methimazole and Cardiomyopathies

The study examined the myocardial ultrastructural alterations in rats maintained on various atherogenic diets. It revealed the complex ultrastructural alterations of cardiomyocytes and endotheliocytes (including the lytic and destructive changes of the intracellular organelles, upregulation of the autophagocytosis in the cardiomyocytes, and necrobiosis with apoptosis of endotheliocytes) reflecting the cytopathic features of circulating cholesterol and lipoproteins, whose elevation determined the intensity of destructive processes. The revealed peculiarities in the changes of lipid inclusions (their osmiophilic transformation) in cardiomyocytes can be provoked by entry of cholesterol into the cells and its further metabolic modifications. During moderate dyslipidemia, the cardiomyocytes demonstrated the ultrastructural signs of induction of intracellular regeneration (marked with the clusters of polysomes in the intermyofibrillar and subsarcolemmal spaces with appearance of neogenic myofilaments) and upregulated pinocytotic activity. In all cases, up-regulated autophagocytosis in cardiomyocytes was accompanied by accumulation of myelin- and vacuole-like structures in the intercellular spaces and capillary lumens paralleled with appearance of activated forms of macrophages and fibroblasts in the myocardium.

Topics: Animals; Antithyroid Agents; Cardiomyopathies; Cholesterol; Cytoplasm; Diet, Atherogenic; Diet, High-Fat; Dyslipidemias; Endothelial Cells; Methimazole; Myocytes, Cardiac; Myofibrils; Polyribosomes; Rats; Rats, Wistar; Sarcolemma

Thyrotoxicosis and diabetic ketoacidosis (DKA) both may present as endocrine emergencies and may have devastating consequences if not diagnosed and managed promptly and effectively. The combination of diabetes mellitus (DM) with thyrotoxicosis is well known, and one condition usually precedes the other. Furthermore, thyrotoxicosis is complicated by some degree of cardiomyopathy in at least 5% de patients; but the coexistence of DKA, thyroxin (T₄) toxicosis, and acute cardiomyopathy is extremely rare. We describe a case of a man, previously diagnosed with DM but with no past history of thyroid disease, who presented with shock and severe DKA that did not improve despite optimal therapy. The patient evolved with acute pulmonary edema, elevated troponin levels, severe left ventricular systolic dysfunction, and clinical and laboratory evidence of thyroxin (T₄) toxicosis and thyrotoxic cardiomyopathy. Subsequently, the patient evolved favorably with general support and appropriate therapy for DKA and thyrotoxicosis (hydrocortisone, methimazole, Lugol's solution) and was discharged a few days later.

Topics: Adult; Cardiomyopathies; Diabetic Ketoacidosis; Diagnosis, Differential; Echocardiography; Heart Failure, Systolic; Humans; Hydrocortisone; Iodides; Male; Methimazole; Pulmonary Edema; Radiography; Thyrotoxicosis; Treatment Outcome; Troponin

Topics: Amiodarone; Anti-Arrhythmia Agents; Antithyroid Agents; Cardiomyopathies; Cardiopulmonary Resuscitation; Catecholamines; Defibrillators, Implantable; Echocardiography; Electrocardiography; Female; Humans; Hyperthyroidism; Hypokinesia; Methimazole; Middle Aged; Multiple Organ Failure; Perchlorates; Sodium Compounds; Thyroidectomy; Thyrotropin; Ventricular Fibrillation

Jaundice related to thyrotoxicosis and not as an effect of antithyroid drugs is a rare complication that usually occurs in the presence of heart failure (HF) or hepatitis. We report a case of a 54-year-old white woman with hyperthyroidism caused by Graves's disease and jaundice despite methimazole suspension. Bilirubin fluctuated at high values, between 30.0 and 52.3 mg/dL, transaminases were slightly increased, on admission ALT = 46 U/L and AST = 87 U/L; coagulation indices and serum proteins were on the lower limit of the normal range with PT 68% and albumin = 2.5 g/dL. Serology for hepatitis was negative. After the first radioiodine therapy (RT), bilirubin reached its maximum, which coincided with the worst period of HF exacerbation. Bilirubin normalized 4 weeks after the second RT, with the stabilization of HF and normalization of thyroid hormones. We discuss the possible etiologies of severe jaundice in hyperthyroid patients, as well as the difficult anticoagulant therapy with warfarin.

Topics: Antithyroid Agents; Cardiomyopathies; Female; Heart Atria; Humans; Jaundice; Methimazole; Middle Aged; Severity of Illness Index; Thrombosis; Thyrotoxicosis

The major limiting factor in long-term administration of doxorubicin is the development of cumulative dose-dependent cardiomyopathy and congestive heart failure that limit the use of this drug. The present study was undertaken to find out the chemo protective role of methimazole against doxorubicin-induced cardiotoxicity in experimental animals. In the present study, doxorubicin treatment in a dose of 3mg/kg, i.p., every other day for six doses showed a significant 2.6-, 3- and 10.5-fold increase in the cardiac enzyme activities CK-MB and LDH and troponin-I, respectively, in the serum of the animals. Histopathological investigation of heart tissues showed swollen muscle fibers with interstitial edema and inflammatory exudate. Pretreatment of the animals with methimazole at a dose level of 40 mg/kg, i.p., 30 min before doxorubicin, returned the cardiac enzyme levels to nearly normal value with partial reversal of the inflammatory lesions and the swollen muscle fibers induced by doxorubicin. Moreover, methimazole pretreatment, decreased the doxorubicin level in the heart tissues with a significant increase in plasma level and non significant effect on doxorubicin level in tumor cells. At the same time, methimazole pretreatment did not significantly interfere with the antitumor activity of doxorubicin.

Topics: Animals; Animals, Outbred Strains; Antibiotics, Antineoplastic; Antithyroid Agents; Carcinoma, Ehrlich Tumor; Cardiomyopathies; Creatine Kinase, MB Form; Doxorubicin; Drug Screening Assays, Antitumor; Drug Therapy, Combination; Female; Heart; L-Lactate Dehydrogenase; Methimazole; Mice; Myocardium; Neoplasm Transplantation; Thyroid Hormones; Troponin I