Endocrine Heart Disease

Deepak R. Talreja, MD
Gregory W. Barsness, MD
Address
Division of Cardiovascular Diseases, Mayo Clinic,
200 First Street, SW, Rochester, MN 55905, USA.
E-mail: barsness.gregory@mayo.edu
Current Treatment Options in Cardiovascular Medicine 2002, 4:181–192
Current Science Inc. ISSN 1092-8464
Copyright © 2002 by Current Science Inc.

Opinion statement
• With the increasing prevalence of obesity and diabetes mellitus in the United
States, associated cardiovascular disease is reaching epidemic proportions with
staggering economic and societal impact. Numerous studies have demonstrated
the poorer prognosis associated with chronic coronary artery disease and acute
coronary syndromes in patients with diabetes compared with nondiabetic patients.
Although the therapeutic strategy is largely the same for the two populations,
proper management of the diabetic patient with cardiovascular disease must
account for the associated metabolic disturbances.
• Thyroid disease is the next most common endocrine disorder that affects proper
function of cardiovascular patients; all patients presenting with coronary
artery disease or cardiac arrhythmias should undergo screening with a sensitive
thyroid-stimulating hormone assay and appropriate treatment when necessary.
• Though these areas are the most common points of intersection between the
cardiologist and endocrinologist, a thorough understanding of the impacts
of each endocrine system on cardiac function is essential to recognize disease
entities that often present with a cardiovascular manifestation or affect patients
with a primary cardiovascular disease.

Introduction
Proper functioning of the endocrine system is essential
to the health of the cardiovascular system. The practic-
ing clinician is reminded constantly of the importance
of this relationship when faced with cardiovascular
symptoms and signs that are the first presentation of a
hitherto unrecognized excess or deficiency of endocrine
function. For example, patients with hyperthyroidism
often present initially with a tachyarrhythmia causing
palpitations, presyncope, and even angina, and dyspnea
may be the first sign of a cardiomyopathy secondary to
pheochromocytoma or acromegaly. Furthermore,
diabetes mellitus is now widely considered the most
prognostically significant cardiovascular risk factor
[1••], and aggressive diagnosis and treatment of associ-
ated hypertension, lipid abnormalities, and obesity are
perhaps the most valuable interventions performed in
the current practice of cardiology. In the course of this
discussion, we review the key cardiovascular manifesta-
tions of a number of endocrine disorders (Table 1) and
their treatment strategies.
GLUCOSE METABOLISM (DIABETES MELLITUS)
Diabetes mellitus is a disease of metabolic dysregula-
tion, especially of glucose metabolism, accompanied by
long term micro- and macrovascular complications. For
the purpose of this review, we limit our discussion to
type II diabetes mellitus, although many of these princi-
ples extend to type I diabetes as well.
Coronary and peripheral vascular atherosclerotic
disease is present in more than 50% of patients with
diabetes, occurring at an earlier age and in a more diffuse
pattern than in nondiabetic patients. Vascular disease is
the primary cause of death in 80% of individuals with
diabetes. People with diabetes with no prior history of
heart disease have the same risk for myocardial infarction
as nondiabetic patients with a known prior history of
heart disease. In addition to accelerated atherosclerosis,
these patients often demonstrate endothelial dysfunction
secondary to the early development of coronary artery
disease (CAD), impaired nitric oxide release, increased
serum levels of free fatty acids, and advanced end-
182 Cardiopulmonary Disease
Table 1. Endocrine functions affecting the
cardiovascular system
Glucose metabolism: diabetes mellitus
Thyroid function
Hyperthyroidism
Hypothyroidism
Parathyroid function and calcium metabolism
Hyperparathyroidism and hypercalcemia
Hypoparathyroidism
Adrenal and related peripheral sympathetic
nervous system function
Hyperaldosteronism
Hypercortisolism (Cushing’s syndrome)
Pheochromocytoma
Hypoaldosteronism
Growth hormone function
Growth hormone excess (acromegaly)
Growth hormone deficiency
Estrogen and the cardiovascular system
Carcinoid syndrome
products of glycosylation [2]. Diabetes leads to impaired
regeneration after vascular injury and impaired formation
of functional collaterals (arteriogenesis). Dyslipidemia in
patients with diabetes is predominantly characterized by
increased triglycerides and low high-density lipoprotein
level; classically, the low-density lipoprotein (LDL) level is
not elevated, but the LDL particles tend to be smaller,
denser, and more susceptible to oxidation leading, to
increased atherogenicity. Hypercoagulability secondary to
increased levels of fibrinogen and plasminogen activator
inhibitor type I and enhanced platelet aggregation [3] is
present. Also present is the insulin resistance syndrome
(formerly known as syndrome X), which is a cluster of
metabolic disorders including hyperglycemia, insulin
resistance, obesity, hypertension, hyperlipidemia, and
hypercoagulability [4]. Diabetic cardiomyopathy, which is
a distinct entity from ischemic cardiomyopathy, is often
seen in patients with diabetes, and may be related to
impaired energy utilization and diastolic dysfunction.
Autonomic nervous system dysfunction may produce
increased sympathetic tone at baseline and may contrib-
ute to silent myocardial ischemia, impaired heart rate
variability, and poor prognosis. Patients may present with
atypical anginal features such as dyspnea and fatigue.
According to the American Diabetes Association
criteria, a formal diagnosis of diabetes mellitus can be
made when a patient has symptoms of polyuria,
polydipsia, and unexplained weight loss, along with
any two of the following:
• A random plasma glucose level of 200 mg/dL or more.
• An 8-hour fasting plasma glucose level more
than 125 mg/dL.
• A postprandial glucose level more than 200 mg/dL
within 2 hours after a 75-g glucose load.
Following control with hemoglobin A1C is essential; in
UKPDS (UK Prospective Diabetes Study), a hemoglobin
A1C concentration of more than 6.2% was associated
with an increased risk of macrovascular disease; the risk
of coronary heart disease increased by about 10% for
each 1% increase in glycosylated hemoglobin level
[5••]. Proteinuria is an excellent marker for generalized
vascular damage and portends a poor prognosis. An ele-
vated C-reactive protein is associated with increased risk
and denotes that more aggressive therapy is required.
THYROID FUNCTION
Hyperthyroidism Hyperthyroidism is defined as any
condition in which body tissues are exposed to supra-
physiologic doses of endogenous or exogenous thyroid
hormones (either or both of thyroxine or tri-iodothyro-
nine). Cardiac manifestations of hyperthyroidism include
tachycardias (especially sinus tachycardia and atrial
fibrillation with a rapid ventricular response), palpita-
tions, hypertension with a wide pulse pressure, enhanced
myocardial contractility with increased cardiac output,
and decreased systemic vascular resistance [6]. These
symptoms are due in part to increased sensitivity to cate-
cholamines produced by the sympathetic nervous system,
although the absolute levels of catecholamines are not
increased. Evidence suggests that the tissue density of beta
receptors is increased, contributing in part to this effect
[7]. An increased cardiac workload typically is accompa-
nied by increased coronary flow, though this may be
impaired by otherwise hemodynamically insignificant
coronary stenoses or by vasospasm [8] causing angina
pectoris and even myocardial infarction. High output
heart failure can result from decreased contractile reserve
in a heart already in a suboptimal position on the Starling
curve. Hyperlipidemia, typically with an elevated LDL and
low HDL, may be present.
Findings on physical examination include a loud
first heart sound, loud pulmonic component of the
second heart sound, a third heart sound, and a systolic
flow murmur. A sensitive thyroid-stimulating hormone
(TSH) assay is the best screening test (low in all cases of
hypothyroidism except for hypothyroidism of pituitary
origin); hyperthyroidism classically is associated with
an elevated free T4 level [9,10].
Hypothyroidism Hypothyroidism is defined as any
condition in which the body tissues lack sufficient stim-
ulation by thyroid hormones. Cardiac manifestations
include a decrease in adrenergic tone indicated by sinus
bradycardia (not related to catecholamine levels, but
rather to adrenergic sensitivity as described in hyperthy-
roidism), decreased myocardial contractility, prolonged
diastolic relaxation, hypotension (though patients with
mild disease often have diastolic hypertension), vaso-
constriction, decreased blood volume, congestive heart
failure (CHF), pericardial effusion rarely associated
with pericardial tamponade, myxedema, and in its most