methimazole and Liver-Cirrhosis

A 58-year-old woman was admitted because of jaundice, ascites and marked oedema. For three years she had suffered from nervousness, decreasing fitness and weight loss, which had been assumed as due to chronic alcoholism. Liver biopsy revealed extensive fibrosis, in part with early cirrhotic transformation. This was followed by cardiac failure with atrial fibrillation (ventricular rate 140/min) and marked pleural effusions. The thyroid was diffusely enlarged and there were signs of exophthalmos.. Bilirubin concentration was 3 mg/dl, lactate dehydrogenase activity was 310 U/l, cholesterase 1.3 kU/l and the prothrombin test was 21%. The TSH level was 0.01 microU/ml while the free thyroxine level was 4.7 ng/dl and that of free triiodothyronine 13.5 pg/ml. Chest radiograph revealed cardiomegaly, bilateral peripheral pulmonary congestion and pleural effusions to midfield. Right heart catheterization excluded pulmonary hypertension; cardiac output was 10l/min. The thyroid was enlarged on ultrasound and diffusely echopoor, as in immune thyroid disease.. Cardiac failure regressed and thyroid function normalized within ten days on propranolol, 4 x 40 mg and thiamazole 3 x 40 mg daily intravenously. Subtotal thyroidectomy was performed three weeks later with subsequent thyroid hormone substitution. Liver functions were normal six months later and ultrasound showed no signs of cirrhotic change and the ascites had resolved.. Hyperthyroidism is frequently associated with changes in liver functions. In extreme cases, high-output cardiac failure may occur, with liver congestion and clinical as well as histological changes like those in liver cirrhosis.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Antithyroid Agents; Arrhythmias, Cardiac; Autoimmune Diseases; Female; Heart Failure; Humans; Hyperthyroidism; Liver Cirrhosis; Methimazole; Middle Aged; Propranolol; Thyroid Hormones; Thyroidectomy; Ultrasonography

The thyreostatic therapy of a hyperthyroidism in coincident chronic hepatopathy is problematic. On the one hand, this therapy may be an additional load, particularly by the development of a cholestasis for the ill liver. On the other hand, due to the hyperthyroidism disturbance of the liver function and liver diseases up to cholestatic hepatitis may develop. At the instance of two patients with liver cirrhosis, whose simultaneous hyperthyroidism was treated thyreostatically, the therapeutic problems are represented. On the basis of the treatment of a not small number of patients with this constellation of findings we recommend the use of Thiamazol as therapy of choice in the at present, usual lower initial dosage. If functional disturbances of the liver and other side effects appear under this therapy, the radio-iodine therapy offers itself as alternative.

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Liver Cirrhosis; Male; Methimazole; Middle Aged

A RIA for the antithyroid drug methimazole [1-methyl-2-mercaptoimidazole (MMI)] has been developed. A MMI derivative, 5-COOH-MMI, was conjugated to porcine thyroglobulin, and antibodies to the conjugate were raised in rabbits. [35S]MMI was used as the tracer. At a final antibody dilution of 1:100, the assay could detect MMI in amounts as low as 2.5 ng. The putative MMI metabolites 3-methyl-2-thiohydantoin and 1-methylimidazole had minor cross-reactivities of 2.1% and 0.5%, respectively. There was no effect of serum proteins on MMI immunoactivity. MMI was given orally to normal subjects (n = 6), hyperthyroid patients (n = 5), patients with hepatic cirrhosis (n = 4), and normal lactating women (n = 4). After a single dose of 60 mg, peak MMI levels were similar in the normal subjects and the hyperthyroid patients (approximately 1.5 micrograms/ml). Patients with hepatic cirrhosis had similar peak MMI serum levels [1.31 +/- 0.3 (+/- SEM) micrograms/ml], but the half-time of MMI disappearance from serum was significantly prolonged compared with the normal value (21.2 vs. 6.0 h; P less than 0.001). The lactating women received 40 mg MMI as a single dose. Over the next 8 h, mean MMI levels in serum and milk were nearly identical, with a mean serum to milk ratio of 1.03 +/- 0.16. A total of 70.0 +/- 6.0 micrograms MMI was excreted in the milk over the 8-h time period. This amount of MMI could affect neonatal thyroid function.

Topics: Adolescent; Adult; Female; Graves Disease; Humans; Kinetics; Lactation; Liver Cirrhosis; Male; Methimazole; Middle Aged; Milk, Human; Pregnancy; Radioimmunoassay