propylthiouracil and Goiter--Nodular

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Diagnosis, Differential; Goiter, Nodular; Graves Disease; Humans; Prognosis; Propranolol; Propylthiouracil; Thyrotoxicosis; Triiodothyronine

Graves' hyperthyroidism and multinodular toxic goiter lead to high serum T(3) compared with serum T(4). The source of this high T(3) has not been clarified.. Our objective was to assess the role of iodothyronine deiodinase type 1 (D1) and type 2 (D2) for T(3) production and to estimate the sources of T(3) in hyperthyroidism.. The study was a prospective, randomized, open-labeled study in a secondary care setting.. Consecutive patients with hyperthyroidism caused by Graves' disease or by multinodular toxic goiter were randomized to be treated with high-dose propylthiouracil (PTU) to block D1, PTU plus KI, or PTU plus sodium ipodate to additionally block D2. T(3) and T(4) were measured in serum, and we estimated the sources of T(3).. PTU reduced the T(3)/T(4) in serum to 47.7 +/- 2.5% (mean +/- sem) of the initial value on d 4 of therapy in patients with Graves' disease. The addition of KI to PTU led to a greater fall in T(3) and T(4), but the balance was unaltered. After PTU plus ipodate, T(3)/T(4) on d 4 was lower, 34.1 +/- 1.2% of the initial value. Similar variations were observed in patients with multinodular toxic goiter. Thus, the major source of the excess T(3) was D1-catalyzed T(4) deiodination, with a minor role for D2. It was estimated that the majority of this D1-catalyzed T(3) production takes place in the hyperactive thyroid gland.. Although thyroidal T(3) contributes only around 20% of total T(3) production in normal individuals, this is much higher in patients with a hyperactive thyroid, ranging up to two thirds. The major part is produced from T(4) deiodinated in the thyroid.

Topics: Adolescent; Adult; Antithyroid Agents; Child; Drug Therapy, Combination; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodide Peroxidase; Iodothyronine Deiodinase Type II; Ipodate; Male; Middle Aged; Propylthiouracil; Prospective Studies; Thyroxine; Treatment Outcome; Triiodothyronine

Contrary to the usual inhibitory role of tumor necrosis factor-alpha (TNF-alpha) in thyroid metabolism, it also has specific stimulatory effects in autoimmune thyroid disorders, including induction of HLA class II antigen-presenting cell-T cell interaction. Despite high intrathyroidal concentrations, various studies were not able to demonstrate high serum levels of TNF-alpha in patients with Graves' disease. To investigate this discrepancy we determined TNF-alpha and interleukin 6 (IL-6) levels in 25 hyperthyroid patients who responded to propylthiouracil treatment (16 with Graves' disease and nine with toxic multinodular goiter) and compared them with the levels found in euthyroid patients with simple diffuse goiter (n = 15) and normal healthy controls (n = 15). Median IL-6 levels were high in both Graves' disease and toxic multinodular goiter patients before propylthiouracil treatment (23 and 26.5 pg/ml, respectively). After restoring euthyroidism there was a statistically significant decline to near-normal levels (3 and 10 pg/ml, respectively). On the other hand, median serum TNF-alpha levels were high only in Graves' disease patients (20 pg/ml) and could not be normalized with antithyroid medication (20 pg/ml) compared to that of controls (5 pg/ml). Tumor necrosis factor-alpha, but not IL-6, was found to be high in the sera of Graves' disease patients when euthyroid, which may be due to an ongoing antigen-antibody interaction, a feature of autoimmune attack. It remains to be determined whether the degree of TNF-alpha and/or IL-6 elevation will be a predictor of disease recurrence.

Topics: Adult; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Interleukin-6; Male; Middle Aged; Propylthiouracil; Thyrotoxicosis; Thyroxine; Triiodothyronine; Tumor Necrosis Factor-alpha

The association of adverse health with high fat intake has long been recognized. However, the lack of research focusing on the interrelationship of thyroid and liver function, and the pathogenesis of a high fat diet leaves these topics poorly understood. The objective of this study was to evaluate and compare the physiological changes in euthyroid and thyroid altered animal model fed saturated and unsaturated high fat diets. To achieve this objective adult male Sprague Dawley rats (n = 100) were fed one of five diets; a control or one of four test diets containing 25% saturated or unsaturated, and 37% saturated or unsaturated fats for a period of eight weeks. Each experimental group consisted of ten euthyroid and ten thyroid altered animals. An altered thyroid state was chemically induced with the addition of 0.05% propylthiouracil (PTU) in the drinking water. Euthyroid animals fed high fat diets increased in body weights and body lengths, compared to thyroid altered animals (P < 0.05). Alanine aminotransferase (ALT) and asparte aminotransferase (AST) levels increased across all experimental groups. HbA1C values and urinary glucose values were within normal range for all animals. Liver morphology showed increased hepatic stellate (ito) and vacuole cells in thyroid altered animals. These findings suggest that altered thyroid status negatively impacts growth and weight gain, and simultaneously affected lipid metabolism, resulting in abnormal liver morphology.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Diet, High-Fat; Glycated Hemoglobin; Goiter, Nodular; Lipid Metabolism; Liver; Male; Propylthiouracil; Rats; Rats, Sprague-Dawley; Thyroid Gland

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

Topics: Female; Goiter, Nodular; Humans; Lupus Nephritis; Middle Aged; Prednisone; Propylthiouracil

This paper describes a patient treated for 12 months with propylthiouracil for multinodular toxic goiter who developed vasculitis. The clinical picture consisted of nasal septal necrosis, pulmonary infiltrations and skin rash. Patient's serum were positive for anti neutrophil cytoplasmatic antibodies (c-ANCA). Histopathological examination revealed the presence of small vessel vasculitis without granuloma formation. This condition resulted in patient's critical state with respiratory failure and severe cardiovascular complications. The article also contains a brief review of available literature concerning this very rare complication. Conclusion. Propylthiouracil, a widely-used medicine, can cause severe life-threatening complication. It is associated with propylthiouracil-induced immunological disturbances.

Topics: Anti-Inflammatory Agents; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Goiter, Nodular; Humans; Methylprednisolone; Middle Aged; Prednisone; Propylthiouracil; Severity of Illness Index; Vasculitis

Low serum paraoxonase (PON) activity is thought to be a risk factor for the development of atherosclerosis. The present study was designed to evaluate PON1 activity and its relationship with preatherosclerotic markers such as lipid peroxidation and insulin resistance in hyperthyroid patients before and after propylthiouracil (PTU) treatment and in subjects with iatrogenic subclinical hyperthyroidism.. Twenty patients with hyperthyroidism, 20 patients with euthyroid multinodular goiter (MNG) and 20 age- and sex-matched healthy controls were enrolled in the study. Insulin sensitivity index, PON activity and lipid peroxidation were measured at baseline and 2 months after achieving euthyroidism or subclinical hyperthyroidism. Levothyroxine was given as a part of TSH suppression therapy in multinodular goitre patients.. Insulin sensitivity was determined by an oral glucose tolerance test (OGTT) based on the insulin sensitivity index (ISI) formula, serum paraoxonase activity was determined with a spectrophotometric method. Lipid peroxidation was measured by the formation of thiobarbituric acid reactive substances (TBARs).. ISI was significantly lower in the hyperthyroid group than baseline levels in MNG patients and controls (P < 0.001). While ISI increased after treatment in the hyperthyroid group (P < 0.01), it significantly decreased with L-T4 treatment in the MNG group (P < 0.01). Serum paraoxonase activity was significantly lower in the hyperthyroid group before treatment than baseline and final measurements of other groups (P < 0.05). While PON activity increased after restoration of the euthyroid state in the hyperthyroid group (P < 0.05), it decreased with L-T4 treatment in the MNG group (P < 0.05). Lipid peroxidation was significantly higher in hyperthyroid group compared to baseline levels of other groups (P < 0.05). It decreased after treatment in the hyperthyroid group (P < 0.05) but a significant increase was observed following L-T4 treatment in the MNG group (P < 0.05). Serum paraoxonase activity was found to be negatively correlated with serum TT4 (r = -0.32, P = 0.003), TT3 levels (r = -0.31, P = 0.004), TBARs levels (r = 0.32, P = 0.003) and positively correlated with ISI (r = 0.35, P = 0.001) and high-density lipoprotein (HDL) cholesterol levels (r = 0.35, P = 0.0011) in the hyperthyroid and MNG groups.. Iatrogenic thyroid hormone excess seems to mimic the effects of endogenous thyroid hormone excess on paraoxonase activity, insulin sensitivity and oxidative stress. These findings suggest that TSH suppression with levothyroxine may increase oxidative stress and LDL oxidation and thereby promote atherogenesis.

Topics: Adult; Analysis of Variance; Antithyroid Agents; Arteriosclerosis; Aryldialkylphosphatase; Case-Control Studies; Female; Goiter, Nodular; Humans; Hyperthyroidism; Insulin Resistance; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Propylthiouracil; Thyroid Function Tests

Erythrocyte, serum and plasma antioxidant activities and the effects of propylthiouracil (PTU) treatment on these activities were studied in patients with toxic multinodular goiter. The activities of the erythrocyte antioxidant enzymes (glucose-6-phosphate dehydrogenase, catalase, Cu/Zn-superoxide dismutase, selenium (Se)-dependent glutathione peroxidase and glutathione reductase) and the levels of erythrocyte Se, serum ceruloplasmin and plasma malondialdehyde were significantly higher while serum vitamin E, plasma vitamin C and plasma Se were lower in hyperthyroid patients. PTU treatment, not for 1 but for 3 months caused a partial reversal of antioxidant activities to euthyroid levels. It is suggested that alterations in blood antioxidant activities following PTU treatment might be due to the antioxidant and/or antithyroid effect of this drug.

Topics: Adult; Aged; Antioxidants; Antithyroid Agents; Ceruloplasmin; Female; Goiter, Nodular; Humans; Lipid Peroxidation; Male; Middle Aged; Propylthiouracil; Time Factors

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

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

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

1. The effect of the standard 15 mCi dose of 131I on the thyroid function of 25 patients from an endemic goiter region with toxic multinodular goiter of different sizes was determined. 2. The patients were followed for 1 to 5 years and 7 months (mean: 2 years and 10 months). Eighteen patients were treated with the antithyroid drugs propylthiouracil or methimazole before 131I and seven only received 131I. 3. All but three patients achieved euthyroidism after a single dose of 131I. Two patients in the antithyroid treatment group became hypothyroid 2 months and 2 years after the isotope therapy, respectively. Pretreatment with antithyroid drugs did not significantly modify the effectiveness of 131I treatment. 4. This simplified dose regimen of 131I was effective in the treatment of hyperthyroidism caused by multinodular goiter in an endemic region, and the efficacy was independent of the size of the goiter.

Topics: Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Radiation; Female; Goiter, Nodular; Humans; Iodine Radioisotopes; Male; Middle Aged; Propylthiouracil; Radiotherapy Dosage; Thyroid Gland; Thyrotoxicosis

The clinical management of the hyperthyroid patient is controversial, because there is no perfect treatment. Factors that influence the choice of therapy include the patient's age, sex, and type of hyperthyroidism, as well as patient and physician preference.

Topics: Adenoma; Adolescent; Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Child; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Male; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Neoplasms; Thyroxine; Triiodothyronine

Iodine-induced hyperthyroidism has been frequently described when iodine is introduced into an iodine-deficient area. However, it may also occur in patients with and without previous thyroid disease residing in iodine-sufficient areas. Five patients with iodine-induced hyperthyroidism seen in a 12-month period are described. All were exposed to iodine in the form of commonly used drugs (Betadine, Iodo-Niacin, amiodarone, and radiographic contrast dyes). The cause of iodine-induced hyperthyroidism is unclear, but it is probably more common in patients with goiters containing previously existing areas of autonomous function or iodine-poor thyroglobulin. Iodine-induced hyperthyroidism usually abates after iodine withdrawal in patients with multinodular goiters or normal thyroid glands. The hyperthyroidism is usually treated with beta-blockers and antithyroid thionamide drugs, although reinstitution of iodine to block thyroid hormone release or corticosteroids occasionally may be necessary. Iodine-containing drugs should be given with caution to patients with underlying thyroid disease.

Topics: Adult; Amiodarone; Chlorobutanol; Coloring Agents; Coronary Artery Bypass; Drug Combinations; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Male; Middle Aged; Niacinamide; Postoperative Complications; Povidone-Iodine; Propylthiouracil; Radiographic Image Enhancement; Sodium Iodide; Thyroid Hormones

The sonographic diagnosis of a fetal goiter, confirmed at delivery, is described in a fetus exposed to large doses of propylthiouracil, which was administered to the mother. The pregnancy was also complicated by recalcitrant premature labor secondary to polyhydramnios. The intraamniotic instillation of thyroxine decreased the size of the fetal goiter, and numerous therapeutic amniocenteses permitted continuation of the pregnancy, so a mature infant with a goiter but no airway obstruction was delivered. Amniotic fluid reverse-T3 assays confirmed fetal utilization of the thyroxine. Fetal thyroid physiology is discussed briefly along with the benefits of the antenatal sonographic diagnosis of fetal goiter.

Topics: Adult; Female; Fetal Diseases; Goiter; Goiter, Nodular; Humans; Lung; Maternal-Fetal Exchange; Polyhydramnios; Pregnancy; Propylthiouracil; Thyroxine

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