Antithyroid hormone antibodies induced by interferon-alpha.

A 40-yr-old woman known for a multinodular goiter had hyperthyroidism. Treatment with antithyroid drugs and iodine therapy was effective. One year later, she received interferon-alpha for treatment of essential cryoglobulinemia. At that time, the patient was euthyroid. Testing for antithyroglobulin, antimicrosome, anti-TSH receptor, and antithyroid hormone antibodies was negative. After a 1-yr course of interferon-alpha, goiter enlargement was noticed. Apparently elevated free T3 and T4 serum values were measured by RIA, contrasting with clinical euthyroidism and normal TSH values. High serum levels of antithyroid hormone antibodies were found in the patient's serum, using a radiolabeled hormone immunoprecipitation assay. Antithyroglobulin and antimicrosome antibodies titers were also elevated and paralleled antithyroid hormone antibodies. After cessation of interferon-alpha therapy, clinical status and TSH levels remained normal, while thyroid hormone values and antithyroid hormone antibody levels progressively normalized. To our knowledge, this is the first report of antithyroid hormone antibodies induced by interferon-alpha. Since thyroid dysfunction is described in 10-15% of treated patients, the fact that interferon-alpha can induce antithyroid hormone antibodies has important implications: 1) the prevalence or intensity of thyroid dysfunction could be overestimated; and 2) artifactually elevated free T3 and T4 serum values could lead to inappropriate therapy of thyroid disease or cessation of interferon treatment.     

Autoimmune thrombocytopenia induced by PEG-IFN-alpha plus ribavirin in hepatitis C

Mild thrombocytopenia is a common adverse effect of interferon-alpha and pegylated interferon-alpha, largely ascribed to bone marrow suppression. Nevertheless, rare cases of autoimmune thrombocytopenia following standard or pegylated interferon treatment have been reported in the literature. In this report, we have presented a patient who developed an immune-mediated thrombocytopenia during the course of therapy with pegylated interferon/ribavirin for hepatitis C virus infection. After cessation of pegylated interferon/ribavirin treatment, thrombocytopenia was treated successfully with danazol and intravenous gamma-globulin.     

Fatal cardiomyopathy associated with pegylated interferon/ribavirin in a patient with chronic hepatitis C

We report the case of a 45-year-old man with HCV treated with pegylated interferon-alpha/ribavirin, in whom fatal cardiomyopathy occurred. Cardiomyopathy is a rare complication of high dose of standard interferon but has never been reported with pegylated interferon. The relationship between pegylated interferon-alpha/ribavirin and the development of cardiomyopathy is highly probable for the following reasons: (1) a cardiologist consultation with specific investigations had been performed before treatment excluding a pre-existing cardiomyopathy; (2) symptoms of advanced dilated cardiomyopathy appeared immediately after the end of treatment; (3) other causes of cardiomyopathy have been ruled out. In all except one of the 21 reported cases with standard interferon, cardiomyopathy was reversible. In our patient, fatal cardiomyopathy occurred with a usual dose of pegylated interferon-alpha. Clinicians should be aware of this potential complication when evaluating the ratio benefit/risk of treatment in patients with chronic hepatitis C infection.     

Thyroid function and changes in ultrasound morphology during antiviral therapy with pegylated interferon and ribavirin in patients with chronic hepatitis C

Summary. Thyroid disease is a common side‐effect of interferon‐based antiviral therapy for chronic hepatitis C, which may lead to dose reduction or discontinuation of therapy. The aim of this study was to investigate changes in ultrasound morphology, thyroid function, autoimmunity as well as predictive factors for the development of thyroid dysfunction in patients with hepatitis C virus infection treated with pegylated interferon‐α (PEG‐IFN‐α) and ribavirin. A total of 59 patients with chronic hepatitis C assigned for antiviral treatment with PEG‐IFN‐α and ribavirin were enrolled into the study. All patients were subjected to an ultrasound examination of the thyroid gland before treatment, and after 1, 3 and 6 months of antiviral therapy. In addition, thyroid function and autoimmune status were determined at fixed time‐points. Prior and during the course of therapy, 11 patients (19%) developed thyroid dysfunction (one hypothyroidism, nine hyperthyroidism, one hyperthyroidism followed by hypothyroidism). Hyperthyroidism was shown to be Graves’ disease in one patient and destructive thyroiditis in nine patients. Power‐Doppler ultrasound could differentiate between destructive thyroiditis and Graves’ disease. A reduction in echogenicity suggestive for a destructive process of the thyroid gland was observed even before changes in thyroid function of antibody status could be measured. Risk factors for the development of thyroid dysfunction were age, female gender, pre‐treatment thyroid volume, pre‐existing thyroglobulin/thyroid peroxidase antibodies and viral load. Changes in thyroid function are a common side‐effect occurring during antiviral therapy with PEG‐IFN‐α and ribavirin. Ultrasound presents a simple complementary tool for screening and follow‐up during antiviral therapy, which helps to differentiate between the common types of hyperthyroidism and gives insight into morphological changes of the thyroid gland during antiviral therapy.     

Efficacy and safety of chronic hepatitis C treatment in hemophilic patients

BACKGROUND/AIMS: Chronic hepatitis C infection is very common among hemophiliacs in the developed World. METHODOLOGY: Retrospective evaluation of the treatment results in hemophiliacs with chronic hepatitis C, all infected with genotype 1b. Twelve patients were treated with interferon-alpha monotherapy, 21 patients with interferon-alpha and ribavirin, and 3 patients with pegylated interferon and ribavirin, all for 48 weeks. RESULTS: Sustained virologic response (defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed) was not achieved in any of 12 patients treated with interferon-alpha alone. Combination therapy with interferon-alpha and ribavirin was associated with better results: 4/10 (40%) patients still untreated with interferon-alpha, 2/4 (50%) relapsers, and 2/7 (29%) non-responders to previous interferon-alpha monotherapy achieved sustained virologic responses. Combination therapy with pegylated interferon and ribavirin has been used in 3 patients. Sustained response was achieved in one patient who had relapsed after treatment with interferon-alpha and ribavirin and in 1 of 2 non-responders to this combination therapy. There were no serious adverse events and it was not necessary to reduce dosages or even cease therapy prematurely. CONCLUSIONS: The efficacy and tolerability of antiviral treatment in hemophiliacs did not differ from other patients with chronic hepatitis C.     

Reversible myopathy during successful treatment with pegylated interferon and ribavirin for acute hepatitis C

There is no standard approved treatment for acute hepatitis C and the combination of pegylated interferon-alpha and ribavirin, currently recognized as the standard of care for chronic hepatitis C, has not been evaluated for acute hepatitis C. Adverse events induced by interferon therapy are numerous but myopathy is rare and has not been described with the use of pegylated interferon-alpha. We report the case of a 33-year-old Caucasian man who was successfully treated for acute hepatitis C with the combination of pegylated interferon-alpha2b and ribavirin, and who during treatment developed myopathy which proved reversible.     

Front-line treatment of Philadelphia positive chronic myeloid leukemia with imatinib and interferon-alpha: 5-year outcome

In 2004, we reported the short-term results of a multicentric, phase 2 study of imatinib 400 mg daily and pegylated interferon-alpha in the treatment of 76 early chronic phase Philadelphia-positive chronic myeloid leukemia patients. In this report, we update the results with an observation time of five years. After two years of treatment, all but 10 patients (13%) had discontinued pegylated interferon-alpha. The complete cytogenetic response rate at five years was 87%, and 94% of complete cytogenetic responders maintained the complete cytogenetic response after five years. All but one complete cytogenetic response also achieved a major molecular response. These data confirm the excellent response to imatinib front-line and the stability of the complete cytogenetic response. Any possible additional benefit of the combination with interferon-alpha remains uncertain, due to low patient compliance.     

The effect of pegylated interferon-alpha on the treatment of lamivudine resistant chronic HBeAg positive hepatitis B virus infection

BACKGROUND/AIMS: To determine the response to pegylated interferon-alpha treatment of HBeAg-positive hepatitis B patients with proven lamivudine resistance. METHODS: Sixteen HBeAg-positive HBV patients with YMDD mutations were treated with pegylated interferon. Median treatment duration was 52 weeks (range 20-53), with a 26-week follow-up. RESULTS: Two of 16 (12.5%) patients seroconverted to HBeAg negative and achieved sustained virological (HBV-DNA levels below 10log 5 copies/ml) together with biochemical (normalization of serum ALT levels) responses. Compared with the strong signal in all other patients, only these two patients had a faint signal in the lamivudine resistance assay. For all patients, the median viral load decreased from 10log 9.4 to 7.9 copies/ml (P = 0.001) during treatment but rebounded to a median of 10log 8.7 copies/ml after treatment cessation. Similarly, elevated median ALT levels at baseline decreased with treatment but rebounded after the end of treatment. CONCLUSIONS: In the largest cohort study to date, pegylated interferon-alpha therapy showed marginal efficacy in the presence of lamivudine resistance but such therapy may be beneficial in patients with only small amounts of mutant virus. In our opinion, an analysis of the patient subgroup harbouring an YMDD-mutation should be included in all future studies of pegylated interferon-alpha in chronic hepatitis B.     

Evolution and predictive factors of thyroid disorder due to interferon alpha in the treatment of hepatitis C

AIM： To study predictive factors of thyroid dysfunction associated with interferon-alpha （IFNa） therapy in chronic hepatitis C （CHC） and to describe its long-term evolution in a large population without previous thyroid dysfunction. METHODS： We performed a follow-up of thyroid function and detection of thyroid antibodies in 301 patients treated for CHC with IFNα from 1999 to 2004. RESULTS： Thyroid disorder developed in 30/301 （10%） patients with a mean delay of 6 ± 3.75 mo： 13 patients had hyperthyroidism, 11 had hypothyroidism, and 6 had biphasic evolution. During a mean follow-up of 41.59 ± 15.39 mo, 9 patients with hyperthyroidism, 3 with hypothyroidism, and 4 with biphasic evolution normalized thyroid function in 7.88 ± 5.46 mo. Recovery rate of dysthyroidism was not modified by treatment discontinuation, but was better for patients with negative thyroid antibodies before antiviral treatment （P = 0.02）. Women had significantly more dysthyroidism （P = 0.05）. Positive thyroid peroxidase and thyroglobulin antibodies were more frequent before antiviral treatment in patients who developed dysthyroidism （P 〈 0.0003 and P = 0.0003, respectively）. In a multivariate model, low fibrosis was found to be a predictive factor of dysthyroidism （P = 0.039）.
CONCLUSION： In this monocentric population of CHC, dysthyroidism, especially hyperthyroidism, developed in 10% of patients, Low fibrosis was found to be a predictive factor of dysthyroidism, Thyroid disorder recovered in 16/30 patients （53%） and recovery was better in the non-autoimrnune form,     

HLA antigens in patients with interferon-alpha-induced autoimmune thyroid disorders in chronic hepatitis C.

BACKGROUND/AIMS: To determine the immunological predisposition to autoimmune thyroid disorders induced by interferon-alpha therapy, human leukocyte antigen (HLA) was analyzed in patients with chronic hepatitis C who developed autoimmune thyroid disorders during or after treatment with interferon-alpha. METHODS: Four hundred and thirty-nine patients with chronic hepatitis C (278 males and 161 females, aged 20-73 years) were treated with interferon-alpha (natural-alpha, 169; alpha-2a, 82; alpha-2b, 188) for 24 weeks. RESULTS: Seventeen of 439 (3.9%) patients developed symptomatic autoimmune thyroid disorders; these included nine cases of hyperthyroidism and eight cases of hypothyroidism. The incidence of HLA-A2, B46 and Cw7 increased in patients with interferon-alpha-induced autoimmune thyroid disorders. Especially, the incidence of HLA-A2 (15/17; 88.2%) was significantly higher than that observed in the general population in Japan (corrected p-value (p(c)): p(c)<0.003). The odds ratios for the relative risk of the autoimmune thyroid disorders were A2, 10.6 [95% confidence interval, 2.4-46.5]; B46, 4.8 [1.6-14.0]; and Cw7, 3.0 [1.1-7.9]. CONCLUSIONS: Our study revealed that HLA-A2 is highly linked to the autoimmune thyroid disorders induced by interferon-alpha-therapy in patients with chronic hepatitis C.     

Interferon-alpha-induced hyperthyroidism: a three-stage evolution from silent thyroiditis towards Graves' disease

Autoimmune thyroid disease is a common side-effect of interferon-alpha (IFN-alpha) treatment of viral hepatitis C. We have described three patients with hepatitis C for whom IFN-alpha and ribavirin were prescribed and who developed two successive phases of silent thyroiditis followed by hyperthryroidism relapse due to Graves' disease. These three men had no known history of familial or personal thyroid disease. Destructive thyrotoxicosis appeared 4-6 months after starting IFN-alpha, followed by Graves' hyperthyroidism within 8 to 11 months. The thyrotropin (TSH) level was normal before IFN-alpha was started. The diagnosis of destructive thyroiditis was confirmed by anti-TSH receptor antibody (TSHRAb) negativity and the absence of radionuclide ((123)I or (99)Tc) uptake on thyroid scintiscans. Eight to eleven months after starting treatment, TSHRAb positivity and intense scintigraphic uptake confirmed the appearance of Graves' disease. IFN-alpha was continued in only one patient. Hence, hyperthyroidism induced by IFN-alpha could correspond to the first phase of silent thyroiditis, to Graves' disease or to the succession of both. Rigorous diagnostic procedures with repeated scintiscans and TSHRAb titering are necessary to avoid a false diagnosis and inappropriate therapy.     

Multiple relapses of hyperthyroidism after thyroid surgeries in a patient with long term follow-up of sporadic non-autoimmune hyperthyroidism

Constitutively activating thyrotropin receptor (TSHR) germline mutations have been identified as a molecular cause of congenital hyperthyroidism. Patients with relapsing hyperthyroidism were previously treated with surgery and radioiodine. We report on a 22-year-old male patient who was treated for his multiple relapses of hyperthyroidism by repeated subtotal thyroidectomies (STE). During the 22 years of follow-up, the patient developed several relapses of hyperthyroidism, four of them after thyroid surgeries. Sequencing of the TSHR gene revealed a gain-of-function mutation with an amino acid exchange of aspartate to tyrosine in codon 633 which is located in the sixth transmembrane domain of the TSH receptor. The absence of the mutation in all other family members identifies the patient's TSHR mutation as a sporadic germline mutation. In this patient, thyroid tissue growth and hyperthyroidism could repeatedly be controlled only for limited periods by near total thyroidectomy. Therefore, this case confirms that early combined treatment with near-total thyroidectomy plus radioiodine therapy seems to be the treatment of choice for patients with sporadic non-autoimmune hyperthyroidism.     

Pegylated interferon-alpha2beta in combination with ribavirin does not aggravate thyroid dysfunction in comparison to regular interferon-alpha2beta in a hepatitis C population: meta-analysis

BACKGROUND: Interferon (IFN) has been well documented to cause thyroid dysfunction, especially in high risk patients and when combined with ribavirin (RBV). There is very sparse data to assess if pegylated IFN will further aggravate the thyroid disease risk in comparison to regular IFN. The purpose of this study was to assess the risk of developing thyroid disease with pegylated IFN (pIFN) versus regular IFN (rIFN) therapy (in combination with RBV). We also pooled our results with previous studies in a meta-analysis. METHODS: An observational study was made retrospectively of 24 patients who underwent a combination of rIFN and RBV therapy for hepatitis C virus (HCV) infection. As these patients failed to obtain an initial satisfactory response, they were retreated using pIFN and RBV. Monthly thyrotropin (TSH) levels were assessed while undergoing both treatment regimens. A meta-analysis was performed using available published data in PubMed. RESULTS: No difference in TSH levels was observed when comparing rIFN/RBV with pIFN/RBV. None of the patients developed hypo- or hyperthyroidism. TSH levels fluctuated during the treatment but did not extend outside the reference range. No further investigation was carried out in the absence of clinical and biochemical thyroid disease. The result of the meta-analysis failed to find any excess risk of thyroid dysfunction using pIFN above that of rIFN. CONCLUSIONS: The pegylation of IFN, in combination with RBV, did not aggravate thyroid diseases in the hepatitis C population. This finding is reassuring and dictates that no deviation from current practice regarding thyroid surveillance is required whilst undergoing HCV treatment.     

Coincidence of hot thyroid nodules and primary hyperparathyroidism.

Hyperthyroidism is frequently associated with hypercalcemia, which usually subsides after successful treatment of hyperthyroidism. Moreover, thyroid nodules are frequently detected by preoperative thyroid ultrasound in patients with primary hyperparathyroidism. Sensitised by the observation of a patient with coexisting hyperthyroidism and hyperparathyroidism we prospectively evaluated thyroid nodules in euthyroid patients with hyperparathyroidism by thyroid scintigraphy. Whereas the first patient with hyperparathyroidism was hyperthyroid the subsequent four patients with hyperparathyroidism and thyroid nodules had normal fT3 and fT4. Two patients had hypercalcemia and nephroureterolithiasis. Three patients suffered from hypercalcemia and bone pain due to osteoporosis. In the hyperthyroid patient hypercalcemia persisted after euthyroidism was achieved intact parathyroid hormone was found to be elevated. Subsequently, thyroid nodules, detected by preoperative ultrasound in four euthyroid patients with primary hyperparathyroidism, were identified as compensated hot nodules by thyroid scintigraphy. All patients underwent combined subtotal thyroidectomy and parathyroid resection. Histology showed hyperplastic parathyroid glands in one patient and a single parathyroid adenoma in four cases. Postoperatively calcium and PTH levels returned to normal and TSH levels increased in all patients. Persistence of hypercalcemia after successful treatment of hyperthyroidism should be reason for the determination of parathyroid hormone. Thyroid nodules detected by preoperative ultrasound in patients with hyperparathyroidism living in areas of iodine deficiency should be further evaluated by scintigraphy even if TSH is normal. In the case of hot thyroid nodules both parathyroid and partial thyroid resection should be performed.     

Interferon-alpha induced and ribavirin induced thyroid dysfunction in patients with chronic hepatitis C

Chronic hepatitis C (CHC) is one of the commonest infectious diseases of the liver and may lead to cirrhosis or hepatocellular carcinoma. Combination therapy with pegylated interferon (PEG-IFN) and Ribavirin is the treatment of choice for CHC. Combination therapy is thought to act by means of antiviral mechanisms and immunomodulation. Thyroid dysfunction is the most common autoimmune adverse effect associated with combination therapy; hypothyroidism is more common than hyperthyroidism. Antithyroid antibodies and female sex have a predictive value in the development of interferon induced thyroid disease (IITD). Patients with CHC should be informed of the possibility of side effects on the thyroid gland. Screening for antithyroid antibodies and thyroid function tests should be performed in patients with CHC before the commencement of antiviral treatment, and during and after it. This article reviews different aspects of IITD, including its pathogenesis, clinical manifestations, association with treatment regimens and treatment response and the outcome of thyroid dysfunction.     

抗丙型肝炎病毒治疗过程中甲状腺功能异常与病毒学应答关系研究*

目的探讨聚乙二醇干扰素（Peg-IFN）联合利巴韦林（RBV）治疗慢性丙型肝炎患者发生甲状腺功能异常的转归及其对抗病毒疗效的影响。方法204例（HCV基因1b型感染173例,2a型9例,3b型2例,未分型20例）慢性丙型肝炎患者应用Peg-IFN联合RBV抗病毒治疗。对于基因1型和未分型者治疗48 w,对于基因2型和3型治疗24 w。采用化学发光免疫分析法检测血清游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、超敏促甲状腺激素（sTSH）;采用间接免疫荧光法检测血清抗甲状腺球蛋白抗体（Tg-Ab）、抗甲状腺过氧化物酶抗体（TPOAb）、抗促甲状腺激素受体抗体（TRAb）、抗甲状腺微粒体抗体。结果在治疗过程中,发生甲状腺功能异常43例（19.0%）,其中甲状腺功能减退症7例（16.3%）,亚临床甲状腺功能减退症17例（39.5%）,甲状腺功能亢进症11例（25.6%）,亚临床甲状腺功能亢进症8例（18.6%）;甲状腺功能异常集中发生于治疗后24~36 w;在观察结束时,37例甲状腺功能异常患者自发或者经药物治疗后甲状腺功能恢复正常,6例患者仍需要密切监测甲状腺功能或服用抗甲状腺药物;43例甲状腺功能异常与161例无甲状腺功能异常患者RVR、EVR、ETVR、SVR、治疗结束后96 w病毒学应答率差异均无统计学意义（P>0.05）。结论Peg-IFN联合RBV治疗慢性丙型肝炎患者诱发甲状腺功能异常的发生率为19.0%,大部分是可逆的,甲状腺功能异常不影响抗病毒疗效。     

Ischemic colitis during pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C.

Rare cases of ischemic colitis associated with interferon-alpha (IFN-alpha) treatment for chronic hepatitis C (HCV) infection and metastatic cancer have been reported. The present study describes the first case of ischemic colitis attributable to pegylated IFN-alpha and ribavirin combination therapy in an HCV-infected patient after 34 weeks of treatment. The clinical presentation, endoscopic appearance and histopathology of the colon were consistent with ischemic colitis, and the patient's symptoms rapidly resolved with cessation of therapy. The association between the therapy and the pathogenesis of ischemic colitis is unclear, but immunoregulatory, vasospastic and procoagulant mechanisms have been proposed. Physicians should be aware of this complication, and should consider it in any HCV-infected patient taking pegylated IFN-alpha and ribavirin who develops abdominal discomfort and gastrointestinal bleeding.     

Hyperthyroidism due to inappropriate secretion of thyrotropin in 10 patients.

PURPOSE: The syndrome of inappropriate thyroid-stimulating hormone (TSH) secretion, characterized by elevated serum free thyroxine and triiodothyronine levels in association with measurable serum TSH concentrations, remains an uncommon cause of hyperthyroidism that is being recognized with increasing frequency. The hyperthyroidism may be due to either neoplastic pituitary TSH secretion or selective pituitary resistance to thyroid hormone. In an effort to better understand this rare cause of hyperthyroidism, we undertook a retrospective analysis of our institution's experience with this condition. PATIENTS: We reviewed our cumulative experience (10 patients) with hyperthyroidism due to the syndrome of inappropriate secretion of TSH. RESULTS: Six patients were diagnosed with TSH-secreting pituitary adenomas and four were found to have selective pituitary resistance to thyroid hormone. One patient with tumor had a TSH-secreting pituitary adenoma in the setting of multiple endocrine neoplasia syndrome. In all patients with tumor, hyperthyroidism was successfully treated with transsphenoidal adenomectomy with or without pituitary radiotherapy. All four patients with pituitary resistance had thyroid ablation or resection prior to their correct diagnosis. Therefore, therapy for this group of patients involved thyroid hormone replacement and efforts to suppress TSH hypersecretion. All 10 patients have done well clinically, with follow-up ranging from 2 weeks to 13 years. CONCLUSIONS: Adequate treatment exists for the two primary causes of TSH hypersecretion. TSH-secreting pituitary adenomas are treated with surgery and, if necessary, adjuvant pituitary radiotherapy. The results are generally good if the tumor is diagnosed and treated at an early stage. Primary therapy for hyperthyroidism due to selective pituitary resistance to thyroid hormone is aimed at suppression of pituitary TSH hypersecretion. The evaluation of any patient with hyperthyroidism must be thorough and, in some cases, should include measurement of TSH to determine the presence of inappropriate secretion. Eliminating this diagnosis will help avoid improper and potentially harmful treatment of hyperthyroid patients.     

Iodine excess and hyperthyroidism.

150 microg iodine are daily required for thyroid hormone synthesis. The thyroid gland has intrinsic mechanisms that maintain normal thyroid function even in the presence of iodine excess. Large quantities of iodide are present in drugs, antiseptics, contrast media and food preservatives. Iodine induced hyperthyroidism is frequently observed in patients affected by euthyroid iodine deficient goiter when suddenly exposed to excess iodine. Possibly the presence of autonomous thyroid function permits the synthesis and release of excess quantities of thyroid hormones. The presence of thyroid autoimmunity in patients residing in iodine-insufficient areas who develop iodine-induced hyperthyroidism has not been unanimously observed. In iodine-sufficient areas, iodine-induced hyperthyroidism has been reported in euthyroid patients with previous thyroid diseases. Euthyroid patients previously treated with antithyroid drugs for Graves' disease are prone to develop iodine-induced hyperthyroidism. As well, excess iodine in hyperthyroid Graves' disease patients may reduce the effectiveness of the antithyroid drugs. Occasionally iodine-induced hyperthyroidism has been observed in euthyroid patients with a previous episode of post-partum thyroiditis, amiodarone destructive or type II thyrotoxicosis and recombinant interferon-alpha induced destructive thyrotoxicosis. Amiodarone administration may induce thyrotoxicosis. Two mechanisms are responsible for this condition. One is related to excess iodine released from the drug, approximately 9 mg of iodine following a daily dose of 300 mg amiodarone. This condition is an iodine-induced thyrotoxicosis or type I amiodarone-induced thyrotoxicosis. The other mechanism is due to the amiodarone molecule that induces a destruction of the thyroid follicles with a release of preformed hormones. This condition is called amiodarone-induced destructive thyrotoxicosis or type II thyrotoxicosis. Patients developing type I thyrotoxicosis in general have preexisting nodular goiter whereas those developing type II thyrotoxicosis have a normal thyroid gland. The latter group of patients, after recovering from the destructive process, may develop permanent hypothyroidism as the consequence of fibrosis of the gland.     

Myasthenia gravis and hyperthyroidism: two cases

It is well known that hyperthyroidism occurs in approximately 2 to 17.5% of patients with myasthenia gravis. Hyperthyroidism may influence the clinical course of myasthenia gravis. We report the cases of two patients, a 53-year-old man and an 18-year-old woman, who had both severe myasthenia gravis and hyperthyroidism due to Graves' disease. Myasthenia gravis affected in particular facio-ocular areas with diffuse myopathy and signs of neuromuscular block on the electromyogram. In one patient, the diagnosis of thyroid disease was made three months before the diagnosis of myasthenia gravis while in the other, thyroid disease was recognized four months after myasthenia gravis. Myasthenia gravis worsened after the development of hyperthyroidism in the second patient. Both patients were given anti-cholinesterase drugs. One underwent thymectomy. Radioiodine used for the treatment of hyperthyroidism improved the symptoms of myasthenia gravis in the first patient. The association of myasthenia gravis and hyperthyroidism is more than a coincidence; our cases illustrate the difficult diagnosis and management of these diseases. Clinicians should look for myasthenia gravis in hyperthyroid patients and vice versa, especially when symptoms of myasthenia gravis or hyperthyroidism worsen.