Life-threatening amiodarone-induced thyrotoxicosis – Personalized approach to radical treatment

Objective Amiodarone is an iodine-rich molecule and an effective antiarrhythmic drug. It is a first-line treatment for patients with life-threatening ventricular arrhythmias and for prevention in patients at high risk. The use of amiodarone may cause serious adverse effects such as pharmacotherapy-resistant, life-threatening amiodarone-induced thyrotoxicosis (AIT)leading to rapid deterioration of the patient's condition. According to the European Thyroid Association (ETA) guidelines, emergency thyroidectomy is the first-line treatment option in these cases. ; however, is not always feasible in the clinical setting due to the high anesthetic risk. We aimed to assess the clinical course and results of urgent thyroidectomy and 131-I therapy in patients with severe AIT with worsening of cardiac status. Methods Retrospective analysis of the clinical course and outcomes of life-threatening AIT refractory to pharmacotherapy in patients hospitalized at a tertiary endocrinology center between 2014 and 2022. Results An electronic database search identified 75 patients hospitalized for severe AIT. At the time of AIT diagnosis, median Thyroid-stimulating hormone (TSH) concentration was 0.001 mIU/L (range 0.001–0.35), fT4 63.2 pmol/L (range 9.0 - >100), and fT3 10.2 pmol/L (range 3.8–49.3). All patients received optimal conservative treatment. Among them, 20 required urgent radical therapy due to worsening arrhythmias and/or AIT-related heart failure. In this group, 6 patients died before any radical treatment was applied, 6 underwent total thyroidectomy, while 8 patients were successfully treated with 131-I (in 6 cases after rhTSH stimulation). The median dose of 131-I used for the therapy was 784MBq (range 627–860). The decision to treat with 131-I despite low but detectable 131-I uptake (median value 6 %) was made in cases of significant contraindications to anesthesia due to refractory ventricular arrhythmias, exacerbation of severe heart failure unresponsive to cardiac treatment, myocardial infarction during AIT course, massive pulmonary embolism. Conclusion The decision regarding the optimal time and type of radical treatment of AIT refractory to pharmacotherapy is critical for patients management and should not be delayed. Urgent therapy with 131-I may be an effective therapeutic option in patients who are unsuitable for thyroidectomy due to the high risk of anesthesia.


Thyrotoxicosis AIT Amiodarone Salvage therapy 131-I A B S T R A C T
Objective: Amiodarone is an iodine-rich molecule and an effective antiarrhythmic drug.It is a firstline treatment for patients with life-threatening ventricular arrhythmias and for prevention in patients at high risk.The use of amiodarone may cause serious adverse effects such as pharmacotherapy-resistant, life-threatening amiodarone-induced thyrotoxicosis (AIT)leading to rapid deterioration of the patient's condition.According to the European Thyroid Association (ETA) guidelines, emergency thyroidectomy is the first-line treatment option in these cases.; however, is not always feasible in the clinical setting due to the high anesthetic risk.We aimed to assess the clinical course and results of urgent thyroidectomy and 131-I therapy in patients with severe AIT with worsening of cardiac status.Methods: Retrospective analysis of the clinical course and outcomes of life-threatening AIT refractory to pharmacotherapy in patients hospitalized at a tertiary endocrinology center between 2014 and 2022.Results: An electronic database search identified 75 patients hospitalized for severe AIT.At the time of AIT diagnosis, median Thyroid-stimulating hormone (TSH) concentration was 0.001 mIU/ L (range 0.001-0.35),fT4 63.2 pmol/L (range 9.0 ->100), and fT3 10.2 pmol/L (range 3.8-49.3).All patients received optimal conservative treatment.Among them, 20 required urgent radical therapy due to worsening arrhythmias and/or AIT-related heart failure.In this group, 6 patients died before any radical treatment was applied, 6 underwent total thyroidectomy, while 8 patients were successfully treated with 131-I (in 6 cases after rhTSH stimulation).The median dose of 131-I used for the therapy was 784MBq (range 627-860).The decision to treat with 131-I despite low but detectable 131-I uptake (median value 6 %) was made in cases of significant contraindications to anesthesia due to refractory ventricular arrhythmias, exacerbation of severe heart failure unresponsive to cardiac treatment, myocardial infarction during AIT course, massive pulmonary embolism.

Introduction
Amiodarone is a widely used therapeutic option for the management of life-threatening ventricular arrhythmias and for the prevention of ventricular tachyarrhythmias in high-risk patients.It is also widely used to treat supraventricular tachyarrhythmias such as atrial fibrillation [1].
The early effect of amiodarone on serum thyroid hormone concentrations is well known.During the first month of amiodarone use, a 20-40 % increase in free thyroxine (fT4) and a 30 % decrease in free triiodothyronine (fT3) are often observed, accompanied by a slight increase in TSH- [1].Normalization of TSH concentration is usually seen up to 6 months, while fT4 values remain near the upper limit of normal or slightly elevated and fT3 decreases to the lower limit of normal or even below this range [2].
In 15-20 % of patients, the use of amiodarone leads to thyroid dysfunction requiring medical intervention [3].Amiodarone-induced hypothyroidism is quite common, especially in regions deficient in iodine; however, it is usually easily managed with replacement therapy.Amiodarone-induced thyrotoxicosis (AIT) is less common, constitutes 3-9% [3,4] of thyroid dysfunction cases, and may lead to life-threatening complications.Furthermore, management of AIT is often considered a clinical challenge resulting from the prolonged biological half-life of amiodarone (2 weeks-3 months) and the large amount of iodine in amiodarone molecules (200 mg of amiodarone releases approximately 6 mg of iodine) [5].Because of this, post-amiodarone side effects may occur or persist for a long period of time after discontinuation of treatment [5].
There are 2 main pathomechanisms of AIT.Type 1 AIT usually occurs in patients with pre-existing thyroid disease.Type 2 AIT is associated with destructive thyroiditis that leads to excessive release of thyroid hormones and occurs in patients with initially normal thyroid function [6].According to epidemiological studies, type 1 AIT is more common in regions deficient in iodine, while type 2 AIT is most common in iodine-replete environments [7].The differential diagnosis of both types of AIT can be difficult, and in such cases, a clinical diagnosis of mixed/undefined form of AIT is accepted [8].
Complications of prolonged and refractory to treatment AIT, result in increased mortality, especially in elderly patients with heart failure and life-threatening arrythmias.It should be noted that this high-grade thyrotoxicosis also affects the cardiovascular system by exacerbating heart failure and arrhythmias [9].A multicenter study that analyzed the causes of thyroid storm in French patients showed that AIT was the most common cause among patients hospitalized in 31 intensive care units, with a mortality rate of 17 % in intensive care units and 22 % at 6 months [10].
The main goal of AIT treatment is to achieve euthyroidism as soon as possible.Short-term therapeutic options for AIT include amiodarone cessation, thioamide administration, sodium perchlorate, glucocorticoids, and plasmapheresis [11]; however, in some M. Opalińska et al. cases, this treatment is ineffective.
In AIT which is refractory to medical treatment, persistent thyrotoxicosis with progressive deterioration of cardiovascular function requires urgent resolution.
Another key clinical issue is the possibility of amiodarone withdrawal.The decision to discontinue amiodarone should take into account the possible clinical benefit of amiodarone use in life-threatening arrhythmias, the risk of long-term exposure to excess thyroid hormones, and the type of AIT.The withdrawal of amiodarone unblocks T3 receptors in myocardial cells and may exacerbate lifethreatening arrhythmias.Drug withdrawal can be especially useful in type 1 AIT and in mixed/indeterminate types of AIT [11].
There are two main treatment options for the management of radical thyrotoxicosis: total thyroidectomy or 131-I therapy.In some cases of AIT, the first option may not be possible due to the high risk associated with anesthesia, while the second option is often hampered by low 131-I uptake.
We aimed to assess the clinical course and results of urgent thyroidectomy or 131-I therapy in patients with severe AIT who were hospitalized due to worsening of circulatory insufficiency and/or arrythmias.

Materials and methods
An electronic database search was conducted among patients hospitalized due to AIT at a tertiary endocrinology center between 2014 and 2022.Of these, patients who required urgent treatment consisting of thyroidectomy or 131-I therapy (with or without recombinant human thyrotropin (rhTSH) stimulation) due to aggravation of arrhythmias and/or AIT-related heart failure were selected.Finally, demographic data, clinical presentation of AIT, diagnostic tests, choice of treatment method, response to routine treatment, and results of urgent therapy were evaluated.The consort diagram for the study population is presented in Fig. 1.

AIT identification and outcome definition
Amiodarone-induced thyrotoxicosis was diagnosed if thyroid dysfunction was related to the use of amiodarone up to 3 months before the onset of thyrotoxicosis.Possible misdiagnosis due to "euthyroid sick syndrome" or the effects of medication (i.e., heparin, dopamine, glucocorticoids) [12] were excluded based on a patient's medical history.The results of diagnostic procedures such as thyroid ultrasound (USG) (with assessment of thyroid echogenicity, presence of thyroid nodules, the vascularity in ultrasound color Doppler, and estimation of thyroid volume), thyroid scintigraphy, and presence of thyroid specific antibodies were recorded.The reference values for all laboratory tests are shown in Table 1.
AIT was defined as suppression of TSH with elevated or normal T4 and/or T3 levels after exclusion of sick euthyroid syndrome and drug effects.Type 1 AIT was defined by the presence of nodular thyroid goiter or diffuse goiter >20 g or a positive TRAb (TSH receptor antibodies) concentration.AIT type 2 was defined as the presence of a normal thyroid gland or a small diffuse goiter <20 g with a negative concentration of TRAb.In cases not qualifying as type 1 or 2, a mixed/undefined form of AIT was diagnosed.
The first day of AIT was assumed to be the date on which the constellation of results typical for AIT was identified for the first time.In the case of surgical treatment, we considered the day of surgery to be the day of recovery.In the case of patients treated with 131-I or with pharmacotherapy alone, the day of recovery was considered the day of fT3 and fT4 normalization.Thyroid scintigraphy was performed with a 131-I dose of 6MBq.Radioiodine uptake (RAIU) was measured 24 h after 131-I application (24 h RAIU).A low 24 h RAIU was considered as below 4 % in the context of AIT.
In the case of rhTSH stimulation before 131-I therapy, patients received 0.9 mg of thyrotropin alfa intramuscularly 24 h before 131-I therapy.
The cardiac status was evaluated using left ventricular ejection fraction (LVEF, measured by echocardiography), NT-proBNP concentration, and appearance of hemodynamic instability.Events related to the duration of hospitalization and the appearance of clinical complications were recorded.

Statistical analysis
Demographic and clinical characteristics were analyzed by producing frequency tables for categorical variables and by calculation of the median and range for continuous variables due to the small cohort size and non-normal data distribution.Categorical variables were provided as numbers (n) and percentages (%).Statistical analyses comparing groups of patients were performed using nonparametric tests, including the Wilcoxon rank-sum test for continuous variables and Fisher's exact test for binary variables.A pvalue <0.05 was considered statistically significant.
IBM SPSS Statistics for Windows, version 27 (IBM Corp., Armonk, NY, USA) was used for the statistical analysis.

Results
In total, 75 patients who met the inclusion criteria were enrolled in the study.

Incidence and baseline characteristics at the time of AIT diagnosis
There were significantly more males than females among the patients eligible for the study: 56 males (74.7 %) vs 19 females.The median age at the time of diagnosis was 64 years (range 31-93).Significant cardiovascular risk in patients included: a history of sudden cardiac arrest in 11 (14.7 %) patients, coronary artery disease in 38 (50.7 %) cases, and arrhythmias, mainly supraventricular in 70 (93.3%) patients.A cardioverter defibrillator or cardiac pacemaker was present in 23 (30.7 %) and 5 (6.7 %) patients, respectively.Detailed baseline characteristics and clinical data of the patients are presented in Table 2.
Most of the patients were symptomatic and had classic symptoms of thyrotoxicosis, such as palpitations, weight loss, sweating, and heat intolerance.The most prominent cardiac and endocrine symptoms related to AIT observed during hospitalization are provided in Table 2.
The median thyroid volume was 23.5 mL (range 8.8-152.36).In 46 cases, hypoechogenicity typical of thyroiditis and/or decreased tissue vascularity was observed on the power Doppler.Nodular goiter was found in 33 cases.Both pathologies overlapped in 11 patients.In 7 cases, the blood flow was not assessed by USG.Five (12.8 %) patients had been diagnosed with thyroid dysfunction prior to the use of amiodarone, but they received amiodarone in the emergency unit without prior consideration of thyroid history.During thyroid evaluation, pathological values of TSH receptor antibodies (TRAb) were observed in 7 patients.

Amiodarone use
One patient without previous thyroid dysfunction received a single dose of amiodarone.The rest of the patients received prolonged amiodarone treatment for a median time of 21.3 months (range 0.1-48.0).Amiodarone was discontinued in 73 (97.0 %) patients after the diagnosis of AIT (following consultation with a cardiologist), except one patient with a 3-year history of sudden cardiac arrest due to ventricular tachycardia, recurrent episodes of VT despite the use of several antiarrhythmic drugs (b-blockers, verapamil, xylocaine, mexiletine, propafenone), and repeated RF ablations.In this case, it was decided to maintain amiodarone with concomitant thyreostatic treatment.

Medical management of thyrotoxicosis
Hyperthyroidism during hospitalization was treated with antithyroid drugs (ATD) in all 75 (100 %) cases, mainly by intravenous injections (in 71 cases).Treatment with thiamazole was initiated in all cases.In 6 patients, thiamazole was discontinued due to adverse effects (neutropenia, skin rash, deterioration of liver function), and the administration of propylthiouracil was initiated.Glucocorticosteroids were used in 60 (80 %) patients, sodium perchlorate in 38 (50.7 %), lithium carbonate in 10 (13.3 %) and albumin in 16 (21.3%) cases.The sequence of medication use depended on the individual course of the disease, including the type of AIT.Usually, ATD was initiated upon suspicion of type 1 AIT, while ATD, glucocorticosteroids, and/or sodium perchlorate were initiated upon suspicion of type 2 AIT as well as in the case of mixed/undefined type.If there was no clinical or biochemical effect, additional medication was added to the therapy.The drug regimens used during hospitalization are shown in Table 3.The average and maximumdoses of the medication used in AIT treatment are provided in Table 4.

Therapy outcome
The median duration of hospitalization time for all AIT patients was 17 days (range 2-107).During this time, urgent radical treatment was indicated in 20 (26.7 %) patients.These indications included severe thyrotoxicosis refractory to medical treatment with worsening cardiac condition, intolerance or contraindication to ATD, and in a single case, severe metabolic side-effects of prolonged glucocorticoid use (Table 5).The comparison of thyroid function assessment at the time of AIT diagnosis as well as concentration of anti-thyroid antibodies, liver enzymes, and NT-proBNP serum concentrations in patients who required urgent radical therapy are shown in Table 6.
Among the 20 patients whose condition deteriorated, 6 patients died before any radical treatment (thyroidectomy or 131-I therapy) was started, despite having received the best possible medical treatment, including plasmapheresis in 1 case.Total thyroidectomy was performed successfully in 6 patients; 1 patient developed cardiogenic shock in the perioperative period.Nine patients who were disqualified from surgery due to severe heart failure, life-threatening ventricular arrhythmias, and massive pulmonary embolism were treated with urgent 131-I therapy.Six of them (6/9) received 0.9 mg of rhTSH intramuscularly 24 h before the therapy due to low RAIU.The median dose of 131-I used for the first therapy was 784MBq (range 627-860).In 4 patients, a single dose of 131-I was successful in achieving hypothyroidism.Repeat therapy with 131-I was required in 4 patients due to a recurrence of thyrotoxicosis (with less severe symptoms).Among this group, 3 patients required a third dose of 131-I treatment to achieve hypothyroidism.In all cases of repeated 131-I therapy, the doses were 784MBq and were administered without the use of rhTSH.In one of these patients, there was no improvement after 131-I therapy and the patient finally underwent a thyroidectomy.
In the remaining cases (55/75), thyrotoxicosis was successfully controlled with the use of conservative management.Among these patients, 29 were subsequently treated with 131-I to radically cure hyperthyroidism or prevent recurrence of AIT in the future.The relevant clinical data for these patients are provided in the Supplementary Materials.In 48 out of 55 (87.3 %) patients who did not require urgent AIT therapy, a treatment regimen using ATD in alternation with glucocorticoids and/or sodium perchlorate was sufficient.
For all patients treated with 131-I, the median time from the last use of amiodarone to the 131-I therapy was 7.00 months (range 1-27).The median 24 h RAIU was 6.0 %, measured after administration of 6 MBq of 131-I.The example of RAIU in pre-and posttreatment scintigraphy in the patient with a good response to 131-I after rhTSH stimulation is shown in Fig. 2. The median time to ATDantithyroid drugs.

Discussion
Refractory AIT overlapping with severe heart failure, pre-existing arrhythmias, or unstable coronary artery disease can lead to a life-threatening condition.In our study, 20 of 75 (26.7 %) patients hospitalized for exacerbation of cardiac symptoms in the course of AIT required urgent therapy, despite having received the best available medical treatment (ATD, glucocorticosteroids, sodium perchlorate, lithium carbonate, albumin, plasmapheresis).Among this group, 6 patients underwent successful thyroidectomy and 8 patients were successfully treated with urgent 131-I therapy.Six patients died before any radical treatment was applied.
According to the guidelines of the European Thyroid Association (ETA), emergency total thyroidectomy is recommended in cases of cardiac deterioration due to thyrotoxicosis which do not respond to medical treatment, the appearance of adverse effects of AIT   TSH -Thyroid-stimulating hormone, T4 -thyroxine, T3 -triiodothyronine, TRAb -TSH receptor antibodies, aTPO -anti-thyroid peroxidase antibodies aTg -thyroglobulin antibodies NT-proBNP -N-terminal prohormone of brain natriuretic peptide, AST -Aspartate transaminase, ALT -alanine aminotransferase.
medical therapy, and in patients who may need amiodarone treatment in the future [11].This procedure may not always be possible due to the risks associated with anesthesia.In such cases, radical therapy using 131-I treatment is possible, optionally with (off-label) rhTSH stimulation in the case of low RAIU.Although thyroidectomy should be considered first-line treatment according to ETA guidelines, this procedure has well-documented perioperative risks [12].For this reason, our objective was to summarize our experience with urgent 131-I therapy.Although it may be associated with a delayed clinical response compared to thyroidectomy, 131-I therapy has a better risk-benefit profile and should be considered in certain patients with high surgical risk.
Our cohort consisted of predominantly middle-aged and elderly patients with clinically significant cardiac dysfunction and was therefore, a high-risk population at baseline.Among patients who underwent thyroidectomy, rapid resolution of thyrotoxicosis was documented, although a transient worsening of the cardiac condition and a single case of successfully treated cardiac arrest were observed.It is worth mentioning, that the data available in the literature tend to show a long-term improvement in LVEF after thyroidectomy [13], however, thyroidectomy complications in AIT patients were reported in 41 % of cases [12], and this prevalence is greater than in patients with Graves' disease [14] or toxic multinodular goiter [15].Among the most serious complications, stroke or respiratory failure were with a frequency of 5.9 % in both cases.The overall mortality in these patients was 5.9 % [12].In our cohort, no perioperative deaths occurred due to careful qualification for surgery and consideration of 131-I therapy in patients with a high risk associated with anesthesia.However, it should be noted that 6 patients died before the decision was taken regarding the optimal time and type of radical treatment to be used.
In patients with high perioperative risk, effective treatments with fewer adverse effects are still being investigated.As reported in the literature, plasmapheresis [16,17], plasma exchange [18,19], thyroid arterial embolization techniques [20], or atrioventricular node ablation [21] may be successful therapeutic options in the management of AIT.Among these, plasmapheresis and plasma exchange are the most documented, and both can be an option prior to surgery for the rapid reduction of free thyroid hormones and excess iodine.Unfortunately, their effects are rather transient and their use may be associated with an escalation of circulatory instability [22].The only patient in our cohort who qualified for plasmapheresis prior to urgent thyroidectomy died before surgery due to exacerbation of heart failure.Endovascular embolization techniques appear to be relatively effective and safe [20], but their availability is limited.
Amiodarone-induced thyrotoxicosis remains a diagnostic and therapeutic challenge, and we tried to distinguish AIT subtypes in all cases.Even with a primary suspicion of type 1 AIT, not all patients respond well to ATD, and often require combined therapy with ATD and glucocorticoids or sodium perchloride [23].However, standard therapy consisting of ATD, glucocorticoids and/or sodium perchloride was effective in 88.9 % of patients, therfore, the ineffectiveness of such a drug mixture may indicate a higher risk of deterioration and the need for subsequent radical treatment.
The decision to continue or discontinue amiodarone after the diagnosis of AIT is often difficult and there is no clear consensus in this regard [11].Amiodarone and its metabolites have a long half-life, so there is no immediate benefit of its withdrawal.Furthermore, the continuation of amiodarone can be beneficial in the case of life-threatening arrhythmias, so its sudden withdrawal may cause an initial exacerbation of symptoms of thyrotoxicosis [23].In our cohort, we discontinued amiodarone in the vast majority of patients (97 %) and no sudden worsening of clinical symptoms was observed.
According to previously published data, recurrence of AIT after amiodarone reintroduction is 4 times more frequent in patients with type 1 AIT when compared to patients with type 2 AIT [24].For this reason, thyroid ablation with 131-I should always be considered before reintroducing amiodarone in patients with a history of type 1 AIT.In one of the previous studies, even patients with a 24 h RAIU of 1.3 % ± 0.9 responded well to 131-I therapy, although the response time to 131-I therapy was significantly longer than in the group with 24 h RAIU equal to 14.1 % ± 0.3 [25].In the case of an urgent need for 131-I therapy, the situation is more complicated.131-I therapy is considered ineffective and unfeasible in patients with AIT due to the frequently observed low RAIU.Furthermore, a possible delay in response to treatment (when compared to surgery) may pose an additional high risk.Our results indicate that 131-I therapy may be an effective option, despite low RAIU, and appears to be safe.One of the well-known methods for increasing RAIU is the use of rhTSH stimulation [26].In theory, the use of rhTSH may be associated with a sustained increase in serum thyroid hormone concentrations, which may exacerbate cardiac failure.In our study, no significant cardiac symptoms were observed among the patients who qualified for urgent 131-I therapy and who received a single dose of rhTSH 24 h before 131-I treatment, which confirmed the safety of this procedure.We would like to stress that rhTSH was used only in patients with low RAIU as seen on pre-treatment scintigraphy.The results of the 131-I therapy obtained in our cohort were satisfactory; only a single patient did not respond to the 131-I therapy and was finally referred for thyroidectomy.Due to the partial response to 131-I treatment in patients who had a recurrence of thyrotoxicosis during the follow-up period, it was possible to repeat 131-I therapy during the period of cardiac stability.
The mechanisms leading to resistance to AIT treatment are largely known, but it is not entirely clear what factors may determine the differential response to treatment.Among other things, it is unclear whether amiodarone itself or its main metabolite desethylamiodarone (formed by metabolism of the drug by cytochrome P4503A) more strongly affects thyroid function.An increased ratio of desethylamiodarone to amiodarone was observed in patients with AIT (prior to the development of thyroid dysfunction), so perhaps it could be a potential predictive marker for the development of AIT [27].
The main limitations of our study are its retrospective design and the small sample of patients undergoing urgent radical treatment exposes our findings to bias, so a multicenter clinical trial could enhance the value of 131-I therapy in this challenging clinical setting.Due to the small sample size and the difficulty with accurate assessment of the AIT type (performed on the basis of available medical records), we were unable to compare treatments in the different subtypes of AIT.Furthermore, the retrospective design of the study limited our ability to accurately compare forms of radical therapy in terms of effectiveness and the associated risks.However, the effectiveness and the good safety profile of 131-I salvage therapy are encouraging.The decision regarding the optimal time and form of radical AIT therapy should take into account the risks and benefits of treatment, which requires an individual approach depending on the severity of thyrotoxicosis, cardiac status, and dysfunction of other organs.In clinical settings, the therapeutic plan should include the coordinated efforts of endocrinologists, thyroid surgeons, cardiologists, and anesthesiologists.In summary, the need for urgent AIT therapy due to a life-threatening cardiac condition affects a relatively small number of patients.The majority of patients, whose condition worsened, even after receiving the best medical treatment required a prompt decision on radical treatment, as its delay could be associated with an unfavorable outcome.The decision to undergo surgery or 131-I therapy should depend on the patient's clinical condition.
In our study, thyroidectomy resulted in rapid resolution of thyrotoxicosis in all analyzed patients.A similar final outcome was observed among patients treated with urgent 131-I therapy.Low RAIU values observed frequently in the course of AIT can be overcome using rhTSH, which in our patients was considered safe.The prevalence of complications in patients after 131-I therapy was negligible.

Fig. 2 .
Fig. 2. Low RAIU in pre-treatment (A) and good RAIU in post-treatment scintigraphy (B) (after rhTSH i.m. injection 24 h before therapy) in the patient with life-threatening AIT complicated by massive pulmonary embolism, successfully treated with 131-I.

Table 1
Results of thyroid function assessment and concentration of anti-thyroid antibodies at the time of AIT diagnosis, liver enzymes, and NT-proBNP serum concentrations during hospitalization in the whole group of patients.

Table 2
Patient Characteristics and Clinical Presentation at diagnosis.

Table 3
AIT medical management during hospitalization.

Table 4
Average and maximal doses of drugs used for AIT treatment.

Table 5
Clinical indications for urgent AIT radical treatment.
a Including one case of amiodarone-induced severe pulmonary fibrosis.

Table 6
Comparison of thyroid function assessment and anti-thyroid antibodies concentration, liver enzymes, and NT-proBNP serum concentrations in patients who underwent urgent radical therapy.