Blockchain Papers

NAHUM A. FREEDBERG

In the differential diagnosis of supraventricular tachycardia, pacing maneuvers or observation rarely provide a diagnosis when used individually.1 The introduction of transcatheter therapy for cardiac arrhythmia transforms electrophysiology from an exclusive, scholarly, almost Talmudic, field to an interventional goal-oriented field where successful elimination of the arrhythmia by “burning” often serves as “proof” of the arrhythmia mechanism (Learning by Burning). In a series of papers by Callans et al.2–4 published in this Journal, the term “learning while burning” was coined, emphasizing that in contrast to the goal oriented approach, ablation procedure is indeed a powerful tool for understanding the interplay between anatomical substrate and the pathophysiology of clinical arrhythmia. The authors in the present Journal article5 put a new twist on that concept by utilizing junctional beats induced during ablation procedure of AV nodal slow pathway modification to gain a new insight to the differential diagnosis of atrioventricular node reentry tachycardia (AVNRT) versus junctional tachycardia (JT). The authors should be applauded for a meticulous execution of the study protocol and a rigorous validation of their findings that showed convincingly that the mean H-A during JT is shorter than the mean H-A during AVNRT and that the mean delta H-A (defined as retrograde H-A during ventricular pacing minus H-A during tachycardia) is negative during AVNRT, as opposed to positive during JT. In the study design, both AVNRT and JT were induced in each patient. When these measurements were compared on an individual basis (meaning that every patient's measurements during AVNRT were compared with his or her own measurements during JT controlling for variability between patients), these findings hold true in most patients (see Figs. 2 and 3). How can we explain these finding based on our present knowledge about the electrophysiological properties of these arrhythmias? AVNRT is the most common cause of supraventricular tachycardia in patients referred for electrophysiological study (EPS).1 The “common,”“typical,”“slow-fast” type is present in over 80% of all cases of AVNRT.6 In a simplistic model, AVNRT results from reentry involving two anatomically distinct AV node structures7,8 (i.e., “slow” and “fast” pathways). In “slow-fast” AVNRT, the reentry circuit consists of anterograde conduction through the slow pathway and retrograde conduction by the fast pathway with the earliest retrograde atrial activation in the “fast pathway region” at the apex of the triangle of Koch, recorded on the His-bundle electrogram from the right septum.9,10 Unfortunately, life is not that simple: the three-dimensional anatomy and cytoarchitecture of the AV junction is complex11,12 and the exact location of the atrionodal connections and slow and fast pathways are still controversial. Although several elegant models based on functional characteristics of different areas of the compact AV node and surrounding structures were proposed to explain dual-AV node physiology, the sheer bulk of the literature on the subject and the ongoing debate attest that none of them is proven.13,14 In as many as 40% of the patients with AVNRT, there are multiple AV nodal pathways.15 Even in patients with typical AVNRT, recording with close-spaced electrodes in the His, coronary sinus (CS), and the slow-pathway areas has shown that there is heterogeneity of the retrograde fast pathway conduction pattern.16 Recording of the His bundle potential from the right and left sides of the septum has shown that the earliest retrograde atrial activation during AVNRT is most often recorded on the left side of the septum.17 Thus, it is not surprising that there is a considerable variability in H-A intervals in patients with typical AVNRT, making it difficult at times to differentiate between typical AVNRT and other arrhythmias (including JT) based on H-A interval alone. According to the slow-fast pathway model, the retrograde atrial activation sequence during right ventricular pacing at the tachycardia cycle length, immediately after typical AVNRT, propagates retogradely from the His bundle through the lower common pathway to the fast pathway, and should be similar to the activation sequence during typical AVNRT. Retrograde H-A interval during ventricular pacing (H-Ap; measured from the end of the most proximal His potential to earliest A) is the sum of retrograde conduction time of the lower common pathway and the retrograde fast pathway. The H-A of typical AVNRT (H-At) according to this model is retrograde conduction time of the fast pathway minus anterograde conduction time of the lower common pathway. The difference between H-Ap and H-At (so called delta H-A) equals retrograde plus anterograde conduction time of the lower common pathway13 (assuming that the retrograde fast pathway conduction time is identical during pacing and AVNRT). A positive delta HA suggests that a lower common pathway is present. A negative delta HA, which, in fact, was found in the present study5 and by others,18 cannot be explained by this simple model. Although there are several explanations for this phenomenon, including difference in conduction velocity, activation path,19 and a combination thereof,13 a negative delta HA probably reflects a very short or an absent lower common pathway. Automatic JT as described by Coumel20 is a rare arrhythmia seen mainly in the pediatric population21 and postcardiac surgery21,22 and very rarely in adults.23 In the few cases studied, abnormal automaticity within or in close proximity to the His bundle was found.24–26 JT is frequently seen during radio frequency ablation using the AV node modification by slow pathway approach. In fact, the presence of JT is associated with successful slow pathway ablation.27,28 The pathophysiology of JT during ablation is thought to be enhanced automaticity due to heating of the tissue29,30 or local release of norepinephrine.31 Studies in pig and rabbit heart models have shown that heating in a discrete area located in the middle of the triangle of Koch that was located in close proximity to the compact AV node induced JT. In that area, no slow pathway potential was seen and it was distant from the site of earliest retrograde atrial activation. There was a large variation between individual animals regarding the location of these sites.30 In canine blood-perfused atrioventricular node preparations, JT was induced by heating anterior to the CS os with the earliest retrograde atrial activation site at the His-potential recording site or in the middle of Koch's triangle. After interruption of the posterior input to the AV node, atrial activation during JT spread from the low posterior to the high anterior septum.29 In humans, VA block during junctional ectopy is a harbinger of AV block in patients undergoing RF ablation of the slow pathway,27 suggesting that the retrograde atrial activation during JT may involve the His area or the common lower pathway. However, in that same paper, the authors observed that “VA conduction should be expected during the junctional ectopy that accompanies slow pathway ablation, even when there is poor VA conduction during baseline ventricular pacing,” and that the AV block was proximal to the His.27 These astute observations suggest that the site of VA conduction during JT is proximal to site of VA block during ventricular pacing. Wagshal et al.32 reported that higher temperature lesions simultaneously abolish all slow pathway activity as well as the focus of JT, which suggests that the JT source is located or triggered by slow pathway tissue. In a study by Lee et al.,33 atrial activation sequences were assessed by comparing H-A interval (measured at the high right atrium) during various forms of AVNRT and JT induced by ablation. In 27 patients with slow-fast AVNRT, H-A during JT was shorter than during AVNRT: 58 ± 24 msec compared with 68 ± 21 msec, respectively (P < 0.01). In the present study,5 a similar trend in mean H-A interval was observed: 35 msec versus 54 msec during JT and AVNRT, respectively. These findings call into question the concept that JT seen during RF ablation originates or has an exit point near the His area as described in the rare “de novo” automatic JT.24 Obviously, if a junctional beat originates near the His, distally to a common pathway, the H-A interval during JT will be longer than H-A interval during AVNRT that has a more proximal turn-around point to the fast pathway. In that situation, one would expect near-zero delta H-A in JT and positive delta H-A in AVNRT—in contrast to the finding of present5 and other33 studies. Studies in animal models and high resolution mapping in humans have demonstrated several mechanisms that can account for the shorter H-A interval during JT compared with AVNRT: changes in activation sequences that may cause direct activation of the atria, compact AV node,29 anisotropic spread from one more AV nodal transitional zone,34 fibers connecting to the fast pathway,35 or fibers connecting the slow pathway ablation area directly to the fast pathway in a more proximal location.33 Local heating may cause an increase in conduction velocity due to a direct effect30 or adrenergic stimulation. A recent study in a canine complete AV block model has shown that the application of RF energy caused a shift from the distal portion of the AV junctional area to a more proximal one. This enhanced junctional automaticity was suppressed by esmolol but not affected by atropine.31 In conclusion, differential diagnosis of a short RP tachycardia can be challenging. The paper by Srivathsan et al.5 adds a valuable new technique regarding the diagnosis of JT versus AVNRT, as well as provides insight into the electrophysiological mechanism of this fascinating and elusive arrhythmia. Further research is needed to ascertain whether these findings can be extended to the clinical forms of JT. Acknowledgment: The author would like to thank Dr. Shaul Atar for critical review of the manuscript.

Gilbert H. Daniels

Appropriate therapy for amiodarone-induced thyrotoxicosis (AIT) requires a diagnostic precision that may be difficult to achieve (1). Individual cases are rarely straight forward. On June 14, 1999, a 71-yr-old man was hospitalized with a 1-week history of exertional shortness of breath, foot swelling, and feeling poorly. In 1982, he was hospitalized with congestive heart failure and atrial fibrillation, attributed to myocarditis. In 1985, atrial fibrillation recurred and responded to chronic quinidine therapy. In early 1996, quinidine was stopped, followed by paroxysmal and then persistent atrial fibrillation with congestive heart failure (ejection fraction, 20–25%). Amiodarone (200 mg/day) and coumadin were prescribed. In May 1996, his serum TSH was 0.9 μU/mL. In September 1996, he suffered an acute myocardial infarction and underwent angioplasty of stenoses of the left anterior descending and diagonal coronary arteries. He remained in normal sinus rhythm; coumadin was discontinued. Amiodarone was discontinued in 1997 but successfully restarted in March 1998 when atrial fibrillation recurred (TSH 2.3μ U/mL). Atrial fibrillation recurred and persisted, and amiodarone was discontinued in September 1998, 9 months before admission. On admission (June 1999) he was in atrial fibrillation with a ventricular response of 180. His blood pressure was 90 systolic. He had mild proptosis (left greater than right), lid retraction, neck vein distension, and a slightly enlarged (20–25 g) thyroid. Although bilateral pleural effusions were present on the chest x-ray, interstitial edema was absent. A myocardial infarction was ruled out. His ventricular response was difficult to control despite escalating doses of β-blockers. Laboratory studies are summarized in Table 1. Laboratory data Normal range: T4, 4.5–10.9 μg/dL; free T4 index, 4.5–10.9; T3 RIA, 60–180 ng/dL; TSH, 0.5–5.0 μU/mL. Free T4, 0.7–1.5 (ng/dl); TSI, 0–129%; TBII, 0–9.9%; urine iodide, 42–350 μg/L. Laboratory data Normal range: T4, 4.5–10.9 μg/dL; free T4 index, 4.5–10.9; T3 RIA, 60–180 ng/dL; TSH, 0.5–5.0 μU/mL. Free T4, 0.7–1.5 (ng/dl); TSI, 0–129%; TBII, 0–9.9%; urine iodide, 42–350 μg/L. His 20-min 99m pertechnetate uptake was low at 0.19% (normal range, 0.5–3.75). AIT was diagnosed, possibly secondary to Graves’ disease. He was begun on methimazole (10 mg, po, tid), prednisone (40 mg, po, daily), iopanoic acid (500 mg, po, bid), metoprolol (200 mg, 4 id), and heparin, coumadin, and verapamil in doses up to 120 mg, tid. At the time of discharge his heart rate was 100–120. He was discharged on June 23, 1999, on methimazole (10 mg, po, tid), prednisone (40 mg, po, daily), iopanoic acid (500 mg, po, bid), lopressor (75 mg, 4 id), verapamil (20 mg, tid), lasix (20 mg, po, qd), and coumadin. Prednisone was discontinued after June 24. On July 2, he was in atrial fibrillation with a ventricular response of 104–108; his blood pressure was 90/60. He had lost 12 lbs since his hospital admission and noted less exertional shortness of breath. Mild proptosis, left greater than right, was noted (Hürthle exophthalmometer: left, 20 mm; right, 19 mm). TSH-binding inhibitory immunoglobulin titers (TBIIs) had been completed and were weakly positive. Graves’ disease was considered likely. On July 22, his pulse was 120 (AF). His dyspnea was unchanged, but he had a single episode of angina relieved by nitroglycerine. He noted increased fatigue and heat sensitivity. Methimazole was increased to 20 mg three times daily. Iopanoic acid was continued. On August 6, his radial pulse was 116–120. His ventricular rate on electrocardiogram was 139, increased compared with his previous electrocardiogram, and worsening ST segment depression was present. Although his dyspnea was stable, edema had increased to the mid-calf. His cardiologist considered hospital admission, but careful outpatient observation was the final recommendation. On August 17, thyroidectomy was recommended, in part, based on a serum T4 of 25.9 μg/dL, although his serum T3 had fallen to 140 ng/mL. A bilateral thyroidectomy was performed on September 10 without incident or complications. Pathological examination revealed an enlarged thyroid gland (right lobe, 5 × 2.5 × 1.5 cm; left lobe, 4.5 × 2.5 × 3 cm), but no weight was recorded. The final pathology report read: “Enlarged thyroid with fibrosis and mild chronic inflammation. There is no evidence of malignancy.” We asked to have the pathological material re-assessed. An addendum was reported: “The thyroid is diffusely affected with the lesions described as follows. Approximately half of the areas contained islands of dilated thyroid follicles that were lined by attenuated follicular epithelial cells. These islands are separated by areas of collapsed thyroid follicles admixed with fibrosis and prominent vasculature. Nonspecific findings including histocytes and eosinophilic bodies were present. These changes are consistent with those described in amiodarone-associated thyrotoxicosis” (2). Subsequent hypothyroidism was treated with levothyroxine. In December 1999, he remained in atrial fibrillation, but his ventricular response was 60. Amiodarone is an iodinated benzofuran derivative that is approved for the therapy of life-threatening recurrent ventricular arrhythmias (3) but is also used to treat angina, paroxysmal supraventricular tachycardia, and atrial fibrillation and to maintain normal sinus rhythm after cardioversion for atrial fibrillation (4). Amiodarone contains 75 mg iodine per 200-mg tablet and releases∼ 10% of the iodine as free iodide daily (5). Amiodarone is highly lipophilic and is concentrated in adipose tissue, cardiac and skeletal muscle, as well as the thyroid (6). With prolonged use, amiodarone has an elimination half-life as long as 100 days (6) Amiodarone effects on thyroid function result from iodine release and intrinsic drug properties (7). Pharmacologic iodide administration to euthyroid individuals with intrinsically normal thyroid glands results in transient inhibition of thyroid hormone synthesis and release, decreased thyroidal iodide trapping, and enhanced T4 (3,3′,5,5′ tetraiodothyronine) rather than T3 (3,3′,5 triiodothyronine) production by the thyroid, so-called autoregulatory functions (8). The net effect is a slight serum TSH increase that occasionally exceeds the normal range (9, 10). With chronically higher iodide intake, the prevalence of Hashimoto’s thyroiditis increases in genetically susceptible human and animal populations (11–13). In addition, pharmacologic iodide administration may precipitate hypothyroidism in patients with Hashimoto’s thyroiditis (14). Approximately 6% of patients receiving amiodarone develop iodine-induced hypothyroidism; the prevalence is higher in areas of iodine sufficiency and lower in iodine-deficient areas (15). Hypothyroidism may develop as soon as 2 weeks and as long as 39 weeks after starting amiodarone (7). Iodide supplementation in iodine-deficient endemic goiter populations triggers epidemics of hyperthyroidism in a minority of the population, the so-called Jod-Basedow phenomenon (16). Eighty-five percent of these hyperthyroid patients have nodular goiters. Autonomous areas within the nodular thyroid gland overproduce thyroid hormone when exposed to excess substrate (iodide) but are relatively impervious to the autoregulatory effects of iodine (17). However, some hyperthyroid patients have diffuse thyroidal uptake suggestive of Graves’ disease (18). As in the Hashimoto’s thyroiditis example above, excess iodide seems to trigger or facilitate an immunological attack on the thyroid (19). Additionally, borderline iodine-deficient patients with Graves’ disease in remission commonly relapse after adding 500 μg iodide daily (20), an amount comparable with the daily iodide intake in many iodide-sufficient areas. Pharmacologic doses of iodide may also precipitate hyperthyroidism in euthyroid individuals with nodular thyroid glands in iodine-sufficient regions (21). Case reports (22) and the amiodarone experience suggest that iodine excess may also precipitate Graves’ hyperthyroidism in iodine-sufficient areas, but this conclusion is uncertain. Amiodarone also has powerful effects on thyroid hormone metabolism (7). Amiodarone inhibits the peripheral conversion of T4 to T3 and may inhibit T3 receptor binding and action (23–25). In euthyroid individuals, T4 and free T4 concentrations increase by 42% due to decreased T4 clearance (7). Reverse T3 (3,3′5′ triiodothyronine) concentration rises by 172%. Efficacy and toxicity of amiodarone may be proportional to reverse T3 concentration (26). Serum T3 concentrations initially decline by 20–25%, subsequently an average 16% below baseline, but may be frankly low in some patients (7, 27). Serum TSH rises, occasionally out of the normal range, but with chronic administration generally remains in the normal to high normal range. It is uncertain whether TSH elevation in the 10–20 μU/mL range represents peripheral subclinical hypothyroidism or is a pituitary specific effect of amiodarone. Some authors accept subnormal serum TSH concentrations with normal T3 concentrations as compatible with the euthyroid state. However, I interpret these findings as evidence of amiodarone-induced subclinical hyperthyroidism. The 24-h radioiodine uptake decreases to low levels (<4%) in euthyroid individuals taking amiodarone (28). This is to be expected because 15 mg inorganic iodide daily, after a loading dose of 30 mg, decreases mean 24-h radioiodine uptake to less than 2% after 12 days (10). When added to antithyroid drugs, amiodarone facilitates the treatment of severe hyperthyroidism (29), by inhibiting T4 to T3 conversion, thyroid hormone release, and possibly T3 receptor binding and action. Unfortunately, 3% of patients exposed to amiodarone develop hyperthyroidism (30), with a higher prevalence in iodine-deficient regions (15). AIT may have a male predominance (31), reflecting the higher cardiovascular disease prevalence in men. Hyperthyroidism may occur 4 months to 3 yr after initiating therapy or after drug withdrawal (28) and is not related to cumulative drug dosage (7). Knowledge of three distinct types of AIT is required to understand this case (1, 30). Amiodarone-induced toxic nodular goiter, a form of iodine-induced thyrotoxicosis, was described in Europe where large nodular goiters are more prevalent than in the United States. Despite antithyroid drug therapy, some patients demonstrated refractory hyperthyroidism (28). The addition of perchlorate to antithyroid drugs decreased the time to euthyroidism in uncontrolled trials (32, 33). Perchlorate inhibits the thyroidal iodide trap and permits the back diffusion of free (nonorganified) iodide from the thyroid gland, so-called perchlorate “discharge” (34). Doses of perchlorate higher than 1.5 g per day may cause aplastic anemia, whereas doses of 1 g per day used in these studies are apparently safe. Emergency thyroidectomy was required in some patients, a courageous approach in these critically ill patients. The mechanism of refractory hyperthyroidism is uncertain. Thyroidal iodine stores are much higher in hyperthyroid compared with euthyroid patients receiving amiodarone (34A ). The expanded iodide pool is invoked to explain refractory hyperthyroidism, because antithyroid drugs prevent thyroid hormone synthesis but not hormone release. However, pharmacologic iodide inhibits thyroid hormone release from autonomous nodular thyroid glands when new hormone production is blocked by antithyroid drugs (35). Although amiodarone was often discontinued at the onset of thyrotoxicosis, a continued high iodide environment persisted due to its long half-life. A second group of patients treated with amiodarone developed Graves’ hyperthyroidism characterized by diffuse thyroid enlargement, a prolonged course, and the presence of thyroid autoantibodies (30). T-cell populations specific for Graves’ disease have been demonstated as well (36). Most authors infer that “latent” Graves’ disease was made overt by an iodine-stimulated immune attack on the thyroid. Proof of this assumption requires specific markers for genetic Graves’ disease. Toxic nodular goiter and Graves’ disease comprise Type I AIT, hyperthyroidism in patients with preexisting or “latent” thyroid disease. Type II AIT is a form of “destructive thyroiditis” (37), which develops in patients with baseline normal thyroid glands. Hyperthyroidism is due to release of stored thyroid hormone. The thyroid is usually nontender, but pain may occur. The sedimentation rate is generally within normal limits. Amiodarone, its metabolites, and intrathyroidal iodide have all been implicated in cellular toxicity, however, amiodarone is also toxic to cells that do not incorporate iodine (38, 39). Hyperthyroidism lasts for 1–3 months, until thyroid hormone stores are depleted, but resolves more quickly after glucocorticoid therapy. Transient and rarely permanent hypothyroidism may ensue, but the prevalence is uncertain (37). Subacute lymphocytic thyroiditis (“silent thyroiditis”) and subacute granulomatous thyroiditis (“painful subacute thyroiditis”, de Quervain’s thyroiditis) are worthy of study as other examples of destructive thyroiditis that follow a similar course (40). Hyperthyroidism with a nil 24-h radioiodine uptake is often followed by hypothyroidism. Subacute lymphocytic thyroiditis is an autoimmune disorder with a predilection for the postpartum period (postpartum thyroiditis). Thyroid autoantibodies are generally present, diffuse lymphocytic infiltration is found on biopsy, and permanent hypothyroidism occurs in a significant minority of patients. Subacute granulomatous thyroiditis is characterized by intense thyroid pain, a very high sedimentation rate, severe thyroid follicle disruption, and multinucleate giant cells. Permanent hypothyroidism is rare (41). Amiodarone-induced destructive thyroiditis seems not to be an autoimmune disorder because antithyroid antibodies are generally absent. Hypothyroidism, when it occurs, is usually transient. Although limited numbers of such thyroids have been examined, follicular disruption, zones of fibrosis, and mild inflammatory changes are usually present, but dense lymphocytic infiltration and multinucleated giant cells are usually absent (2, 38). Type II AIT was diagnosed on histological examination of our patient’s thyroid gland; hyperplastic changes of Graves’ disease were absent. Type II is the most common variety of AIT in our clinic. Type I AIT is more common in Europe; the geographic differences likely reflect the higher iodine intake in the United States. Many patients with AIT II demonstrate minimal transient hyperthyroidism, diagnosed by fully suppressed TSH alone (personal observation). Permanent hypothyroidism is rare, even when amiodarone is continued (personal observation). Some episodes of Type II AIT may represent subacute lymphocytic thyroiditis precipitated by amiodarone (42). Occasional patients develop repeated cycles of hypothyroidism, followed by hyperthyroidism (43) Appropriate therapy of AIT requires a clear distinction between Type I and Type II AIT. How can this be accomplished (Table 2)? AIT-differential diagnosis and therapy Based on European experience (see text). AIT-differential diagnosis and therapy Based on European experience (see text). Given the high iodine content of amiodarone, a nil 24-h radioiodine uptake might be expected in all patients taking this drug. However, detectable or normal 24-h radioiodine uptake is found in 80% of patients with amiodarone-associated hypothyroidism in Europe (44). Furthermore, in Europe type I AIT is accompanied by low, normal, or high 24-h radioiodine uptake, a possible consequence of baseline borderline low iodide intake (45, 46). The radioiodine uptake is near zero in all patients with Type II AIT. A normal or high radioiodine uptake effectively excludes Type II AIT, however, a nil uptake cannot distinguish between Type I or Type II. All patients with Type I and Type II AIT seen in our Thyroid Clinic have a near nil uptake. Systemic radiodine studies of Type I AIT are needed in the United States. If confirmed, our observations suggest that 24-h radioiodine uptakes are superfluous in AIT in the United States. A low (0.19%) 20-min 99m pertechnetate uptake was measured in our patient. In contrast to the 24-h radioiodine uptake, this test can be performed while receiving antithyroid drugs, allowing therapy to begin immediately. Thyroid ultrasonography may allow us to discriminate between Type I and Type II AIT. Thyroid nodules are easily diagnosed by ultrasound and in their toxic nodular goiter is effectively However, destructive thyroiditis may with a nodular thyroid Thyroid ultrasound with can thyroid blood Type I AIT with Graves’ disease has normal or increased blood whereas Type II AIT a with decreased In patients with Type I from Type II AIT Many studies on thyroid nodules but not When ultrasonography in patients with AIT, thyroid gland studies be Thyroid as the but experience in iodine-sufficient areas such as the United be before it can be fully other studies antibodies are present in at of patients with Graves’ hyperthyroidism and are generally absent in AIT II. antibodies and are considered specific for Graves’ disease. When thyroid autoantibodies are no can be were found in our Graves’ disease. Serum is a that and T-cell is in Type II AIT and normal to at most slightly in Type in Type II AIT are and in Type I AIT I are However, have seen low concentrations in patients with Type II AIT, reflecting of was not measured in our patient. T3 is a of Graves’ hyperthyroidism. The of serum T3 to T4 concentration is a that can be in Graves’ hyperthyroidism from destructive when radioiodine uptakes cannot be In of patients with Graves’ hyperthyroidism had a T3 to T4 greater than whereas of those with “destructive thyroiditis” and 6% of euthyroid individuals were in this range This has not been in AIT. A low is to be because amiodarone inhibits T4 to T3 conversion, however, a high AIT patients receiving amiodarone have a mean T3 to T4 of whereas AIT patients have a mean of 12 (7). of I and II AIT have not been patient’s T3 to T4 of the diagnosis of Graves’ hyperthyroidism. Type I AIT with Graves’ disease and Type II AIT present with a normal to diffusely enlarged thyroid. or a thyroid Graves’ disease. However, pharmacologic doses of iodide mg/day) thyroidal blood in Graves’ disease and a may within days of iodide administration (personal In our thyroid was to Graves’ hyperthyroidism was diagnosed based on findings and TBII, although this to be We not an ultrasound or in our studies that in might have been The of is uncertain because pathological changes in Type II AIT are often Table 2 the therapy of I and II AIT. of toxic nodular goiter methimazole or perchlorate may be With prolonged hyperthyroidism, or continued amiodarone be considered The of radioiodine therapy in patients with normal or high 24-h radioiodine uptake is uncertain. Type I AIT due to Graves’ disease is treated in a similar 12 patients with Type I AIT (10 with toxic nodular goiters and 2 with Graves’ were treated with a of methimazole and perchlorate All normal free T3 concentrations by 4 weeks A diagnosis of Graves’ hyperthyroidism was made in our patient. Methimazole was and iopanoic acid was added to hormone release and inhibit T4 to T3 conversion, functions also by amiodarone. The 24-h urine iodide was perchlorate was not It is to amiodarone for weeks after starting antithyroid drugs in Type I AIT patients, but this is of Although amiodarone serum half-life is the of T4 to T3 inhibition after drug is Hyperthyroidism in Type II AIT is but some patients critically ill with cardiovascular therapy the hyperthyroidism of Type II AIT and may be treated 12 Type II AIT patients with prednisone (40 mg/day) for with a 3 Free T3 and after an average of and In our many patients euthyroid after weeks of However, hyperthyroidism then prednisone be A response to glucocorticoid therapy is an in difficult a diagnosis seems therapy at Type I and Type II AIT including when from and antibodies often days to weeks to was ill on admission. Amiodarone had been discontinued. Although Graves’ disease was the diagnosis based on his methimazole and iopanoic were all prescribed. When the results prednisone was discontinued. The was attributed to iopanoic acid but may have been due to prednisone therapy. In a course of prednisone therapy have been and might have been A for was made when the was When for the was but the and his a The diagnosis was in and therapy with antithyroid drugs might have been In more with a diagnostic approach might have been amiodarone be discontinued in all cases of When the cardiac amiodarone in AIT but therapy for weeks after starting antithyroid Many authors amiodarone in Type II AIT, however, this is the diagnosis is cases of Type II are had been amiodarone for 9 months, Type II thyroid before starting The drug is usually begun in an or by without for thyroid disease. However, a approach be to a history of autoimmune thyroid disease and serum TSH and antithyroid These studies might be in amiodarone-associated hypothyroidism and possibly allow of “latent” Graves’ disease. Thyroid ultrasound patients with nodular thyroid glands at for AIT but its might be more in Europe where AIT I is more AIT to our Although clear are diagnosis and therapy for an may be studies in the United and in AIT are or 99m pertechnetate uptake is but may be superfluous in the United States. Although in some this case the that with AIT.