Jod Basedow Phenomenon

Article Author:
Hannah Rose
Article Editor:
Hassam Zulfiqar
Updated:
10/8/2019 12:26:00 PM
PubMed Link:
Jod Basedow Phenomenon

Introduction

Jod-Basedow syndrome, also known as iodine-induced hyperthyroidism, is a rare cause of thyrotoxicosis seen typically after the administration of exogenous iodine. This syndrome is often associated with iodinated contrast media used in conjunction with computed tomography (CT) scans, angiography, and various other imaging studies.

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. Since iodine excretion occurs via the kidneys, chronic kidney disease and end-stage renal disease are also risk factors for iodine-induced hyperthyroidism.[1] Moreover, it merits noting that the Jod-Basedow phenomenon or iodine-induced hyperthyroidism is typically associated with the administration of ICM however, it may be seen secondary to other exogenous sources such as iodinated antiseptic solutions and oral supplements. Thyrotoxicosis seen secondary to amiodarone is a recognized separate entity, and the underlying mechanism might well be different.

Epidemiology

Jod-Basedow phenomenon appears to be a rare condition, with only a small collection of case reports describing its features. It is likely, however, that this condition is under-reported. Increased awareness of this entity may lead to more clinicians considering this diagnostic possibility.[2]

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 occurs with ICM administration, may impact thyroid functioning.[3] The expected initial response is a transient reduction in thyroid hormone production. This phenomenon is known by the name of 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.[4] Some patients, however, exhibit the opposite response. Instead of the transitory hypothyroidism, they develop hyperthyroidism by escaping the physiologic negative feedback mechanism of Wolf-Chaikoff effect. This pathologic response to the exogenously administered iodine load is referred to as the Jod-Basedow phenomenon. It is thought to occur as a result of impaired autoregulation.

History and Physical

Symptoms of Jod-Basedow syndrome are similar to those of hyperthyroidism from other causes. Symptoms include increased sweating, tachycardia, restlessness, diarrhea, heat intolerance, and insomnia. Severe cases may lead to thyroid storm, typically presenting with a constellation of including tachycardia, fever, diarrhea, and altered levels of consciousness.[5] Rare cases have also carry correlations with the development of atrial fibrillation.[6]

Evaluation

The diagnosis of iodine-induced hyperthyroidism will be very 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. Lab tests will show an increase in T3 and T4 and a reduced TSH level. Urinary levels of iodide are increased up to three times the normal value. Nuclear imaging of the thyroid will show low radioiodine uptake.[7] Testing for thyroid hormone levels before and after the administration of ICM will lead to a better evaluation of change in thyroid function.

Treatment / Management

Prophylactic anti-thyroid medications (methimazole or perchlorate) may be a consideration for patients at risk for developing iodine-induced hyperthyroidism and scheduled for imaging with ICM.  For patients who develop iodine-induced hyperthyroidism, steroid therapy is recommended to hasten the return of thyroid hormones to normal levels. Additionally, symptoms are manageable with a beta-blocker and anti-thyroid medications, such as methimazole.[8] If anti-thyroid drugs fail to suppress hormone production, clinicians may consider prescribing lithium, due to its inhibitory effects on the thyroid. [9]

Differential Diagnosis

It is crucial to consider an underlying thyroid disease as a cause of the patient's symptoms of hyperthyroidism.  A thyroid-stimulating hormone (TSH) antibody level should be checked to rule out Graves disease. Hyperfunctioning thyroid nodules should also be a consideration, but these should have a high level of radioiodine uptake with nuclear imaging of the thyroid. A diagnosis of preexisting thyroid disease, however, does not preclude the diagnosis of Jod Basedow phenomenon.  Underlying thyroid disease is a risk factor for the development of iodine-induced hyperthyroidism. A detailed past medical history is critical to establish the correlation of the symptoms with the exposure to ICM or other iodinated substances.

Prognosis

The prognosis for iodine-induced hyperthyroidism is generally favorable, with most patients returning to their baseline thyroid state. A minority of patients, however, do suffer permanent sequelae from iodine-induced hyperthyroidism.

Complications

Complications of iodine-induced hyperthyroidism include thyroid storm, permanent hyperthyroidism, and atrial fibrillation.[6] Persistent hyperthyroidism will increase the stress on the cardiovascular system through increased preload, which may exacerbate any underlying cardiac disease. 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 development. Continued exposure of the neonate to iodine in the first few weeks of life may lead to permanent hypothyroidism.[4]

Deterrence and Patient Education

Patients with documented thyroid conditions should receive education regarding the association of the Jod-Basedow phenomenon with ICM. If they need contrast-enhanced imaging in the future, they may communicate their risk of iodine-induced hyperthyroidism with the ordering provider. Together, with the provider, a decision can 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 a beta-blocker. Clinicians should also perform a thorough medication review before ordering ICM, as many supplements and medications 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 to minimize the risk of iodine-induced hyperthyroidism.[10]

Enhancing Healthcare Team Outcomes

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

Medical providers considering 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 taken into consideration, as these conditions increase the risk for iodine-induced hyperthyroidism.  If the imaging is still deemed to be worth the risk, the ordering clinician should communicate his or her concern with the radiology department and the clinical team, so the patient is 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, as future ICM may be contraindicated.

We live in a world where a significant number of people take all types of supplements, including iodide; thus, there is always the potential of Job Basedow reaction. Hence, the pharmacist, nurse practitioner, and primary care provider should educate the patient on the risks associated with supplements and what to do when symptoms appear.

Acute symptoms of Job Basedow syndrome usually require management in the emergency department, and hence, the triage nurse should be familiar with this endocrine emergency, and communicate their findings to the healthcare team. Patients need to be quickly admitted, resuscitated, stabilized, and have the symptoms treated by the interprofessional team that includes the emergency department physician, endocrinologist, and pharmacist.

If hyperthyroid symptoms become permanent, the patient may benefit from an endocrinology consult. Rare complications, such as atrial fibrillation, may need to be managed by cardiology. Obstetrics and pediatrics teams should be involved in cases of gestational exposure to ICM.

Outcomes

Because the condition is rare, long term outcomes remain unknown. However, those patients who receive appropriate treatment do have good outcomes.  Some patients may need long term treatment with antithyroid drugs and beta blockers.

The interprofessional healthcare team must function not only to treat iodine-induced hyperthyroidism but to engage actively in prophylaxis. Managing clinicians need to weigh the benefit vs. risk of iodine contrast diagnostic procedures carefully. They will also coordinate with specialists, as listed above, should it become necessary. Nursing needs to perform a thorough medication and supplement history to discern if a potential problem exists, and communicate these findings to the managing clinician. They can coordinate this type of activity with a pharmacist. If medication therapy is needed (e.g., beta-blockers, methimazole), the pharmacist should perform medication reconciliation, and report any issues to the other healthcare team members. Nursing can also monitor for adverse effects or worsening condition. Only through this type of interprofessional collaboration can patient outcomes be driven to the most successful possible result. [Level V]


References

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