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C
ardiologists encounter thyroid disor-
ders frequently. Hyperthyroidism transcription of the calcium ATPase gene, and
causes and may present with atrial enhanced calcium and glucose uptake. These
fibrillation, while hypothyroidism is a risk changes make contraction less eYcient and
factor for coronary artery disease. Moreover, increase heat production. Afterload is reduced,
the use of amiodarone may precipitate a variety with a reduction of as much as 5070% in sys-
of thyroid disorders, and severe heart disease, temic vascular resistance, caused by the direct
such as left ventricular failure or acute myocar- eVects of T3 and the indirect eVects of excess
dial infarction, can cause confusing distur- lactate production (increased tissue thermo-
bances in thyroid function tests.
genesis) on vascular smooth muscle. Blood
flow, particularly to skin, muscle, and heart, is
Hyperthyroidism therefore greatly increased. The preload of the
heart rises because blood volume is expanded
owing to increases in the serum concentrations
Hyperthyroidism is a common condition with a
prevalence of approximately 1%; it aVects pre- of angiotensin converting enzyme and erythro-
dominantly women aged 3050 years and is poietin, with resultant increases in renal
usually (70%) caused by Graves disease which sodium absorption and red cell mass.
is characterised by diVuse goitre, orbitopathy, Hyperthyroidism is characterised by a high
pretibial myxoedema, and the presence of left ventricular ejection fraction (LVEF) at rest
stimulating thyrotrophin (TSH) receptor anti- but, paradoxically, by a significant fall during
body in the serum. Most of the remaining cases exercise. Restoration of euthyroidism is accom-
(20%) are caused by autonomous production panied by the anticipated rise in LVEF on
of thyroid hormones by a nodular goitre. exercise at the same workload and heart rate.3
This reversible cardiomyopathy could ex-
Effects of thyroid hormones on the plain the reduced exercise tolerance of patients
cardiovascular system with hyperthyroidism. Rather than being an
Correspondence to:
The thyroid secretes two active hormones: thy- intermediate state between normal left ven-
Dr A D Toft, Endocrine
Clinic, Royal roxine (T4) which is a prohormone and tricular function and left ventricular dysfunc-
Infirmary, Edinburgh tri-iodothyronine (T3) which acts as the final tion at rest, the failure of LVEF to increase on
EH3 9YW, UK mediator. In hyperthyroidism there is excessive exercise is perhaps better viewed as a conse-
quence of the additional burden of exercise
induced increase in afterload on a heart
performing near its maximum capacity.
The characteristic tachycardia is caused by a
combination of more rapid diastolic depolari-
sation and shortening of the action potential of
the sinoatrial cells. The refractory period of the
atrial cells is also shortened which may explain
the well known propensity to atrial fibrillation.
There is a complex interaction between thy-
roid hormones and the adrenergic system, and
many of the clinical features of hyperthy-
roidism such as tachycardia, increased pulse
pressure, and tremor resemble the heightened
adrenergic state of phaeochromocytoma.
However, serum and urinary catecholamine
concentrations are normal or even low in
hyperthyroidism, and there is no good evidence
of greater sensitivity to catecholamines despite
an increased density of 1 adrenoceptors in
cardiac muscle. It may well be that thyroid
hormones and catecholamines act independ-
Figure 1. Effects of hyperthyroidism on the cardiovascular system and the ently at the cellular level but share a signalling
possible outcomes. TBV, total blood volume; LVEDV, left ventricular end diastolic pathway. This would explain why non-selective
volume; LVESV, left ventricular end systolic volume; SV stroke volume; SVR adrenoceptor antagonists, such as pro-
systemic vascular resistance; CO, cardiac output; increased; decreased.
Solid arrows indicate direct effects, and dashed arrows potential outcomes. pranolol or nadolol, improve but do not abolish
*Features for which T3 is directly responsible. many of the symptoms of hyperthyroidism.
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Clinical features A
Most patients with hyperthyroidism complain I aVR V1 V4
of palpitations and breathlessness on exertion,
although symptoms such as weight loss in the
presence of a normal or increased appetite,
heat intolerance, and irritability tend to pre- II aVL V2 V5
dominate. Established angina may become
456 worse and may, exceptionally, be a new
development. Myocardial ischaemia is presum-
ably caused by the increased demands of the
thyrotoxic myocardium. However, coronary III aVF V3 V6
spasm may be an additional factor and
myocardial infarction can occur in the absence
of significant atheroma.4 The ECG is usually
normal but in severe hyperthyroidism there Rhythm strip: II
may be impressive ST-T wave changes in the 25 mm/sec; 1 cm/mV
absence of ischaemic chest pain (fig 2).
Characteristically there is a sinus tachycardia
of approximately 100 per minute with a good LOC 000000000 F 40 11797
Atrial fibrillation LOC 000000000 Speed: 25 mm/sec Limb: mm/mV Chest: 10 mm/mV F 50~ 0.5 100 Hz W 05744
A variety of atrial and ventricular tachycardias
Figure 2. (A) ECG in a 48 year old woman in whom there was an exacerbation
have been described in hyperthyroidism, but of hyperthyroidism 72 hours after treatment with iodine131. (B) The pronounced ST
the most common arrhythmia is atrial fibrilla- changes slowly resolved and the tracing was normal three months after the
tion. In unselected series 1015% of patients patient became euthyroid.
with thyrotoxicosis were in atrial fibrillation at
presentation; however, the prevalence is prob-
ably falling because the widespread availability example, a low serum TSH was associated with
of accurate tests of thyroid function means that a threefold increase in the incidence of atrial
hyperthyroidism is now diagnosed at an earlier fibrillation among clinically euthyroid elderly
stage in its natural history. Atrial fibrillation is subjects, 28% of whom developed atrial fibril-
rare in patients under 40 years of age unless lation during 10 years of follow up.7
there is longstanding severe thyrotoxicosis or Sixty per cent of patients with hyperthyroid
coexistent structural heart disease. The preva- atrial fibrillation will revert spontaneously to
lence increases with age and is higher in men sinus rhythm within a few weeks of restoration
such that in the authors experience 50% of of normal tests of thyroid function; approxi-
hyperthyroid males over the age of 60 are in mately half of the remainder will respond to
atrial fibrillation at presentation. DC cardioversion if serum TSH concentra-
In one series, 13% of patients with idio- tions are normal or raised at the time of the
pathic or lone atrial fibrillation attending a procedure. Failure to achieve stable sinus
cardiology clinic were found to have overt or rhythm is most likely in those in whom the
subclinical hyperthyroidism; the discovery of diagnosis of hyperthyroidism has been delayed.
atrial fibrillation, in the absence of an obvious
These are usually patients with mild hyperthy-
cause, should therefore prompt a request for
roidism caused by a small multinodular goitre
thyroid function testing.5
Atrial fibrillation may be the dominant in whom only serum T3 may be elevated (T3
feature of hyperthyroidism in older patients toxicosis) and in whom other useful diagnostic
and is not necessarily accompanied by pro- features, such as ophthalmopathy or major
nounced elevation of the serum concentrations weight loss, are missing.
of T3 and T4. Increases of thyroid hormones Hyperthyroid atrial fibrillation is typically
within their respective reference ranges associ- resistant to digoxin, caused in part by an
ated with a suppressed serum TSH concentra- increase in the renal clearance and the apparent
tion (subclinical hyperthyroidism) may be suf- volume of distribution of the drug. It is often
ficient to trigger atrial fibrillation in susceptible necessary to add a non-selective adrenocep-
individuals.6 In the Framingham study, for tor antagonist to achieve adequate rate control.
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