Hypothyroidism
	The widened heart shadow and low electrocardiographic voltage that Zondek originally described are attributable in part to pericardial effusion, which is echocardiographically demonstrable in 30% of hypo patients. Accumulations of fluid in the pericardial and other serous spaces of patients with hypo are the result of both increased plasma albumin egress from blood and decreased lymphatic clearance of interstitial fluid proteins (42). Pericardial effusions are seldom hemodynamically significant even when large, presumably because their slow accumulation permits pericardial compliance. The prevalence and size of pericardial effusions have been correlated with the severity of hypo, they typically resolve after 2 to 12 months of T4 therapy. Rarely, hypo alone may cause heart failure, typically in patients with severe and prolonged T4 deprivation. However, already in short-term hypo, a highly significant decrease in myocardial contractility and a prolongation of diastolic relaxation could be demonstrated (56). Hypo patients with heart failure have some form of intrinsic cardiac disease on which T4 deficiency has been superimposed. No specific pathophysiologic changes can be identified that characterise the myxedema heart. The cardiac silhouette is enlarged, however heart weight is usually normal. Cardiac papillary muscle obtained from animals with hypo shows a depression of the force velocity curve and reduced rate of tension development, indicating significant contractile abnormalities. After administration of T4, all of these abnormalities revert to normal (57). In addition to decreased direct effects of T3 in cardiac myocytes, indirect effects occur through decreases in peripheral oxygen consumption and changes in hemodynamic parameters. Myofibril swelling with loss of striation and some degree of interstitial fibrosis occurs on histologic examination of hypo hearts. In addition, accumulation of mucopolysaccharides can be demonstrated. On electron microscopic examination, mitochondria show disruption and loss of cristae with lipid inclusion (5).