methimazole and Cardiomegaly

We report a 49-year-old man with primary hyperthyroidism who presented with pancytopenia. The patient presented with leg edema, sinus tachycardia, cardiomegaly, and pleural effusions, all from congestive heart failure. Laboratory data showed pancytopenia and primary hyperthyroidism; echocardiogram showed diffuse hyperkinesis of the left ventricular wall and right ventricular overloading. The bone marrow was moderately hypercellular and compatible with arrested hematopoiesis. Pancytopenia and heart failure improved after administration of methimazole and diuretics. However, high levels of thyroid hormone recurred with pancytopenia 4 months after admission. Therefore, subtotal thyroidectomy was performed, and the levels of thyroid hormones and peripheral blood cell counts have remained normal. Pancytopenia may be caused by hyperthyroidism.

Topics: Antithyroid Agents; Blood Cell Count; Bone Marrow; Cardiomegaly; Diuretics; Edema; Heart Failure; Humans; Leg; Male; Methimazole; Middle Aged; Pancytopenia; Pleural Effusion; Recurrence; Tachycardia, Sinus; Thyroidectomy; Thyrotoxicosis

The effects of methimazole, an antithyroid drug, on blood pressure and other parameters were evaluated in the established phase of Goldblatt two-kidney one clip (G2K-1C) hypertension. Methimazole was administered via drinking water for five weeks, starting five weeks after hypertension had been induced. After this period of treatment, similarly high blood pressures were observed in methimazole-treated and non-treated G2K-1 C rats, despite the fact that a hypothyroid state had been achieved in methimazole-treated rats. Methimazole-treated G2K-1 C rats showed reductions in heart rate, ventricular weight, ventricular/body weight ratio and mortality in comparison with rats not treated with methimazole. These results clearly demonstrate that hypothyroidism induced by methimazole: a) does not reverse G2K-1 C hypertension, but b) improves the rate of survival and c) reduces relative cardiac hypertrophy, possibly by the reduction in cardiac work observed in Goldblatt hypothyroid rats.

Topics: Animals; Blood Pressure; Body Weight; Cardiomegaly; Hypertension; Kidney; Male; Methimazole; Rats; Rats, Inbred Strains; Renin

Previous studies have suggested that thyroid hormones influence the number of membrane-bound cardiac adrenoceptors, but their effect on the intracellular distribution of adrenoceptors has not been examined. A plasma cell membrane and a vesicular fraction devoid of membrane markers were prepared from hearts of euthyroid and hyperthyroid rats and were used to compare beta- and alpha-adrenoceptors. During daily injection of l-thyroxine, cardiac hypertrophy developed within 4 days and remained unchanged thereafter. The number of membrane-bound beta-receptors increased progressively and plateaued within 2 weeks of thyroxine administration. Vesicular beta-receptors, on the other hand, increased more gradually and to a lesser extent so that after 2 weeks of l-thyroxine injection, they constituted a smaller proportion of the total beta-receptor population compared to normal rats. In contrast, the number of cardiac alpha 1-adrenoceptors declined rapidly to about 80% of that in euthyroid animals and did not change further for the duration of the study. Membrane-bound and vesicular alpha 1-adrenoceptors were affected to the same extent in hyperthyroidism. During regression of cardiac hypertrophy following cessation of thyroxine administration, alpha 1-adrenoceptors rose rapidly (within 2 days) to normal values while beta-receptors declined more gradually to normal levels within 2 weeks. In hypothyroid rats, there was a significant decline in the density of both alpha 1- and beta-adrenoceptors, with a shift away from the vesicular fraction. These results indicate that both the total numbers of cardiac adrenoceptors and their distribution between the plasma membrane and vesicular fraction are influenced by the thyroid status.

Topics: Animals; Cardiomegaly; Cell Membrane; Dihydroalprenolol; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Methimazole; Myocardium; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Thyroid Hormones; Thyroxine

Effects of streptozotocin-induced diabetes (8 weeks) on the performance of perfused hearts from spontaneously hypertensive (SH) rats were compared with effects on normotensive Wistar-Kyoto (WK) and Sprague-Dawley (SD) rat hearts. Diabetes markedly decreased systolic arterial pressure (SAP) of SH rats in vivo but did not affect SAP of either of the normotensive strains. Diabetes also reduced heart size of SH and normotensive rats and reversed absolute left ventricular hypertrophy (wall-to-lumen ratios and left-to-right ventricular weight ratios) of SH rats. Heart perfusion at the end of the 8-week period revealed that diabetes (i) reduced hydraulic work at high pressure loads and efficiency of contraction (work/mu LO2 consumed) of SH rat hearts but not of WK or SD hearts, and (ii) depressed left ventricular pulse pressure development (LVPP) and contractility (LV + dP/dt) of SH hearts more extensively than it reduced these variables in either of the normotensive control groups. Effects of diabetes which were similar in hypertensive and normotensive hearts were reductions in stroke work at high volume loads and depressions in LV-dP/dt. Attendant hypothyroidism probably contributed to the reductions in SAP, heart size, LVPP, LV+ and -dP/dt, and stroke work but not to the decreased efficiency or reversal of hypertrophy of SH rat hearts. Malnutrition of SH rats, like hypothyroidism, also decreased heart size without reversing hypertrophy but had no effect on SAP and only reduced LV-dP/dt. The results show that diabetes reversed hypertrophy and selectively reduced contraction efficiency, contractility, and LVPP of SH hearts, but otherwise the effects of diabetes in hypertensive and normotensive rat strains were similar to each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cardiomegaly; Coronary Circulation; Diabetes Mellitus, Experimental; Food Deprivation; Heart; Hypertension; Male; Methimazole; Myocardial Contraction; Oxygen Consumption; Perfusion; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Thyroxine; Vascular Resistance