, and the underlying mechanisms might be different.[4]

Epidemiology

Jod-Basedow syndrome appears to be a rare condition, with only a small collection of case reports in the literature describing its features.[5][6][7] However, this condition is likely under-reported, with many cases either not being correctly diagnosed or not always properly correlated with exposure to the iodine load.[8][9] Increased awareness of this entity may lead to more clinicians recognizing this diagnostic possibility so it can be properly and more timely treated, as well as being careful and helping to prevent it.[10]

Pathophysiology

Iodine is crucial for the normal functioning of the thyroid. Without iodine, the body would not be able to synthesize the thyroid hormones T3 and T4, which are essential for maintaining metabolic homeostasis. Excess iodide, such as that occurs with ICM administration, may impact thyroid functioning.[11] After a high load of iodine is administered, the expected initial response will be a transient reduction in thyroid hormone production. This phenomenon is known as the Wolff-Chaikoff effect and is thought to be caused by a temporary downregulation of the sodium iodide transporter in the thyroid. Most patients can return to a euthyroid state within 24 to 48 hours.[12][13] 

Some patients, however, exhibit the opposite response. Instead of transitory hypothyroidism, they develop hyperthyroidism by escaping the physiologic negative feedback mechanism of the Wolf-Chaikoff effect. This pathologic response to the exogenously administered iodine load is referred to as the Jod-Basedow syndrome, and it is thought to occur as a result of impaired autoregulation. This does not happen in patients with normal thyroid glands but only in patients with background thyroid abnormalities with some kind of thyroid problems, like autoimmune diseases or nodular goiters.

History and Physical

Symptoms of Jod-Basedow syndrome are similar to those of hyperthyroidism due to other causes. Symptoms include increased sweating, palpitations feeling and tachycardia, restlessness and anxiety, diarrhea or frequent bowel movements, heat intolerance, and insomnia. Severe cases may lead to thyroid storm, typically presenting with a constellation of symptoms, including tachycardia, fever, diarrhea, and altered levels of consciousness.[14] Rare cases also carry correlations with the development of atrial fibrillation or other cardiac arrhythmias.[15]

Evaluation

The diagnosis of iodine-induced hyperthyroidism is similar to diagnosing hyperthyroidism. Obtaining a thorough clinical history is critical in correlating ICM exposure with the onset of symptoms. Most patients will develop symptoms less than a month after exposure to ICM, ranging from hours or days into weeks. Lab tests will show increased T3 and T4 and reduced TSH levels. Urinary levels of iodide are increased up to three times the normal value. Nuclear imaging of the thyroid will show low to undetectable radioiodine uptake.[16] Physicians thinking of this possibility in advance and considering testing the thyroid hormone levels before and after the administration of ICM could potentially lead to an easier and better evaluation of the change in the thyroid function.

Treatment / Management

Prophylactic anti-thyroid medications (methimazole or perchlorate) may be a consideration for patients at risk for developing iodine-induced hyperthyroidism that is scheduled for imaging with ICM.[1] For patients who develop iodine-induced hyperthyroidism, corticosteroid therapy is recommended to hasten the return of the thyroid hormones to normal levels. Additionally, symptoms are manageable with the temporary use of beta-blockers and anti-thyroid medications, such as methimazole.[17] If anti-thyroid drugs fail to suppress hormone production, clinicians may consider prescribing lithium due to its inhibitory effects on the thyroid.[18] 

Differential Diagnosis

It is crucial to consider an underlying thyroid disease as a cause of the patient's symptoms of hyperthyroidism. A thyroid-stimulating immunoglobulin (TSI) level should be checked to rule out Graves disease. Hyperfunctioning thyroid nodules should also be a consideration, but these would present with a high level of radioiodine uptake at the nuclear imaging of the thyroid. However, a diagnosis of preexisting thyroid disease does not preclude the diagnosis of Jod Basedow syndrome. In many instances, some underlying thyroid disease is a risk factor for developing iodine-induced hyperthyroidism. A detailed medical history is critical for establishing the correlation of the symptoms with exposure to ICM or other iodinated substances.

Prognosis

The prognosis of iodine-induced hyperthyroidism is generally favorable, with most patients returning to their baseline thyroid state with the time of recovery varying. Thyroid function will return to normal within weeks or months, and patients are advised to follow up with their physicians. A small percentage of patients, however, could suffer permanent sequelae from iodine-induced hyperthyroidism, and that is why most patients will need to be followed closely and re-evaluated with repeat thyroid function tests. 

Complications

Complications of iodine-induced hyperthyroidism include thyroid storm, permanent hyperthyroidism, and atrial fibrillation.[15] Persistent hyperthyroidism will increase the stress on the cardiovascular system through increased preload, which may exacerbate any underlying cardiac disease, including heart failure.[19][20] 

Caution is necessary when ordering ICM in pregnant patients due to the ability of iodine to cross the placenta. Exposure to iodine in utero correlates with fetal hypothyroidism and goiter development. Fetal hypothyroidism is thought to be due to the failure of the fetus to escape the physiologic Wolff-Chaikoff effect. Although fetal hypothyroidism after maternal ICM is usually transitory, it can still have detrimental effects on fetal development. Continued exposure of the neonate to iodine in the first few weeks of life may lead to permanent hypothyroidism.[12][21]

Recent case reports reported patients who suffered either from hypokalemic periodic paralysis after the use of iodinated substances inducing hyperthyroidism or pericardial tamponade, which is very unusual in thyrotoxic states as it is mostly seen in hypothyroid states.[19]

Deterrence and Patient Education

Patients with documented thyroid conditions should receive education regarding the association of the Jod-Basedow syndrome with ICM. If they require contrast-enhanced imaging in the future, they need to communicate the previous problems and report their potential risk of iodine-induced hyperthyroidism to the ordering provider. Together with the provider, a decision will need to be made about the necessity of the test. If the test is deemed necessary, the provider may consider treating the patient prophylactically with an anti-thyroid medication, such as methimazole, or with a beta-blocker. The clinicians should also perform a thorough medication review before ordering ICM, as many supplements and medications may contain significant amounts of iodine. If the treatment history is significant for supplemental iodine, it may be necessary to adjust the patient's medication regimen in anticipation of ICM use to minimize the risk of iodine-induced hyperthyroidism.[22]

Enhancing Healthcare Team Outcomes

Job Basedow syndrome is a rare disorder, but it can present suddenly in both inpatients and outpatients who receive agents containing iodide. It can lead to thyroid storm and serious cardiac complications, including arrhythmias and heart failure; thus, its diagnosis and management require an interprofessional team approach.

Medical providers looking into ordering radiologic imaging with ICM should perform a thorough patient history before ordering the test. Any prior history of thyroid or renal disease should be considered seriously, as these conditions increase the risk for iodine-induced hyperthyroidism. If the imaging is still deemed to be worth the risk, the ordering clinicians should communicate their concerns with the radiology department as well as the primary clinical team so that the patient can be watched closely for adverse reactions during and following the imaging procedure. Additionally, if iodine-induced hyperthyroidism develops, this should be clearly stated in the patient's medical record to help prepare appropriate treatment and prevent similar complications in the future whenever ICM use is considered necessary.

In our era and more frequently in recent years, a significant number of people consume all types of supplements, including isolated iodide and other substances that might contain iodine, so there is always the potential risk of the Jod Basedow reaction. Hence, pharmacists, nurse practitioners, and primary care providers should educate their patients on the risks associated with supplements and what to do when symptoms appear.

Acute symptoms of Jod Basedow syndrome usually require management in the emergency department, and in that case, the triage nurses should be familiar with this endocrine emergency and communicate their findings to the healthcare team. Patients need to be quickly evaluated, admitted, resuscitated, stabilized, and have their symptoms treated by the interprofessional team that should include the emergency department physician, an endocrinologist, and a pharmacist.

If hyperthyroid symptoms become permanent, the patient may benefit from a specialized endocrinology consultation. Rare complications, such as atrial fibrillation and heart failure, may need to be managed by cardiology. Obstetrics and pediatrics teams should be involved in cases of gestational exposure to ICM as well as the presentation of the syndrome in younger children and teenagers.

Outcomes

Because the condition is rare, long-term outcomes remain unknown. However, the patients who receive appropriate treatment usually have very good outcomes. Occasionally, some patients may need long-term treatment with antithyroid drugs and beta-blockers.

The interprofessional healthcare team must function to treat iodine-induced hyperthyroidism and engage actively in prophylaxis. Managing clinicians must carefully weigh the benefits versus the risks of iodine contrast diagnostic procedures. They will also need to coordinate the patient's care with specialists, as listed above, if necessary. Nursing staff must perform a thorough medication and supplement history to discern if a potential problem exists and communicate these findings to the managing clinician. They should also coordinate this type of activity with a pharmacist. If medication therapy is needed (e.g., beta-blockers or methimazole), the pharmacist should perform medication reconciliation and report any issues to the other healthcare team members. Nursing staff can also monitor for adverse effects or worsening of the condition. Only through this type of interprofessional collaboration can patient outcomes be driven to the most successful possible results. [Level 5]