The effect of metabolism and endocrine disorders on the heart is multifaceted, and there are no specific cardiac features or findings to point to a specific systemic disease. Endocrine disorders such as thyroid disease and diabetes are known to profoundly affect cardiac function in ways that are not clearly understood.

Maternal diabetes, especially insulin-dependent diabetes, results in transient and nonfamilial cardiomyopathy that is part of generalized organomegaly. The incidence is as high as 38%, as determined by echocardiography.¹ Pathologically, there is thickening of the septum, but typical histologic findings of myofiber disarray are absent.² The condition regresses with age and is considered transitory to the altered intrauterine environment of increased glucose exposure.

Diabetes’ effects on the heart are mediated by alterations in serum lipids, direct effects of hyperglycemia and hyperinsulinemia, effects on the autonomic system, and changes in the cardiac microcirculation. The term “diabetic cardiomyopathy” is frequently used in the clinical literature to describe systolic and diastolic dysfunction in diabetic patients that appears to be independent of epicardial coronary disease and the effects of hypertension.^3,4

There are several mechanisms by which diabetes affects cardiac contractility (Table 146.1). Diabetes is associated with dyslipidemia (“metabolic syndrome”) that accelerates atherosclerosis and may increase oxidative stress within the myocardium.⁵ Increases in advanced glycation end products may lead to endothelial and myocyte damage⁶ and have been demonstrated by immunolocalization techniques in the atherosclerotic plaques within the coronary arteries.⁷ Glycation of apolipoprotein B may be associated with an increased risk of coronary events, and advanced glycation end products may result in the up-regulation of vascular adhesion molecules. An increased level of myocyte autophagy has been reported in experimental forms of diabetic cardiomyopathy.⁸

Epidemiologic data show a 2.5- to 5-fold increased risk of heart failure in diabetics, independent of hypertension and coronary disease.^9,10,11 Approximately 60% of adults with well-controlled type II diabetes have some evidence of cardiomyopathy based on echocardiographic findings of diastolic dysfunction and cardiac hypertrophy. Although clinical studies suggest the existence of “diabetic cardiomyopathy,” causality has been questioned.^12,13 Echocardiographic studies in long-term diabetics have not supported a link between left ventricular dysfunction and type I diabetes.¹⁴

In addition to cardiomyopathy, the clinical manifestations of cardiac disease among diabetics include acute myocardial infarction and cardiac autonomic dysfunction. Pathologic studies of coronary artery disease in patients dying suddenly show diabetics are more likely to have extensive and distal disease, organized thrombi, and healed myocardial infarcts and are less likely to have acute thrombi than are normoglycemics.¹⁵

As mentioned above, pathologic findings in diabetic cardiomyopathy are nonspecific; many have been described in experimental models. Findings in the extracellular matrix include distortion of myocardial capillaries, thickening of capillary walls, and disorganization of contractile fibers within cardiac myocytes. A human study showed basement membrane thickening in the capillaries, small arterioles and venules, arteriolar hyalinization, and perivascular fibrosis.¹⁴ Other findings include increased interstitial collagen and myocyte hypertrophy, which may be related to up-regulation of β-myosin heavy chain gene.¹³ Increases in necrosis and apoptosis of myocytes, fibroblasts, and endothelial cells appear related to oxidative stress and are augmented by hypertension.¹⁶

Hypothyroidism results from decreased levels of T4 and T3, with increases in serum thyroid-stimulating hormone. The cardiovascular manifestations of hypothyroidism include diastolic hypertension, sinus bradycardia due to sinus node dysfunction, and failure of the sinus node to accelerate normally under conditions of stress. Other cardiac manifestations may include heart block, pericarditis, and pericardial effusion. Approximately 4% of patients with hypothyroidism develop
pericarditis. Less commonly, there is cardiomyopathy, endocardial fibrosis, and myxomatous valvular changes¹⁷ (Table 146.2).

Hypothyroidism, if long standing and untreated, may result in a constellation of cardiac effects historically termed “myxedema heart”.^18,19,20 These include cardiac dilatation, low cardiac output, low electrical voltages on electrocardiogram, and flattened or inverted T waves: all findings that reverse with treatment. Massive pericardial effusions may also be the initial presentation of untreated hypothyroidism.²¹ Physiologic effects of hypothyroidism on the circulation include decreased cardiac output, decreased stroke volume, and increased circulation time. There appears to be an increased risk of hypertension, due to a persistent low-renin state and increased peripheral vascular resistance. Even subclinical hypothyroidism is associated with decreased cardiac preload, increased afterload, and reductions in stroke volume and cardiac output.²²

Biopsies of patients with heart failure secondary to myxedema are nonspecific and may show vacuolated myocytes indicative of chronic ischemia.¹⁹ There is typically extensive basophilic degeneration of myocytes, although the finding is not specific for thyroid disease (Fig. 146.1).