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

OBJECTIVE: To determine how expert European thyroidologists assess and treat amiodarone-induced thyrotoxicosis (AIT). DESIGN: 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. RESULTS: 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. CONCLUSION: 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.     

European and US guidelines for arterial hypertension: similarities and differences

Hypertension is one of the most common chronic diseases in adults and a leading cause of disability and mortality worldwide. Recently, new Guidelines for the diagnosis and management of hypertension have been released in Europe and in the United States, with changes regarding how to diagnose and treat the condition, and the extent to which intensive blood pressure control should be pursued.Important differences between the Guidelines exist in the classification of blood pressure levels and definition of treatment goals. Diagnosis of hypertension starts at 140/90 mmHg for the European Guidelines, and 130/80 mmHg for the US Guidelines. Besides, the European guidelines introduced the concept of “safety boundaries”, consisting of BP thresholds not to be exceeded towards lower levels (120 mmHg for age < 65 years, 130 mmHg for older people) because of the fear of important adverse events associated with overtreatment. Such discrepancies can indeed have an impact on treatment attitudes and outcome incidence. Hence, we appraised facts in favor and against each of these controversial issues. In conclusion we believe that, instead of fixing rigid BP targets and boundaries, modern hypertension management should be aimed to achieve in each patient an optimal balance between intensive BP reduction and treatment safety.     

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中美酒精性肝病(ALD)诊疗指南在2010年相继发表,由于东西方社会在人群、经济、文化方面存在一定差异,就酒精性肝病诊疗共识方面的理解和操作也存在一些差异,本文从流行病学、危险因素、诊断标准、评估系统和治疗5个方面就中美酒精性肝病诊疗指南的异同展开比较和阐述,分析各自特点和论点依据。     

Issues in amiodarone-induced thyrotoxicosis: Update and review of the literature

Amiodarone, a benzofuranic iodine-rich pan-anti-arrhythmic drug, induces amiodarone-induced thyrotoxicosis (AIT) in 7–15% of patients. AIT is a major issue due to its typical severity and resistance to anti-thyroid measures, and to its negative impact on cardiac status. Classically, AIT is either an iodine-induced thyrotoxicosis in patients with abnormal thyroid (type 1), or due to acute thyroiditis in a “healthy” thyroid (type 2). Determination of the type of AIT is a diagnostic dilemma, as characteristics of both types may be present in some patients. As it is the main etiological factor in AIT, it is recommended that amiodarone treatment should be stopped; however, it may be the only anti-arrhythmic option, needing to be either continued or re-introduced to improve cardiovascular survival. Recently, a few studies demonstrated that amiodarone could be continued or re-introduced in patients with history of type-2 AIT. However, in the other patients, it is recommended that amiodarone treatment be interrupted, to improve response to thioamides and to alleviate the risk of AIT recurrence. In such patients, thyroidectomy is recommended once AIT is under control, allowing safe re-introduction of amiodarone.     

Management of amiodarone-induced thyrotoxicosis in Latin America: an electronic survey

OBJECTIVE: To assess diagnostic and therapeutic approaches to amiodarone-induced thyrotoxicosis (AIT) among members of the Latin American Thyroid Society (LATS). METHODS: LATS members responded to an online questionnaire that presented an index case (a 62-year-old man on amiodarone, with thyrotoxic symptoms and a nodular goitre) and a variant (same patient, no goitre). RESULTS: About 25% of invited members responded to the questionnaire. Most respondents lived in iodine-sufficient areas and observed that amiodarone-induced hypothyroidism (AIH) is more common than AIT. Nearly all assessed TSH, and the most used combination of tests was TSH and free T4 (37%). Thyroid autoimmunity was assessed by about 90%. Interleukin-6 (IL-6) was useful to 80%. Additional tests ordered for the index case were: radioactive iodine uptake (RAIU; 57%), echo-colour Doppler sonography (ECDS; about 50%) and fine-needle aspiration biopsy (FNAB; 44%). For the variant, ECDS and RAIU were judged unhelpful by 16%. Most defined the index case as type I AIT and the variant as type II AIT, but 16% in LATS suggested a mixed form in the index case. As initial treatment, nearly all used thionamides in the index case [with potassium perchlorate (KClO(4)) in one-third], while glucocorticoids were indicated to the variant by 66%. Only about 5% considered amiodarone withdrawal unnecessary. If initial strategy is ineffective in type I AIT, KClO(4) (half) or glucocorticoids (a third) are added; in type II, glucocorticoids are indicated by most. Once euthyroidism is restored, ablative therapy is prescribed by a third of respondents for type I AIT. CONCLUSIONS: There are several points of disagreement among thyroidologists regarding AIT management, mainly in the radiological evaluation and the approach to the already stabilized patient if amiodarone needs to be restarted.     

Clinical characteristics of amiodarone-induced thyrotoxicosis and hypothyroidism in Japan.

Since amiodarone was introduced in Japan in 1992, the incidence of the drug-induced thyroid dysfunction has been increasing. We studied the thyroid function of 13 patients with amiodarone-induced thyrotoxicosis (AIT) and 11 patients with amiodarone-associated hypothyroidism (AAH) who had been referred to our Institute in the last 6 years. AIT and AAH developed after 39+/-21 and 20+/-16 months of amiodarone treatment, respectively. One patient developed AAH followed by AIT. The AIT ranged from subclinical to overt thyrotoxicosis. Four patients with moderate to marked AIT were treated with methimazole. Their thyrotoxicosis persisted for 3 to 9 months, despite administration of antithyroid agents. One patient with mild thyrotoxicosis was treated with prednisolone, resulting in a euthyroid state in a few months. Eight patients with asymptomatic to moderate thyrotoxicosis resolved spontaneously without any treatment. In four asymptomatic patients with AIT, serum levels of T3 and T4 were in the upper normal range or slightly high (< 12 microg/dl), accompanied by suppressed TSH (<0.1 microU/ml) and high thyroglobulin levels, suggesting destruction-induced thyrotoxicosis. Such a subclinical thyrotoxicosis developed repeatedly in one patient. Ultrasonographic studies revealed no nodular lesion in the thyroid, and color flow Doppler sonography demonstrated no hypervascularity in the thyroid gland in any AIT patient. Although it is postulated in Europe that there are two types of AIT, namely type I, which develops in patients with latent Graves' disease or toxic multinodular goiter, and type II, which develops in an apparently normal thyroid as destructive thyroiditis, all AIT patients we have seen so far had developed destructive type AIT. Sufficient intake of iodide and a very low incidence of toxic multinodular goiter may account for the rare incidence of type I AIT in our country. Mild to moderate AIT resolved spontaneously without discontinuing amiodarone, but it was discontinued in two of 13 AIT patients because of extrathyroidal adverse reactions.     

Incidence, predictability, and pathogenesis of amiodarone-induced thyrotoxicosis and hypothyroidism

PURPOSE: To determine the incidence and predictability and to elucidate the pathogenesis of amiodarone-induced thyrotoxicosis (AIT) and hypothyroidism (AIH). PATIENTS AND METHODS: A prospective study was performed in 58 consecutive euthyroid patients living in an area with moderately sufficient iodine intake, who had never been treated for thyroid disease and who started amiodarone therapy for the first time. MAIN OUTCOME MEASURES: Development of thyrotoxicosis or hypothyroidism. RESULTS: The follow-up period was 6 to 54 months (mean, 21 months). The incidence of AIT was 12.1%. A steady occurrence of new cases was observed. The development of AIT was unpredictable and of unexplained sudden onset. The incidence of AIH was 6.9%. All AIH cases occurred early in the course of amiodarone therapy. The development of AIH was related to pre-existent thyroid disease: the relative risk for women with microsomal and/or thyroglobulin autoantibodies prior to treatment was 13.5 (95% confidence interval 3.2 to 57.4). The development of AIT or AIH was not related to the extent of iodine overload or to the occurrence of de novo thyroid autoantibodies. When a decreased thyrotropin (TSH) response to thyrotropin-releasing hormone occurred (in the absence of AIT), continuation of amiodarone medication was associated with a normalization of the TSH response in eight of 11 cases (73%); in contrast, an increased TSH response (in the absence of AIH) returned to normal in one of four cases (25%). CONCLUSION: In euthyroid subjects living in an area with a moderately sufficient intake of iodine, there is a higher incidence of AIT than of AIH. AIH is an early event, occurring especially in women with thyroid autoantibodies prior to treatment. Cases of AIT continue to occur during amiodarone therapy; its development is unpredictable and of unexplained sudden onset. The value of regular thyroid function testing is therefore limited during amiodarone administration.     

Differences in European and North American approaches to the management of heart failure

In recent years many guidelines on the treatment of specific medical conditions have been published with the goal of advising physicians, promoting good clinical care, and achieving a degree of equity and equality in the delivery of care. Differences exist between European and American guidelines for the management of heart failure not just because of differences in health systems but also because there is little agreement on how to assess clinical trials and convey conclusions in a clear format. Current recommendations can be confusing and often do not reflect the complexities of modern personalized medicine.     

胃食管反流病和肠易激综合征的异同

胃食管反流病（GERD）和肠易激综合征（IBS）的临床表现有很高的症状重叠现象，其发生机制可能与其有共同的危险因素、相同的病理生理学和遗传易感性等有关。治疗GERD和IBS时，应针对其病理机制给予综合治疗，这样才能提高疗效，改善生活质量。     

Osteoporosis: gender differences and similarities.

Although osteoporosis has traditionally been considered a disease of women, men also incur substantial bone loss with aging, and elderly men have age-specific hip fracture incidence rates and vertebral fracture prevalence rates that are at least half those in women. Early postmenopausal bone loss (which results in the syndrome of type I osteoporosis) is due to the direct skeletal consequences of estrogen deficiency, manifested by an increase in bone resorption without an adequate increase in bone formation. Recent evidence indicates that even late postmenopausal bone loss (type II or 'smile' osteoporosis) in women may be due to estrogen deficiency. In particular, the late consequences of estrogen deficiency in elderly women result in abnormalities in calcium homeostasis and increases in parathyroid hormone secretion, leading to increased bone resorption and bone loss. The etiology of bone loss in aging men has remained relatively unclear. Recent evidence from a male deficient in estrogen receptor-alpha and in two males with aromatase deficiency indicate that estrogen may play a significant role in bone metabolism in men. Moreover, several large epidemiologic studies have found that bone mineral density correlates better with serum estrogen than testosterone in aging men. Thus estrogen deficiency may lead to bone loss in men.