IODINATED CONTRAST MEDIA INDUCED THYROID STORM AND ACUTE CORONARY SYNDROME: A CASE REPORT

Abstract

Background

A thyroid storm is an extreme disorder that occurs in severe thyrotoxicosis. This condition is life-threatening, with mortality rates up to 10-20%. A typical dose of iodinated contrast media (ICM) contains approximately 13,500 μg of free iodide and 15–60 g of bound iodine, representing an acute iodide load of 90 to several hundred thousand times the recommended daily intake of 150 μg. As a result of sudden exposure to high iodide loads, thyroid hormone regulation can be disrupted, leading to hypothyroidism (Wolff-Chaikoff effect) or hyperthyroidism (Jod-Basedow phenomenon), particularly in those with underlying nodular thyroid disease.

Case description

A 37-year-old man presented to the emergency room (ER) with clinical and electrocardiographic signs of acute myocardial infarction. Primary PCI with iodinated contrast was performed. After the intervention, laboratory analyses revealed thyrotoxicosis, and the patient was administered initial thyrosuppressive therapy along with cardiac therapy and discharged from the hospital. One week later, he returned to the hospital with signs of a thyroid storm.

Conclusion

This case report aimed to raise awareness regarding the routine evaluation of thyroid function in patients with and without previous signs and symptoms of thyrotoxicosis who had undergone acute myocardial infarction and coronary angiography.

INTRODUCTION

The thyroid storm is an extreme disorder that occurs in severe thyrotoxicosis. This condition is life-threatening, with mortality rates up to 10-20%. The etiology of thyroid storm is most commonly Graves’ disease. Nevertheless, it can be triggered by acute myocardial infarction, infection, surgery, trauma, diabetic ketoacidosis, pregnancy, and the administration of iodinated contrast (1, 2). The clinical signs of thyroid storm include fever, profuse sweating, cardiac decompensation, tachyarrhythmia, neurological dysfunctions, seizures, coma, and liver dysfunction with or without jaundice, and it is often accompanied by nausea, vomiting, and diarrhea (1). A typical dose of iodinated contrast media (ICM) contains approximately 13,500 μg of free iodide and 15–60 g of bound iodine, representing an acute iodide load of 90 to several hundred thousand times the recommended daily intake of 150 μg. Sudden exposure to high iodide loads can disrupt thyroid hormone regulation, leading to hypothyroidism (Wolff-Chaikoff effect) or hyperthyroidism (Jod-Basedow phenomenon), particularly in those with underlying nodular thyroid disease (3-6). Iodine-induced thyrotoxicosis is more frequently observed in areas with low iodine intake. The incidence of iodine-induced hyperthyroidism is as high as 1.7%, compared with a very low incidence in iodine-sufficient areas (6).

We present the case of a patient with acute myocardial infarction (AMI) who developed a thyroid storm precipitated by cardiac angiography performed using ICM and was later complicated by drug-induced vasculitis.

CASE REPORT

A 37-year-old man presented to the emergency room (ER) with severe chest pain, sweating, and nausea. The patient was not taking any medications, and he did not have a history of heart disease. An electrocardiogram (ECG) showed ST elevation in leads D1, aVL, and V1-5. Emergency cardiac angiography revealed subocclusion of the proximal left anterior descending artery (LAD) with a large thrombus, which was treated with primary angioplasty and drug-eluting stent placement (Cre8 4.0x25mm). During the intervention, he received 300-ml Ioversol, an iodine-based contrast solution. Echocardiography after the intervention showed an enlarged left ventricle, remodeled and akinetic apex of the heart with the formation of an aneurysm, multiple regional wall motion abnormalities, and reduced systolic function and ejection fraction (EF) 25-35%. Persistent sinus tachycardia was present. Laboratory analyses revealed highly elevated thyroid hormone levels, free serum T4 of 93 (normal 12-22) pmol/l, and suppressed TSH of 0.007 (normal 0.270-4.2) mUI/L. He did not have any clinical signs of Graves' disease. Antibodies and echo examination of the thyroid were not performed at presentation. Therapy with thiamazole at a dose of 60 mg/day was initiated for 5 days followed with dose of 40mg/day until the end of hospitalization.

After 10 days of hospitalization, the patient was discharged from the cardiology department with thiamazole 40 mg/day, along with the other cardiology medications he had been receiving during his stay: acetylsalicylic acid (ASA) 100 mg/day, ticagrelor 180 mg/day, bisoprolol 5 mg/day, ramipril 2.5 mg/day, furosemide 40 mg/day, spironolactone 25 mg/day, potassium chloride 3 g/day, rosuvastatin 20 mg/day, pantoprazole 20 mg/day, and bromazepam 1.5 mg/day. During this hospitalization, thyroid hormone levels were not rechecked, and freeT3 was not measured (See relevant laboratory analyses in Table 1).

Table 1.

Relevant laboratory analyses

1st hospitalisation	Day 1	Day 3	Day 5	Day 7	Day 10
FT4 (pmol/l) /11.5-22.7/	93.02
TSH (mIU/L) /0.550-4.780/	0.007
Potassium (mmol/l) /3.5-5.1/	3.2	3.7	3.6	3.8	3.4
Sodium (mmol/l) /136-145/	141	143	140	142	139
AST (U/l) /<34/	45	222	173	121	108
ALT(U/l) /10-49/	95	80	79	74	76
Creatinine (mcmol/l) /49-90/	91	110	117	110	105

Seven days later, he returned to the ER with symptoms including dizziness, nausea, vomiting, sweating, and sub-febrile temperature, and he was readmitted to the Department of Cardiology. The patient stated that they had been taking thyro-suppressive and other prescribed therapy regularly and correctly. After two days, he developed a maculopapular rash and an episode of tonic-clonic seizures. His thyroid hormone levels were high (FT4 260 pmol/l, TSH levels undetectable), which, along with clinical features, indicated a thyrotoxic storm; he scored 45 points on the Burch-Wartofsky Point Scale (7). Anti-thyroid peroxidase antibodies, TSH receptor antibodies, and thyroglobulin antibodies were negative (see relevant laboratory analyses in Table 2). His therapy was changed to Propylthiouracil 4x300 mg, Dexamethasone 2x4 mg, and Lugol’s solution, after which his general condition improved.

Table 2.

Relevant laboratory analyses

2nd hospitalisation	Day 1	Day 12	Day 27	Day 40	Day 60	Day 70	Day 80	Day 92
FT4(pmol/l) /11.5-22.7/	260	>100	97.32	78.26	75.74	45.27	33.94	23.56
TSH(mIU/L) /0.550-4.780/	<0.005	<0.005	<0.005	<0.005	0.006	0.008	0.005	0.005
FT3 (pmol/l)					6.91
antiTPO (IU/ml) <60	12.95
antiTG (IU/ml) <4.5	<0.01
antiTSHrec(IU/ml) <1.7	0.87
AST (U/l) <34	50	50	32	76	45	35	35	14
ALT (U/l) /10-49/	132	150	444	280	78	135	75	41

A few days later, he experienced another episode of syncope with tonic-clonic convulsions. Both episodes of tonic-clonic seizures occurred with normal electrolyte levels. He was examined by a neurologist, and brain MRI was performed. Examination showed a large arachnoid cyst (65x24x30 mm) in the right frontoparietal region of the brain, which the neurologist considered congenital and not associated with the present symptomatology. Serial EEG was examined, with normal findings. Lugol’s solution was discontinued. Control echocardiogram findings showed improvement in systolic function (EF 38%). Blood cultures were sent for microbiological analyses due to elevated inflammatory parameters, and Staphylococcus epidermidis was isolated. The infection was treated with ciprofloxacin and vancomycin. After 25 days of hospitalization, thyroid hormone levels were decreasing (free serum T4=93 pmol/l), and the patient was transferred to the Department of Endocrinology. PTU dose was reduced to 900mg/day. Corticosteroid therapy was gradually tapered and ultimately discontinued on the 38^th day of hospitalization, after which the patient developed a severe rash, initially on the hands and later spreading to the face. The infectologist ruled out an infectious cause for the rash. Blood samples were taken for autoimmune antibody analysis. Vancomycin was discontinued due to suspected adverse reactions. Skin lesions resembling vasculitis began to spread. Given the suspicion that the medication might have triggered this response, acetylsalicylic acid (ASA) and angiotensin-converting enzyme (ACE) inhibitors were removed from the treatment regimen. Concerns arose about the possibility of Propylthiouracil-induced vasculitis, prompting a switch to thiamazole 60mg/day on the 40^th day of hospitalization. Dexamethasone 2x4mg was reintroduced due to the persistent spreading of the skin lesions, which then began to regress. The dexamethasone dose was gradually reduced, and the patient was transitioned to oral prednisone, with a gradual tapering of the dose. Antibody analysis did not indicate systemic vasculitis, but rather a cutaneous form (ANCA results were negative). Systemic connective tissue disease was ruled out. No further skin lesions were observed. The patient had a transient increase in liver enzymes, predominantly AST, with a maximum value on the 27^th day of hospitalization most likely due to increased metabolic state and PTU therapy, which was monitored and subsequently declined. Ultrasound examination of the thyroid did not reveal any nodules, and there were no signs of increased vascularization of the gland tissue.

On the 60^th day of hospitalization, the panel of endocrinologists and surgeons concluded that, given the patient's elevated free T4 levels, recent myocardial infarction with subsequent reduced heart function, and the necessity to suspend thyro-suppressive therapy for two weeks prior to radioactive iodine treatment, the most effective and timely therapeutic approach is surgical ablation. Lugol's solution was reintroduced, and a successful total thyroidectomy was performed on the 97^th day of hospitalization, after the FT4 level dropped below 30 pmol/l. The patient was discharged on the seventh postoperative day, in good general condition, with the following medications: acetylsalicylic acid (ASA) 100 mg/day, ticagrelor 180 mg/day, bisoprolol 2.5 mg/day, ramipril 1.25 mg/day, furosemide 40 mg on the second day, and spironolactone 25 mg/day. Pathophysiological examination of the thyroid gland revealed a colloid nodule goiter, which was not consistent with the echocardiographic findings. Levothyroxine supplementation was initiated at 100 mcg/day, and was subsequently increased to 175 mcg/day during follow-up to reach euthyroidism. The patient is feeling well while on levothyroxine therapy.

DISCUSSION

We presented an unusual case of thyroid storm in a patient who developed acute myocardial infarction and had no history of thyroid disease before cardiac angiography. Mild or subclinical hyperthyroidism was assumed to be present before primary angiography. However, because an urgent diagnostic procedure was performed on a patient without a history of thyroid disease, thyroid hormone concentrations were not determined before the development of acute myocardial infarction. Therefore, it is uncertain whether thyroid hormone levels were increased before ICM administration.

Thyroid storm can occur in patients with undiagnosed hyperthyroidism who experience stressful events, such as acute myocardial infarction (8, 9). Severe thyrotoxicosis can be induced by the application of iodine-based contrast (8, 10-13). A single injection of 200 ml contrast based on iodine provides free iodine equivalent to roughly 45 times the daily recommended intake for filling iodine deposits in the thyroid gland for up to two months (10). Our patient had a myocardial infarction and received 300-ml contrast medium during coronary angiography. Very few studies have described the development of thyrotoxicosis following ICM administration. However, most studies have suggested an association between ICM exposure and incident hyperthyroidism (3, 6). We have not found any case reports in the literature showing AMI as the only factor leading to thyrotoxicosis, likely because it is always followed by coronary angiography that includes the administration of ICM, causing the two etiological factors to overlap.

Treatment for thyroid storm consists of supportive care, preferably intensive care, blockage of the peripheral effects of thyroid hormones, and inhibition of thyroid hormone synthesis and release (7). The patient received full treatment for thyroid storm, but an adverse drug reaction further complicated his condition. Propylthiouracil is an antithyroid drug that inhibits the synthesis of thyroid hormones. It is used in the treatment of hyperthyroidism. It is traditionally preferred over methimazole in the management of thyrotoxic storms because of its more rapid onset of action and the additional benefit of inhibiting the peripheral deiodinase enzyme that mediates the conversion of T4 into T3 (1). Multiple case reports described vasculitis associated with the administration of PTU, mostly ANCA positive with similar symptoms to those our patient developed (14-16). Vasculitis associated with PTU may affect any organ, but skin lesions are most common, as observed in our patient. However, it can also cause life-threatening pulmonary-renal syndrome with high mortality (16). We could not confirm whether our patient developed vasculitis due to PTU. Moreover, there is a possibility that some other drug induced this adverse reaction although it is not likely.

In 2010, the American Food and Drug Administration issued an advisory on the use of PTU due to its potential for liver toxicity. Since no head-to-head trial demonstrated a clear advantage of using PTU, many experts now recommend using either carbimazole or methimazole in the treatment of thyroid storm and achieving T4-to-T3 conversion inhibition with beta-blockers and corticosteroids (1). In our case, the initial drug was thiamazole, but despite its administration (even though it was not at maximum dosage), our patient developed a severe thyroid storm.

This case report aimed to raise awareness regarding the routine evaluation of thyroid function in patients with and without previous signs and symptoms of thyrotoxicosis who had undergone acute myocardial infarction and coronary angiography. Moreover, this approach could be beneficial as progressively more people with coronary diseases will undergo this procedure. If increased thyroid hormone levels are detected, patients should be carefully monitored in intensive care units. This approach could be the only way to prevent the progression of hyperthyroidism to a life-threatening condition, such as thyroid storm, especially in patients with impaired heart function.

The 2021 European Thyroid Association Guidelines recommend an individualized approach to managing hyperthyroidism induced by iodine-based contrast media. This approach should consider clinical symptoms, the cause and severity of the hyperthyroidism, as well as the patient's age, existing health conditions (especially heart-related), and overall health status. In most mild cases, close monitoring, avoiding additional iodine exposure, and using β-blockers are advised. For severe cases, starting treatment with antithyroid drugs is recommended, and if there's a partial response, combining with perchlorate may help control the condition. (17).

Conflict of interest

The authors declare that they have no conflict of interest.