COMPARISON BETWEEN WEEKLY VS DAILY

DOSING L-THYROXINE FOR THE TREATMENT OF

HYPOTHYROIDISM IN RAMADAN – A PILOT

RANDOMIZED CONTROLLED TRIAL

BY

NURUL AULIA BINTI ZAKARIA

A dissertation submitted in fulfilment of the requirement for

the degree of Master of Medicine (Internal Medicine)

Kulliyyah of Medicine

International Islamic University Malaysia

DECEMBER 2018

ii

ABSTRACT

INTRODUCTION: Hypothyroidism, a common endocrine disorder, also affects

Muslims who fast during the month of Ramadan. Muslim who fast during Ramadan

find it difficult to take Levothyroxine (L-thyroxine) as recommended every morning

on empty stomach during sahur. Furthermore, the changes in eating patterns and

gastric motility during Ramadan might affect the absorption and efficacy of L-

thyroxine replacement. OBJECTIVE: (1)To compare the efficacy of weekly vs daily

L-thyroxine dosing, in terms of changes in thyrotropin (TSH), free T4 (fT4) and free

T3 (fT3) (2) To compare the frequency of side-effects of weekly vs daily dosing of L-

thyroxine in Ramadan in terms of symptoms, cardiac function, lipid parameters,

cognitive and psychological function. (3) To assess patient’s preference of L-

thyroxine dosing during Ramadan. METHOD: This is a randomized open-label

controlled trial among hypothyroid patients on L-thyroxine replacement who fasted

during Ramadan 2017 and 2018 in a tertiary centre located in Kuantan. Hypothyroid

patients who fulfil the inclusion criteria were randomized into two arms, weekly (W)

and daily (D) arm. The weekly arm took seven times their usual L-thyroxine dose at

least 30 minutes pre-sahur once a week whereas the daily arm took their usual L-

thyroxine dose daily at least 2 hours after their last meal before bed. Thyroid function

test (TSH, fT3, fT4), cardiac parameters (electrocardiography, echocardiography and

24-hours Holter monitoring), symptoms, cognitive and psychological assessment were

done at week zero, w0 (baseline). A repeat cardiac assessment was done at week 2

(w2) for the weekly arm within 24-hours of high dose L-thyroxine administration. At

the end of week 4 (w4), thyroid function, lipid parameters, symptoms, cognitive and

psychological assessment of both group were reassessed. Patient’s preference for

weekly arm were assessed on their last visit at week 4. The efficacy, safety and

patient’s preference were analysed. RESULTS: A total of eighteen patient were

randomized into two groups (n = 9 for each arm). The median age of the patients for

weekly and daily group were [W 34(27.5,48.5); D 45(36.5,51); p=0.22] with majority

(66.7% each arm) were diagnosed with post-radioiodine hypothyroidism. All other

parameters were comparable at baseline. At the end of study, there were no significant

change in the median level of thyroid hormones for weekly arm however significant

increment of TSH was observed in daily arm [TSH w0 1.8(0.23,5.57) vs w4

3.65(0.45,16.1); p= 0.011]. Thyroid hormones levels between both arms were

comparable at the end of study. There was no hyperthyroid symptoms or cardiac

toxicity observed despite significant increment of fT4 within 24hours of weekly

dosing [fT4 w0 13.21(8.19,14.63) vs w2 17.43(12.38,22.55); p=0.011]. All patients

were euthyroid and no side effects were reported at the end of study. Majority (83.3%)

of patients prefer weekly dosing of L-thyroxine during Ramadan. CONCLUSION:

From this pilot study, weekly L-thyroxine dosing during Ramadan appeared to be safe

and efficient and was the more preferred dosing method.

iii

APPROVAL PAGE

I certify that I have supervised and read this study and that in my opinion, it conforms

to acceptable standards of scholarly presentation and is fully adequate, in scope and

quality, as a thesis for the degree of Master of Medicine (Internal Medicine)

…………..……………………………..

Mohammad Arif Bin Shahar

Supervisor

………….……………………………..

Azarisman Shah Bin Mohd Shah

Co-Supervisor

I certify that I have read this study and that in my opinion it conforms to acceptable

standards of scholarly presentation and is fully adequate, in scope and quality, as a

thesis for the degree of Master of Medicine (Internal Medicine)

………………….……………………..

Ahmad Marzuki Bin Omar

Internal Examiner

This dissertation was submitted to the Department of Internal Medicine and is

accepted as a fulfilment of the requirement for the degree of Master of Medicine

(Internal Medicine)

……………….………………………..

Che Rosle Bin Draman

Head, Department of Internal Medicine

This dissertation was submitted to the Kulliyyah of Medicine and is accepted as a

fulfilment of the requirement for the degree of Master of Medicine (Internal Medicine)

………………….……………………..

Azmi Bin Md Nor

Dean, Kulliyyah of Medicine

iv

DECLARATION

I hereby declare that this dissertation is the result of my own investigations, except

where otherwise stated. I also declare that it has not been previously or concurrently

submitted as a whole for any other degrees at IIUM or other institutions

Nurul Aulia Binti Zakaria

Signature..................................................... Date.........................................

v

INTERNATIONAL ISLAMIC UNIVERSITY MALAYSIA

DECLARATION OF COPYRIGHT AND AFFIRMATION OF

FAIR USE OF UNPUBLISHED RESEARCH

COMPARISON BETWEEN WEEKLY VS DAILY DOSING

L-THYROXINE FOR THE TREATMENT OF

HYPOTHYROIDISM IN RAMADAN- A PILOT RANDOMIZED

CONTROLLED TRIAL

I declare that the copyright holders of this dissertation are jointly owned by the

student and IIUM.

Copyright © 2018 .Nurul Aulia Binti Zakaria and International Islamic University Malaysia. All

rights reserved.

No part of this unpublished research may be reproduced, stored in a retrieval

system, or transmitted, in any form or by any means, electronic, mechanical,

photocopying, recording or otherwise without prior written permission of the

copyright holder except as provided below

1. Any material contained in or derived from this unpublished research

may be used by others in their writing with due acknowledgement.

2. IIUM or its library will have the right to make and transmit copies

(print or electronic) for institutional and academic purposes.

3. The IIUM library will have the right to make, store in a retrieved

system and supply copies of this unpublished research if requested by

other universities and research libraries.

By signing this form, I acknowledged that I have read and understand the IIUM

Intellectual Property Right and Commercialization policy.

Affirmed by Nurul Aulia Binti Zakaria

……..…..…………….. ………………………..

Signature Date

vi

ACKNOWLEDGEMENTS

In the name of Allah S.W.T, The Most Gracious and Most Merciful, I would like to

thank Him for giving me guidance and strength to complete this dissertation.

Thank you to my dedicated and helpful supervisor, Associate Professor Dr.

Mohammad Arif Bin Shahar for helping me throughout this research journey. I would

also like to thank the endocrine team of HTAA especially Dr Miza Hiryanti and Dr

Goh Kian Guan for their contribution in this research. Not to forget all the support

staff especially cardio technician Siti Asiyah Bt Kamarudin, Nasrul Naim Bin Rosli

and all medical clinic staff.

A special thanks to my husband and my family for their endless support and

encouragement. Finally, thank you to all who contributed to this research either

directly or indirectly, only Allah S.W.T can repay your deeds.

vii

TABLE OF CONTENTS

Abstract .......................................................................................................................... ii

Approval Page ............................................................................................................... iii Declaration .................................................................................................................... iv Acknowledgements ....................................................................................................... vi List of tables .................................................................................................................. ix List of figures ................................................................................................................. x

Abbreviations ................................................................................................................ xi

CHAPTER ONE: INTRODUCTION ........................................................................ 1

1.1 Background of the Study .............................................................................. 1 1.2 Statement of the Problem ............................................................................. 2 1.3 Hypothesis .................................................................................................... 2 1.4 Research Objectives ..................................................................................... 2

CHAPTER TWO: LITERATURE REVIEW………………………………………………3

2.1 L-Thyroxine Intake During Ramadan .......................................................... 3

2.2 Physiological Changes & Challenges in Ramadan....................................... 4 2.3 Consequences of Inadequate Thyroxine Replacement ................................. 5 2.4 Weekly Dosing in Ramadan ......................................................................... 5

CHAPTER THREE: METHODOLOGY ................................................................. 7 3.1 Study Design................................................................................................. 7

3.2 Study Population........................................................................................... 7

3.3 Sample Size .................................................................................................. 7 3.4 Ethics and Funding ....................................................................................... 8 3.5 Inclusion and Exclusion Criteria .................................................................. 8

3.6 Study Visit and Procedure ............................................................................ 9 3.7 Materials And Tool ..................................................................................... 13

3.7.1 Billewicz Score (Hypothyroid) ........................................................ 13 3.7.2 Zulewski’s score (Hypothyroid) ...................................................... 13 3.7.3 Wayne’s score (Hyperthyroid) ......................................................... 13

3.7.4 Mini Mental State Examination (MMSE) ........................................ 14 3.7.5 Depression Anxiety Stress Scale (DASS21) .................................... 14

3.7.6 Serum Assay for Thyroid Hormones & Lipid profile ...................... 15 3.7.7 Cardiac Assessment Equipment ....................................................... 15

3.8 Study Outcome ........................................................................................... 16

3.9 Statistical Analysis ..................................................................................... 17

CHAPTER FOUR: RESULT AND DISCUSSION ................................................ 18 4.1 Baseline Characteristics .............................................................................. 18

4.2 Efficacy – Thyroid Hormones .................................................................... 21 4.3 Side Effect .................................................................................................. 24

4.3.1 Thyroid Hormones after High Dose L-Thyroxine ........................... 24 4.3.2 Cardiac Parameters after High Dose L-thyroxine ............................ 25

viii

4.3.3 Cognitive / Psychological / Symptoms ............................................ 25

4.3.4 Lipid Parameters .............................................................................. 27 4.4 Patient’s Preference .................................................................................... 27 4.5 Limitation ................................................................................................... 28

4.6 Discussion…………………………………………………………………28

CHAPTER FIVE: CONCLUSION AND CLINICAL IMPLICATION…………………33

REFERENCES ……………………………………………………………………………...35

APPENDIX A ……………………………………………………………………………….38

APPENDIX B ............................................................................................................. 44 APPENDIX C ............................................................................................................. 45 APPENDIX D ............................................................................................................. 55

ix

LIST OF TABLES

Table 4.1 Baseline Characteristic 19

Table 4.2 Median level of Thyroid Hormones Pre-Post Ramadan 21

Table 4.3 Cardiac Parameters in weekly arm within 24 hrs of L-thyroxine

ingestion 25

Table 4.4 Cognitive, Psychological, Symptoms Assessment Week 4 26

Table 4.5 Lipid Parameters Week 4 27

x

LIST OF FIGURES

Figure 3.1 Visit & procedure 11

Figure 3.2 Flow chart study 12

Figure 4.1 Median level of thyroid hormones pre-post Ramadan 22

Figure 4.2 Absolute change of thyroid hormone at the end of Ramadan 23

Figure 4.3 Median level of thyroid hormones within 24hrs of high

dose L-Thyroxine ingestion 24

Figure 4.4 Preference of dosing method during Ramadan 28

xi

ABBREVIATIONS

L-thyroxine Levothyroxine

TSH Thyroid stimulating hormone

fT3 Free Triiodothyronine

fT4 Free Thyroxine

Vs Versus

HTAA Hospital Tengku Ampuan Afzan Kuantan

IIUMMC International Islamic University Malaysia (IIUM)

Medical Centre

RWMA

STI

Regional wall motion abnormality

Systolic time interval

pmol/L Pico-mole/litre

mmol/L Milli-mole/litre

mIU/L Milli-International Unit/Litre

CVD

Cardiovascular disease

1

CHAPTER ONE

INTRODUCTION

1.1 BACKGROUND OF THE STUDY

Hypothyroidism, a common endocrine disorder, also affects Muslims who fast during

the month of Ramadan. However, to date, guidelines and recommendations on

management of hypothyroidism and Levothyroxine (L-thyroxine) replacement during

Ramadan are scarce. Furthermore many recommendations are made based on

postulations not substantiated by clinical studies. L-thyroxine should be taken on

empty stomach usually 30 minutes before breakfast to ensure optimal absorption. In

Ramadan, patient may find it difficult to wake up early before sahur to take their L-

thyroxine and in many cases L-thyroxine are taken with sahur meal or even missed.

Weekly thyroxine replacement is an experimental regime of L-thyroxine replacement

that may be considered for fasting patient to help them comply to treatment. Thus the

objective of this study is to compare the efficacy, side effects and patient preference of

daily vs weekly L-thyroxine replacement for Muslims in the month of Ramadan. This

will be a four-week pilot randomized open labelled clinical trial involving

hypothyroid patients taking weekly L-thyroxine replacement vs daily dosing. Data on

efficacy (serum thyroid stimulating hormone (TSH) levels, free T4 levels and T3

levels changes, hypothyroid symptoms, cognitive and psychological dysfunction),

cardiovascular side effects, and patients’ preferences will be collected.

Comparative analysis of efficacy, side effects and patients’ preference of weekly and

daily L-thyroxine dosing will be done. The results from this study will be used as

recommendation for management of hypothyroid patients on L-thyroxine during

Ramadan.

2

1.2 STATEMENT OF THE PROBLEM

Compliance is an issue in taking L-thyroxine during Ramadan as the medication need

to be taken on empty stomach before sahur. Missed medication or improper

absorption of L-thyroxine will lead to hypothyroidism. Weekly dosing instead of daily

dosing of L-thyroxine during Ramadan specifically will improve patient’s compliance

and render good thyroxine supplementation in hypothyroid patients.

1.3 HYPOTHESIS

i. Weekly L-thyroxine dosing is as good as daily dosing in terms of efficacy

(<30% change in TSH, free T4 and free T3)

ii. There is no increase in the frequency of side effects in weekly L-thyroxine

(Symptoms, cardiac toxicity, psychological and cognitive function, lipid

level)

iii. Patients prefer weekly dosing compared to daily dosing during the month

of Ramadan.

1.4 RESEARCH OBJECTIVES

i. To compare the efficacy of weekly L-thyroxine dosing with daily dosing

(in terms of changes in TSH, free T4, free T3) during Ramadan

ii. To compare the frequency of side effects of weekly thyroxine dosing

from daily L-thyroxine dosing during Ramadan (in terms of symptoms,

cardiac toxicity, cognitive and psychological function and lipid level)

iii. To determine patient’s preference of dosing method of L-thyroxine

(weekly vs daily) during Ramadan.

3

CHAPTER TWO

LITERATURE REVIEW

2.1 L-THYROXINE INTAKE DURING RAMADAN

Recommendations of management of hypothyroidism in Ramadan are mainly based

on postulations. Several papers on hypothyroidism, Levothyroxine (L-thyroxine)

replacement and Ramadan have been published to date (Raza et al, 2012; Karoli et al,

2013; Hadjzadeh et al, 2014; Azizi, 2015). However these recommendations are made

based on physiological changes of thyroid hormone during fasting, L-thyroxine

pharmacokinetics and dynamics. Hadjzadeh et al, 2015 for example, recommended

that L-thyroxine dose be increased at the end of Ramadan based on literature review

on thyroid hormone profile, hypothyroidism, fasting and food restriction in animal and

human studies. Azizi, 2015 mentioned that although there are changes in thyroid

stimulating hormone (TSH) and reduction in thyroxine (T4) during Ramadan, the

patient remained biochemically euthyroid. An increase in dose may not be necessary;

however, food intake in relation to the timing of L-thyroxine administration should be

taken into consideration. Thus, he postulated that the best time for L-thyroxine

administration is at least half an hour before sahur. Raza et al (2012) on the other

hand recommend that L-thyroxine should be taken at bedtime rather than before

sahur.

The only clinical study looking at different treatment regimes in Ramadan is

published by Karoli et al (2013). She compared evening dose L-thyroxine in the

month of Ramadan as an alternative to morning administration of the drug. She

conducted an observational prospective study comparing hypothyroid patients who

4

takes L-thyroxine prior to Ramadan and evening dose (pre-bed) during the month of

Ramadan. She noted that variation in TSH level (ranging from 0.6-8 mIU/l) in

Ramadan was associated with the timing of L-thyroxine ingestion pre-bed and

subsequently recommended that L-thyroxine should be taken at least two hours after

last meal before bedtime.

All patients remained euthyroid despite changes in TSH levels and she

concluded that pre-bed L-thyroxine is a reasonable option for L-thyroxine replacement

in the month of Ramadan. No other randomized clinical trial comparing different

regimes of L-thyroxine replacement in Ramadan are available to date.

2.2 PHYSIOLOGICAL CHANGES & CHALLENGES IN RAMADAN

During Ramadan, changes in gastric motility (due to prolonged fasting), interference

with heavy meals, possible alteration in the circadian rhythm and the effect of the

deiodinase activity might alter the absorption and metabolism of the L-thyroxine in

the body (Raza et al, 2012). Apart from physiological changes patients experienced

during Ramadan, patients may also find it difficult to wake up early just for

administration of L-thyroxine before sahur (Azizi, 2015, Raza et al, 2012). This may

be a cause for non-compliance. Previous study on drug intake during Ramadan

observed that >50% of patients didn’t comply with drug intake and some even stop

taking their medications during Ramadan (Aslam et al, 1986).

Both factors (physiological changes and non-compliance) may contribute to

suboptimal L-thyroxine replacement in hypothyroid patients during Ramadan.

5

2.3 CONSEQUENCES OF INADEQUATE THYROXINE REPLACEMENT

The effect of inadequate L-thyroxine replacement includes hypothyroid symptoms,

cognitive and psychological function and metabolic profile abnormalities such as

dyslipidemia. Hypothyroid symptoms and dyslipidemia from hypothyroidism are well

known and widely discussed. The association between cognitive and psychological

dysfunction is well established (Samuels, 2015). Interestingly, cognitive and

psychological functions among hypothyroid patients are also affected even if they are

adequately replaced. Wekking et al, (2005) reported that hypothyroid patients showed

poor performance in various neurocognitive functions despite being adequately

replaced (TSH within reference range). Samuels et al, (2007) also reported that

hypothyroid patients have decrement in health status, psychological functions and

working memory despite being adequately replaced biochemically.

Therefore, hypothyroid patients who fast during Ramadan are also at risk of

developing such complications especially when the risk of compliance and suboptimal

replacement is present. Furthermore patient may experience cognitive and

psychological symptoms despite normal TSH level. Unfortunately, to date, no study

on assessment of hypothyroid symptoms, metabolic derangements, cognitive and

psychological function has been done on fasting hypothyroid patient in the month of

Ramadan.

2.4 WEEKLY DOSING IN RAMADAN

Weekly L-thyroxine is a feasible option to improve compliance and to ensure

adequate replacement during Ramadan. Weekly L-thyroxine dosing has been

investigated as an alternative regime to overcome non-adherence. Grebe et al (1996)

found that weekly administration of L-thyroxine causes slight increase in TSH level,

6

however patient remained euthyroid. There was no evidence of thyroxine toxicity

including cardiac complications. Bornschein et al (2015) reported that weekly dosing

cause slightly higher T4 levels after administration of thyroxine and low levels at the

end of the week. However TSH levels remained in euthyroid range. There was also no

increase in hyperthyroid symptoms and cardiac complications following the weekly

administration of thyroxine. Weekly regime has not been tested during Ramadan.

Considering the interplay between the unique physiological and lifestyle

changes during the month of Ramadan, it would be of interest to see whether weekly

thyroxine dosing would be able to sustain euthyroid state clinically, cognitively,

psychologically and biochemically compared from daily dosing in the holy month of

Ramadan.

7

CHAPTER THREE

RESEARCH METHODOLOGY

3.1 STUDY DESIGN

This is a randomized, open label, parallel two arm trial. Samples were randomized via

simple randomization (drawing lots). Sample were randomized into weekly (W) and

daily (D) arm. This study was approved by the Malaysia Medical Research and Ethics

Committee (MREC) and IIUM Research Committee (IREC)

3.2 STUDY POPULATION

Hypothyroid patients from HTAA / IIUM Medical Centre who met the inclusion and

exclusion criteria.

3.3 SAMPLE SIZE

Sample size was calculated via open epi using mean difference. Based on study by

Grebe et al, Treatment of hypothyroidism with once weekly thyroxine sample size was

calculated by using means of T4 at 24hrs with G1 (daily) and G2 (weekly) were

246pg/dl ±25 and 285pg/dl ±42, respectively. The calculated sample size is 13

subjects each arm. Considering 20% dropout the sample size for this study will be 15

each arm with a total of 30.

8

3.4 ETHICS AND FUNDING

This study has been funded by IIUM Research Initiative Grant (RIGS) and has

received ethics approval from :

1. Malaysia Medical Research and Ethics Committee (MREC) ;

NMRR-17-621-34080

2. IIUM Research Ethics Committee (IREC) : IREC 757

3.5 INCLUSION & EXCLUSION CRITERIA

INCLUSION EXCLUSION

Hypothyroid patient from any causes;

(e.g. Primary hypothyroidism, post

thyroidectomy, post radio-ablative iodine

therapy)

Taking L-thyroxine for other indications

(e.g. TSH suppression therapy for

thyroid carcinoma)

Secondary hypothyroidism

Taking L-thyroxine therapy Presence of co-morbidity (uncontrolled

diabetes mellitus, uncontrolled

hypertension, ischaemic heart disease,

chronic kidney disease, familial

dyslipidemia, high Framingham CVD

risk score (score >10)

Age 18-60 years old Pregnant

Fast during Ramadan Patient taking any medication or any

preparation which may interfere with L-

thyroxine absorption such as calcium,

anti-tuberculous drugs, anti-epileptics

etc.

On stable dose of thyroxine (at least 1

month)

Patients with any abnormalities either on

resting ECG, Echocardiography and/or

24-hours Holter ECG monitoring.

(Abnormalities that investigator

consider as clinically significant e.g.:

heart block, arrhythmia, ischemia,

frequent ectopic, poor EF <45%,

significant valve lesion or

cardiomyopathy etc.)

BMI >30 kg/m²

9

3.6 STUDY VISIT AND PROCEDURE

This was a parallel two arm study that was conducted in Ramadan 2017 and 2018. A

total of sixty one patients were invited to join this study, however only twenty two

patients were interested and consented. They underwent screening process which

includes symptoms, cognitive, psychological assessment, blood investigations (thyroid

hormones, lipid profile) and cardiac screening (electrocardiography,

echocardiography, 24-hours Holter monitoring). Four out of twenty two patients were

excluded; one patient- overt hypothyroid, two patients- overt hyperthyroid, one

patient- cardiac arrhythmia. Total of eighteen patients were randomized into two arms;

weekly and daily arm. We used simple randomization in which patients were divided

into two arms by drawing lots. The patients in weekly arm took seven times their

usual L-thyroxine dose at least 30 minutes pre-sahur once a week while patients in

daily arm took their usual dose of L-thyroxine daily at least two hours after their last

meal before bed. Patients were started on their allocated dosing regime on the first day

of Ramadan. There was no washed out procedure done prior starting the study as all of

the patients were on daily regime before enrollment. We chose pre-sahur dosing

period for weekly arm to avoid any high dose toxicity occurring at night if it is taken

pre-bed. However patients in daily arm took L-thyroxine pre-bed for their

convenience’s sake. The timing is important as the absorption of thyroxine is best on

empty stomach.

Patients were assessed using Billewicz and Zulewski’s score for

hypothyroidism and Wayne’s score for hyperthyroidism, cognitive assessment via

Mini Mental State Examination (MMSE) and psychologically using DASS21 scoring

system. Ten mililitres (10 mls) of blood samples were taken on every visit using plain

tubes. Blood will be left to sit for 30 minutes then centrifuged at 3500 rpm for 10

10

minutes. The serum will be tested for thyroid stimulating hormone (TSH), free

thyroxine (free T4), free triiodothyronine (free T3) and lipid profile at a centralized

laboratory. All specimen will be discarded after three months.

Clinical and laboratory assessment were done at baseline (week 0) and week 4

for both arms. Repeated cardiac assessment (only for weekly arm) was done at week 2

(24-hours within the weekly L-thyroxine administration). Patient’s diary was reviewed

at every visit to ensure compliance. During the last visit (week 4) patient’s preference

was assessed by asking few question regarding preference as stated in clinical research

form.

Those who refused to take L-thyroxine as allocated, non-compliance (missed

taking L-thyroxine for more than three days for daily group or more than 4 days for

weekly group), defaulted study visit, or developed any side effects that investigator

think will cause harm to the subjects were withdrawn from the study.

At the end of this study (after Ramadan), patients were asked to resume back

their previous dose and dosing method of L-thyroxine. They will also continue their

usual endocrine clinic follow up.

11

Figure 3.1 Visits and procedures flow

12

FLOW CHART OF THE STUDY

Figure 3.2 Flow Chart of Study

4 were excluded:

2-overt hyperthyroid

1-overt hypothyroid

1-arrhythmia

61 patients were invited to join

the study

22 patients were interested and

consented

WEEKLY

N:9

DAILY

N:9

N=18 were randomized

13

3.7 MATERIALS AND TOOL

A few scoring systems were adopted in this study to assess symptoms, cognitive and

psychological function. Besides scoring system, lab biochemical assay also aid in

quantifying thyroid hormones and lipid level. Equipment such as electrocardiograph,

echocardiograph and Holter was used for cardiac assessment in this study.

3.7.1 Billewicz Score (Hypothyroid)

The Billewicz score utilizes eight symptoms and six signs to assess the thyroid status,

and diagnose hypothyroidism. The score may range from + 67 to – 47, with the

highest weightage being given to a sluggish ankle jerk and slow movements. A score

of +25 or more suggests hypothyroidism, while a score of –30 or less excludes the

condition.

3.7.2 Zulewski’s score (Hypothyroid)

Zulewski et al reevaluate the classical signs and symptoms of hypothyroidism in the

light of modern laboratory tests. The most sensitive features were delayed ART (77%)

and dry skin (76%), while the most specific were slow movements (98.7%) and

diminished hearing (97.5%). A score >5 points defined hypothyroidism, while a score

of 0-2 points defined euthyroidism.

3.7.3 Wayne’s score (Hyperthyroid)

Wayne’s Index was earlier used to help to diagnose hyperthyroidism and limit the

number of investigations required. Nine symptoms and ten signs were included in

Wayne’s score, each with differential weightage in scoring. The score ranges from +