methimazole and Goiter--Nodular

This study compared the degree of sustained control of hyperthyroidism in patients with toxic multinodular goiter (TMNG) treated with long-term methimazole (LT-MMI) or radioactive iodine (RAI).. In this clinical trial, 130 untreated patients with TMNG were randomized to either LT-MMI or RAI treatment. Both groups were followed for 108 to 148 months, with median follow-up durations of 120 and 132 months in the LT-MMI and RAI groups, respectively. Both groups of patients were followed every 1 to 3 months in the first year and every 6 months thereafter.. After excluding patients in whom the treatment modality was changed and those who were lost to follow-up, 53 patients in the LT-MMI group and 54 in the RAI group completed the study. At the end of the study period, 50 (96%) and 25 (46%) patients were euthyroid, and two (4%) and 25 (46%) were hypothyroid in LT-MMI and RAI groups, respectively. In the RAI group, four (8%) patients had subclinical hyperthyroidism. The mean time to euthyroidism was 4.3±1.3 months in LT-MMI patients and 16.3± 15.0 months in RAI recipients (P<0.001). Patients treated with LT-MMI spent 95.8%±5.9% of the 12-year study period in a euthyroid state, whereas this proportion was 72.4%±14.8% in the RAI-treated patients (P<0.001). No major treatment-related adverse events were observed in either group.. In patients with TMNG, LT-MMI therapy is superior to RAI treatment, as shown by the earlier achievement of euthyroidism and the longer duration of sustained normal serum thyrotropin.

Topics: Goiter, Nodular; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Thyroid Neoplasms

It is possible to raise the rate of the uptake of. Thirty-one patients with NMG received. Radioiodine treatment of NMG preceded with appropriate application of MMI is efficient thanks to increased RAIU, shorter period of treatment, and lower frequency of

Topics: Goiter; Goiter, Nodular; Humans; Iodine Radioisotopes; Methimazole; Thyrotropin

Topics: Adult; Female; Goiter, Nodular; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged

Relatively low radioiodine uptake (RAIU) represents a common obstacle for radioiodine ((131)I) therapy in patients with multinodular goiter complicated by hyperthyroidism.. To evaluate whether thiamazole (MTZ) pretreatment can increase (131)I therapeutic efficacy.. Twenty-two patients with multinodular goiter, subclinical hyperthyroidism, and RAIU < 50% were randomized to receive either a low-iodine diet (LID; n = 10) or MTZ 30 mg/d (n = 12) for 42 days. Thyroid function and 24-hour RAIU were measured before and after treatment. Thyroid volume was evaluated by either magnetic resonance imaging or single photon emission computed tomography.. Mean 24-hour RAIU increased significantly from 32 ± 10% to 63 ± 18% in the MTZ group (P < .001). Consequently, there was a 31% decrease in the calculated median therapeutic (131)I activity after MTZ (P < .05). No significant changes in 24-hour RAIU were observed after diet. In the MTZ group, median serum TSH levels increased significantly by 9% and mean serum free T4 and free T3 concentrations decreased by 22% and 15%, respectively, whereas no changes in thyroid function were observed in the LID group. Thyroid volume did not significantly change in either of the two groups. At 12 months after radioiodine treatment, median serum TSH was within the normal range in both groups.. MTZ treatment before (131)I therapy resulted in an average 2-fold increase in thyroid RAIU and enhanced the efficiency of radioiodine therapy assessed at 12 months. MTZ pretreatment is therefore a safe, easily accessible alternative to recombinant human TSH stimulation and a more effective option than LID.

Topics: Aged; Aged, 80 and over; Antithyroid Agents; Case-Control Studies; Combined Modality Therapy; Drug Administration Schedule; Female; Goiter, Nodular; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Organ Size; Radiotherapy Dosage; Thyroid Function Tests; Thyroid Gland

Interleukine-16 (IL-16) and RANTES (regulated upon activation, normal T cell expressed and secreted) are 2 cytokines with the function of T helper cell recruitment, which might play a key role in pathogenesis of autoimmune thyroid diseases (AITD). This study was aimed to evaluate the IL-16 and RANTES in patients with AITD. Serum IL-16 and RANTES levels were measured in patients with Graves' disease (GD; n=45), Hashimoto's thyroiditis (HT; n=68), nontoxic multinodular goiter (NTMNG; n=20), and healthy individuals (n=61). The results showed that serum IL-16 and RANTES levels were elevated both in HT and higher in untreated GD patients when compared to NTMNG patients and the healthy individuals, which were decreased after MMI therapy in untreated GD patients. However, in HT patients, serum IL-16 and RANTES levels were comparable among the conditions of hyperthyroid and euthyroid received by l-thyroxine therapy and untreated hypothyroid. Furthermore, serum IL-16 levels were correlated with FT3, FT4, TRAb in GD, but not in HT patients. The data did not show any correlation between RANTES levels and clinical factors. In conclusion, IL-16 and RANTES might be involved in the pathogenesis of GD and HT, and serum IL-16 levels in GD maybe a potential marker of disease activity and severity.

Topics: Adult; Antithyroid Agents; Case-Control Studies; Chemokine CCL5; Female; Goiter, Nodular; Graves Disease; Hashimoto Disease; Humans; Interleukin-16; Male; Methimazole; Thyroid Function Tests

Lack of consensus regarding the antithyroid drug regimen in relation to radioiodine ((131) I) therapy of hyperthyroidism prompted this randomized trial comparing two strategies.. Patients with Graves' disease (GD, n = 51) or toxic nodular goitre (TNG, n = 49) were randomized to (131) I either 8 days following discontinuation of methimazole (-BRT, n = 52, median dose: 5 mg) or while on a continuous block-replacement regimen (+BRT, n = 48, median dose 15 mg methimazole and 100 μg levothyroxine). results: Patients in the +BRT group required more radioactivity. In this group, thyroid function did not change in the early post (131) I period, while serum-free T3 index was higher in the -BRT group (P < 0·05). One year posttherapy, the fraction of cured patients (euthyroid or hypothyroid) was 48% and 61% in the +BRT and -BRT group, respectively (P = 0·014 unadjusted; P = 0·004 adjusted), but the outcome depended on the type of disease. In GD, treatment failure in the +BRT group correlated positively with the 24-h thyroid (131) I uptake (P = 0·017), while no correlations existed in the -BRT group. In addition to +BRT allocation, patients with TNG were at higher risk of treatment failure with lower thyroid radiation doses (P = 0·048), higher doses of methimazole (P = 0·026) and lower levels of serum TSH (P = 0·009).. A continuous block-replacement regimen results in a stable thyroid function during (131) I therapy but is hampered by the higher amounts of radioactivity required. The study demonstrates that the outcome in GD is highly unpredictable, while treatment failure in patients with TNG is correlated with a number of factors.

Topics: Adult; Aged; Antithyroid Agents; Combined Modality Therapy; Drug Administration Schedule; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Radiotherapy Dosage; Thyroid Hormones; Thyroxine; Treatment Outcome

Radioiodine ((131)I) is an alternative to surgery for the treatment of multinodular goiter (MNG). Frequently, high activities of (131)I are required for effective thyroid volume reduction (TV), due to the low and heterogeneous radioactive iodine uptake (RAIU). Thiamazole (MTZ) may be used as an adjuvant to (131)I, by increasing RAIU.. To evaluate the effects of MTZ in the treatment of MNG with (131)I, in terms of TV reduction.. Nine female patients (aged 73.8 +/- 7.4 years) with MNG (eight with subclinical hyperthyroidism) were treated with MTZ. Doses started at 10 - 20 mg, and were adjusted monthly based on thyroid hormone levels. RAIU and TV were measured at baseline, and repeated when TSH levels > 6 mU/l were achieved. At that time, 1.11 GBq of (131)I were administered.. Patients were treated with MTZ for 2.8 +/- 0.8 months. When a tracer activity of (131)I was administered, the mean serum TSH was elevated to 11.7 +/- 5.4 mU/l. MTZ led to significant increases in 24-h RAIU, from 21.3 +/- 8.1% to 78.3 +/- 15.3% (p < 0.001). One year after (131)I, median TV decreased from 97 ml (range 47 - 555 ml) to 56 ml (range 13 - 350 ml), a mean reduction of 46.2 +/- 17.8% (p = 0.012). Eight patients (89%) had subclinical hyperthyroidism, which was reversed in all patients after 1 year. Five patients (56%) developed overt hypothyroidism, and no clinical adverse events were observed.. Pretreatment with MTZ targeting against an increased serum TSH did not impair the effects of (131)I. In our patients with MNG, MTZ increased RAIU and possibly enhanced (131)I efficacy, leading to significant TV reduction and reversion of hyperthyroidism in all patients.

Topics: Aged; Female; Goiter, Nodular; Humans; Iodine Radioisotopes; Methimazole; Radiotherapy, Adjuvant

A randomized clinical trial was performed to clarify whether continuous use of methimazole (MTZ) during radioiodine ((131)I) therapy influences the final outcome of this therapy.. Consecutive patients with Graves' disease (n = 30) or a toxic nodular goiter (n = 45) were rendered euthyroid by MTZ and randomized to stop MTZ 8 d before (131)I (-MTZ; n = 36) or to continue MTZ until 4 wk after (131)I (+MTZ; n = 39). Calculation of the (131)I activity included an assessment of the (131)I half-life and the thyroid volume.. The 24-h thyroid (131)I uptake was lower in the +MTZ group than in the -MTZ group (44.8 +/- 15.6% vs. 62.1 +/- 9.9%, respectively; P < 0.001). At 3 wk after therapy, no significant change in serum free T(4) index was observed in the +MTZ group (109 +/- 106 vs. 83 +/- 28 nmol/liter at baseline; P = 0.26), contrasting an increase in the -MTZ group (180 +/- 110 vs. 82 +/- 26 nmol/liter; P < 0.001). The number of cured patients was 17 (44%) and 22 (61%) in the +MTZ and -MTZ groups, respectively (P = 0.17). Cured patients tended to have a lower 24-h thyroid (131)I uptake (50.1 +/- 13.8% vs. 56.4 +/- 17.1%; P = 0.09). By adjusting for a possible interfactorial relationship through a regression analysis (variables: randomization, 24- and 96-h thyroid (131)I uptake, type and duration of disease, age, gender, presence of antithyroid peroxidase antibodies, thyroid volume, dose of MTZ), only the continuous use of MTZ correlated with treatment failure (P = 0.006), whereas a low 24-h thyroid (131)I uptake predicted a better outcome (P = 0.006).. Continuous use of MTZ hinders an excessive increase of the thyroid hormones during (131)I therapy of hyperthyroid diseases. However, such a strategy seems to reduce the final cure rate, although this adverse effect paradoxically is attenuated by the concomitant reduction of the thyroid (131)I uptake.

Topics: Adult; Aged; Antithyroid Agents; Combined Modality Therapy; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Logistic Models; Male; Methimazole; Middle Aged; Recurrence; Thyrotropin; Treatment Outcome

Oxidative stress plays an important role in hyperthyroidism-induced tissue damage, as well as in development of autoimmune disorders. To clarify influence of thyroid metabolic status and autoimmune factors on blood extracellular indices of reactive oxygen species (ROS) generation and free radical scavenging in hyperthyroidism, we studied patients with newly diagnosed and untreated Graves' disease without infiltrative ophthalmopathy (17 female and 8 male, aged 41.8 +/- 8.9) and toxic multinodular goiter (15 female and 9 male, aged 48.4 +/- 10.1) under the same antithyroid treatment protocol. Initially and after achievement of stable euthyroidism with methimazole, plasma levels of hydrogen peroxide (H202), lipid hydroperoxides (ROOH) and ceruloplasmin (CP) and serum concentrations of thiobarbituric acid-reacting substances (TBARS) were determined. Similarly, activities of plasma superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were assayed. The results were compared to those of age- and sex-matched controls. Average duration of hyperthyroidism and treatment period were similar in both patients groups. H202, ROOH and TBARS concentrations were significantly higher in hyperthyroid patients compared to controls. Hyperthyroidism caused an evident increase in SOD and CAT activities and CP level, as well as a decrease in GPx and GR activities. Achievement of euthyroidism resulted in normalization of all analyzed parameters in both hyperthyroid patients groups. These findings suggest that the changes in blood extracellular indices of oxidative stress and free radical scavenging in hyperthyroid patients are influenced by thyroid metabolic status, and are not directly dependent on autoimmune factors present in Graves' disease.

Topics: Adult; Age Factors; Antioxidants; Antithyroid Agents; Biomarkers; Female; Free Radicals; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Oxidation-Reduction; Reactive Oxygen Species; Sex Factors

Retrospective studies have indicated that anti-thyroid drugs (ATD) might possess a radioprotective effect, leading to a higher rate of recurrence of hyperthyroidism after iodine-131 ((131)I) therapy.. A randomized clinical trial was performed to clarify whether resumption of methimazole after (131)I influences the final outcome of this treatment.. We assigned 149 patients with Graves' disease or a toxic nodular goitre to groups either to resume (+ATD) or not to resume (-ATD) methimazole 7 days after (131)I. Before (131)I therapy, all patients were rendered euthyroid by methimazole, which was discontinued 4 days before the (131)I therapy.. During the follow-up period of 12 Months, 13 patients developed hypothyroidism, 42 were euthyroid, and 18 had recurrence of hyperthyroidism in the +ATD group; the respective numbers in the -ATD group were 16, 42 and 18 (P=0.88). At 3 weeks after (131)I therapy, the serum free-thyroxine index was slightly decreased (by 5.7%; 95% confidence interval (CI) -15.5 to 5.4%) in the +ATD group, in contrast to an increase of 35.9% (95% CI 18.8 to 55.5%) in the -ATD group (P<0.001 between groups). In the subgroup that remained euthyroid during follow-up, thyroid Volume reduction, assessed by ultrasonography, was smaller in the +ATD group [38.7% (95% CI 33.3 to 44.1%)] than in the -ATD group [48.6% (95% CI: 41.5-55.6%)] (P<0.05).. No radioprotective effect could be demonstrated, with regard to final thyroid function, for the resumpton of methimazole 7 days after (131)I therapy. Although resumption of methimazole slightly reduced the magnitude of shrinkage of the goitre obtained by (131)I, the prevention of a temporary thyrotoxicosis in the early period after radiation favours this regimen.

Topics: Aged; Antithyroid Agents; Combined Modality Therapy; Female; Follow-Up Studies; Goiter, Nodular; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Radiation-Protective Agents; Recurrence; Treatment Outcome

Accelerated metabolism is a hallmark of thyrotoxicosis, but the underlying biochemical mechanisms are incompletely understood. In order to elucidate these metabolic events further, we studied 12 patients with newly diagnosed diffuse (10 patients) or nodular (two patients) toxic goitre (ten women, two men; age 42.8 +/- 3.2 yr; BMI: 21.6 +/- 0.7 kg/m2) before ("TOX") and after ("TRE") 11.2 +/- 1.0 weeks treatment with methimazole and compared these patients to a control group ("CTR") of 11 subjects (nine women, two men; age 40.5 +/- 3.9 yr; BMI 22.5 +/- 1.0 kg/m2). All were studied for three hours in the basal state, using indirect calorimetry, isotope dilution for measurement of glucose turnover and the forearm technique for assessment of muscle metabolism. Prior to treatment patients with thyrotoxicosis were characterized by: Increased (p < 0.05) levels of T3 (3.75 +/- 0.23 [TOX], 1.89 +/- 0.08 [TRE] and 1.75 +/- 0.11 [CTR] nmol/l), resting energy expenditure (130.5 +/- 3.5 [TOX], 107.7 +/- 2.7 [TRE] and 106.3 +/- 3.1 [CTR] percent of predicted), protein oxidation (0.67 +/- 0.03 [TOX], 0.54 +/- 0.06 [TRE] and 0.46 +/- 0.05 [CTR] mg/kg/min), lipid oxidation (1.34 +/- 0.08 [TOX], 1.00 +/- 0.06 [TRE] and 1.02 +/- 0.04 [CTR] mg/kg/min), endogenous glucose production (2.51 +/- 0.13 [TOX], 1.86 +/- 0.12 [TRE] and 1.85 +/- 0.12 [CTR] mg/kg/min), non-oxidative glucose turnover (1.28 +/- 0.16 [TOX], 0.75 +/- 0.18 [TRE] and 0.71 +/- 0.11 [CTR] mg/kg/min) and a 50% increase in total forearm blood flow. Glucose oxidation (1.23 +/- 0.09 [TOX], 1.13 +/- 0.10 [TRE] and 1.13 +/- 0.09 [CTR] mg/kg/min), exchange of substrates in the muscles of the forearm and circulating levels of insulin, C-peptide, growth hormone or glucagon were not influenced by hyperthyroidism. Propranolol (20 mg thrice daily) given to seven of the patients for two days did not affect circulating levels of thyroid hormones, energy expenditure or glucose turnover rates. These results suggest that all major fuel sources contribute to the hypermetabolism of thyrotoxicosis and that augmented non-oxidative glucose metabolism may further aggravate the condition. All abnormalities recede with medical treatment of the disease.

Topics: Adult; Antithyroid Agents; Energy Metabolism; Female; Glucose; Goiter; Goiter, Nodular; Humans; Male; Methimazole; Substrate Cycling; Thyroid Hormones; Thyrotoxicosis

The enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) is higher in thyrotoxicosis. Bile-salt sequestrants bind iodothyronines and thereby increase their fecal excretion. We, therefore, evaluated the effect of colestipol-hydrochloride administration on clinical and biochemical indices of patients with hyperthyroidism. In a prospective, controlled trial, ninety-two adult volunteers with Graves' disease, toxic autonomous nodule or toxic multinodular goiter were randomly assigned into the following treatment protocols: Group 1, 30 mg of methimazole (MMI) and 20 g of colestipol-hydrochloride (COL) daily; Group 2, 30 mg of MMI daily; and Group 3, 15 mg of MMI 20 g of COL daily. The patients were further classified into Group A, severe hyperthyroidism (baseline levels of total T3 (TT3) > or =5 nmol/l) and Group B, mild to moderate thyrotoxicosis (baseline levels of TT-3<5 nmol/l). Crook's clinical index, serum free T4 (FT4), TT3 and thyroid stimulating hormone (TSH) levels were determined before (WO), following one week (W1) and two weeks (W2) of treatment. Serum TT3 level decreased (mean+/-SE) at W1 by 40.8+/-2.6% of WO in Group1 and by 29.2+/-2.4% in Group 2 (p<0.001), and down further to 47.8+/-3.0% at W2 in Group 1, and 40.6+/-2.8% in Group 2 (p=0.01). Serum FT4 level decreased (mean+/-SE) from WO to W1 by 31.7+/-2.7% in Group 1 and by 16.2+/-3.1% in Group 2 (p=0.005), and down to 49.1+/-2.8% of WO at W2 in Group 1 and to 38.7+/-3.5% in Group 2 (p=0.07). In sub groups B COL was not effective in reducing thyroid hormone levels nor in ameliorating the clinical status of the patients. However, in Group A3 COL lowered FT4 (p=0.001) and TT3 (p=0.05) levels as compared to group A2. At W2 the clinical hyperthyroidism score improved faster in Group A1 (p<0.001) and Group A3 (p=0.012) as compared to the control Group A2. In conclusion, COL is an effective and well tolerated adjunctive agent in the treatment of hyperthyroidism. Its main effect is in severe cases of thyrotoxicosis, and in the first phase of treatment. As adjunctive COL treatment in hyperthyroidism allows reducing MMI dosage it may decrease the rate of dose dependent MMI side effects.

Topics: Adult; Antithyroid Agents; Colestipol; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Ion Exchange Resins; Male; Methimazole; Middle Aged; Prospective Studies; Thyroid Nodule; Thyrotropin; Thyroxine; Treatment Outcome; Triiodothyronine

Thyrotoxicosis is the state of thyroid hormone excess. But, in sub-Saharan Africa (SSA), specifically Northern Ethiopia, scientific evidence about thyrotoxicosis and its cardiac complications like dilated cardiomyopathy is limited. Therefore, this study aimed to explore the thyrotoxicosis presentation and management and identify factors associated with dilated cardiomyopathy in a tertiary hospital in Northern Ethiopia.. An institution-based cross-sectional study was conducted in Ayder Comprehensive Specialized Hospital from 2017 to 2018. Data from 200 thyrotoxicosis cases were collected using a structured questionnaire. After describing variables, logistic regression was conducted to identify independent predictors of dilated cardiomyopathy. Statistical significance was declared at p < 0.05.. Mean age at presentation of thyrotoxicosis was 45 years and females accounted for 89 % of the cases. The most frequent etiology was multinodular toxic goiter (51.5 %). As well, the most common symptoms and signs were palpitation and goiter respectively. Thyroid storm occurred in 6 % of the cases. Out of 89 patients subjected to echocardiography, 35 (39.3 %) of them had dilated cardiomyopathy. And, the odds of dilated cardiomyopathy were higher in patients who had atrial fibrillation (AOR = 15.95, 95 % CI:5.89-38.16, p = 0.001) and tachycardia (AOR = 2.73, 95 % CI:1.04-7.15, p = 0.040). All patients took propylthiouracil and 13.0 % of them experienced its side effects. Concerning β-blockers, propranolol was the most commonly (78.5 % of the cases) used drug followed by atenolol (15.0 %). Six patients underwent surgery.. In developing countries like Ethiopia, patients with thyrotoxicosis have no access to methimazole which is the first-line anti-thyroid drug. Besides, they greatly suffer from dilated cardiomyopathy (due to late presentation) and side effects of propylthiouracil. Therefore, we recommend that patients should get adequate health information about thyrotoxicosis and anti-thyroid drugs including their side effects. Additionally, hospitals and other concerned bodies should also avail of TSH tests and methimazole at an affordable cost. Furthermore, community awareness about iodized salt and iodine-rich foods should be enhanced.

Topics: Adolescent; Adult; Antithyroid Agents; Cardiomyopathy, Dilated; Cross-Sectional Studies; Developing Countries; Ethiopia; Female; Goiter, Nodular; Humans; Iodine; Male; Methimazole; Middle Aged; Sodium Chloride, Dietary; Thyrotoxicosis; Young Adult

Agranulocytosis is a rare but very serious complication of thyrostatic therapy. In severe hyperthyroidism, the removal of circulating thyroid hormones by plasmapheresis may be an effective therapeutic option. This report describes the therapeutic difficulties and successful preoperative treatment with plasmapheresis in a 63-year-old patient admitted to the Endocrinology Clinic with severe hyperthyroidism, during the course of giant toxic nodular goiter and agranulocytosis, which occurred after 2 weeks of taking methimazole. During hospitalization, methimazole treatment was discontinued and therapy with steroids, a beta blocker, propylthiouracil, Lugol's solution, lithium carbonate, and antibiotics were initiated. Granulocyte colony growth stimulating factor was also used to resolve agranulocytosis. Due to the failure to achieve euthyreosis using this approach, we decided to conduct thyroid surgery, as a life-saving action, after preparation of the patient by plasmapheresis. Two plasmapheresis procedures were performed, resulting in a decrease in the concentration of free thyroid hormones. Total thyroidectomy was performed and there were no complications during surgery. We conclude that plasmapheresis may be considered as an effective alternative treatment option for the preparation of patients with hyperthyroidism for surgery, when the clinical situations prevent the use of conventional treatments for hyperthyroidism and when immediate life-saving surgery is necessary.

Topics: Agranulocytosis; Antithyroid Agents; Electrocardiography; Female; Goiter, Nodular; Humans; Hyperthyroidism; Methimazole; Middle Aged; Plasmapheresis; Preoperative Care; Thyroidectomy; Treatment Outcome

A 51-year-old woman with a personal history of vitiligo, normal thyroid hormone studies, a simple hysterectomy for multiple uterine myomas at age 35 years, and childhood adenotonsillectomy was seen for progressive hearing loss. She reported mild asthenia, cold intolerance, mild dysphagia with frequent choking while eating and drinking, and a progressive increase in inspiratory effort, especially in the supine position. Her partner described a progressively worsening history of snoring and witnessed apneic episodes, mostly in the supine position. Mild to moderate daytime sleepiness was also present.

Topics: Antithyroid Agents; Female; Goiter, Nodular; Hearing Loss; Humans; Hyperthyroidism; Lingual Thyroid; Magnetic Resonance Imaging; Methimazole; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Sleep Apnea, Obstructive; Sodium Pertechnetate Tc 99m; Supine Position; Tomography, X-Ray Computed

We report a case of apathetic hyperthyroidism associated with unrecognized slowly growing functional thyroid adenoma (Plummer's disease), atrial fibrillation and heart failure. An 81-year-old woman with worsening thyroid dysfunction was admitted to our hospital for the treatment of heart failure. The patient had developed heart failure associated with chronic atrial fibrillation at 76 years of age, and one year later was found to have asymptomatic hyperthyroidism. Anti-thyroid autoantibodies were negative, but thyroid echography showed a 32-mm tumor devoid of internal blood flow in the left lower lobe. Free thyroxine 4 (FT4) decreased from 3.30 to 2.60 ng/dl without treatment. The patient was diagnosed with transient thyroiditis and was followed-up without treatment. However, a repeat thyroid echography showed growth of the tumor to 41 mm in 4 years. Thyroid scintigraphy showed uptake that matched the thyroid mass. Based on these findings, the established diagnosis was Plummer's disease complicated with heart failure. The patient was treated with anti-thyroid drugs, which resulted in improvement of FT4 and reduced the severity of heart failure. In this rare case of an elderly patient, Plummer's disease was associated with a slowly-growing functional thyroid adenoma, apathetic hyperthyroidism, repeated episodes of atrial fibrillation and heart failure. Since symptoms of thyrotoxicosis are likely to be missed in the elderly, it is necessary to include hyperthyroidism in the pathoetiology of heart failure and atrial fibrillation in this population.

Topics: Aged, 80 and over; Antithyroid Agents; Atrial Fibrillation; Female; Goiter, Nodular; Heart Failure; Humans; Hyperthyroidism; Methimazole; Receptors, Thyrotropin; Recurrence; Thyrotoxicosis; Treatment Outcome

Topics: Antithyroid Agents; Atenolol; Chorea; Dibenzothiazepines; Female; Goiter, Nodular; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Patient Compliance; Prednisone; Propylthiouracil; Quetiapine Fumarate; Thyrotoxicosis; Thyrotropin; Thyroxine; Triiodothyronine; Young Adult

Hyperthyroidism is mainly caused by Graves' disease and toxic adenoma or multinodular goiter. In Europe, treatment of both disorders is usually started with antithyroidal drugs such as methimazole. Complications include agranulocytosis and the risk is dose-dependent. The starting dose of methimazole should not exceed 15-20 mg/d. Propylthiouracil can cause severe liver failure, leading to liver transplantation or death. Propylthiouracil, therefore, should not be used as first line agent and is only recommended when an antithyroid drug is to be started during the first trimester of pregnancy or in individuals who have experienced adverse responses to methimazole. Toxic adenoma is finally treated with radioioidine. To reduce the risk of treatment failure, antithyroidal drugs should be stopped at least one week prior to radioiodine. For Graves' disease, remission is unlikely if antibodies against the TSH-receptor remain above 10 mU/l after 6 months of antithyroidal treatment and radioiodine or thyroidectomy can be recommended. Thyroidectomy should be performed as (near) total thyreoidectomy.

Topics: Adenoma; Agranulocytosis; Antithyroid Agents; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Neoplasms; Thyroidectomy

Treatment of toxic nodular goiter with ¹³¹I is a first-line therapy for hyperthyroidism. To avoid a thyrotoxic storm, ¹³¹I is usually administered after pretreatment with antithyroid drugs, with thyroid-stimulating hormone (TSH) increase and functional recruitment of inhibited normal tissue. Therefore, both autonomous nodule(s) and normal tissue are irradiated. This may be a reason for late hypothyroidism occurring in 15-25% of patients. This study aimed at assessing different pretreatment modalities with combined methymazole and triiodothyronine, achieving euthyroidism with suppressed TSH.. After diagnosis of autonomously functioning toxic nodule, patients were subjected to thyrostatic medication. Two months later, TSH was checked; if >0.5 mU/L triiodothyronine treatment was associated. After 2 more months, if the TSH level was suppressed, patients received ¹³¹I-therapy. A total of 149 patients were consecutively enrolled, 41 of whom with uninodular and 108 with multinodular goiter. They were evaluated at diagnosis, pretreatment, 3 and 6 months after therapy and at late follow-up (6.8+/-4.2 years; range: 1-22 years).. Administered activity was calculated according to ¹³¹I uptake and gland weight. Methymazole was discontinued 6 days before treatment and T3 was maintained until administration of ¹³¹I-therapy. Euthyroidism was achieved in 88% of patients. At late follow-up, subclinical hypothyroidism was observed in 10 patients (6.7%) and overt hypothyroidism in 5 patients (3.3%). No pathological consequences or side effects of ¹³¹I-therapy were found during the 6.8+/-4.2 year follow-up period.. Treatment of toxic nodular goiter with ¹³¹I-therapy, under combined thyrostatic-thyromimetic treatment is a simple, safe, well-tolerated, and effective procedure.

Topics: Adult; Aged; Aged, 80 and over; Antithyroid Agents; Combined Modality Therapy; Female; Goiter, Nodular; Humans; Hypothyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Thyrotoxicosis; Time Factors; Triiodothyronine

The Bcl-2 family proteins that control homeostasis of cells play an important role in apoptosis. This group consists of antiapoptotic (Bcl-2, Bcl-XL) and proapoptotic (Bcl-2 associated protein X, Bax; B-cell homologous antagonist/killer, Bak) molecules. In the thyroid, abnormal apoptotic activity may be involved in a variety of diseases such as autoimmune thyroid diseases. The aim of the current study was to estimate the expression of pro- and antiapoptotic proteins in thyroid tissues from young patients with Graves' disease (GD), nontoxic nodular goiter and toxic nodular goiter using Western Blot and immunohistochemistry. Identification of the antiapoptotic Bcl-2 and Bcl-XL molecules in the thyrocytes revealed higher expression of both proteins in patients with GD (assessed as +++/++ and ++/+, respectively). In adolescents with toxic and nontoxic nodular goiter, this expression was lower (Bcl-2 ++/+ , ++/+; Bcl-XL +, +). The tissue material was additionally subjected to Western Blot analysis, which in GD patients showed the presence of Bcl-2 and Bcl-XL in one band p26 kDa. In patients with toxic and nontoxic nodular goiter, the intensity of expression for these two antiapoptotic proteins was lower (referred to band 26 kDa for Bcl-2 and Bcl-XL). Identification of the proapoptotic proteins Bax and Bak revealed their predominance in thyrocytes of GD patients (+, ++/+, respectively) as compared to patients with toxic and nontoxic nodular goiter (0/+, 0/+ for Bax and 0/+, 0/+ for Bak). In GD patients, Western Blot analysis showed Bax expression in one band 21 kDa and Bak in two bands p50, p24 kDa. In patients with nodular goiter, the degree of expression of both proapoptotic proteins was lower and referred to band 21 kDa for Bax (toxic and nontoxic goiter) and 24 kDa for Bak (toxic goiter only). Patients with GD showed a statistically significant correlation between Bcl-2 expression and antibodies against receptor for thyroid stimulating hormone (R = 0.47, p < 0.03); however, such a correlation was not observed in patients with nodular goiter. In conclusion, our findings suggest that the changes in the expression of regulatory proteins of the Bcl-2 family in the thyroid follicular cells indicate the involvement of apoptosis in the pathogenesis of GD.

Topics: Adolescent; Adult; Antithyroid Agents; Apoptosis; Blotting, Western; Child; Female; Goiter, Nodular; Graves Disease; Humans; Immunohistochemistry; Male; Methimazole; Proto-Oncogene Proteins c-bcl-2; Thyrotropin; Thyroxine; Triiodothyronine

CXC chemokine ligand 10 (CXCL10) plays a pivotal role in the self-perpetuation of the inflammatory processes in patients with autoimmune thyroid disease. Treatment with methimazole (MMI) reduces serum CXCL10 in patients with Graves' disease. In isolated human thyrocytes, tumor necrosis factor (TNF)alpha demonstrates a potent synergistic effect on interferon (IFN)gamma-induced CXCL10 secretion. We investigated the mechanism underlying the synergism between IFNgamma and TNFalpha and the effect of MMI on CXCL10 secretion in human thyrocytes. A peroxisome proliferator-activated receptor gamma agonist, rosiglitazone (RGZ), a known inhibitor of T helper 1 (Th1)-mediated responses, was also studied for comparison. Experiments were carried out in human thyrocytes isolated from internodular parenchyma of thyroid tissues derived from patients who had undergone surgery for multinodular goiter. ELISA was used to measure CXCL10 levels in culture supernatant. Flow cytometry was used to assess IFNgamma membrane receptor expression. Specific mRNA analysis was performed by Taqman real-time PCR. Immunofluorescence was performed to detect nuclear translocation of nuclear factor-kappaB (NF-kappaB). In human thyrocytes, the synergistic effect of TNFalpha with IFNgamma on CXCL10 secretion is due to the upregulation of IFNgamma receptor expression. MMI decreased cytokine-induced CXCL10 secretion by reducing TNFalpha-induced upregulation of the IFNgamma receptor. RGZ decreased the cytokine-induced CXCL10 secretion by impairing NF-kappaB translocation, without affecting IFNgamma receptor. MMI and RGZ targeted thyrocytes with the same pharmacological potency, likely acting throughout different mechanisms. Targeting T helper 1-mediated autoimmune thyroid disease with drugs that impair different intracellular pathways could be a novel pharmacological tool.

Topics: Antithyroid Agents; Cells, Cultured; Chemokine CXCL10; Depression, Chemical; Flow Cytometry; Goiter, Nodular; Humans; Interferon-gamma; Methimazole; NF-kappa B; Reverse Transcriptase Polymerase Chain Reaction; Rosiglitazone; Thiazolidinediones; Thyroid Gland; Tumor Necrosis Factor-alpha

CXCL10 plays an important role in the initial phases of Graves' disease (GD) and autoimmune thyroiditis (AT); however, until now, CXCL10 serum levels (sCXCL10) in patients with GD have never been evaluated in relation to thyroid function and treatment.. To evaluate sCXCL10 in GD.. Cross-sectional.. One hundred and three GD, 164 AT, 20 nontoxic multinodular goitre (NTMNG), 16 toxic nodular goitre (TNG) patients and 70 healthy controls (age- and sex-matched).. We measured sCXCL10 in patients and controls, to relate this parameter to the clinical phenotype.. Mean sCXCL10 in GD and AT patients were comparable (122+/-81 and 133+/-102 pg/ml) and significantly higher (P<0.01) than in controls or NTMNG patients (73+/- 32 and 76+/- 25 pg/ml, respectively). Hyperthyroid GD had significantly higher sCXCL10 than euthyroid or hypothyroid GD (145+/- 92, 107+/- 56 and 105+/- 46 pg/ml, respectively; P=0.01). GD patients with untreated hyperthyroidism had higher sCXCL10 than hyperthyroid or euthyroid GD patients under methimazole (MMI) treatment (166+/-125, 124+/- 41 and 94+/- 35 pg/ml, respectively; P=0.006). Comparable sCXCL10 levels were observed in newly diagnosed untreated hyperthyroid GD patients with respect to untreated patients with relapse of hyperthyroidism after a previous MMI course (176+/-125, 155+/- 97 pg/ml, respectively). GD had similar sCXCL10 to AT and higher than TNG patients or controls (all age- and sex-matched) (144+/- 81, 149+/- 114, 101+/- 27 and 86+/- 44 pg/ml, respectively; P=0.02).. sCXCL10 is associated with the active phase of GD in both newly diagnosed and relapsing hyperthyroid patients. The reduction in sCXCL10 in treated patients with GD may be related to the immunomodulatory effects of MMI.

Topics: Adult; Antibodies; Antithyroid Agents; Chemokine CXCL10; Chemokines, CXC; Cross-Sectional Studies; Female; Goiter, Nodular; Graves Disease; Humans; Interferon-gamma; Male; Methimazole; Middle Aged; Phenotype; Receptors, Thyrotropin; Thyroid Gland; Thyroiditis, Autoimmune; Thyrotropin; Treatment Outcome; Triiodothyronine

CD28 and CTLA-4 are glycoprotein molecules providing the potent costimulatory signal for T cells activation and proliferation via interactions with their ligands B7/BB1 molecule, present on the surface of Ag-presenting cells (APC). The present study was performed to elucidate the relationship between CTLA-4/CD28 molecules and stimulating (TSAb) or blocking (TBAb) antibodies to the TSH-receptor in Graves' disease. The aim of the study was to estimate the expression of CTLA-4 (cytolitic T lymphocyte associated antigen-4, CD152), CD28, B7.1 (CD80) and CD7.2 (CD86) molecules on peripheral blood cells in patients with Graves' disease (GD) (n=28, mean age 15.4), in patients with nontoxic nodular goiter (NTNG) (n=28, mean age 15.6 years) in comparison with sex- and age-matched healthy control subjects (n=28, mean age 15.9 years). The expression of the costimulatory molecules on mononuclear cells was analyzed by the three-color flow cytometry using a Coulter EPICS XL cytometer. Detection of stimulating and blocking antibodies to the TSH-receptor using JPO9 CHO cells in unfractionated serum was measured by a highly sensitive commercial radioimmunoassay. In untreated Graves' patients we observed a significant increase of CD152+ (p<0.004, p<0.004, p<0.001) and CD28+ (p<0.02, p<0.02, p<0.02) T lymphocytes in comparison to the non-toxic nodular goiter patients, healthy control subjects and euthyroid Graves' patients. After 2-6 months of methimazole therapy, the percentages of these cells in the peripheral blood of hyperthyroid patients returned to normal values. The analysis of CD3+ T lymphocytes co-expressing CD152 and CD28 antigens on peripheral blood revealed increased percentages of CTLA-4/CD28 positive cells in patients with Graves' disease (p<0.004, p<0.04) compared to the controls and euthyroid Graves' patients, while B7.1 (CD80) and B7.2 (CD86) molecules were detected only in some hyperthyroid patients on activated monocytes. In addition, 75% of children with untreated hyperthyroidism had positive TSAbs, whereas TBAbs were measured in 3 out of 7 TSAb negative patients with Graves' disease. In untreated Graves' patients a correlation between percentage of CD152+ T cells and serum level of stimulating and blocking antibodies to the TSH-receptor was found, while no such correlation was detected in relation to CD28+ T cells. We conclude that the changes of the expression of costimulatory molecules on peripheral blood mononuclear cells could be an important marker

Topics: Adolescent; Antigens, CD; Antigens, Differentiation; Antithyroid Agents; B7-1 Antigen; B7-2 Antigen; Case-Control Studies; CD28 Antigens; Child; Chromatography, High Pressure Liquid; CTLA-4 Antigen; Female; Flow Cytometry; Gene Expression; Goiter, Nodular; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Membrane Glycoproteins; Methimazole; Poland; Receptors, Thyrotropin; Regression Analysis; Statistics, Nonparametric; Time Factors

Topics: Airway Obstruction; Asthma; Diagnosis, Differential; Goiter, Nodular; Humans; Methimazole

It has been shown that human thyrocytes can synthesize cytokines which activate T and B lymphocytes. These immune cells play important roles in the initiation and continuation of thyroid autoimmunity. The aim of this study was to estimate serum concentrations of soluble interleukin-6 receptor (sIL-6R), interleukin-6 (IL-6) and interleukin-8 (IL-8) in patients with Graves' disease (GD) (n=44, mean age 14.8 years), in patients with nontoxic nodular goiter (NTNG) (n=36, mean age 15.6 years) and in a group of healthy controls (n=20, mean age 14.5 years). ELISA was used to determine the concentration of cytokines, antithyroglobulin and antithyroid peroxidase antibodies in patients with thyroid disease. Radio receptor assay (RRA) was performed to detect anti-TSH receptor autoantibodies (TRAb). Serum levels of IL-6, sIL-6R and IL-8 were markedly elevated in patients with GD before treatment with methimazole (p<0.0001 for IL-6, p<0.006 for sIL-6R, p<0.004 for IL-8) and after 8 weeks of therapy (p<0.011 for IL-6, p<0.04 for IL-8). However, following 24 months of treatment, normal serum concentrations of these cytokines were restored. Furthermore, patients with NTNG showed a slightly elevated concentration of cytokines (IL-6, IL-8). Serum levels of tri-iodothyronine in patients with GD positively correlated with serum concentrations of IL-6 (r = 0.35, p<0.025) and sIL-6R (r = 0.31, p<0.047), while no correlation was found between thyroxine and cytokines. Moreover, we observed a positive correlation between serum levels of TPO-Abs, TRAb and IL-6 (r = 0.43, p<0.008; r = 0.5, p<0.003) and between TPO-Abs and IL-8 (r = 0.67, p<0.0001). However, in patients with NTNG no correlation was observed between serum levels of antithyroid antibodies or thyroid hormones and serum levels of cytokines. We conclude that the cytokines (IL-6, sIL-6R, IL-8) could play an important role in the development of Graves' disease and that their levels are modulated by thyreostatic treatment.

Topics: Adolescent; Antithyroid Agents; Autoantibodies; Child; Female; Goiter, Nodular; Graves Disease; Humans; Interleukin-6; Interleukin-8; Male; Methimazole; Receptors, Interleukin-6; Thyroid Gland; Thyroid Hormones; Thyroxine

There is controversy over the factors that may influence the outcome of radioiodine therapy for benign thyroid diseases. Antithyroid medication has been claimed to negatively influence the effectiveness of radioiodine therapy in Graves' disease. In a longitudinal study, we assessed the influence of sex, age, antithyroid drugs, target radiation dose, target mass, applied activity, delivered dose, interval between last meal and application, and TSH, FT3 and FT4 levels on the outcome of radioiodine therapy. One hundred and forty-four patients (111 female, 33 male) suffering from Graves' disease (GD) and 563 patients (434 female, 129 male) with toxic nodular goitre (TNG) were entered in the study and followed up until 8 months after therapy. Treatment was defined as successful when the TSH level was found to be normal or elevated. Ninety-eight GD patients and 418 TNG patients were successfully treated. Forward stepwise multiple regression analysis models retained only the target mass in GD and the applied activity in TNG as significantly associated with the outcome of therapy. The predictive value of all variables involved was extremely low in both disease groups. Whereas concomitant antithyroid medication had no influence in GD, it adversely influenced radioiodine therapy of TNG. This effect may be attributed to a radioiodine "steal phenomenon" induced by TSH-stimulated normal thyroid tissue, which causes overestimation of the uptake in toxic nodules.

Topics: Aged; Antithyroid Agents; Carbimazole; Female; Goiter, Nodular; Graves Disease; Humans; Iodine Radioisotopes; Longitudinal Studies; Male; Methimazole; Middle Aged; Prospective Studies; Radiotherapy Dosage; Thyrotropin; Thyroxine; Treatment Outcome; Triiodothyronine

In hyperthyroid Graves' disease, short-term methimazole is sufficient to induce lasting remission in some patients, but even long-term treatment fails to do so in others. We have evaluated the role of autoimmune abnormalities in the helper T cell type 2 (TH2)-interleukin-13 (IL-13)-TSH receptor system in maintaining hyperthyroidism by comparing IgE levels in patients with various thyroid diseases. One hundred and ninety-three patients with hyperthyroid Graves' disease were treated with methimazole, and blood samples were obtained to measure serum levels of T4, T3, TSH, thyroglobulin, antimicrosomal antibody, TSH binding inhibitory Ig (TBII), thyroid-stimulating antibody, thyroid stimulation-blocking antibody, IgE, interferon-gamma, IL-4, and IL-13. Elevation of serum IgE (> or = 170 U/mL) was found in 35.5% of patients with hyperthyroid Graves' disease, and serum levels of T4, T:1, antimicrosomal antibody, and TBII were significantly greater in patients with IgE elevation than in those with normal serum IgE. During methimazole treatment, there was a parallel decrease in the serum T4 concentration in the presence or absence of an IgE elevation. However, there was a significantly smaller decrease in TBII in patients with elevated IgE than in those with normal IgE. As a result, the remission rate was significantly greater in patients with normal IgE than in those with IgE elevation. Serum levels of IL-13 were elevated in 64.7% of patients with IgE elevation in the absence of detectable TH1 marker, interferon-gamma. These findings suggest that in one third of patients with hyperthyroid Graves' disease, TH2 cells are stimulated and secrete excess amounts of IL-13, which subsequently stimulates B cells to synthesize more TSH receptor antibody and IgE, so that during methimazole treatment TBII decreases less in patients with IgE elevation, producing a lower remission rate.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Biomarkers; Female; Goiter; Goiter, Nodular; Graves Disease; Humans; Immunoglobulin E; Male; Methimazole; Middle Aged; Reference Values; Th2 Cells; Thyroiditis, Autoimmune; Thyroxine; Time Factors; Triiodothyronine

The objective of the study was to investigate the efficacy of long term thyrostatic versus radioiodine treatment of hyperthyroidism in old age. Our study is a retrospective analysis of the therapeutical outcome in 66 patients over 60 years of age with toxic nodular goitre. The patients were divided in two groups: Group A: 28 patients on methimazole treatment: starting dose 5-30, median (M) 10 mg, maintenance dose 2.5-15 (M = 5) mg, follow up 6 to 240 months (M = 23.5 months). Group B: 38 patients treated by either 100-300 MBq (N = 14, subgroup B1) or 325-1000 MBq (N = 24, subgroup B2) 131I, follow up: 18 to 156 months (M = 48 months). The efficacy of the different therapeutical approaches were compared by calculating the occurrence rate of persisting and relapsing thyroid dysfunctions and associated side effects. The 28 patients on methimazole treatment became euthyroid after 1-16 (M = 5) months but numerous relapses occurred in the follow up: hyperthyroidism, clinical: 5, subclinical 13, (relapse duration: M = 8 months; associated symptoms: hypertension in 4, cardiac arrhythmia in 3, cerebral embolism in 1, angina pectoris in 2, weight loss in 2 cases). Poor patient's compliance (9/28) or dose reduction by the physician (5/28) were the main causes of the relapses. Transient clinical (3 cases) or subclinical (6 cases) hypothyroidism also occurred (duration: 1-3 M = 2 months, no clinical symptoms). In 7 out of 14 (50%) patients receiving 100-300 MBq 131I (Group B1) hyperthyroidism persisted (versus 4/24 -16.7%- in Group B2 following 325-1000 MBq 131I; chi2(1) = 4.78 P = 0.028), methimazole treatment had to be continued in 9/14 patients (64.3%) (versus 5/24 -20.8%)- in Group B2., chi2(1) = 7.18 P = 0.0074) and in 5/14 (35.7%) the radiotherapy had to be repeated (versus 5/24 -020.8%- in Group B2, not sign.). Our conclusions are: 1) long term thyrostatic treatment is not safe in elderly patients with toxic nodular hyperthyroidism, mainly because of poor compliance or dose reduction by the physician; 2) radioiodine treatment as the first choice should be recommended for these patients and higher doses should be preferred.

Topics: Aged; Antithyroid Agents; Female; Goiter, Nodular; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Patient Compliance; Recurrence; Retrospective Studies; Treatment Outcome

Two cases are reported in which a rare hyperthyroidism appeared: in a female after radioiodine therapy for toxic multinodular goiter and in a male after spontaneous regression of a toxic adenoma. Both subjects showed a relapse of hyperthyroidism after a period of well-being lasting almost eight months in the first and three years in the second. Thyroid scans were consistent with an immunogenic hyper-thyroidism because there was a diffuse trapping of 131I in the thyroids while the previous autonomously functioning nodules became "cold". Serum TSH was undetectable, free thyroid hormones were increased, TgAb and TRAb were always normal in both patients, TPO became moderately positive only in the female. TRAb were evaluated only by radioimmunoassay. In these patients a diagnosis of Graves'-like disease was made because of the clinical and scintigraphic pattern. Moreover US did not reveal nodular areas different from those highlighted by scans. None of the subjects developed ophthalmopathy and/or dermopathy. Our remarks show that in particular subjects, genetically susceptible to autoimmunity, the release of antigenic materials secondary to destruction of thyroid nodules can trigger an autoimmune thyroid response resembling Graves' disease. Therefore all patients carrying autonomous nodules should be carefully evaluated for a possible autoimmune disposition before treatment and after admission. Radionuclide imaging is a simple, reliable, non invasive technique which can be applied in the evaluation of the etiology of the relapses.

Topics: Adenoma; Aged; Antithyroid Agents; Autoimmune Diseases; Female; Goiter, Nodular; Graves Disease; Humans; Male; Methimazole; Middle Aged; Radionuclide Imaging; Thyroid Neoplasms

131I treatment is an effective alternative to surgery in patients with a large, (non-)toxic, compressive goiter. Late development of hyperthyroidism after 131I therapy for nontoxic nodular goiter is considered rare. We have seen this complication in 3 of approximately 80 patients treated with radioiodine for volume reduction of a large, multinodular goiter. Three women, aged 60 to 71 years, had large, multinodular goiters causing tracheal compression. They were clinically euthyroid before 131I therapy and had normal free thyroxine (FT4) levels. Serum thyroid-stimulating hormone (TSH) levels were normal in 2 patients and undetectable in 1 patient. Patients 1 and 2 received a single dose of 86 and 48 mCi 131I, respectively. Patient 3 received 20 mCi 131I twice (interval 1 month). Clinical and biochemical thyrotoxicosis with high thyroid radioactive iodide uptake (RAIU) developed 10, 6, and 3 months after 131I therapy, respectively, although at control visits 1 to 3 months earlier, serum TSH and FT4 levels were normal. Thyrotoxicosis responded well to methimazole in all three patients. The late occurrence of thyrotoxicosis, high RAIU, and good response to methimazole argue against thyroiditis as the cause of thyrotoxicosis. Serum levels of TSH receptor antibodies, which were undetectable before therapy (patients 1 and 2), were clearly elevated in all three patients during thyrotoxicosis. This is in favor of autoimmune hyperthyroidism as the cause of thyrotoxicosis. These cases illustrate that severe autoimmune hyperthyroidism may occur several months after radioiodine treatment for nontoxic, multinodular goiter. Information about symptoms of hyperthyroidism and regular control visits in the first year after therapy are important in these patients.

Topics: Aged; Autoantibodies; Autoimmune Diseases; Female; Goiter, Nodular; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Middle Aged; Receptors, Thyrotropin; Thyrotropin; Thyroxine

Amiodarone-induced thyrotoxicosis (AIT) occurs both in abnormal thyroid glands (nodular goiter, latent Graves' disease) (type I AIT) or in apparently normal thyroid glands (type II AIT). Differentiation of the two forms is crucial, because type I AIT responds well to methimazole and potassium perchlorate combined treatment, whereas type II AIT is effectively managed by glucocorticoids. Differential diagnosis is often difficult, although thyroid radioactive iodine uptake is usually low-to-normal in type I and low-suppressed in type II, and serum interleukin-6 levels are normal/slightly elevated in type I, markedly elevated in type II. Color flow Doppler sonography (CFDS) is a technique that shows intrathyroidal blood flow and provides real-time information on thyroid morphology and hyperfunction. To investigate the usefulness of CFDS in differentiating the two types of AIT, 27 consecutive AIT patients, 11 type I and 16 type II, were evaluated by CFDS before starting antithyroid treatment. Gender, age, severity of thyrotoxicosis, and cumulative amiodarone dose were similar in the two groups. All type II AIT patients had a CFDS pattern 0 (ie, absent vascularity), in agreement with the pathogenesis of the disease, due to thyroid damage. Likewise, nine patients with subacute thyroiditis, another destructive process of the thyroid gland, also had a CFDS pattern 0. Eleven patients with type I AIT had a CFDS pattern ranging from pattern I (presence of parenchymal blood flow with patchy uneven distribution) (7 patients, 64%) to pattern II (ie, mild increase of color flow Doppler signal with patchy distribution) (1 patient, 9%) and pattern III (markedly increased color flow Doppler signal with diffuse homogeneous distribution)(3 patients, 27%), similar to that found in patients with untreated Graves' disease patients, thus indicating a hyper-functioning gland. Control subjects and euthyroid patients under long-term amiodarone treatment had absent thyroid hypervascularity and a CFDS pattern 0. These findings demonstrate that CFDS distinguishes type I and II AIT. Because of its rapidity and noninvasive features, CFDS represents a valuable tool for a quick differentiation between the two types of AIT. This can avoid any delay in initiating the appropriate treatment for a rapid control of thyrotoxicosis in patients whose tachyarrhythmias or other cardiac disorders make thyroid hormone excess extremely deleterious.

Topics: Adult; Aged; Amiodarone; Antithyroid Agents; Diagnosis, Differential; Female; Glucocorticoids; Goiter, Nodular; Graves Disease; Humans; Male; Methimazole; Middle Aged; Perchlorates; Potassium Compounds; Thyrotoxicosis; Ultrasonography, Doppler, Color

Topics: Antithyroid Agents; Arthritis; Female; Goiter, Nodular; Humans; Methimazole; Middle Aged; Propylthiouracil

Radioiodine therapy has become a cornerstone of treatment of hyperthyroidism. However, the timing of its administration varies between 1) the time of initial diagnosis with concurrent therapy with beta adrenergic blocking drugs or 2) following induction of euthyroidism with thioamide, Propylthiouracil or Methimazole. This study assessed 24-HR 131I uptake values and the thyroid scan in 24 subjects with hyperthyroidism at the time of diagnosis and again after attaining the euthyroid state with Propylthiouracil or Methimazole. Propylthiouracil of Methimazole was withdrawn seven days prior to the second 24-HR 131I uptake and scan. In all subjects, as a group, 24-HR 131I uptake increased following antithyroid therapy as compared to the time of initial of diagnosis [76 + 5% Vs. 54 + 4%; p < 0.01]. The thyroid gland size decreased in nine of twenty-four subjects, but remained unchanged in the remaining subjects. Since 24-HR 131I uptake and the gland size are the major factors influencing the therapeutic radioiodine dosage, it is possible that initial therapy with thioamide drugs may reduce the therapeutic dose of 131I in subjects with hyperthyroidism belonging to both groups, i.e., Graves' disease and Multinodular toxic goiter by inducing a rise in 24-HR 131I uptake. Furthermore, the shrinkage of thyroid glands may further decrease the radioiodine dosage in patients with Graves' disease.

Topics: Adult; Aged; Combined Modality Therapy; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Gland

Topics: Adenoma; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Neoplasms

A 78-year-old woman is presented with a multinodular toxic goiter and euthyroidism under continuous low-dose treatment with antithyroid drugs. A period of hyperthyroidism had been documented 3 years previously. In the preoperative management, prior to resection of a benign ovarian tumour, an intravenous urogram was performed. Perchlorate was given for thyroid protection. One day after surgery the clinical signs of thyroid storm were observed. Immediately, high-dose antithyroid drug therapy was started. Nevertheless, the patient died of acute cardiovascular failure 3 days later. This case report focuses on the risk of thyroid storm following iodine excess in the presence of relevant functional thyroid autonomy without adequate thyroid protection.

Topics: Aged; Cystadenoma; Fatal Outcome; Female; Goiter, Nodular; Humans; Hysterectomy; Iodine; Methimazole; Ovarian Neoplasms; Perchlorates; Postoperative Complications; Sodium Compounds; Thyroid Crisis; Thyroid Function Tests; Urography

The chance of permanent remission after prolonged drug therapy was investigated in 41 patients with toxic multinodular goiter. For purposes of comparison a group of 41 patients with Graves' disease was also studied. After euthyroidism was achieved all patients received a combination of thionamide and thyroxine for at least 12 months. The minimum follow-up period was 2 yr. Relapse of thyrotoxicosis occurred in 95.1% of patients with toxic multinodular goiter and 34.1% of patients with Graves' disease (p < 0.001). It is concluded that for patients with toxic multinodular goiter early radioiodine therapy or surgery is preferred since prolonged drug therapy seldom produces permanent remission.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Carbimazole; Drug Therapy, Combination; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Radionuclide Imaging; Recurrence; Thyroid Gland; Thyroxine

A high prevalence of antibodies to double-stranded DNA (AbDNAds) has been recently reported in serum of patients with autoimmune thyroid disorders, but the specificity of this finding has been questioned. For this reason, the prevalence of several antibodies to DNA-related nuclear antigens (AbDRENA) has been evaluated in sera of patients with autoimmune and non-autoimmune thyroid disease. The study group included: 46 Graves' disease patients, 28 Hashimoto's thyroiditis patients, 25 patients with toxic nodular goitre and 11 with non-toxic nodular goitre. Twenty-eight Graves' patients were retested during methimazole (MMI) therapy, and 5 after radioiodine administration. Twenty-two patients with systemic lupus erythematosus and 28 normal subjects served as positive and negative controls, respectively. AbDRENA included: AbDNAds by RIA or immunofluorescence (IF); antibodies to single-stranded DNA (AbDNAss) and antibodies to histone (AbHist) by ELISA methods; antibodies to nuclear antigens (ANA) by immunofluorescence. RIA values were considered to be abnormal when 2 SD above the mean of normal controls. In our study 13% of Graves' patients were positive for AbDNAds by RIA: all of them had negative tests by IF; 11% were positive for AbDNAss, 2% for AbHist and 7% for ANA. A comparable prevalence of positive results for AbDNAds by RIA, with negative IF tests, was found in Hashimoto's thyroiditis patients. No significant changes of antibody levels were observed in Graves' patients during MMI treatment or after radioiodine administration. A positivity for AbDNAds or AbDNAss was found in 8% of patients with toxic nodular goitre, but in none of those with non-toxic goitre.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Antibodies, Antinuclear; Child; Female; Goiter, Nodular; Graves Disease; Humans; Immunoassay; Iodine Radioisotopes; Lupus Erythematosus, Systemic; Male; Methimazole; Middle Aged; Thyroiditis, Autoimmune

We measured soluble interleukin 2 receptor, a part of the Tac protein (p55), in peripheral blood to study the immunological condition of the T cell in autoimmune thyroid disease. In 26 patients with untreated Graves' disease and 7 hyperthyroid patients with Hashimoto's thyroiditis, the mean levels of soluble IL-2 receptor were both significantly higher than in normal controls (1497 +/- 649 (mean +/- SD), 641 +/- 137 vs 221 +/- 63 10(3) U/l, p less than 0.001). There was good correlation between soluble IL-2 receptor levels and blood thyroxine levels (r = 0.684, p less than 0.001) in patients with untreated Graves' disease, but no correlation of soluble IL-2 receptor with TSH-inhibitory immunoglobulins, TS-ab, thyroidal autoantibodies to thyroglobulin and thyroidal microsomal antigen was found. We thought that the level of soluble IL-2 receptor is not dependent only on immunological conditions, but also on thyroid hormone status. When T3 was administered to subjects in remission from Graves' disease and in normal controls, the soluble IL-2 receptor levels significantly increased. Moreover, the mean level of soluble IL-2 receptor in patients with toxic multinodular goitre was also significantly higher than in normal controls (411 +/- 148 vs 221 +/- 63 10(3)U/l, p less than 0.05). We conclude that the soluble IL-2 receptor levels are higher in sera of subjects with elevated levels of thyroid hormone.

Topics: Adult; Aged; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Female; Goiter, Nodular; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Microsomes; Middle Aged; Propylthiouracil; Receptors, Interleukin-2; Thyroglobulin; Thyroiditis, Autoimmune; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Goiter, Nodular; Humans; Methimazole; Radionuclide Imaging; Thyroid Gland

Synthesis of "sex-hormone binding globulin" (SHBG) is influenced by thyroid hormones and its concentration in the serum of female subjects may be a marker of thyroid hormone effect at the peripheral tissue (liver) level. Compared to the levels found in euthyroid females (n = 46), the mean (+/- S.D.) serum SHBG concentration was found elevated in overt hyperthyroidism (Graves' disease: n = 56; 141.6 +/- 37.6 vs. 48.3 +/- 16.2; toxic nodular goiter: n = 16; 119.9 +/- 50.7 vs. 48.3 +/- 16.2 nmol/l; P less than 0.001). In contrast, it was decreased in manifest hypothyroidism (n = 25; 24.9 +/- 14.8 vs. 48.3 +/- 16.2; P less than 0.001). In the group of preclinical hyperthyroidism (n = 43), despite suppressed TSH secretion, the serum value of SHBG was normal (47.4 +/- 16.8), while its serum level approached the lower border of the normal range in subclinical hypothyroidism (n = 10; 33.6 +/- 6.1 vs 48.3 +/- 16.2 nmol/l; P less than 0.01). Data indicate that the pituitary responds more sensitively than the liver to a slight change of the serum thyroid hormone level. During thyroid hormone replacement for hypothyroidism, measurement of serum SHBG may provide help to assess the response of the target organ to the given therapy. In patients with generalized resistance to thyroid hormone, the serum SHBG level is within the normal range (51.3 +/- 9.8 nmol/l), thus, its determination supports the diagnosis of this disease.

Topics: Biomarkers; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Methimazole; Reference Values; Sex Hormone-Binding Globulin; Thyroidectomy; Thyrotropin; Thyroxine; Triiodothyronine

Despite sufficient iodine supply, goiter continues to be of considerable surgical significance in formerly endemic countries. It now appears that iodine deficiency and increased thyrotropin stimulation are not the only causes of goiter. Xenotransplantation of human thyroid tissue onto nude mice allowed study of the regulation of growth and function in human goiter tissue. Grafts of human thyroid tissue growing in nude mice could be shown to react to endogenous mouse thyrotropic stimulation and suppression. 131I autoradiographs of xenotransplanted goiter tissue showed as marked a heterogeneity as did the original goitrous tissue prior to transplantation. There was no firm correlation between the morphologic appearance of a follicle and its iodine metabolism. Scintigraphically "cold" and "hot" goiter tissue differed from each other quantitatively but not qualitatively; i.e., both "hot" and "cold" tissue were composed of metabolically active and nonactive follicles. Iodine organification was not completely suppressible by thyroxine treatment; this indicates autonomous functional activity. The distribution of proliferating tissue labeled by 3-H-thymidine did not parallel the distribution of functionally active tissue labelled by 131I. Thyroxine treatment did not completely inhibit 3-H-thymidine incorporation, indicating autonomous growth. Thus, our pathogenetic concept of goiter formation is based on three mainstays: (1) goiter heterogeneity, (2) autonomy of growth and function, and (3) dissociation of growth and function in human goiter tissue. Thus, the surgeon dealing with goiter ought to remove all pathologically altered tissue, i.e., nodular tissue, irrespective of its appearance on scintiscans.

Topics: Animals; Autoradiography; Goiter, Nodular; Humans; Iodine Radioisotopes; Methimazole; Mice; Mice, Inbred ICR; Mice, Nude; Thymidine; Thyrotropin; Thyroxine; Transplantation, Heterologous

Thyroid glands from six 8- to 10-week-old fetuses obtained at the time of legal abortion were cryopreserved in liquid nitrogen and transplanted into nude nu/nu mice. Histological and autoradiographic studies of the grafts labeled with [3H]thymidine and [125I]iodine showed proliferation and functional differentiation of the fetal thyroid tissue. Despite T4-mediated suppression of host TSH secretion, up to 36% of the follicular cell nuclei incorporated the thymidine label, reflecting autonomous proliferation, while iodine organification was almost entirely obliterated. Methimazole-induced TSH hypersecretion readily stimulated both growth and function of the transplanted tissue. Thus, during early development, the human thyroid largely depends on TSH for function, but not for growth. Similar findings were obtained in newborn mice, in whom 58% of the thyroid follicular cells proliferated autonomously, i.e. in the absence of TSH. The number of autonomously proliferating cells gradually declined with increasing age to about 1% in 60-day-old animals and, as reported previously, in xenotransplanted normal human thyroid tissue, whereas the number of autonomously proliferating cells was previously found to be several times higher in xenotransplanted human multinodular goiters. We, therefore, hypothesize that the rapidly and autonomously replicating cells that initiate nodule formation in human multinodular goiters reflect the persistence in the adult gland of cells with fetal growth potential.

Topics: Age Factors; Animals; Cell Differentiation; Goiter, Nodular; Humans; Methimazole; Mice; Mice, Nude; Thymidine; Thyroid Gland; Thyrotropin

One hundred and twenty-four patients with newly diagnosed hyperthyroidism received a combined thionamid-thyroxine medical therapy for approximately 2 years. According to the estimated goitre size before therapy and the type of goitre the patients were divided into 4 groups: Graves' disease no goitre (n = 19), Graves' disease small goitre (n = 57), Graves' disease medium or large goitre (n = 23), multinodular goitre (n = 25). The median follow-up period after cessation of medication was 64 (range 11-141) months. The remission rates in the different groups during follow-up were calculated using life table analysis. Graves' patients with no goitre or a small goitre had a significantly better outcome (remission % after 5 years 82.5 +/- 15.4 (SE) and 71.5 +/- 7.8, respectively) than Graves' patients with a medium size or large goitre (remission % after 5 years 37.0 +/- 11.1)(P less than 0.025). Most patients with multinodular goitre had a relapse within the first year after stop of medication (remission % after 5 years 15.5 +/- 10.1). Hence patients with Graves' disease having a small thyroid gland should be treated medically while surgery or radioiodine may be a more reasonable choice in Graves' patients with medium size or large goitres. Medically treated patients with toxic multinodular goitres have a very small chance of prolonged remission if medication is stopped.

Topics: Adult; Aged; Female; Follow-Up Studies; Goiter, Nodular; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prognosis; Thyroxine; Triiodothyronine

Topics: Cytochrome Reductases; Goiter, Nodular; Graves Disease; Humans; Iodide Peroxidase; Lactates; Lactic Acid; Lithium; Lithium Carbonate; Methimazole; NADH Dehydrogenase; Oxidation-Reduction; Preoperative Care; Pyruvates; Pyruvic Acid; Succinate Dehydrogenase; Thyroid Gland; Thyroidectomy

Topics: Adult; Aged; Autoimmune Diseases; Carbimazole; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Middle Aged; Thyroidectomy; Thyroxine

We have investigated the thyroid uptake of Tl-201 in 37 patients with various types of goiter, and in six with normal thyroids. Significant thallium uptake was found in all cases in which there was thyroid enlargement, including Graves' disease, toxic thyroid nodule, primary hypothyroidism, simple goiter, Hashimoto's disease, thyroid carcinoma, and thyroid adenoma. If goiter was absent, however, there was no demonstrable uptake--e.g., in secondary hypothyroidism, subacute thyroiditis, and the normal controls. Thallium uptake did not correlate with thyroid function tests such as BMR, T3-RU, T3, T4, TSH, antithyroid antibodies, or the 24-hr I-131 uptake. In 23 patients with diffuse goiter, on the other hand, maximum Tl-201 uptake correlated well with thyroid weight: r = 0.836 (p less than 0.001); y = 0.02 x + 0.06.

Topics: Adenoma; Antithyroid Agents; Contrast Media; Goiter; Goiter, Nodular; Graves Disease; Humans; Hypothyroidism; Iodipamide; Methimazole; Radioisotopes; Radionuclide Imaging; Syndrome; Thallium; Thyroid (USP); Thyroid Diseases; Thyroid Function Tests; Thyroid Neoplasms; Thyroiditis; Thyroiditis, Autoimmune; Thyrotropin

The effect of endogenous thyroid stimulating hormone (TSH) on the thyroid secretion of triiodothyronine (T3) and thyroxine (T4) was evaluated by serial determinations of serum T3. T4 and TSH concentrations in the following groups of patients: a) three patients submitted to surgical removal of a solitary, autonomous thyroid nodule which had completely inhibited the extranodular tissue; b) five subjects, with the same disease, in whom functional recovery of the extranodular tissue was induced by increased circulating TSH levels, produced by treatment with methimazole; c) one patient submitted to hemithyroidectomy for multinodular goitre; d) two hyperthyroid patients who had been treated with methimazole. In all these patients serum T3 and T4 levels progressively decreased, with a consequent progressive increase in serum TSH concentrations, leading to stimulation of the thyroid gland. During this TSH-induced stimulation of thyroid tissue, a significant positive correlation was found between the serum TSH concentrations and the corresponding ratio between the serum levels of T3 and T4 (T3/T4), both within each patient group (P less than 0.001) and among all patients (P less than 0.001). The same correlation also governs the relationship between the TSH and the T3/T4 values of 34 euthyroid control subjects and one patient with incipient hypothyroidism. These data strongly suggest that endogenous TSH can induce a preferential secretion of T3 over T4 by the human thyroid.

Topics: Goiter; Goiter, Nodular; Humans; Hyperthyroidism; Methimazole; Thyroid Gland; Thyroidectomy; Thyrotropin; Thyroxine; Triiodothyronine

Lithium acetate treatment of 6 patients with hyperthyroid Graves' disease and 6 patients with toxic nodular goiter is reported. Lithium acetate was administered either as monotherapy (group A) or combined with 45 mg carbimazole or methimazole (group B). A control group of 8 patients received methimazole or carbimazole only (group C). Lithium either alone or combined with thionamide drugs consistently lowered serum thyroxine and triiodothyronine with marked clinical improvement. After 7 days of treatment thyroxine was reduced by 28% (group A), 43% (group B) and 36% (group C). The respective decrease in triiodothyronine was 42%, 50% and 46%. The differences between three groups were not statistically significant. We conclude that lithium is a useful antithyroid agent for selected patients, since it is safe and effective even in severe cases, does not interfere with radioiodine uptake for diagnostic or therapeutic purposes and provides an alternative for patients allergic to thionamides.

Topics: Acetates; Adult; Aged; Carbimazole; Drug Evaluation; Drug Therapy, Combination; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Lithium; Methimazole; Middle Aged

Topics: Adult; Chromatography, Paper; Depression, Chemical; Diiodotyrosine; Female; Goiter, Nodular; Graves Disease; Humans; Iodine; Iodine Isotopes; Male; Metabolic Clearance Rate; Methimazole; Middle Aged; Potassium Iodide; Propylthiouracil; Thyroid Function Tests; Thyroid Gland

Topics: Eye Manifestations; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodides; Iodine Isotopes; Male; Methimazole; Neurotic Disorders; Pregnancy; Pregnancy Complications; Propylthiouracil; Psychotic Disorders; Skin Manifestations; Thyroidectomy; Triiodothyronine

Topics: Adolescent; Adult; Aged; Blood Glucose; Depression, Chemical; Diazepam; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Goiter; Goiter, Nodular; Half-Life; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Thyroid Function Tests; Thyroid Gland; Time Factors

Topics: Adult; Antithyroid Agents; Female; Goiter; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Imidazoles; Male; Methimazole; Middle Aged; Thyroid Function Tests

Topics: Antineoplastic Agents, Hormonal; Antithyroid Agents; Goiter; Goiter, Nodular; Hyperthyroidism; Methimazole; Thyrotoxicosis