Clinical Study Changes in Serum TSH and T4 Levels after ...downloads.hindawi.com/journals/ije/2015/156375.pdf · Clinical Study Changes in Serum TSH and T4 Levels after Switching

Clinical StudyChanges in Serum TSH and T4 Levels afterSwitching the Levothyroxine Administration Timefrom before Breakfast to before Dinner

S Ala12 O Akha3 Z Kashi3 A Bahar3 H Askari Rad4 N Sasanpour15 and A Shiva16

1Department of Clinical Pharmacy Faculty of Pharmacy Mazandaran University of Medical Sciences SariMazandaran Province Iran2Pharmaceutical Sciences Research Center Mazandaran University of Medical Sciences Sari Mazandaran Province Iran3Diabetes Research Center Mazandaran University of Medical Sciences Sari Mazandaran Province Iran4Department of Pharmaceutics Faculty of Pharmacy Mazandaran University of Medical Sciences Sari Mazandaran Province Iran5Student Research Committee Mazandaran University of Medical Sciences Sari Mazandaran Province Iran6Department of Clinical Pharmacy Faculty of Pharmacy Urmia University of Medical Sciences Urmia Iran

Correspondence should be addressed to O Akha zr akhayahoocom

Received 24 February 2015 Revised 25 May 2015 Accepted 28 May 2015

Academic Editor Constantinos Pantos

Copyright copy 2015 S Ala et al This is an open access article distributed under the Creative Commons Attribution License whichpermits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Background Levothyroxine is commonly used in the treatment of patients with hypothyroidism Levothyroxine is most oftenadministered in themorning on an empty stomach in order to increase its oral absorptionHowevermany patients have difficultiestaking levothyroxine in the morningAimThe aim of this study was evaluating the effect of changing levothyroxine administrationtime from before breakfast to before dinner on the serum levels of TSH and T4 Subjects and Methods Fifty patients between 18and 75 years old with hypothyroidism were included in the study and were randomly divided into two groups Each group receivedtwo tablets per day (one levothyroxine tablet and one placebo tablet) 30 minutes before breakfast and 1 hour before dinner Aftertwo months the administration time for the tablets was changed for each group and the new schedule was continued for a furthertwo-month period The serum TSH and T4 levels were measured before and after treatment in each group Results Changing thelevothyroxine administration time resulted in 147 plusmn 051 120583IUmL increase in TSH level (119901 = 0001) and 035 plusmn 105 120583gdL decreasein T4 level (119901 = 03) Conclusions Changing the levothyroxine administration time from before breakfast to before dinner reducedthe therapeutic efficacy of levothyroxine

1 Introduction

Hypothyroidism is permanent in most patients and requireslifelong thyroid hormone replacement Replacement withsynthetic levothyroxine (LT4) is themainstay of therapy [1 2]Combination therapy with levothyroxine and liothyronine(triiodothyronine or T3) has been suggested as an alternativehowever the present evidence from clinical trials does notshow any benefit for the combination therapy comparedwith monotherapy with levothyroxine [3ndash7] Recent evi-dence suggests that the dose of levothyroxine replacementis dependent on sex and body mass but not age as waspreviously thought [1 8 9]Many factors affect the absorption

of levothyroxine medications such as calcium and ironcompounds aluminium hydroxide selenium magnesiumzinc cholestyramine sucralfate raloxifene proton pumpinhibitors and H2 blockers as well as caffeine soybeanand fibers can impair absorption of ingested levothyroxine[1 2 10ndash12] Phenytoin carbamazepine phenobarbital andrifampicin can increase the clearance of levothyroxine [2]Thus it should be taken on an empty stomach withoutother medications supplements or food for 1 hour or ina similar fashion 4 hours after the last meal A fastingregimen of administration helps to ensure that the TSHremains within a narrow target range [1 2] The usual timeschedule for taking levothyroxine tablets in patients with

Hindawi Publishing CorporationInternational Journal of EndocrinologyVolume 2015 Article ID 156375 5 pageshttpdxdoiorg1011552015156375

2 International Journal of Endocrinology

hypothyroidism is everymorning before breakfast Howeversomepatients have difficulties taking theirmedication at earlymorning due to gastrointestinal disturbance Thus severalstudies have been performed on the efficacy of evening dosesof levothyroxine [13ndash16] However the literature data areinconsistent and contradictory It has been demonstratedin studies by Bartalena et al [13] and Bolk et al [14 15]that changing the levothyroxine administration time frommorning (before breakfast) to bedtime (after dinner) leads toincreased absorption and increased efficacy of levothyroxine(as evident from reduced levels of TSH) On the other handBach-Huynh et al [16] reported increased serum TSH levelsand reduction in serum T4 levels in response to changing thelevothyroxine administration time frommorning to eveningA more recent study by Rajput et al [17] demonstrated equalefficacy for morning and evening doses of levothyroxine

The objective of this study was investigating the effect ofchanging the levothyroxine administration time from beforebreakfast to before dinner on serum TSH land T4 levels inpatients with primary hypothyroidism This administrationschedule was opted for in order to evade the possibility oftaking the levothyroxine tablets on a full stomach as a result ofshort interval between dinner time and bedtime (according tothe general trait in the regionwhere the studywas conducted)and to reduce the possibility of forgetting the bedtime doses

2 Subjects and Methods

21 Trial Design The present study was a prospective ran-domized double-blind crossover placebo controlled studyThe study was approved by the Medical Research EthicsCommittee of Mazandaran University of Medical Sciencesand registered at Iranian Registry of Clinical Trials withregistration number IRCT138903223014N2 (the full trialprotocol could be accessed online at httpwwwirctir)

22 Patient Selection Patients between 18 and 75 years ofboth sexes with hypothyroidism (based on the physiciansdiagnosis) referred to Tuba Medical Center Sari Iran wereconsidered for inclusion in the study Informed writtenconsent was obtained from all of the patients prior to enroll-ment in the study Patients with a history of gastrointestinaldisorders chronic pulmonary disorders chronic cardiovas-cular diseases renal failure diabetes concomitant use ofmedications that interfere with absorption or metabolismof levothyroxine (such as cholestyramine and antibiotics)and pregnant women were excluded from the study Toensure the normal levels of TSH and T4 all of the patientsunderwent 3 laboratory tests (with 15-day intervals) beforecommencement of the study In cases of TSH and T4 valuesabove or below the normal range the patients were subjectedto levothyroxine dose adjustment and followed up untilnormal serum levels of TSH and T4 were achieved

23 Trial Procedure The patients were randomly dividedinto two groups following simple randomization procedureusing a computer generated list of random numbers Patientsof both groups received one batch of levothyroxine andone batch of placebo and were recommended to take the

tablets with a 12-hour interval (one before breakfast andone before dinner) with the predetermined dosage Thelevothyroxine tablets and the placebo tablets were preparedby the samemanufacturer (Iran Hormone Co Tehran Iran)were identical in shape color and size and were packed insimilar blistersTheblisterswere codedwith labels of differentcolors (yellow in the case of placebo and green in the case oflevothyroxine) Neither the patients nor the physicians wereaware of the randomization codes until the end of the study

The study consisted of two 60-day courses During thefirst course group A received the levothyroxine tablets in themorning 30 minutes before breakfast and the placebo tablet1 hour before dinner whereas group B received the levothy-roxine andplacebo tablets in reverse orderDuring the secondcourse the levothyroxine and placebo administration timeswere switchedwithin each groupTheprimary outcomeswerethe serum levels of T4 and TSH which were measured at theend of the first and second course (at the 60th and 120th day ofthe study) by ELISA (enzyme linked immunosorbent assay)technique Blood samples were drawn between 8 AM and 9AMThe serum concentration values of 039ndash61 120583IUmL forTSH and 48ndash116 120583gdL for T4 were considered to be normal

24 Statistical Analysis Thestatistical analysis of the datawascarried out by SPSS software version 16 The paired sample 119905-test was used to compare the data and values of 119901 less than005 were considered to denote a significant difference in allcases

3 Results

A total number of 54 patients between 18 and 67 years wererecruited in the study Of these two patients (one in eacharm) discontinued the study due to fear that changing thetherapeutic regimen might deteriorate their disease and twopatients (one in each arm) were lost to follow-up leaving50 patients for analysis (25 patients in each group) Thefull participant flow diagram is depicted in Figure 1 Theaverage administered dose of levothyroxine in the wholestudy population was 01mgday

The study population was rather young as the majority ofpatients (33 or 66) were less than 40 years (Table 1)

In both groups the within group differences in the serumTSH and T4 levels as a result of changing the administrationtime were similar There was significant increase in averageTSH level (119901

1= 004 119901

2= 0035 for group A and

group B resp) whereas the decrease in average T4 level wasinsignificant (119901

1= 07 119901

2= 064 for group A and group B

resp) Since the results in both crossed over groups was thesame the two groups could be regarded as one

From the 50 patients included in the study in 38 patients(76) changing the levothyroxine administration time frommorning to evening increased the serum levels of TSHsignificantly (119901 lt 005) and in the remaining 12 patients(24) the TSH levels decreased or remained constant inregard to T4 in 33 patients (66) the serum levels of T4decreased whereas in the remaining 17 patients (34) theserum levels of T4 increased as a result of changing thelevothyroxine administration time frommorning to evening

International Journal of Endocrinology 3

Group AGroup B

Analysed (n = 25) Analysed (n = 25)

Assessed for eligibility (n = 75)

Excluded (n = 21)(i) Not meeting inclusion criteria (n = 15)

(ii) Declining to participate (n = 6)

Randomized (n = 54)

Allocated to intervention (n = 27)(i) Received allocated intervention (n = 27)


Discontinued intervention due to anxiety (n = 2)

Discontinued intervention due to being lost tofollow-up (n = 2)

Figure 1 Participant flow diagram (according to guidelines of CONSORT 2010)

Table 1 Demographic characteristics of the patients (119899 = 50)

Characteristic ValueFemalemale ratio 446Mean age (years) 37 plusmn 132Age groups

18ndash30 years 18 (36)30ndash40 years 15 (30)gt40 years 17 (34)

Body mass index19ndash25 18 (36)25ndash30 18 (36)gt30 14 (28)

Familial history of hypothyroidismYes 10 (20)No 40 (80)

Etiology of hypothyroidismAutoimmune disease 41 (82)Thyroidectomy 5 (10)Radiation therapy 4 (8)

Concurrent diseaseNone 39 (78)Iron deficiency anemia 5 (10)Hyperlipidemia 2 (4)Hypertension and hyperlipidemia 4 (8)

however the difference was not significant (119901 gt 005) Theaverage values of TSH and T4 at different points during thetrial are depicted in Tables 2 and 3 To investigate the effectof age on the dependant variables the data were evaluated inregard to different age groups (less than 40 years and morethan 40 years) There were not any significant differences in

Table 2 Changes to the serum levels of TSH during the study (alldata are reported as mean plusmn SD)

Age group Serum TSH (120583IUmL)BB1 BD2 Difference 119901 value

le40 years(119899 = 33) 226 plusmn 119 352 plusmn 159 126 plusmn 04 000

gt40 years(119899 = 17) 155 plusmn 114 299 plusmn 198 144 plusmn 084 002

Total population(119899 = 50) 203 plusmn 122 335 plusmn 173 147 plusmn 051 000

1Before breakfast 2before dinner

Table 3 Changes to the serum levels of T4 during the study (all dataare reported as mean plusmn SD)

Age group Serum T4 (120583gdL)BB1 BD2 Difference 119901 value





the values of TSH or T4 between the two age groups whenlevothyroxine was administered before breakfast (119901

1= 0051

and 1199012= 06 resp) or when levothyroxine was administered

before dinner (1199011= 03 and 119901

2= 01 resp) Thus it

seems that the patientsrsquo age did not influence the therapeuticoutcome


4 Discussion

The current therapeutic procedure for hypothyroidism ismainly focused on hormone replacement therapy by sodiumlevothyroxine The patients are usually advised to take themedication in the morning 30ndash60 minutes before break-fast However for many patients this time schedule is notappropriate and they feel more comfortable to take themedication in the evening In this study the effect of changinglevothyroxine administration time from morning to eveningon the serum levels of TSH and T4 was evaluatedThe effectsof changing the levothyroxine administration time on serumTSH and T4 levels were previously studied [13ndash17] but theliterature data were inconsistent and contradictory

Bartalena et al demonstrated that greatest variations inserum concentrations of TSH are obtained when levothyrox-ine is administrated either early in the morning or late in theevening [13] Bolk et al studied the effects of levothyroxineadministration time (morning versus evening) on the serumlevels of TSH and T4 in 12 female patients for 4 months andfound that administration of levothyroxine in the eveningresults in decreased serum levels of TSH [14] However dueto the small sample size in this study the results were notconsidered to be generalizable Thus in a more extendedstudy by Bolk et al later on 105 patients were studied for aperiod of 6 months with a shift in levothyroxine administra-tion time from morning to evening and the results showedgreater absorption for levothyroxine decreased serum levelsof TSH and increased levels of T4 when levothyroxine wasadministered at bed time [15] Bach-Huynh et al conducted asimilar study including 105 patients for 24 weeksTheir studyin contrast demonstrated an increase in the serumTSH levelsand reduction in serum T4 levels in response to changing thelevothyroxine administration time from morning to evening[16] In a more recent study Rajput et al studied 152 drugnaıve patients with primary hypothyroidism for the effectsof morning versus evening administration of levothyroxineon the clinical profile and quality of life The patients weredivided into two groups receiving levothyroxine either in themorning or in the evening on an empty stomach for a periodof 12 weeks The results demonstrated considerable improve-ment in clinical profile for majority of patients in bothgroupswith no significant between group differences and theevening administration of levothyroxinewas reported to be asefficacious as the morning administration [17]

In the present study changing the administration time oflevothyroxine from before breakfast to before dinner resultedin a considerable increase in the serum levels of TSH in theentire study population (119901 = 0001) However the changesin serum T4 levels were insignificant and negligible (119901 =03) This is in accordance with the results reported by Bach-Huynh et al [16] who demonstrated a 125120583IUmL increasein average serum level of TSH as a result of changing thelevothyroxine administration time frommorning to eveningOne possible proposed mechanism is that dinner contentmay have more impact on levothyroxine absorption versusbreakfast even if eaten an hour after ingestion of the tablet

Rajput et al [17] found equal efficacy of the two admin-istration times but this contradicted the results obtained by

Bolk et al [14 15] This inconsistency might be in part dueto the nutrition regimen in different patients and the effectsof food intake on the absorption and oral bioavailability oflevothyroxine Data from screening large European popula-tion have revealed the influence of dietary iodine intake onthe epidemiology of thyroid dysfunction [18]

Comparison of the TSH and T4 levels between the agegroups less than 40 years and more than 40 years did notdemonstrate any significant difference either in initial orin final levels of TSH and T4 In addition there was norelationship between the BMI and the age group Althoughthe absorption distribution metabolism and excretion oflevothyroxine like any other drug depend on age and BMI ofthe patient since the daily dose of levothyroxinewas preciselydetermined for each patient by the endocrinologist physicianon the basis of the preliminary conditions and the extentof hypothyroidism these factors did not affect the studyvariables in different age groups

The study population was predominantly composed ofwomen (88) reflecting the fact that the prevalence ofhypothyroidism is higher in women compared with menThis was also reported by Assadi et al [19] who studied 2000Iranian patients aged above 20 years for subclinical thyroiddisorders Their study demonstrated higher prevalence ofthyroid disorders in women compared with men (607versus 393 of the study population resp) and higherprevalence of hypothyroidism for women compared withmen (1187 per 10000 versus 49 per 1000)

The main limitations of this study include single-centresite and the inability to monitor patientsrsquo compliance andachieving a stable dose of levothyroxine was not anticipatedas inclusion criterion for this study

Although the serum levels of T4 were not significantlychanged the changes to serum TSH levels were significantsuggesting changing the levothyroxine administration timefrombefore breakfast to before dinner in order to enhance thepatient compliance results in reduced therapeutic outcomeAlso comparing our results with previous studies suggeststhat taking levothyroxine before bedtime that is after foodcould have led to better bioavailability than the predinneradministration used in this study

Disclosure

This study was registered as PharmD thesis of Neda Sasan-pour at the Faculty of Pharmacy

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgments

This study was funded by a grant from the Vice Chancellorfor Research at Mazandaran University of Medical SciencesThe authors acknowledge Dr Adeleh Bahar for her assistancein patient selection and Dr Roja Hadian for her literaturereview


References

[1] J P Almandoz and H Gharib ldquoHypothyroidism etiologydiagnosis and managementrdquoMedical Clinics of North Americavol 96 no 2 pp 203ndash221 2012

[2] A J Chakera S H S Pearce and B Vaidya ldquoTreatmentfor primary hypothyroidism current approaches and futurepossibilitiesrdquoDrug Design Development andTherapy vol 6 pp1ndash11 2012

[3] O E Okosieme ldquoThyroid hormone replacement current statusand challengesrdquo Expert Opinion on Pharmacotherapy vol 12no 15 pp 2315ndash2328 2011

[4] A M Sawka H C Gerstein M J Marriott G M MacQueenand R T Joffe ldquoDoes a combination regimen of thyroxine (T4)and 3 5 31015840-triiodothyronine improve depressive symptomsbetter than T4 alone in patients with hypothyroidism Resultsof a double-blind randomized controlled trialrdquoThe Journal ofClinical Endocrinology amp Metabolism vol 88 no 10 pp 4551ndash4555 2003

[5] H F Escobar-Morreale J I Botella-Carretero F Escobar DelRey and G Morreale De Escobar ldquoTreatment of hypothy-roidism with combinations of levothyroxine plus liothyroninerdquoThe Journal of Clinical Endocrinology and Metabolism vol 90no 8 pp 4946ndash4954 2005

[6] P W Clyde A E Harari E J Getka and K M M ShakirldquoCombined levothyroxine plus liothyronine compared withlevothyroxine alone in primary hypothyroidism a randomizedcontrolled trialrdquo The Journal of the American Medical Associa-tion vol 290 no 22 pp 2952ndash2958 2003

[7] W Siegmund K Spieker A I Weike et al ldquoReplacementtherapy with levothyroxine plus triiodothyronine (bioavailablemolar ratio 14 1) is not superior to thyroxine alone to improvewell-being and cognitive performance in hypothyroidismrdquoClinical Endocrinology vol 60 no 6 pp 750ndash757 2004

[8] M Devdhar R Drooger M Pehlivanova G Singh and JJonklaas ldquoLevothyroxine replacement doses are affected bygender and weight but not agerdquoThyroid vol 21 no 8 pp 821ndash827 2011

[9] F Santini A Pinchera A Marsili et al ldquoLean body mass isa major determinant of levothyroxine dosage in the treatmentof thyroid diseasesrdquo The Journal of Clinical Endocrinology ampMetabolism vol 90 no 1 pp 124ndash127 2005

[10] L Liwanpo and J M Hershman ldquoConditions and drugs inter-fering with thyroxine absorptionrdquo Best Practice and ResearchClinical Endocrinology and Metabolism vol 23 no 6 pp 781ndash792 2009

[11] N Singh and JMHershman ldquoInterference with the absorptionof levothyroxinerdquo Current Opinion in Endocrinology Diabetesand Obesity vol 10 no 5 pp 347ndash352 2003

[12] Y Liel I Harman-Boehm and S Shany ldquoEvidence for aclinically important adverse effect of fiber-enriched diet on thebioavailability of levothyroxine in adult hypothyroid patientsrdquoThe Journal of Clinical Endocrinology amp Metabolism vol 81 no2 pp 857ndash859 1996

[13] L Bartalena E Martino M Falcone et al ldquoEvaluation ofthe nocturnal serum thyrotropin (TSH) surge as assessed byTSH ultrasensitive assay in patients receiving long term L-thyroxine suppression therapy and in patients with variousthyroid disordersrdquo The Journal of Clinical Endocrinology andMetabolism vol 65 no 6 pp 1265ndash1271 1987

[14] N Bolk T J Visser A Kalsbeek R T van Domburg and ABerghout ldquoEffects of evening vs morning thyroxine ingestion

on serum thyroid hormone profiles in hypothyroid patientsrdquoClinical Endocrinology vol 66 no 1 pp 43ndash48 2007

[15] N Bolk T J Visser J Nijman I J Jongste J G P Tijssen andABerghout ldquoEffects of evening vs morning levothyroxine intakea randomized double-blind crossover trialrdquo Archives of InternalMedicine vol 170 no 22 pp 1996ndash2003 2010

[16] T-G Bach-Huynh B Nayak J Loh S Soldin and J JonklaasldquoTiming of levothyroxine administration affects serum thy-rotropin concentrationrdquo The Journal of Clinical Endocrinologyamp Metabolism vol 94 no 10 pp 3905ndash3912 2009

[17] R Rajput S Chatterjee and M Rajput ldquoCan levothyroxinebe taken as evening dose Comparative evaluation of morningversus evening dose of levothyroxine in treatment of hypothy-roidismrdquo Journal of Thyroid Research vol 2011 Article ID505239 5 pages 2011

[18] M P J Vanderpump ldquoThe epidemiology of thyroid diseaserdquoBritish Medical Bulletin vol 99 no 1 pp 39ndash51 2011

[19] M Assadi H Delshad M Tohidi and F Azizi ldquoThe incidenceof subclinical thyroid dysfunction and itrsquos natural course inthe tehranian adultsrdquo Iranian Journal of Endocrinology andMetabolism vol 11 no 6 pp 673ndash736 2010

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Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


hypothyroidism is everymorning before breakfast Howeversomepatients have difficulties taking theirmedication at earlymorning due to gastrointestinal disturbance Thus severalstudies have been performed on the efficacy of evening dosesof levothyroxine [13ndash16] However the literature data areinconsistent and contradictory It has been demonstratedin studies by Bartalena et al [13] and Bolk et al [14 15]that changing the levothyroxine administration time frommorning (before breakfast) to bedtime (after dinner) leads toincreased absorption and increased efficacy of levothyroxine(as evident from reduced levels of TSH) On the other handBach-Huynh et al [16] reported increased serum TSH levelsand reduction in serum T4 levels in response to changing thelevothyroxine administration time frommorning to eveningA more recent study by Rajput et al [17] demonstrated equalefficacy for morning and evening doses of levothyroxine

The objective of this study was investigating the effect ofchanging the levothyroxine administration time from beforebreakfast to before dinner on serum TSH land T4 levels inpatients with primary hypothyroidism This administrationschedule was opted for in order to evade the possibility oftaking the levothyroxine tablets on a full stomach as a result ofshort interval between dinner time and bedtime (according tothe general trait in the regionwhere the studywas conducted)and to reduce the possibility of forgetting the bedtime doses

2 Subjects and Methods

21 Trial Design The present study was a prospective ran-domized double-blind crossover placebo controlled studyThe study was approved by the Medical Research EthicsCommittee of Mazandaran University of Medical Sciencesand registered at Iranian Registry of Clinical Trials withregistration number IRCT138903223014N2 (the full trialprotocol could be accessed online at httpwwwirctir)

22 Patient Selection Patients between 18 and 75 years ofboth sexes with hypothyroidism (based on the physiciansdiagnosis) referred to Tuba Medical Center Sari Iran wereconsidered for inclusion in the study Informed writtenconsent was obtained from all of the patients prior to enroll-ment in the study Patients with a history of gastrointestinaldisorders chronic pulmonary disorders chronic cardiovas-cular diseases renal failure diabetes concomitant use ofmedications that interfere with absorption or metabolismof levothyroxine (such as cholestyramine and antibiotics)and pregnant women were excluded from the study Toensure the normal levels of TSH and T4 all of the patientsunderwent 3 laboratory tests (with 15-day intervals) beforecommencement of the study In cases of TSH and T4 valuesabove or below the normal range the patients were subjectedto levothyroxine dose adjustment and followed up untilnormal serum levels of TSH and T4 were achieved

23 Trial Procedure The patients were randomly dividedinto two groups following simple randomization procedureusing a computer generated list of random numbers Patientsof both groups received one batch of levothyroxine andone batch of placebo and were recommended to take the

tablets with a 12-hour interval (one before breakfast andone before dinner) with the predetermined dosage Thelevothyroxine tablets and the placebo tablets were preparedby the samemanufacturer (Iran Hormone Co Tehran Iran)were identical in shape color and size and were packed insimilar blistersTheblisterswere codedwith labels of differentcolors (yellow in the case of placebo and green in the case oflevothyroxine) Neither the patients nor the physicians wereaware of the randomization codes until the end of the study

The study consisted of two 60-day courses During thefirst course group A received the levothyroxine tablets in themorning 30 minutes before breakfast and the placebo tablet1 hour before dinner whereas group B received the levothy-roxine andplacebo tablets in reverse orderDuring the secondcourse the levothyroxine and placebo administration timeswere switchedwithin each groupTheprimary outcomeswerethe serum levels of T4 and TSH which were measured at theend of the first and second course (at the 60th and 120th day ofthe study) by ELISA (enzyme linked immunosorbent assay)technique Blood samples were drawn between 8 AM and 9AMThe serum concentration values of 039ndash61 120583IUmL forTSH and 48ndash116 120583gdL for T4 were considered to be normal

24 Statistical Analysis Thestatistical analysis of the datawascarried out by SPSS software version 16 The paired sample 119905-test was used to compare the data and values of 119901 less than005 were considered to denote a significant difference in allcases

3 Results

A total number of 54 patients between 18 and 67 years wererecruited in the study Of these two patients (one in eacharm) discontinued the study due to fear that changing thetherapeutic regimen might deteriorate their disease and twopatients (one in each arm) were lost to follow-up leaving50 patients for analysis (25 patients in each group) Thefull participant flow diagram is depicted in Figure 1 Theaverage administered dose of levothyroxine in the wholestudy population was 01mgday

The study population was rather young as the majority ofpatients (33 or 66) were less than 40 years (Table 1)

In both groups the within group differences in the serumTSH and T4 levels as a result of changing the administrationtime were similar There was significant increase in averageTSH level (119901

1= 004 119901

2= 0035 for group A and

group B resp) whereas the decrease in average T4 level wasinsignificant (119901

1= 07 119901

2= 064 for group A and group B

resp) Since the results in both crossed over groups was thesame the two groups could be regarded as one

From the 50 patients included in the study in 38 patients(76) changing the levothyroxine administration time frommorning to evening increased the serum levels of TSHsignificantly (119901 lt 005) and in the remaining 12 patients(24) the TSH levels decreased or remained constant inregard to T4 in 33 patients (66) the serum levels of T4decreased whereas in the remaining 17 patients (34) theserum levels of T4 increased as a result of changing thelevothyroxine administration time frommorning to evening


Group AGroup B





Randomized (n = 54)



























1= 0051



2= 01 resp) Thus it



4 Discussion










Disclosure




Acknowledgments



References


























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Group AGroup B





Randomized (n = 54)



























1= 0051



2= 01 resp) Thus it



4 Discussion










Disclosure




Acknowledgments



References


























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















4 Discussion










Disclosure




Acknowledgments



References


























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















References


























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Documents

Clinical Study Changes in Serum TSH and T4 Levels after ...downloads.hindawi.com/journals/ije/2015/156375.pdf · Clinical Study Changes in Serum TSH and T4 Levels after Switching