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JACC Vol. 14. No. 4

October 19X9:999-100:

999

Effect of Thyroid Replacement Therapy on the Frequency of Benign

Atria1 and Ventricular Arrhythmias

RALF POLIKAR, MD, GREGORY K. FELD, MD, FACC, HOWARD C. DITTRICH, MD, FACC,

JOHANA SMITH, RN, PASCAL NICOD. MD, FACC

Sun Die-p , Caljf~wnirr

Whether thyroid replacement therapy can trigger cardiac

arrhythmias in patients with hypothyroidism is not known.

In this prospective study, 24 h ambulatory electrocardio-

graphic ECG ) monitoring was used to assess the frequency

of atria1 and ven tricular prem ature beats in 25 patients

with hypothyroidism 5 men and 20 women, aged 56 f 3

years) before and 3.5 + 0.5 months mean + SEM ) after

thyroid replacement therapy. Plasma thyroid-stimulating

hormone was 73.6 f 12.3 and 3.1 f 0.6 @/ml and free

thyroxine index was 2.4 + 0.4 and 9.8 f 0.9 pg/lOO ml at

baseline and after thyroid replacement therapy, respec-

tively.

The frequency of ventricular premature beats was not

affected by thyroid replacement therapy from 273 5 221 at

baseline to 352 f 235 beats/2 4 h after therapy), even in

patients with frequent baseline arrhythmias.

In contrast,

Hypothy roidism is classically associated w ith bradyarrhyth-

mias, such as sinu s bradycardia, and rarely atrioventricular

AV)

block (l-7). Tachya rrhythmias and extrasystoles are

infrequent in patients w ith hypothyro idism. Only rare in-

stances of “torsades de pointe” have been described (8-l 1)

in patients with severe hypothyroidism. This low incidence

of tachyarrhythm ias and extrasystoles has led to the belief

that hypothyroidism may have some antiarrhythmic proper-

ties (12,131, although this has not been well documented. If

this assumption is true, one might expect an increased

incidence of arrhythmias during thyroid replacement therapy

in patients with hypothyroidism, particularly in those with

some arrhythmias in the hypothyroid state. Furthermo re,

From the Division of Cardiology, University of California at San Diego.

Medical Center, San Diego, California.

Manuscript rece ived January 23 1989 : rev ised manuscr ip t rece ived

March 15 1989 accepted April 13. 1989.

Address fo r reo r in ts : Pasca l Nicod . MD Card io logy Div is ion H-81 IA.

University of California at San Diego Medical Center. San Diego Californi a

92103.

the frequency of atrial premature beats was slightly in-

creased after thyroid replacement therapy from 47 2 17 to

279 + 197 beats/24 h), largely as a result of changes seen in

three patients. No patient developed new onset of sustained

ventricular or supraventricular arrhythmias. Average,

basal and maximal heart rates during ECG monitoring

increased significantly after thyroid replacement therapy

average 72 + 2 to 80 + 2; basal 64 + 2 to 70 rt 2; maximal

114 f 3 to 130 f 3 beats/min, respectively, p < 0.00 1).

In conclusion, thyroid replacement therapy is safe in

patients with common benign cardiac arrhythmias, and

does not trigger an increase in arrhythmia frequency exc ept

in rare patients with baseline a tria1 prem ature beats. It is,

however, associated with an increase in basal, average and

maximal heart rates.

J Am Co11 ardiol1989;14:999-1002

the effect of thyroid replacement therapy on heart rate has

never been assessed in humans.

In this prospective study, we used 24 h electrocardio-

graphic (ECG) monitoring to assess whether thyroid replace-

ment therapy increased the frequency of atria1 and ventric-

ular arrhythmias in 25 patients w ith hypothyroidism. In

addition, the impact of thyroid replacement therapy on

basal, average and maximal heart rates was evaluated.

Methods

Study patients.

Twenty-five patients, 5 men and 20

women, aged 30 to 80 years (mean f SEM 56 t 3 years) with

primary hypothyroidism were enrolled in this study from

July 19 86 o June 1988. Hypothyroidism was diagnosed with

use of standard thyroid function tests. Eleven patients had a

history of cardiovascular disease: five had systemic hyper-

tension, four had coronary artery dis ease, one had hyper-

trophic cardiomyopathy and one had undergone valve re-

placem ent for aortic sten osis. No patient h ad signs of left

ventricular failure (third heart sound or pulmonary rales, or

both). All patients had sinus rhythm, except two who had

cl989 by the American College of Cardiology

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POLIKAR ET AL.

THYROID REPLACEMENT AND ARRHYTHMIAS

chronic atria1 fibrillation. The protocol wa s approved by the

University of California-San Diego Medical Center Human

Subjects Com mittee, and all patients gave informed consent.

Thyroid function tests.

Plasm a thyroxine, thyroid-

stimulating hormone, triiodothyronine resin uptake and free

thyroxine index were measured and calculated by standard

methods (14-16).

Am bulatory electrocardiographic mon itoring. Twenty-

four hour ambulatory ECG m onitoring was obtained for each

patient before and after thyroid replacement therapy. All

tapes were analyzed on a Del Mar Avionics Innovator

scanner (model 7.50) by the same operator, who had no

knowledge of the status of the thyroid replacement therapy.

Average heart rate was computed by the scanner after

checking the whole tape for any motion artifact. Similarly,

basal heart rate was determined by averaging up to 6 h of

steady heart rate during sleep hours. Maximal heart rate was

also computed by using a 16 beat sliding average after

checking for motion artifacts. Ventricu lar and atria1 arrhyth-

mias were counted by the scanner, in learning

mode, to

directly control the accuracy of the count. Heart rate com-

putation could not be obtained

in four patients as a result of

inadequate calibration of the tapes in two and the presence

of atria1 fibrillation in two.

Treatmentprotocol.

Each patient was studied at baseline

and at 3 t 0.5 months after the initiation of thyroid replace-

ment therapy. All medica tions except thyroxine were kept

constant during the study period. Two patients were taking a

beta-adrenergic blocking agent for their hypertension , two

were taking digoxin, one was taking verapamil and one was

taking flecainide for severe palpitation. The dose of thyrox-

ine used ranged from 3 7.5 to 200 pg/day (mean 117.5 +- 10).

The starting dose was 50 pg/day, which was increased

stepw ise, gen erally in increments of 50 pg every 2 week s, to

a maximum of 100 to 150 pg/day, if this dose was well

tolerated. No patient reported significant cardiac sympto ms

such as angina pectoris or palpitation after replacement

therapy.

Statistics. Comparisons of variables measured before and

after thyroid replacement therapy were made with use of the

paired Student’s

t

test. Values are expressed as mean values

? SEM.

Results

At baseline, patients w ith hypothyroidism had a de-

creased plasm a free thyroxine index (2.4 2 0.4 pg/lOO ml)

and increased plasma thyroid-stimulating hormone (73.6 2

12.3 J/ml). After 3.5 + 0.5 months of thyroid replacement

therapy, thyroid function test results were in the euthyroid

range (free thyroxine index 9.8 2 0.9 pg/lOO ml; thyroid-

stimulating hormone 3.1 -t 0.6 pU/ml).

10,000 -

1000 -

al

k

100

f

s

lo-

l

JACC Vol. 14 No. 4

October 1989:999-1002

0’

HYPO

Euth

Figure Number of atria1 premature beats (APB ’s) recorded during

24 h ambulatory e lectrocardiographic monitoring b efore (Hypo)

(mean 47 ? 17) and after (Euth) (mean 2 79 ? 197) thyroid replace-

ment therapy in 25 patients with hypothyroidism.

Twenty-fourhour electrocardiographicmonitoring Fig. 1

to 3).

There was a small but statistically insignificant in-

crease in the frequency of atria1 prematu re beats after

thyroid replacement therapy (from 47 + 17 to 279 ? 197

beats/24 h) that was mainly due to changes seen in three

patients (Fig. 1). Seven patients w ith hypothyroidism had a

total of 27 runs of supraven tricular tachycardia (ranging from

3 to 41 beats) at a maximal rate of 1 23 o 173 beats/min (m ean

148 2 7). After thyroid replaceme nt therapy, eight patients

had a total of 38 runs of supraventricular tachycardia

(ranging from 3 to 66 beats) at a maximal rate of 10 1 to 192

beats/min (mean 154 + 12). No significant change in the

frequency of ventricular premature beats after thyroid re-

placement therapy was seen (from 273 ? 221 to 352 + 235

beats/24 h) (Fig. 2) and no patient developed malignant

arrhythmias such as ventricular tachycardia.

Figure 2. Number of ventricular premature beats (VPB ’s) recorded

during 24 h ambulatory electrocardiographic monitoring be fore

(Hypo) (mean 2 73 k 221) and after (Euth) (mean 352 k 235) thyroid

replacement therapy in 25 patients with hypothyroidism.

10,000~

1000

I?

c 100

f

-3

2

10

w

1

0-

HYPO

Euth

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October 1989:999 1002

THYROIDREPLACEMENTANDARRHYTHMIAS

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BASAL ~

AVERAGE ~

MAXIMAL

r p

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POLIKAR ET AL.

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AND ARRHYTHMIAS

JACC Vol. 14 No. 4

October 1 989:999-1002

6.

1

8

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1 0

Il.

1 2

1 3

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