Philippine Journal of Internal Medicine
Cardiac Morphology and Function of Hyperthyroid Patients
Admitted at De La Salle University Medical Center
Daveric A. Pagsisihan, M.D.*; Aimee Andag-Silva, M.D.**; Olivia Piores-Roderos, M.D.**; Jose Armand Gurango, M.D.***; Ma. Ailsa Escobin, M.D.****
Abstract
Background: Most characteristics and common signs and
symptoms of hyperthyroidism are the effects of thyroid
hormones on the heart and cardiovascular system.
With the advent of echocardiography, characterizing
the effects of hyperthyroidism on the heart has been
described mainly for overt hyperthyroidism. Data on
subclinical hyperthyroidism are still conflicting.
Objective: To describe and compare the cardiac
morphology and function of Filipino patients with
uncontrolled overt and subclinical hyperthyroidism
through echocardiogram, admitted at De La Salle
University Medical Center (DLSUMC) for a period of
five years and six months
Methodology: This is a retrospective descriptive study
that utilized review of medical records. Seventy-five
hyperthyroid patients were included; 56% with overt
hyperthyroidism and 44% with subclinical hyperthyroidism.
Cardiac morphology and systolic and diastolic functions
were determined in the population and compared
between overt and subclinical hyperthyroidism using
I ntroduction
Hyperthyroidism is common, affecting approximately
2.0% of women and 0.2% of men.1 In the Philippines,
thyroid disorders and goiter are highly prevalent. In
the 2008 Philippine Thyroid Disorder Prevalence Study
(PHILTIDES), the prevalence of overt hyperthyroidism
was found to be 0.61%, while that of subclinical
hyperthyroidism was even higher at 5.33%.2 It has been
well recognized that some of the most characteristics
and common signs and symptoms of hyperthyroidism
are the effects of thyroid hormones on the heart
and cardiovascular system. 3 With the advent of
2-Dimensional echocardiography, changes in cardiac
**Resident-in-Training, Department of Internal Medicine, DLSUMC
**Consultant, Section of Endocrinology, Department of Internal
Medicine, DLSUMC
***Consultant, Section of Cardiology, Department of Internal Medicine,
DLSUMC
****Consultant, Section of Nephrology, Department of Internal
Medicine, DLSUMC
Reprint request to: Daveric A. Pagsisihan, M.D., De La Salle University
Medical Center, Congressional Ave., Pasong Lawin, Cavite, Philippines
Email: cir_evad@yahoo.com
Original Paper
2-dimensional echocardiogram.
Results: Cardiac morphology was slightly compromised
due to slight thickening of interventricular septum
(IVSTd) and left ventricular posterior wall thickness at
diastole (LVPWTd). There was also an increase in left
ventricular mass (LVM), more pronounced in overt
hyperthyroidism. Systolic function parameters such as
fractional shortening (FS) and ejection fraction (EF)
were normal. Impaired left ventricular myocardial
relaxation manifested as low early mitral peak flow
velocity, low E/A ratio and prolonged isovolumetric
relaxation time (IVRT) was observed in most patients,
particularly in overt hyperthyroidism.
Conclusion: Abnormalities noted were comparable
between the two groups of hyperthyroidism. With
cardiac parameters affected even in subclinical
hyperthyroidism, treatment might be indicated regardless
if hyperthyroidism is overt or subclinical.
Keywords: hyperthyroidism, heart function, echocardiogram
morphology and function of hyperthyroid patients
have been reported. However, these changes are
measurable mainly in patients with overt hyperthyroidism.
In subclinical hyperthyroidism, findings have not been
always consistent. 4 In effect, controversies whether to
treat this subclinical hyperthyroidism remain unsettled,
despite the abnormally low thyroid stimulating hormone
(TSH) concentration. 5 To date, there is paucity of
data regarding cardiovascular changes particularly to
cardiac morphology and function in Filipino hyperthyroid
patients, both overt and subclinical.
M ethodology
Objectives
The general objective is to describe the cardiac
morphology and function of adult (>20 years old)
Filipino patients with uncontrolled primary hyperthyroidism
through 2-dimensional echocardiogram admitted at
DLSUMC from January 2006 to July 2011. Specific
objectives are the following:
1) to describe the demographic characteristics of
hyperthyroid patients in terms of age and sex;
2) to describe and compare clinical characteristics of
Volume 52 Number 4 October-December, 2014 1
 Pagsisihan D, et al.
overt and subclinical hyperthyroid patients, in
terms of history, physical findings, diagnostic tests
and current medications; and
3) to determine and compare cardiac morphology,
systolic and diastolic functions of overt and
subclinical hyperthyroid patients.
Study design, setting and subjects
This is a retrospective descriptive study that utilized
review of records. Medical records of patients with
final diagnosis of hyperthyroidism, thyrotoxicosis, Graves’
disease, toxic goiter (diffuse, nodular, multinodular),
thyroid storm, or thyrotoxic heart disease were retrieved.
Inclusion criteria were Filipino patients, 20 years or
older, previously or newly diagnosed with primary
hyperthyroidism, available thyroid function tests (TSH
and FT4 only, or TSH, FT4 and FT3) with a low TSH to
show that the patient is biochemically hyperthyroid, and
two-dimensional echocardiogram done at DLSUMC on
the same admission. Exclusion criteria were presence
of coronary heart disease, cardiomyopathy, rheumatic
heart disease, connective tissue disease, diabetes
mellitus, hypertension, renal disease, liver disease and
previous history of myocardial infarction, rheumatic
fever or infective endocarditis.
Clinical and hormonal data
Baseline demographic and clinical characteristics
were recorded. Body mass index was not included
since weight and height were not completely indicated
in the patients’ charts. SBP, DBP and HR considered
for analysis were the first values recorded during
patient’s admission. Thyroid function test of patients
were evaluated and was classified into either overt
or subclinical hyperthyroidism. Overt hyperthyroidism is
defined as thyroid function tests showing high levels
of FT3 (reference range: 2.50-5.80 pmol/L) and/or
FT4 (reference range: 11.50-23.00 pmol/L), with TSH
level below the reference range (0.27-3.75 μIU/mL).
Subclinical hyperthyroidism is defined as a thyroid
function test showing normal levels of FT3 and FT4
with TSH level below the reference range.5
Cardiologic evaluation
A standard 12-L ECG was also retrieved at the patients’
charts. Official reading of a single cardiologist reader of
DLSUMC was recorded. Baseline rhythm and presence
of premature complexes were noted. Echocardiogram
video compact discs (VCDs) of patients were retrieved
at the Cardiovascular Laboratory of DLSUMC. Each
echocardiographic study was reviewed by a single
cardiologist taking into consideration the following
parameters:
1) Cardiac morphology: left ventricular internal
dimension at diastole (LVIDd), interventricular septal
thickness at diastole (IVSTd), left ventricular posterior
2 Volume 52 Number 4 October-December, 2014
Cardiac Morphology and Function of Hyperthyroid
wall thickness at diastole (LVPWTd), and left ventricular
mass (LVM)
2) Cardiac systolic function: fractional shortening
(FS) and ejection fraction (EF)
3) Cardiac diastolic function: early diastolic mitral
peak flow velocity (peak E), late diastolic mitral peak
flow velocity (peak A), E/A ratio, deceleration time
(DecT), and isovolumetric relaxation time (IVRT)
M-mode echocardiography was used to measure
LVIDd, IVSTd and LVPWTd. LVM was then computed
using the American Society of Echocardiography (ASE)
method.6
D ata Analysis
Mean and standard deviation were computed for
quantitative continuous data and relative frequency
for qualitative nominal data. Values for cardiac
morphology, systolic and diastolic function parameters
of each patient were then categorized as normal
or abnormal, low or high, shortened or prolonged
whichever is appropriate according to the standard
reference for age and/or sex.6 The population was
then divided into overt and subclinical hyperthyroidism
according to their thyroid function test results. The
same data analysis was done for each group and
results were compared.
R esults
Baseline and clinical characteristics
The study population consisted of 75 hyperthyroid
patients, 56% with overt and 44% with subclinical
hyperthyroidism. Baseline demographic and clinical
characteristics are presented in Table I. Mean age of
patients was 51 years old (range of 23 to 90 years
old) and was predominantly women (85.3%, n=64).
Patients with overt and subclinical hyperthyroidism were
matched in terms of age. Overt hyperthyroidism group
has a higher SBP, PP and HR, and lower DBP and
TSH concentration than the subclinical hyperthyroidism
group.
All patients have an initial 12L-ECG done during the
first hour of admission. Figure 1 shows that atrial fibrillation
(AF) was the most common baseline cardiac rhythm of
hyperthyroid patients (48%). Most patients (77.8%) with AF
have AF with rapid ventricular response (RVR) while the
rest has AF in controlled ventricular response. Five (6.7%)
patients have premature ventricular complexes (PVCs).
Of these five patients, four have isolated PVC, and one
has PVC in bigamy pattern.
Cardiac Morphology
Cardiac morphology data are depicted in Table
II. Overt hyperthyroidism group has a slightly larger
LVIDd than the subclinical hyperthyroidism group.
 Cardiac Morphology and Function of Hyperthyroid Pagsisihan D, et al.

Table I: Baseline demographic and clinical characteristics of study population

Overt Hyperthyroidism Subclinical Hyperthyroidism Overall population
(n=42) (n=33) (N=75)

Age (years) 51 + 17 51 + 16 51 + 17
Women 34 (81) 30 (91) 64 (85.3)
SBP (mmHg) 131 + 25 128 + 24 130 + 25
DBP (mmHg) 75 + 13 79 + 13 77 + 13
PP (mmHg) 56 + 23 48 + 16 53 + 20
HR (bpm) 114 + 29 106 + 26 111 + 28
Prior diagnosis of Hyperthyroidism 18 (42.9) 23 (69.7) 41 (54.7)
Current intake of ATDs 6 (14.3) 12 (36.4) 18 (24)
Current intake of β-adrenergic blockers 4 (9.5) 8 (24.2) 12 (16)
TSH (μIU/mL) 0.07 + 0.04* 0.10 + 0.07* 0.08 + 0.06*
FT4 (pmol/L) 50.58 + 19.44† 19.66 + 2.58 36.98 + 21.24†
FT3 (pmol/L) 18.64 + 12.09‡§ 4.60 + 1.23§ 11.89 + 11.2‡§
Values are means + SD or number (%)
*TSH values of <0.06 were set as 0.05 for computation purposes (28 for overt hyperthyroidism and 16 for subclinical hyperthyroidism; total of 44)
†FT4 values with greater than sign (>) were set at 1 pmol/L higher than the actual value for computation purposes (5 for overt hyperthyroidism; total of 5)
‡FT3 values with greater than sign (>) were set at 1 pmol/L higher than the actual value for computation purposes (3 for overt hyperthyroidism; total of 3)
§FT3 values were not determined in some patients (15 for overt hyperthyroidism and 8 for subclinical hyperthyroidism; total of 23)
SBP – systolic blood pressure; DBP – diastolic blood pressure; PP – pulse pressure; HR – heart rate; ATDs – Anti-thyroid drugs

Table II: Cardiac Morphology of study population

Overt Hyperthyroidism Subclinical Hyperthyroidism Overall population
(n=42) (n=33) (N=75)
LVIDd (mm) 45.1 + 4.9 44.1 + 6.9 44.6 + 5.9
IVSTd (mm) 11.2 + 1.4 11.7 + 2.0 11.4 + 1.7
LVPWTd (mm) 11.5 + 1.7 11.5 + 1.5 11.5 + 1.6
LVM (g) 189 + 73 188 + 48 188 + 60
Values are mean + SD
LVIDd – left ventricular internal dimension at diastole, IVSTd – interventricular septal thickness at diastole, LVPWT – left ventricular posterior free wall thickness at diastole, LVM – left
ventricular mass

Table III: Systolic and Diastolic function parameters of study

population
Overt Hyperthyroidism Subclinical Hyperthyroidism Overall population
(n=42) (n=33) (N=75)
FS (%) 36 + 7 36 + 6 36 + 7
EF (%) 67 + 11 67 + 10 67 + 11
Peak E (m/s) 0.8 + 0.3* 1.0 + 0.3* 0.9 + 0.3*
Peak A (m/s) 0.7 + 0.3†‡ 0.7 + 0.3†‡ 0.7 + 0.3†‡
E/A Ratio 1.2 + 0.9†‡ 1.4 + 0.8†‡ 1.3 + 0.9†‡
DecT (ms) 186 + 71§ 175 + 39§ 181 + 59§
IVRT (ms) 105 + 24§ 102 + 21§ 103 + 22§
Values are mean + SD
*Values for 1 patient (overt) and 2 patients (subclinical) are missing; total of 3 (overall)
†Values for 1 patient (overt) and 2 patients (subclinical) are missing; total of 3 (overall)
‡Values for 9 patients (overt) and 6 patients (subclinical) cannot be determined (Echocardiogram done in AF)
§Values for 3 patients (overt) and 2 patients (subclinical) are missing; total of 5 (overall)
FS – fractional shortening, EF – ejection fraction, Peak E – early diastolic mitral peak flow velocity, Peak A – late diastolic mitral peak flow velocity, DecT – deceleration time. IVRT – inter-
ventricular relaxation time

Conversely, the latter has a thicker IVSTd than the 2 shows that 86.7% of hyperthyroid patients still have a
former. In terms of LVPWTd, both groups were normal LVIDd for their age and sex. Notably, more
matched. Lastly, patients in the overt hyperthyroidism patients in the subclinical hyperthyroidism group have
group have a slightly higher LVM than the subclinical an enlarged LVIDd when compared to the overt
hyperthyroidism group. Despite these differences, Figure hyperthyroidism group. IVSTd and LVPWTd were mildly

Volume 52 Number 4 October-December, 2014 3

 Pagsisihan D, et al.
thickened for most of hyperthyroid patients as shown
in Figure 3. Individually, more overt hyperthyroid
patients have a mildly thickened IVSTd whereas more
subclinical hyperthyroid patients have a moderately
thickened IVSTd. Two subclinical hyperthyroid patients
(6.1%) had a severely thickened IVSTd, and none in
the overt hyperthyroidism group. In terms of LVPWTd,
the two hyperthyroidism groups were not very different.
Figure 4 shows that most hyperthyroid patients (46.7%,
n=35) have mildly abnormal LVM according to sex.
Moreover, a greater proportion of overt hyperthyroid
patients has mild abnormality in LVM compared to
subclinical hyperthyroid patients.
Figure 1: Percentage distribution of hyperthyroid patients according
to electrocardiogram rhythm on admission
Figure 2: Percentage distribution of Hyperthyroid patients according
to left ventricular internal dimension at diastole
Figure 3: Percentage distribution of Hyperthyroid patients according
to interventricular septal and left ventricular posterior wall thickness
at diastole
4 Volume 52 Number 4 October-December, 2014
Cardiac Morphology and Function of Hyperthyroid
Figure 4: Percentage distribution of Hyperthyroid patients according
to left ventricular mass
Cardiac Systolic and Diastolic functions
Table III shows systolic and diastolic function
parameters of the different hyperthyroidism groups. In
terms of systolic function, both overt and subclinical
hyperthyroidism groups are comparable. In terms of
diastolic function, peak E velocity and E/A ratio were
lower in the overt hyperthyroidism group compared to
the subclinical hyperthyroidism group, while peak A
was comparable for both hyperthyroidism groups. DecT
and IVRT were longer in the overt hyperthyroidism
group than in the subclinical hyperthyroidism group.
Figure 5 shows that most hyperthyroid patients
have a normal FS and EF for their age and sex.
Both groups also have almost equal proportion of
patients at different levels of abnormalities. Figure
6 shows that 62.5% of hyperthyroid patients have
an abnormally low peak E velocity for age. This is
more pronounced in the overt hyperthyroidism group
than in the subclinical hyperthyroidism group. On the
contrary, most hyperthyroid patients have a normal
peak A velocity according to age, and the proportion
of patients with abnormally low peak A velocity
across different hyperthyroidism groups were almost
equal. Figure 7, shows that 56.1% of hyperthyroid
patients have reduced E/A ratio. However, a larger
proportion of patients in the overt hyperthyroidism
group have a reduced E/A ratio when compared to
the subclinical hyperthyroidism group. Figure 8 shows
that most hyperthyroid patients have a normal DecT
for age, particularly in the subclinical hyperthyroidism
group. A larger proportion of patients in the overt
hyperthyroidism group have a prolonged DecT than
in the subclinical hyperthyroidism group. Isovolumetric
relaxation time was prolonged in 70% of hyperthyroid
patients for age. This was more notable in the
overt hyperthyroidism group than in the subclinical
hyperthyroidism group. Lastly, 7.7% of patients in the
subclinical hyperthyroidism group have a shortened
IVRT, and none in the overt hyperthyroidism group.
Cardiac Morphology and Function of Hyperthyroid
Figure 5: Percentage distribution of hyperthyroid patients
according to systolic parameters
Figure 6: Percentage distribution of Hyperthyroid patients according
to early (Peak E) and late (Peak A) diastolic peak flow velocities
Figure 7: Percentage distribution of Hyperthyroid patients according
to E/A ratio
Figure 8: Percentage distribution of Hyperthyroid patients according
to deceleration and Isovolumetric Relaxation Times
Pagsisihan D, et al.
D iscussion
The present study showed that hyperthyroid patients
have an elevated SBP and HR, and widened PR
which were not only evident among those with overt
hyperthyroidism but also among those with subclinical
hyperthyroidism. Atrial Fibrillation in RVR is the most
common presenting heart rhythm for most of the
patients in the study. The increased heart rate and
widened pulse pressure in hyperthyroidism resemble a
state of increased adrenergic activity despite normal
or low serum concentration of catecholamines due
to both an increase in sympathetic and a decrease
in parasympathetic tones.7,8
The increased incidence of AF in the present
study is in contrast with the present knowledge
that sinus tachycardia is the most common rhythm
disturbance in patients with hyperthyroidism. 7 Vergara
and colleagues reported that in patients with
paroxysmal AF, hyperthyroidism is the most common
underlying cause. 9 In the Framingham Heart Study
population involving people 60 years or older, subjects
with low TSH level have been found to have three-
fold risk of developing AF compared to subjects
with normal TSH level. 10 However, whether it is the
most common or not, AF is a major cardiovascular
morbidity bearing a double mortality rate compared
to the general population.9 This finding indicates that
even in subclinical cases (wherein TSH is also low),
there is a higher cardiovascular risk especially in older
patients, hence probably necessitating early treatment
to prevent such complication.
In this study, heart morphology was also slightly
compromised as evidenced by slight thickening of
IVSTd and LVPWTd, even though LVIDd is normal for
most patients. This thickening of left ventricular walls
is contrary to previous reports.4,11,12 However, the same
thickening is reported for subclinical hyperthyroidism.13-15
The normal LVIDd seen in the present study can be
viewed in the light of the increased resting heart
rate of the study patients. The augmented heart
rate would reduce left ventricular filling time thereby
reducing left ventricular end-diastolic dimension.
However, in most cases of hyperthyroidism, the
concomitant increase in preload would eventually
cause left ventricular internal dimension to become
normal.16 Due to thickening of the left ventricular walls,
LVM is also mildly abnormal for most hyperthyroid
patients in the study. The abnormality in LVM was
more pronounced in the overt hyperthyroid patients,
though still comparable with subclinical hyperthyroid
patients. This is consistent with the report of Dorr
and colleagues,4 but few studies have reported that
the level of TSH is not associated with LVM.11,12 The
same increase in LVM for patients with subclinical
hyperthyroidism has been demonstrated in previous
Volume 52 Number 4 October-December, 2014 5
 Pagsisihan D, et al.
studies.14,17 but not by Rodondi et al.18 The increase in
LVM is the result of chronic cardiac workload present
in a hyperthyroid state.14 Left ventricular hypertrophy
(LVH) would have been a better parameter since
it has been found to predict all-cause mortality,
in particular of cardiovascular origin, and it is an
independent risk factor for atherosclerotic disease,
stroke, cardiac failure, ventricular arrhythmias, and
sudden cardiac death.19,20 LVH was not determined due
to lack of chart data on patients’ body surface area.
Nonetheless, the increased LVM seen in the present
study, even in patients with subclinical hyperthyroidism,
is an important finding especially in the occurrence of
sudden death in middle-aged adults,20 and might be
an important determinant for cardiovascular mortality
in hyperthyroid patients, thus necessitating treatment
in all cases whether hyperthyroidism is subclinical or
overt.
Hyperthyroid patients in the present study have
normal systolic function as measured by FS and EF,
similar to the reports of two large studies, 4,12 and
in one study of subclinical hyperthyroidism. 15 Unlike
in the present study, Petretta et al. 21 reported an
increased systolic function only in patients with overt
hyperthyroidism but not in those with subclinical
hyperthyroidism when compared to controls. Biondi
et al. 14 on the other hand, found a significantly
increased systolic function in patients with subclinical
hyperthyroidism. These studies were small, including only
30 and 23 subjects respectively which could probably
explain the difference. Another reason could be that
even with the increased resting heart rate and a
probable increased preload of patients in the present
study, an increased level of myocardial contractility
might be mandatory before these parameters of
cardiac performance are increased.16
The present study showed that most hyperthyroid
patients have impaired left ventricular relaxation as
evidenced by a low mitral peak E velocity, reduced
E/A ratio and prolonged IVRT. Mitral peak A velocity
was normal for most of the patients. This diastolic
dysfunction is in congruence with the results of
previously published studies.14,21,22 Conversely, these results
have not been consistent with other reports especially
when it comes to subclinical hyperthyroidism. 11,15,23,24
Though inconsistent, the observed diastolic dysfunction
could be brought about by the mildly abnormal
LVM,25-27 which could stiffen the ventricular walls as
the ventricle is filling during early diastole much the
same with the findings of Pettreta and colleagues,21
thus reducing the mitral peak E velocity, reducing E/A
ratio and prolonging IVRT. Hence, the contribution of
atrial contraction to the final diastolic volume greatly
increases hence maintaining a normal mitral peak
A values despite the impaired ventricular relaxation.
However, clinical consequences of isolated diastolic
6 Volume 52 Number 4 October-December, 2014
Cardiac Morphology and Function of Hyperthyroid
dysfunction in subclinical hyperthyroidism are not yet
fully delineated when compared with other conditions
with isolated diastolic dysfunction. An associated
increased morbidity and mortality is noted, hence
emphasizing the clinical relevance of this dysfunction.28
Conclusion
The findings of the present study showed that
hyperthyroidism has a profound effect on the
different cardiovascular parameters. Cardiac rhythm
and morphology as well as diastolic function are
affected, more than systolic function. These are
particularly true for overt hyperthyroid patients,
hence necessitating treatment. Cardiac affectation of
subclinical hyperthyroid patients was comparable with
that of overt hyperthyroid patients in the present
study, but current guidelines do not support treatment
of all cases. However, based on the present study
findings, as well as the others before this, it is
probably misleading to call subclinical hyperthyroidism
subclinical. Treatment might be indicated even for
subclinical cases even if patients are asymptomatic.
Lastly, with the increasing incidence of hyperthyroidism
in the Philippines, both overt and subclinical, Filipino
patients also develop cardiac abnormalities as seen
in other populations.
The present study is mainly limited by non-uniformity
of echocardiogram machines used and technicians
who performed the echocardiography. This could not
be controlled by the present study due to its nature
of review of records.
LIST OF OPERATIONAL DEFINITIONS
SBP: systolic blood pressure
DBP: diastolic blood pressure
HR: heart rate
LVIDd: left ventricular internal dimension at diastole
IVSTd: interventricular septal thickness at diastole
LVPWTd: left ventricular posterior wall thickness at diastole
LVM: left ventricular mass (LVM = 1.04 x [(LVIDd + IVSTd
+ LVPWTd)3 – LVIDd3] x 0.8 + 0.6)
AF: atrial fibrillation
RVR: rapid ventricular response
FS: fractional shortening
EF: ejection fraction
DecT: deceleration time
IVRT: isovolumetric relaxation time
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