Management Of Amiodarone-induced Thyrotoxicosis Research Articles

ODP461 Amiodarone Induced Thyrotoxicosis With Severe Cardiac Disease Refractory to Medical Therapy and Plasmapheresis

Abstract Introduction Management of amiodarone induced thyrotoxicosis (AIT) presents the clinical challenge of differentiating between the two subtypes: Type I AIT, characterized by increased hormonal biosynthesis, and Type II AIT, a destructive thyroiditis since the treatment differs. We present a case of a patient with severe cardiac disease on long-term amiodarone who presented with thyrotoxicosis who was minimally clinically symptomatic despite significant biochemical thyroid function abnormalities and refractory to all medical interventions, including plasmapheresis, ultimately requiring total thyroidectomy. Case Description An 82 year-old-male with severe cardiac disease including coronary artery disease with prior CABG, EF of 25-30% with ICD, and atrial fibrillation on amiodarone, presented to the hospital due to palpitations and multiple shocks delivered by patient's ICD. EKG revealed atrial fibrillation and the ICD demonstrated episodes of sustained ventricular tachycardia. The Burch-Wartofsky score was 25. He had palpitations, tremors, and atrial fibrillation but no thyromegaly, thyroid bruits or thyroid eye disease. Thyroid function testing was TSH <0. 01 ulU/mL (Normal 0.3 - 4.5 ulU/mL), FT4 5.29 ng/dL (Normal 0.5- 1.26 ng/dL). Thyroid ultrasound showed multiple sub-centimeter nodules without increased vascularity. Since patient had characteristics of both AIT subtypes, patient was started on treatments for both including hydrocortisone 100 mg TID, Lugol's Iodine 10 drops TID, methimazole 20 mg QID, propranolol 20 mg QID, cholestyramine 4g BID, and lithium 300 mg TID. Despite extensive medical management, the patient's thyroid levels remained grossly elevated with FT4 nadir of 4.37 ng/dL. Plasmapheresis was initiated every 1-2 days for a total of 6 treatments and the patient's FT4 improved to 3.52 ng/dL before increasing again. During this treatment period, the patient remained relatively asymptomatic but had severe cardiac disease which further complicated the urgency for thyroidectomy. Ultimately, he underwent a total thyroidectomy that caused the resolution of the thyrotoxicosis. He was started on levothyroxine and subsequent pathology revealed multi-nodular goiter with lymphocytic thyroiditis. Discussion This challenging case of amiodarone induced thyrotoxicosis in a patient with severe cardiac disease, refractory to extensive medical therapy including plasmapheresis and requiring total thyroidectomy, highlights the difficulty in management of AIT. Management of refractory AIT involves differentiating between the two clinical subtypes with the goal of expediently achieving a euthyroid state to avoid severe cardiac complications and mortality. This case was particularly challenging since our patient had relatively stable clinical status despite chemical thyrotoxicosis with characteristics of both subtypes of AIT. It was challenging to optimize a patient's thyroid levels prior to thyroidectomy, due to severe cardiac disease and persistent thyrotoxicosis. Ultimately, our patient was refractory to medical treatments for both AIT subtypes and plasmapheresis. The resolution of thyrotoxicosis was not achieved until he underwent total thyroidectomy Presentation: No date and time listed

Management of Amiodarone-Induced Thyrotoxicosis at a Cardiac Transplantation Centre.

Background: Amiodarone-induced thyrotoxicosis (AIT) is associated with significant morbidity and mortality, particularly in patients with cardiac failure. The aim of the study was to evaluate the management of AIT at a tertiary hospital specialising in cardiac failure and transplantation.Methods: Retrospective audit of 66 patients treated for AIT by Endocrinology (2007–2016), classified as type 1 (T1) or type 2 (T2) based on radiological criteria. Main outcome measurements were response rate to initial treatment, time to euthyroidism, and frequency/safety of thyroidectomy.Results: Mean age was 60 ± 2 years; 80% were male. Sixty-four patients commenced medical treatment: thionamides (THIO) in 23, glucocorticoids (GC) in 17 and combination (COMB) in 24. Median thyroxine (fT4) was 35.1 (31.2–46.7) in THIO, 43.1 (30.4 –60.7) in GC, and 60.0 (39.0 –>99.9) pmol/L in COMB (p = 0.01). Initial therapy induced euthyroidism in 52%: 70% THIO, 53% GC, and 33% COMB (p = 0.045) by 100 (49–167), 47 (35–61), and 53 (45–99) days, respectively (p = 0.02). A further 11% became euthyroid after transitioning from monotherapy to COMB. Thyroidectomy was undertaken in 33%. Patients who underwent thyroidectomy were younger (54 ± 3 vs. 63 ± 2 years; p = 0.03), with higher prevalence of severely impaired left ventricular function prior to diagnosis of AIT (38 vs. 18%; p = 0.08). Despite median American Society of Anaesthesiologists classification 4, no thyroidectomy patient experienced cardiorespiratory complications/death.Conclusions: Patients with AIT had limited response to medical treatment. The poorest response was observed in COMB group, likely related to greater hyperthyroidism severity. Thyroidectomy is safe in patients with severe cardiac failure if performed in a centre with cardiac anaesthetic expertise. There should be low threshold for proceeding to thyroidectomy in patients with severe AIT and/or cardiac failure.

Management of Amiodarone-Induced Thyrotoxicosis in Patients with Ventricular Arrhythmias: A Series of Case Reports

Management of Amiodarone-Induced Thyrotoxicosis in Patients with Ventricular Arrhythmias: A Series of Case Reports

Diagnosis and management of amiodarone‐induced thyrotoxicosis: similarities and differences between North American and European thyroidologists*

To investigate how North American thyroidologists assess and treat amiodarone-induced thyrotoxicosis (AIT) and to compare the results with those of the same questionnaire-based survey previously carried out among European thyroidologists. Members of the American Thyroid Association (ATA) with clinical interests were sent by e-mail a questionnaire on the diagnosis and management of AIT, 115 responses were received from the United States and Canada, representing about one-third of ATA members with clinical interests. The majority of respondents (91%vs. 68% in Europe, P < 0.05) see < 10 new cases of AIT per year, and AIT seems less frequent than amiodarone-induced hypothyroidism (AIH) in North America (34% and 66% of amiodarone-induced thyroid dysfunction, respectively, vs. 75% and 25%, respectively, in Europe, P < 0.001). When AIT is suspected, in North America hormonal assessment is mostly based on serum free T4 (FT4) and TSH measurements, while serum free T3 (FT3) determination is requested less frequently than in Europe; thyroid autoimmunity is included in the initial assessment less than in Europe. Most commonly used additional diagnostic procedures include, as in Europe, thyroid colour-flow Doppler sonography, and to a lesser extent, thyroid radioactive iodine uptake and scan, but Europeans tend to request multiple tests more than North Americans. Withdrawal of amiodarone is more often considered unnecessary by North American thyroidologists (21%vs. 10% in Europe in type 1 AIT, P < 0.05, 34%vs. 20% in type 2 AIT, P < 0.05). In type 1 AIT thionamides represent the treatment of choice for North Americans as well as for Europeans, but the former use them as monotherapy in 65%vs. 51% of Europeans (P < 0.05) who more often consider potassium perchlorate as an useful addition (31%vs. 15% of North Americans, P < 0.01). Glucocorticoids are the selected treatment for type 2 AIT, alone (62%vs. 46% in Europe, P < 0.05) or in association with thionamides (16%vs. 25% in Europe, P = NS). After restoration of euthyroidism, thyroid ablation in the absence of recurrent thyrotoxicosis is recommended in type 1 AIT less frequently by North Americans. If amiodarone therapy needs to be reinstituted, prophylactic thyroid ablation is advised by 76% in type 1 AIT, while a 'wait-and-see' strategy is adopted by 61% in type 2 AIT, similar to behaviour of European thyroidologists. Similarities and differences exist between expert North American and European thyroidologists concerning the diagnosis and management of AIT. While differences reflect the frequent uncertainty of the underlying mechanism leading to AIT, similarities may represent the basis to refine the diagnostic criteria and to improve the therapeutic outcomes of this challenging clinical situation.

The usefulness of 99mTc-sestaMIBI thyroid scan in the differential diagnosis and management of amiodarone-induced thyrotoxicosis

Amiodarone-induced thyrotoxicosis (AIT) is caused by excessive hormone synthesis and release (AIT I) or a destructive process (AIT II). This differentiation has important therapeutic implications. To evaluate (99m)Tc-sestaMIBI (MIBI) thyroid scintigraphy in addition to other diagnostic tools in the diagnosis and management of AIT. Thyroid and (99m)Tc-MIBI scintigraphies were performed in 20 consecutive AIT patients, along with a series of biochemical and instrumental investigations (measurement of thyrotrophin, free thyroid hormones and thyroid autoantibodies; thyroid colour-flow Doppler sonography (CFDS) and thyroid radioiodine uptake (RAIU)). On the basis of instrumental and laboratory data (excluding thyroid (99m)Tc-MIBI scintigraphy) and follow-up, AIT patients could be subdivided into six with AIT I, ten with AIT II and four with indefinite forms of AIT (AIT Ind). (99m)Tc-MIBI uptake results were normal/increased in all the six patients with AIT I and absent in all the ten patients with AIT II. The remaining four patients with AIT Ind showed low, patchy and persistent uptake in two cases and in the other two evident MIBI uptake followed by a rapid washout. MIBI scintigraphy was superior to all other diagnostic tools, including CFDS (suggestive of AIT I in three patients with AIT II and of AIT II in three with AIT Ind) and RAIU, which was measurable in all patients with AIT I, and also in four out of the ten with AIT II. Thyroid MIBI scintigraphy may be proposed as an easy and highly effective tool for the differential diagnosis of different forms of AIT.

Color Flow Doppler Sonography in the Differential Diagnosis and Management of Amiodarone-Induced Thyrotoxicosis

Ultrasound Quarterly: December 2007 - Volume 23 - Issue 4 - p 297 doi: 10.1097/01.ruq.0000302207.17812.a0

Color-flow Doppler sonography in the differential diagnosis and management of amiodarone-induced thyrotoxicosis

Amiodarone-induced thyrotoxicosis (AIT) may be caused by excessive thyroidal hormone synthesis and release (type 1) or by a destructive process (type 2). This differentiation is considered essential for therapeutic choice. To evaluate the utility of color-flow Doppler sonography (CFDS) in the differential diagnosis and management of AIT. The clinical and laboratory data, thyroid sonography (grayscale sonography [GSS], CFDS), thyroid radioiodine uptake (RAIU) and thyroid scintigraphy, treatment, and clinical outcome were retrospectively reviewed in 21 AIT patients. The CFDS pattern of thyroid nodules was separately described from that of the perinodular parenchyma, and AIT was classified as type 1 (increased blood flow) or type 2 (low/no blood flow). Type 1 AIT patients were treated with methimazole (alone or associated with potassium perchlorate), while type 2 patients were treated with prednisone or amiodarone withdrawal alone. Eleven patients with increased blood flow were considered as type 1, and 10 with low/no blood flow as type 2. Ten of the 11 patients in the first group showed a hypervascular nodular pattern, while one showed a hypervascular parenchymal pattern. Clinical diagnoses were toxic nodular goiter and Graves' disease, respectively. Of the 10 patients with low/no blood flow, six had normal thyroid volume, three small diffuse goiter, and one small multinodular goiter. The clinical outcome showed that 20 of the 21 patients were treatment responsive. CFDS is a useful tool in the differential diagnosis of AIT. This differentiation appeared to be of clinical relevance as regards therapeutic choice. Separate evaluation of parenchymal blood flow from that of nodules may prove beneficial in the diagnosis of underlying thyroid diseases in patients with type 1 AIT.

Diagnosis and management of amiodarone-induced thyrotoxicosis in Europe: results of an international survey among members of the European Thyroid Association.

To determine how expert European thyroidologists assess and treat amiodarone-induced thyrotoxicosis (AIT). Members of the European Thyroid Association (ETA) with clinical interests were asked to answer a questionnaire on the diagnosis and management of AIT. A total of 124 responses were received: 116 from Europe, seven from USA and one from Brazil. After excluding responses coming from the same centre, 101 responses from 24 European countries were analysed, representing approximately 65% of clinically active European ETA members. The majority of respondents (68%) see 1-10 new cases of AIT/year, and AIT seems to be more frequent than amiodarone-induced hypothyroidism in Europe, where in many instances iodine intake is borderline or moderately deficient. A good collaboration with cardiologists exists in most centres, and patients receiving chronic amiodarone treatment are checked for thyroid function most commonly every 4-6 months. When AIT is suspected, a diffuse or nodular goitre is present or in the absence of apparent abnormalities of the thyroid, free thyroxine (FT4), free triiodothyronine (FT3) and TSH are assayed by almost 90% of respondents. Thyroid autoimmunity is evaluated in the initial assessment by > 80%, while evaluation of urinary iodine excretion is unhelpful for > 60%. Most commonly used additional diagnostic procedures include thyroid ultrasonography, particularly colour flow Doppler sonography, and, to a lesser extent, a thyroid uptake scan. If the thyroid gland is apparently normal, measurement of thyroidal radioactive iodine uptake is considered useful by a large proportion of respondents to establish the destructive nature of the process. Differentiation of type I and type II AIT is difficult and, possibly, not correct for 27% of respondents, who believe that mixed (or indefinite) forms are probably more frequent than previously recognized. Approximately 10-20% do not consider amiodarone withdrawal necessary in the therapeutic strategy of AIT, especially if the thyroid gland is apparently normal. Most respondents (82%) treat type I AIT with thionamides, either alone (51%) or in combination with potassium perchlorate (31%), while the preferred treatment for type II AIT is represented by glucocorticoids (46%). Some respondents, in view of diagnostic difficulties, initially treat all cases of AIT with a combination of thionamides and glucocorticoids. After restoration of euthyroidism, ablative therapy is recommended by 34% in type I and only 8% in type II AIT. If amiodarone therapy needs to be reinstituted, prophylactic thyroid ablation is recommended by 65% in type I AIT, while a wait-and-see strategy is adopted by 70% in type II AIT. Areas of certainty and uncertainty concerning AIT are present among expert European thyroidologists, both from a diagnostic and a therapeutic standpoint. Diagnostic criteria need to be refined in order to improve therapeutic outcome.

Management of amiodarone-induced thyrotoxicosis.

Amiodarone is used increasingly in a number of cardiac conditions. Amiodarone is heavily iodinated and can cause thyroid dysfunction. The diagnosis of amiodarone-induced thyrotoxicosis remains difficult and more common causes of thyrotoxicosis need to be considered and excluded. Amiodarone has a significant side effect profile, which includes thyroid dysfunction. Amiodarone is an effective drug and its withdrawal may have significant impact on a patient's already fragile cardiac status. There are three different types of amiodarone-induced thyrotoxicosis (AIT) (I, II and mixed). Identification of the different subtypes of AIT allows a rational and appropriate management strategy to be chosen. Type I occurs in patients with underlying thyroid disease, whilst type II is thought to result from a destructive thyroiditis. Differentiation is based on clinical grounds together with investigations, which can include thyroid function test, radioiodine uptake scanning, measurement of interleukin-6 levels and colour flow Doppler sonography. Amiodarone should be discontinued in both types of AIT if the indication for its use is not a life-threatening cardiac condition. The management of type I centres around antithyroid drugs to control thyrotoxicosis and later consideration of more definitive treatment. Type II AIT responds to steroid therapy, although antithyroid drugs may be useful if symptoms are severe. Therapeutic options for refractory cases of AIT include surgery, radioiodine and plasmapheresis.

Management of amiodarone-induced thyrotoxicosis.

Amiodarone is used increasingly in a number of cardiac conditions. Amiodarone is heavily iodinated and can cause thyroid dysfunction. The diagnosis of amiodarone-induced thyrotoxicosis remains difficult and more common causes of thyrotoxicosis need to be considered and excluded. Amiodarone has a significant side effect profile, which includes thyroid dysfunction. Amiodarone is an effective drug and its withdrawal may have significant impact on a patient's already fragile cardiac status. There are three different types of amiodarone-induced thyrotoxicosis (AIT) (I, II and mixed). Identification of the different subtypes of AIT allows a rational and appropriate management strategy to be chosen. Type I occurs in patients with underlying thyroid disease, whilst type II is thought to result from a destructive thyroiditis. Differentiation is based on clinical grounds together with investigations, which can include thyroid function test, radioiodine uptake scanning, measurement of interleukin-6 levels and colour flow Doppler sonography. Amiodarone should be discontinued in both types of AIT if the indication for its use is not a life-threatening cardiac condition. The management of type I centres around antithyroid drugs to control thyrotoxicosis and later consideration of more definitive treatment. Type II AIT responds to steroid therapy, although antithyroid drugs may be useful if symptoms are severe. Therapeutic options for refractory cases of AIT include surgery, radioiodine and plasmapheresis.

Heterogeneity of amiodarone-induced thyrotoxicosis: evaluation of colour-flow Doppler sonography in predicting therapeutic response.

Amiodarone-induced thyrotoxicosis (AIT) presents a therapeutic challenge because of its resistance to standard antithyroid therapy. In iodine-deplete environments, colour-flow Doppler sonography (CFDS) has allowed distinction between two types of AIT: (i) Type I AIT, associated with increased vascularity (CFDS I-III) and response to thionamide antithyroid drug and (ii) type II AIT, with no/little thyroid vascularity (CFDS 0) and prednisolone responsiveness. To clarify if CFDS patterns correlated with treatment outcomes in a retrospective study of 24 patients with AIT in an iodine-replete environment. Medical records of patients who presented to a teaching hospital between January 1998 to December 2000 were reviewed. Results of CFDS, ultrasound measurement of thyroid size and technetium scanning of the thyroid were correlated with treatment responses, especially prednisolone responsiveness. Thirteen of 24 patients showed CFDS 0. Twelve of these 13 were evaluable for prednisolone responsiveness, of whom seven (58%) were prednisolone-responsive. Of 11 patients with CFDS I-III, four (36%) responded to antithyroid medication alone and only one of seven (14%) was prednisolone-responsive. Euthyroidism was achieved twice as rapidly in patients with CFDS 0 than those with CFDS I-III. Because of medical treatment failure, seven patients, from both CFDS groups, required urgent near-total thyroidectomy which was successful and uncomplicated in all cases. CFDS is useful in the management of AIT because CFDS 0 correlates better with prednisolone response (58%) than CFDS I-III (14%). However, unlike experience in iodine-deficient regions, the results of the present study revealed that treatment responses to thionamide or prednisolone were heterogeneous within uniform CFDS patterns. Thus, prednisolone--responsiveness was not consistently predicted by CFDS 0, but the presence of flow appeared to correlate with non-response to prednisolone.

Iatrogenic Thyrotoxicosis. Causal Circumstances, Pathophysiology and Principles of Treatment. Review of the Literature

.Thyrotoxicosis is the clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormones. In most instances, thyrotoxicosis is due to hyperthyroidism, a term reserved for disorders characterized by overproduction of thyroid hormones by the thyroid gland. Nevertheless, thyrotoxicosis may also result from a variety of conditions other than thyroid hyperfunction. The present report focuses on the etiologies, pathophysiology and treatment of iatrogenic thyrotoxicosis. Iatrogenic thyrotoxicosis may be caused by 1) subacute thyroiditis (a result of lymphocytic infiltration, cellular injury, trauma or radiation) with release of preformed hormones into circulation, 2) excessive ingestion of thyroid hormones (“thyrotoxicosis factitia”), 3) iodine-induced hyperthyroidism (radiological contrast agents, topical antiseptics or other medications). Among these causes of iatrogenic thyrotoxicosis, that induced by the iodine overload and cytotoxicity associated with amiodarone represents a significant challenge. Successful management of amiodarone-induced thyrotoxicosis requires close cooperation between endocrinologists and endocrine surgeons. Surgical treatment may have a leading yet often underestimated role in view of the potential life-threatening severity of this disease, whereas others kinds of iatrogenic thyrotoxicosis are usually treated conservatively.