This document discusses a study that assessed cardiac autonomic nerve function in patients with hypothyroidism using heart rate variability analysis. The study found that untreated hypothyroid patients had significantly higher sympathetic nervous system activity and lower parasympathetic nervous system activity compared to both healthy individuals and hypothyroid patients receiving treatment. Specifically, untreated hypothyroid patients had higher LF/HF ratios and LF power, and lower HF power, SDNN, and RMSSD values. These findings indicate hypothyroidism causes a sympathovagal imbalance with increased sympathetic and decreased parasympathetic modulation. Treatment was found to normalize most heart rate variability measures in hypothyroid patients.

2. Introduction:
The cardiovascular system is one of the most important
targets of thyroid hormones and very sensitive to a
minimal decrease of circulating thyroid hormones.1
Measurement of heart rate variability is an important
andwidelyusednon-invasivemethodtoassesscardiac
autonomic nerve function. HRV can be analysed by
Simple time domain, statistical time domain and
frequency domain method.Simple time includes mean
R-R interval,mean heart rate; statistical time domain
includes SDNN, RMSSD; frequency domain method
includes total power, VLF power, LF power, HF power.2
Hypothyroidism may be associated with changes in
cardiac autonomic nervous activities(CANA).
Regarding autonomic nerve function, increase in
sympathetic and decrease in parasympathetic activity
are the usual findings in hypothyroids.Increase in
sympathetic activity possibly be due to TRH which
directly stimulates symp. outflow within the CNS.3
Original Article
Assessment of Cardiac Autonomic Nerve Function
Status by Heart Rate Variability in Hypothyroidism
Matia Ahmed1, Noorzahan Begum2, Sultana Ferdousi2, Sakil Arman3,
Tasmina Parveen1, Eram Mustafiz4
Abstract:
Background: Hypothyroidism is one of the common endocrine disorders with high incidence
in women particularly in older age.Impaired cardiac autonomic activity and altered
sympathovagal balance are documented in patients with hypothyroidism.
Objectives: The present study was conducted to assess the cardiac autonomic nervous
activity by heart rate variability in patients with hypothyroidism.
Method: The cross sectional study was carried out in the Department of Physiology,
Banghabandhu Sheikh Mujib Medical University from July 2008 to June 2009 on 60 patients
of 30-50 years with hypothyroidism (group B). For comparison 30 age sex matched
apparently healthy euthyroid subjects (group A) were also studied. Based on treatment,
hypothyroid patients were divided into B1
(patients on their 1st
day of diagnosis, before
starting of treatment) and B2
(patients with medication for 12-18 months). The study group
was selected from the Out Patients Department of Endocrinology, BSMMU. Serum TSH and
FT4
level were measured by AxSYM system. HRV measures were assessed by Polygraph
(Polyrite D, version 2.2), and statistical analysis,Student t test,One way Anova and Pearson’s
correlation coefficient test were done as applicable.
Results: The mean of all HRV measures in euthyroid females were within normal range. In
hypothyroid patients the LF/HF and LF norm were significantly (p<0.001) higher in
comparison to both euthyroids and treated patients. The HF norm,SDNN,RMSSD were
found significantly (p<0.001) lower in untreated hypothyroid in comparison to euthyroids
and treated patients. The LF/HF and LF norm showed significant positive correlation and
HF norm showed significant negative correlations with serum TSH level in all hypothyroid
patients.
Conclusion: Hypothyroidism is in a sympathovagal imbalanced state, characterized by
both increased sympathetic and decreased vagal modulation of the heart rate.
Key words: Hypothyroidism, Cardiac autonomic nerve function, Heate rate variability (HRV).
(J Uttara Adhunik Med Coll. 2012; 2(1) : 3-7).
1. Department of Physiology, Uttara Adhunik Medical College,
Dhaka
2. Department of Physiology, BSMMU, Dhaka
3. I.C.U. UttaraAdhunik Medical College Hospital, Dhaka
4. Department of Biochemistry, UttaraAdhunik Medical College,
Dhaka
Address of Correspondence : Dr. Matia Ahmed, Assistant
Professor, Department of Physiology, Uttara Adhunik Medical
College, Dhaka

3. Some studies found evidence of lower a and â
adrenergic sensitivity in hypothyroid patients.1,4
Power spectral analysis of HRV can demonstrate the
definite impairment in cardiac autonomic control, which
is highly accepted for detection of sympatho-vagal
imbalance1,5
Among time domain measure mean heart rate ,SDNN
and RMSSD was lower in hypothyroids than euthyroids
which are consistent with the findings of different
investigators.6,7,8,9,10.
Again, among frequency domain measures Lower
value of total power, LF power HF power HF norm and
higher value of LF norm and LF/HF ratio were found in
untreated hypothyroids than euthyroids. 8,9,11
Therefore, the present study has been designed to
assess the autonomic nerve function status in
hypothyroid patients. In addition, the relationships
among the thyroid hormone and HRV parameters were
also observed in order to explore any relationships
among them. This study may be useful in screening
of autonomic nerve function status in hypothyroidism
in order to minimize hypothyroid related
complications.
Study procedure:
After selection, the subject was thoroughly informed
about the aim, objectives and detail procedure of the
study before examination and collection of blood
sample. They were encouraged for voluntary
participation and they allowed freedom to withdraw
from the study whenever they liked even after
participation. If they agreed to enroll to the study,
informed written consent were taken from them. For
examination the subjects were advised to have their
meal by 9:00 pm on previous night, to remain free
from any physical or mental stress, not to take any
drugs affecting central nervous system and to have a
good sleep at night before the examination day. The
subjects were advised to avoid tea or coffee at
breakfast and to attend theAutonomic Nerve Function
Test Laboratory
Between 9:00 to 11:00 a.m. on the day of examination
the subjects were interviewed and detail history
regarding personal history, drug history, past medical
history was taken to exclude exclusion criteria. Then
thorough physical examinations and anthropometric
parameters like height, weight, BMI, were taken and
the information were recorded in a prefixed
questionnaire. Then the subjects were kept under
complete bed rest in supine position for 20 minutes in
a cool and calm environment. During this period they
were advised not to talk, eat or drink and also not to
perform physical or any mental activity, even sleep.
Then all preparations for recording of the Heart Rate
Variability parameters were made by connecting the
channels of ECG and 5 minutes recording was taken
in resting supine position and the HRV parameters
were studied by Time and Frequency domain
method.At the end of recording ,5ml of venous blood
wasdrawnfromthesubjects.Theserumlevelofthyroid
hormone was measured by Microparticle enzyme
Immuno assay(MEIA) method.
Results :
All the subjects were matched for age and BMI and
no statistically significant differences were observed
among them.(Table I)
Table I
Age and BMI in different groups (n=90)
Groups Age (years) BMI (kg/m2)
A 38.23±6.3 24.13±3.2
(n=30) (30-50) (16-31)
B1 39.13±6.4 23.7±4.7
(n=30) (30-50) (17-36)
B2 36.33±6.1 23.8±3.8
(n=30) (30-50) (17-31)
Statistical analysis:
Groups p values
A vs. B1 vs. B2
a 0 .668 ns 0.593 ns
A vs. B1
b 0 .946ns 0.706ns
A vs. B21
b 0.457 ns 0.720 ns
B1 vs. B21
b 0.456 ns 0.953 ns
Data were reported as mean ± SD. Figures in parentheses
indicate ranges.
Statistical analysis were done by One way ANOVAa and
Independent sample t test b.
BMI = Body Mass Index.
Group A: Apparently healthy Euthyroids. (control)
Group B: Hypothyroid (study group)
B1 : Untreated .
B2 : Treated .
ns=p>0.05
n=number of subjects.
The mean serrum TSH was significantly
higher(p<0.000) and FT4 was significantly lower
(p<0.000) in group B1 than those of group A and B2.
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4

4. But no statistically significant difference was observed
between group A and B2.(table II)
Table II
Serum TSH and FT4 levels in different
groups (n=90)
Groups TSH(mIU/L) FT4(pmol/L)
A 2.18±1.04 15.13±4.21
(n=30) (0.5-4.1) (10-23)
B1 38.16±30.50 5.12±1.89
(n=30) (8.2-90) (1.5-8.7)
B2 2.04±1.01 15.08±3.95
(n=30) (0.47-4) (9.5-23)
Statistical analysis:
Groups p values
A vs B1 vs B2
a 0.000*** 0.000***
A vs B1
b 0.000*** 0.000***
A vs B2
b 0.608ns 0.964ns
B1 vs B2
b 0.000*** 0.000***
TSH =Thyroid stimulating hormone FT4= Thyroxin (Free form.
*** = P<0.001.
ns =. P>0.05
n = number of subjects.
Themeanvalueofheartratewassignificantly(p<0.001)
lower in group B1 than those of group Aand group B2.
But no statistically significant differences were
observed between groupAand B2.
The mean SDNN and RMSSD were significantly lower
in group B1 than that of group A (p<0.004) and B2
compared to B1 (p<0.009). But there were no
statistically significant difference between groupAand
B2 (p<0.974)
Table III
Statistical time domain measures of HRV (5 min
recording) in different groups (n=90)
Groups SDNN(ms) RMSSD
A 64.16±18.25 41.03±38.16
(n=30) (36.82-85.38) (5.1-89)
B1 50.16±17.43 20.65±20.73
(n=30) (30.24-78.3) (2.57-62.5)
B2 63.99±21.87 41.10±40.59
(n=30) (35-89) (4.6-93)
Statistical analysis:
Groups P values
A vs B1 vs B2
a 0.007** 0.033*
A vs B1
b 0.004** 0.013*
A vs B2
b 0.974 ns 0.995ns
B1 vs B2
b 0.009** 0.017*
SDNN=Standard deviation of NN interval,
NN interval= Normal to normal intervals(Interval
between adjacent QRS complexes from SA node
depolarization)
RMSSD=Square root of mean squared differences of
successive NN intervals, ms=millisecond.
The mean of LF norm, HF norm and LF/HF ratio of all
groups showed statistically highly significant (p<0.000)
differences among them. The mean value of LF n.u
and LF/HF ratio were significantly higher ( p<0.000)
and HF norm was significantly lower in group B1
compared to A and B2.But statistically no significant
differences observed between groupAand group B2.
Table IV
Frequency domain measures of HRV(5 min
recording) in different groups (n=90)
Groups LFnorm(nu) HFnorm(nu) LF/HF
A 63.71±4.07 36 .35±4.12 1.70.3
(n=30) (55.2-70) (30-44.8) (1.2-2.3)
B1 75.32±4.85 24.79±4.89 3.16±.84
(n=30) (68-82.7) (17.3-32) (2.1-4.7)
B2 65.90±5.23 34.55±4.67 1.93±.58
(n=30) (55.1-75.3) (26-44.9) (1.1-2.9)
Statistical analysis:
Groups P values
A vs B1 vs B2
a 0.000*** 0.000*** 0.000***
A vs B1
b 0.000*** 0.000*** 0.000***
A vs B2
b 0.161ns 0.105ns 0.982ns
B1 vs B2
b 0.000*** 0.000*** 0.000***
LFnorm.= LF power in normalized unit,[{LF/total power-VLF}×100]
HF norm.=HF power in normalized unit,[{LF/total power-
VLF}×100] LF/HF= ratio of low frequency and high frequency.Fig.-1: Mean heart rate in different groups
Assessment of Cardiac Autonomic Nerve Function Status by Heart Rate Variability in Hypothyroidism Matia Ahmed et al
5

5. Discussion:
The present study was undertaken to observe the heart
rate variability (HRV) in patients with hypothyroidism
in order to assess their cardiac autonomic nervous
activity. Serum TSH and FT4 levels were also
measured to determine their thyroid hormonal status
and polygraphic recording of HRV was performed to
evaluate some aspects of cardiac autonomic nerve
function status in these hypothyroid patients. The
individual status of both the sympathetic and
parasympathetic nervous system were assessed and
their ratio was also measured to determine their
dominance. Correlations of HRV parameters with
serum TSH level were also studied in order to observe
any relationship among them. All these parameters
were also studied in healthy age and sex matched
adults for comparison (control).
In the present study, the autonomic nerve function
status assessed by HRV parameters in healthy control
group were almost similar to the findings reported by
the various investigators from different countries
1,11,12,13 and also from our country!4,15,16,17.
However ,in our country no published data of these
HRV parameters in hypothyroid patients were available
for comparison.
Serum glucose and creatinine levels were estimated
in all subjects of the present study in order to exclude
presence of diabetes mellitus and chronic renal failure.
In the present study, serumTSH and serum FT4 levels
were measured in all the subjects in order to determine
their thyroid hormonal status. The serum TSH level
was significantly (p<0.001) higher in untreated
hypothyroids than treated hypothyroid patients and
healthy control. However, no statistically significant
difference of serum TSH was observed between the
healthy control and hypothyroid patient after
treatment.The serum FT4 levels were significantly
(p<0.001) lower in untreated hypothyroids in
comparison to healthy euthyroids and treated
hypothyroids .
In this study, mean heart rate, SDNN and RMSSD
were observed to assess the HRV in all subjects. The
mean heart rate, SDNN and RMSSD was significantly
(p<0.001) lower in untreated hypothyroids than those
of healthy control and also that of treated
hypothyroids. But this value showed statistically no
significant difference in treated hypothyroids with that
of healthy control.
in this study, findings suggested that medication return
the heart rate towards the normal. these findings were
consistent with the findings of some other
investigators.1,7,18 Similar significant change in SDNN
values was observed by other investigator.6,9,10
In this study, the LF n.u. and LF/HF ratio were
significantly (p<0.001) higher and HF norm
significantly(p<0.001) lower in untreated hypothyroids
in comparison to that of healthy control. But no
statistical significance difference was observed
between healthy control and treated hypothyroids.
Similar type of findings were also observed by
investigator of different countries.6,10,11
Table V
Correlation of heart rate variability measures with serum TSH level indifferent groups (n = 90)
HRVMeasures Groups
A B1 B2
r p r p r p
Time domain
Mean R-R + 0.093ns 0.652 +0.037 ns 0.844 + 0.153 ns 0.420
Mean HR -0.076 ns 0.690 -0.328 ns 0.077 - 0.073ns 0.701
Frequency domain
Total power + 0.199 ns 0.292 - 0.363 * 0.049 + 0.331 0.074
LF norm + 0.084ns 0.660 + 0.455 * 0.012 + 0.082 n 0.668
HF norm + 0.191 ns 0.311 - 0.419 * 0.021 +0.295ns 0.113
LF/HF - 0.102 ns 0.590 + 0.459 * 0.011 -0.012ns 0.951
Results were analysed by Pearson’s correlation coefficient (r) test.
J Uttara Adhunik Med. College Vol. 02, No. 01, January 2012
6

6. Higher values of LF power and LF n.u. power are
suggestive of sympathetic hyperactivity, whereas lower
values of HF power and HF n.u. power indicate
decrease parasympathetic contribution. It has also
been suggested that increased LF/HF ratio indicate
imbalanced sympathovagal status. Moreover,
significant positive correlation of LF n.u. and LF/HF
ratio and significant negative correlation with HF norm
with serum TSH level, further support autonomic
dysfunction .
Again, improvement of cardiac autonomic functional
state in treated hypothyroids suggested that treatment
improve this dysfunctional state.
Conclusion:
It is difficult to comment on the exact mechanisms
involved for the impairment of cardiac autonomic
nervous activity in hypothyroids with this small sample
size. Therefore to be more conclusive measurement
of serum or urinary catecholamines level and also
assessment of cardiovascular sensitivity to
catecholamines in larger sample size may be helpful.
References:
1. Polikar R, Burger AG, Scherrer U, Nicod P. The thyroid and
the heart. Circulation 1993, 87; 1435-1441
2. Task force of The European Society of Cardiology and
The North American Society of Pacing and
Electrophysiology. Heart Rate Variability: Standards of
measurement, physiological interpretation and clinical use.
Euro Heart J. 1996; 17: 354-381.
3. Polikar R, kennedy B,MaiselA,Ziegler M, Smith J, Dittrich H
and Nicod P.Decreased adrenergic sensitivity in patients
with hypothyroidism.Journal of the American college of
cardiology.1990; 15: 94-98.
4. Stys A, Stys T. Current clinical applications of heart rate
variability. Clin Cardiol. 1998; 21(10): 719-724.
5. Galetta F,Frazoni F,.Fallahi P.Rossi M, Carpi.A, Rubello
Antonelli A,Santoro G.Heart rate variability and QT
dispersion in patients With subclinical hypothyroidism
Biomedicine& Pharmacotherapy 60, 2006, 425-430.
6. Inukai T, Takanashi K, Kobayashi H, Fujiwara Y, Tayama
K, Aso Y, Takemura Y. Power spectral analysis of
variations in heart rate in patients with hyperthyroidism or
hypothyroidism. Horm Metab Res. 1998; 30: 531-535.
7. Galetta F,.Frazoni, F,Fallahi. P,Tocchini.L, Braccini L,
Santoro G, Atonelli, A.Changes in heart rate variability
and QT dispersion in patients with overt hypothyroidism.
Eur J Endocrinol 2008,158:85-90.
8. Sahin I,Turan N,Kosar F.Evaluation of autonomic activity
in patient with subclinical hypothyroidism.J. Endocrinol.
Invest. 2005, 28:209-213
9. Xing H,Shen Y, Chen H, Wang y,Shen W.Heart rate
variability and its response to thyroxine replacement
therapy in patient with hypothyroidism.Clin Med J 2001,
114: 906-8.
10. Cacciatori V,Gemma ML,Bellevare F. Power spectral
analysis of heart rate in hypothyroidism.Eur J Endocrinol.
2000;143:327-33.
11. Nielsen, Friis S,Haunso S, Jensen T. Increased
sympathetic tone in forearm subcutaneous tissue in
primary pothyroidism.Clinical Physiology 1987, 7; 297-
302
12. Fagius J, Westermark K, KarlssonA. Baroreflex-governed
sympathetic outflow to muscle vasculature is increased
in hypothyroidism. Clin Endocrinol. 1990; 33(2): 177-185.
13. Manhem P, Bramnert M, Hallengren B, Lecerof H, Werner
R.Increased arterial and venous plasma noradrenalin
levels in patient with hypothyroidism during hypothyroid
as compared to euthyroid state. J Endocrinol Invest
1992;15 (10): 763-5
14. Alom M. Study on heart rate variability in adolescent male
athlete [Thesis] [Dhaka (Bangladesh)]: BSMMU. 2008
July
15. Kabir R.Study on heart rate variability in patient with
hypothyroidis [Thesis] [Dhaka (Bangladesh)]: BSMMU.
2008 July.
16. Mithun S.Comparative study of cardiac autonomic nerve
function status by heart rate variability between sedentary
and heavy worker [Thesis] [Dhaka (Bangladesh)]:
BSMMU. 2009 July.
17. Tabassum R. Assessment of cardiac autonomic nerve
function status by heart rate variability in essential
hypertension. [Thesis] [Dhaka (Bangladesh)]: BSMMU.
2009 July.
18. Ojamaa K, Balkman C, Klein I. Acute effects of
triiodothyronine on arterial smooth muscle cells. Ann
Thorac Surg. 1993; 56(1): S66-67.
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