research article combined treatment with myo-inositol and

Hindawi Publishing CorporationJournal of Thyroid ResearchVolume 2013 Article ID 424163 5 pageshttpdxdoiorg1011552013424163

Research ArticleCombined Treatment with Myo-Inositol and SeleniumEnsures Euthyroidism in Subclinical Hypothyroidism Patientswith Autoimmune Thyroiditis

Maurizio Nordio1 and Raffaella Pajalich2

1 University of Rome ldquoSapienzardquo Institute of Gynecology and Obstetrics Viale del Policlinico 00155 Rome Italy2 Ars Medica spa Via Ferrero di Cambiano Cesare 29 00191 Rome Italy

Correspondence should be addressed to Maurizio Nordio maurizionordio1gmailcom

Received 8 May 2013 Revised 27 August 2013 Accepted 27 August 2013

Academic Editor Jack R Wall

Copyright copy 2013 M Nordio and R Pajalich This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Background Hashimotorsquos thyroiditis (HT) also known as chronic lymphocytic thyroiditis or chronic autoimmune thyroiditis isthe most common form of thyroiditis affecting more than 10 of females and 2 of males The present study aims to evaluatethe beneficial effect of a combined treatment Myo-Inositol plus selenomethionine on subclinical hypothyroidism MethodsThe study was designed as a double-blind randomized controlled trial Eligible patients were women diagnosed with subclinicalhypothyroidism having Tg antibodies (TgAb) titer higher than 350 IUmL Outcomemeasures wereThyroid Stimulating Hormone(TSH) levels thyroid peroxidase antibodies (TPOAb) and TgAb titer selenium and Myo-Inositol plasma concentration ResultsIn the present paper we demonstrated that the beneficial effects obtained by selenomethionine treatment on patients affected bysubclinical hypothyroidism likely due to the presence of autoantibody (TPOAb and TgAb) are further improved by cotreatmentwith Myo-Inositol Conclusions Indeed due to its action as TSH second messenger Myo-Inositol treatment reduces TSH levelscloser to physiological concentrations

1 Introduction

The pathophysiology of HT can be summarized as fol-lows triggering of humoral immunity by the abnormalstimulation of T-lymphocytes and consequent destructionof thyroid epithelial cells by chemotaxis autoantibodiesand inflammatory cascade Thyrocyte loss is compensatedby the increased thyroid-stimulating hormone TSH levels(Subclinical hypothyroidism) and the hyperplasia of epithelialcells Subclinical hypothyroidism is defined as TSH levelhigher than 4mIUL and a normal free-thyroxine level(06ndash18 ngdL) [1] This condition is associated with anincreased risk for coronary heart disease (CHD) eventsCHD mortality and heart failure (HF) events particularlyin patients with TSH levels ge100mIUL (for review see[1]) In regions with severe selenium deficiency there is ahigher incidence of thyroiditis due to a decreased activity ofselenium-dependent glutathione peroxidase activity withinthyroid cells Selenium-dependent enzymes are also key

actors in regulating immune system Therefore even mildselenium deficiency may contribute to the development andmaintenance of autoimmune thyroid diseases

Myo-Inositol is an isomer of a C6 sugar alcohol Severalstudies suggested that Myo-Inositol plays an important rolein several cellular processes In particular it has been demon-strated that Myo-Inositol is the precursor for the synthesis ofphosphoinositides which are part of the phosphatidylinositol(PtdIns) signal transduction pathway [2] PtdIns is responsi-ble for signal transduction across the plasma membrane viasecondmessenger inositol 145-triphosphate that modulatesintracellular Ca2+ release or by being a docking site for severalsignal transduction proteins [3]

TSH signaling is rather complex indeed two differentsignal cascades are generated One branch of the signal cas-cade involves as second messenger cyclic AMP (cAMP)while another branch is inositol dependent [4 5] Indeedwhile the cAMP is more involved in cell growth differentia-tion and the T4-T3 secretion the inositol-dependent branch

2 Journal of Thyroid Research

regulates H2O2-mediated iodination [4] In particular it has

been shown that relatively lowTSH concentrations are able tostimulate cAMPmediated signal cascade while only 100-foldhigher TSH concentrations are able to stimulate the inositol-mediated signal cascade [6]

The aim of this study was to evaluate whether the as-sociation betweenMyo-Inositol and Selenium can ensure eu-thyroidism in subclinical hypothyroidism patients withautoimmune thyroiditis

2 Materials and Methods

The present study was performed as a prospective ran-domized double-blinded controlled study in women (119899 =48 mean age 38 years) with autoimmune thyroiditis andTPOAb inclusion criteria were TgAb and or TPOAb above350 IUmL TSH levels between 401mIUL and 999mIULand a normal free-thyroxine level (06ndash18 ngdL) as well astypical hypoechogenicity of the thyroid in high-resolutionsonography The primary endpoint of the study was restora-tion of TSH levels (lower than 4mIUL) Secondary endpoints were decreased in serum TPOAb and TgAb concen-trations free thyroid hormone levels and improvement of thethyroid and quality of life estimation All patients enrolledsigned an informed consent Patients were randomized into2 groups according to their initial TPOAb concentrationsgroup A consisted of 24 patients who received orally 83 120583gselenomethionineday in a soft gel capsule group B consistedof 24 patients who received a combined treatment plus Myo-Inositol 600mg also in a 83 120583g selenomethionine soft gelcapsule orally for 6 months The patients were asked totake the medication with water about 2 h before or aftera meal They were not given further treatment such asover-the-counter vitamins or trace elements All patientswere otherwise healthy No patients were substituted with L-T4 TPOAb TgAb TSH and free thyroid hormones weredetermined by commercial assays The echogenicity of thethyroid was monitored with high-resolution ultrasound

21 Laboratory and Technical Investigations A total of 48patients were enrolled in the study two were excludedbecause they become pregnant during the study periodTwenty-four patients received combined treatment withMyo-Inositol 600mg plus 83120583g selenomethioninedie softgel capsule twenty-two received soft gel capsule of 83 120583gselenomethioninedie The mean age in both groups wasidentical

Blood samples were drawn at the beginning and at theend of the treatment Free T4 and T3 concentrations andTSH were measured by an enzyme immunometric assay(Byk-Sangtec Dietzenbach Germany) Plasma total TPOAband TgAb concentrations were measured by a commer-cial chemiluminescence assay (Byk-Sangtec) The specificityfor autoimmune thyroiditis in these assays is greater than90 when antibody concentrations are above 350 IUmLPlasma seleniumwas determined by atomic absorption spec-trometry Plasma Myo-Inositol was determined using GasChromatography-Mass Spectrometry (GC-MS) analysis after

Table 1 Values are listed as mean plusmn SD

MI-SEL (GROUP B) SEL (GROUP A) 119875 valueAge 3795 plusmn 216 3803 plusmn 163 NSTSH 443 plusmn 089 433 plusmn 091 NSFree T4 1887 plusmn 402 1875 plusmn 389 NSFree T3 649 plusmn 236 660 plusmn 166 NSTgAb 101974 plusmn 37421 108080 plusmn 4851 NSTPOAb 9139 plusmn 5439 9056 plusmn 4016 NS

extraction with organic solvents and derivatization Injection(10 120583L) was performed on splitless mode at 270∘C and a cap-illary column Agilent 122ndash5532 DB-5ms (025mm times 30m times025 120583m) was used Total run time was 15 minutes ovenat 70∘C from 0 to 1min 20∘Cmin to 150∘C 10∘Cmin to240∘C 4min at 320∘C in postrun The flow rate was fixed to12mLmin and results were analyzed by anMS 5973NetworkSeries detector in sim mode High-resolution ultrasound(75MHz SONOLINE Elegra Siemens Erlangen Germany)of the thyroid gland was performed and echogenicity as wellas perfusion by Doppler sonography was documented andcompared at the beginning and end of the study by an inde-pendent experienced investigator The subjective wellbeingwas evaluated using the standardized SF 12 protocol beforeand after the studyThe SF 12 protocol is a 12-item short formto survey health status in medical outcome studies

22 Statistics The relative changes in antibody concentra-tions as well as thyroid hormone concentrations in bothgroups were compared using Wilcoxonrsquos matched pairssigned-ranks test In addition the differences in antibodyconcentrations at the beginning and end of the study weredetermined by 119905-test for paired samples The 119875 values werecorrected for the numbers of tests performed

3 Results

At study entry mean TSH levels concentrations free T4 freeT3 TgAb and TPOAb concentrations were not statisticallydifferent in both groups (Table 1) The ultrasound pattern inall patients revealed the typical hypoechoic thyroid tissueNone of the patients had thyroid nodules

Improvement of ultrasound echogenicity was observedin all patients in group B versus ten patients in group A(119875 lt 001) Evaluation of subjective wellbeing revealed animprovement in 18 patients in group B compared with 8 ingroupA no change in 6 patients in group B versus 14 in groupA (119875 lt 005)

Plasma selenium values were identical in both groupsat study entry (1274 plusmn 153 120583gL group A 1292 plusmn 151 120583gLgroup B) In both groups plasma selenium concentrationincreased after treatment by than 75 precisely in theselenomethionine-treated group selenium levels reached2235 plusmn 153 120583gL (119875 lt 001 versus baseline) while in thecombined therapy selenium levels reached 2254 plusmn 125 120583gL(119875 lt 001 versus baseline)

Journal of Thyroid Research 3

As expected plasma Myo-Inositol level significantly in-creased only in the combined therapy group (222plusmn 41120583molL versus 373 plusmn 45 120583molL) while there were no differencesbetween the two groups at baseline

TSH concentrations significantly decreased in group B by31 (44 plusmn 09 versus 31 plusmn 06mIUmL 119875 lt 001) On theother hand there was no change in the TSH level in the groupA

Autoantibody titer TPOAb and TgAb significantly de-creased in both groups In particular TPOAb concentrationdecreased significantly in the group A by 42 (9056 plusmn4016 versus 5226 plusmn 2368mIUmL 119875 lt 001) and TgAbdecreased by 38 (10808 plusmn 4851 versus 6701 plusmn 3008mIUmL119875 lt 001) In group B TPOAb decreased by 44 (9139 plusmn5439 versus 5161 plusmn 3154mIUmL 119875 lt 001) and TgAbdecreased by 48 (1019 plusmn 3742 versus 5339 plusmn 2584mIUmL119875 lt 001)

Eleven patients in the combined treated group showeda reduction of the TgAb below the threshold identified asinclusion criterion compared to three patients in group AUltrasound of the thyroid showed normalized echogenicityin these patients

4 Discussion

In the present study we were able to demonstrate thatin subclinical hypothyroidism patients with autoimmunethyroiditis treated with Myo-Inositol and selenomethionineexperience a reduction of the increased TSH that selenome-thionine supplementation alone was not able to promoteConcomitantly the concentration of the two autoantibodiesdeclined in both groups

Myo-Inositol is a precursor for many inositol-containingcompounds that play critical and several roles in signaltransduction membrane biogenesis vesicle trafficking andchromatin remodeling [7] Indeed many studies support thenotion that MI is one of the precursors for the synthesis ofphosphatidylinositol polyphosphates (PIPs) that are a sourceof a number of secondmessengersThesemessengers includediacylglycerol which regulates some members of the proteinkinase C family inositol-145-triphosphate which modifiesintracellular calcium levels and phosphatidylinositol-345-phosphate which is involved in the signal transduction[7ndash9] Myo-Inositol is a component of cell membranesand plays an important role in cell morphogenesis andcytogenesis lipid synthesis structure of cell membranesand cell growth Related to all of these signaling pathwaysMyo-Inositol is initially incorporated at the level of cellmembranes as phosphatidyl-myo-inositol the precursor ofinositol triphosphate which functions as second messengerregulating the activities of several hormones such as TSHFollicle-Stimulating Hormone and insulin [10 11]

Selenium-dependent enzymes have diverse effects notonly within the thyroid [12 13] but also on the immune sys-tem [14ndash17] It has been shown that during severe seleniumdeficiency the lack of GPx (selenium-dependent enzyme)activitymay contribute to oxidative damage of the thyroid celland initiation of thyroid damage and fibrosis [18] Selenium

supplementation in a rat model could prevent this oxidativedamage [19] It can be speculated that even in mild seleniumdeficiency this mechanism is an important environmentalfactor initiating or maintaining autoimmune thyroiditis inpeople genetically prone to the development of organ specificautoimmunity The immune modulatory effects of selenium-dependent enzymes such as GPx and TxR are involved in theorgan-specific immune response [20]Thiswas demonstratedin selenium-deficient mice where lung tissue damage wassignificantly increased after virus infection compared withselenium-adequate mice [21] Selenium-dependent enzymesare both antioxidative and anti-inflammatory [14 22 23]This is because GPx can reduce hydrogen peroxides andlipid and phospholipid hydroperoxides thereby lowering thepropagation of free radicals and reactive oxygen speciesLower hydroperoxide tissue concentrations diminish the pro-duction of inflammatory prostaglandins and leukotrieneTherespiratory burst is also dampened by selenium-dependentenzymes as well as superoxide production [20] Althoughtissue damage after viral infection is not comparable to organ-specific autoimmunity this study clearly demonstrates thestriking effects of different nutritional selenium supply on theimmune response [17]

This mechanism may also contribute to reduced inflam-matory activity in the organ-specific autoimmune response[15 24] and may explain the improvement of autoim-mune thyroiditis in our study In a nonblinded pilotstudy significant decreases in TPOAb and thyroid bindinginhibitory immunoglobulins but not TgAb concentrationswere described in patients with Hashimotorsquos thyroiditis andGravesrsquo disease [24] in accordance with our findings inpatients with autoimmune thyroiditis The clinical benefit ofselenium supplementation was also shown in double-blindedstudies in patients with rheumatoid arthritis [25] or asthma[26] In Crohnrsquos disease plasma selenium and GPx activitiesare inversely correlated with the activity of the disease [27]We did not find any alterations in thyroid function afterselenium supplementationThis might be due to the fact thatthe selenium deficiency was only moderate and deiodinaseactivity decreases only in severe selenium deficiency [14] Ina previous study in a small cohort of patients with reducedthyroid iodine organification after subacute thyroiditis orpostpartum thyroiditis [28] supplementation selenium hadno effect on thyroid hormone synthesis The thyroid is oneof the organs with the highest selenium concentration [29]but during mild selenium deficiency deiodinase activitiesare unaltered in contrast to GPx activities Therefore intissue samples from patients with autoimmune thyroiditisandnontoxic goiter therewas nodifference in selenium tissueconcentration in selenium sufficient areas [30]The seleniumdeficiency in our patients was mild (089molliter) but it isknown that in individuals with such low plasma seleniumconcentrations GPx activity is impaired The mean plasmaselenium concentration necessary for optimal GPx activitiesis 120molliter (range 112ndash144molliter) [31] This mightexplain the anti-inflammatory activity of selenium withoutaffecting thyroid hormone levels We also determined qualityof life in our study population The change in antibodyconcentrations or inflammatory activity within the thyroid


of course has no impact on quality of life but there arestudies showing that low selenium intake is associated witha significant greater incidence of negative mood states anddepression [32 33] Patients receiving selenium supplementa-tion reported significantly better wellbeing in our trial com-pared with the placebo group which supports these earlierfindingsThe cause is unknown but there are indications thatselenium is important for brain function The turnover rateof some neurotransmitters is altered in selenium deficiency[34] and low plasma selenium concentrations are associatedwith senility and cognitive decline [35]

The beneficial effect obtained by Myo-Inositol is easilyexplained by its biological role in signaling TSH hormoneindeed inositol regulate H

2O2-mediated iodination [4] and

it has been shown that hypothyroidism can be caused by animpairment of the inositol-depended TSH signaling branch(TSH resistance) [5] therefore by increasing the amount ofthe second messenger we can increase the TSH sensitivity

In conclusion in the present paper we demonstrated thatthe beneficial effects obtained by selenomethionine treatmenton patients affected by subclinical hypothyroidism likelydue to the presence of autoantibody (TPOAb and TgAb)are further improved by cotreatment with Myo-InositolIndeed due to its action as TSH second messenger Myo-Inositol treatment reduces TSH levels closer to physiologicalconcentrations

Conflict of Interests

The authors declare that they have no conflict of interests

References

[1] A Sert O Pirgon E Aypar H Yilmaz and D Odabas ldquoSub-clinical hypothyroidism as a risk factor for the development ofcardiovascular disease in obese adolescents with nonalcoholicfatty liver diseaserdquo Pediatric Cardiology vol 34 no 5 pp 1166ndash1174 2013

[2] M J Berridge and R F Irvine ldquoInositol phosphates and cellsignallingrdquo Nature vol 341 no 6239 pp 197ndash205 1989

[3] T G Kutateladze ldquoTranslation of the phosphoinositide code byPI effectorsrdquo Nature Chemical Biology vol 6 no 7 pp 507ndash5132010

[4] H Ohye and M Sugawara ldquoDual oxidase hydrogen peroxideand thyroid diseasesrdquo Experimental Biology and Medicine vol235 no 4 pp 424ndash433 2010

[5] H Grasberger J van Sande A H-D Mahameed YTenenbaum-Rakover and S Refetoff ldquoBrief report a familialthyrotropin (TSH) receptor mutation provides in vivo evidencethat the inositol phosphatesCa2+ cascade mediates TSHaction on thyroid hormone synthesisrdquo Journal of ClinicalEndocrinology and Metabolism vol 92 no 7 pp 2816ndash28202007

[6] J Parma J van Sande S Swillens M Tonacchera J DumontandG Vassart ldquoSomaticmutations causing constitutive activityof the thyrotropin receptor are the major cause of hyperfunc-tioning thyroid adenomas identification of additional muta-tions activating both the cyclic adenosine 3101584051015840-monophosphateand inositol phosphate-Ca2+ cascadesrdquo Molecular Endocrinol-ogy vol 9 no 6 pp 725ndash733 1995

[7] B W Agranoff ldquoTurtles all the way reflections on myo-inositolrdquo Journal of Biological Chemistry vol 284 no 32 pp21121ndash21126 2009

[8] T Balla ldquoPhosphoinositide-derived messengers in endocrinesignalingrdquo Journal of Endocrinology vol 188 no 2 pp 135ndash1532006

[9] T Balla ldquoInositol-lipid binding motifs signal integratorsthrough protein-lipid and protein-protein interactionsrdquo Journalof Cell Science vol 118 no 10 pp 2093ndash2104 2005

[10] G Halet R Tunwell T Balla K Swann and J Carroll ldquoThedynamics of plasma membrane Ptdlns(45)P2 at fertilization ofmouse eggsrdquo Journal of Cell Science vol 115 no 10 pp 2139ndash2149 2002

[11] E Papaleo V Unfer J P Baillargeon and T T Chiu ldquoContri-bution of myo-inositol to reproductionrdquo European Journal ofObstetrics Gynecology and Reproductive Biology vol 147 no 2pp 120ndash123 2009

[12] D Behne and A Kyriakopoulos ldquoEffects of dietary selenium onthe tissue concentrations of type I iodothyronine 51015840-deiodinaseand other selenoproteinsrdquo American Journal of Clinical Nutri-tion vol 57 supplement 2 pp 310Sndash312S 1993

[13] P R Larsen and M J Berry ldquoNutritional and hormonalregulation of thyroid hormone deiodinasesrdquo Annual Review ofNutrition vol 15 pp 323ndash352 1995

[14] J Kohrle R Brigelius-Flohe A Bock R Gartner OMeyer andL Flohe ldquoSelenium in biology facts and medical perspectivesrdquoBiological Chemistry vol 381 no 9-10 pp 849ndash864 2000

[15] L S Harbige ldquoNutrition and immunity with emphasis oninfection and autoimmune diseaserdquo Nutrition and Health vol10 no 4 pp 285ndash312 1996

[16] R C McKenzie T S Rafferty and G J Beckett ldquoSeleniuman essential element for immune functionrdquo Immunology Todayvol 19 no 8 pp 342ndash345 1998

[17] M Bonomini S Forster F de Risio et al ldquoEffects of seleniumsupplementation on immune parameters in chronic uraemicpatients on haemodialysisrdquo Nephrology Dialysis Transplanta-tion vol 10 no 9 pp 1654ndash1661 1995

[18] B Contempre J E Dumont J-F Denef and M-C ManyldquoEffects of selenium deficiency on thyroid necrosis fibrosisand proliferation a possible role in myxoedematous cretinismrdquoEuropean Journal of Endocrinology vol 133 no 1 pp 99ndash1091995

[19] B Contempre O le Moine J E Dumont J-F Denef and MC Many ldquoSelenium deficiency and thyroid fibrosis A key rolefor macrophages and transforming growth factor 120573 (TGF-120573)rdquoMolecular and Cellular Endocrinology vol 124 no 1-2 pp 7ndash151996

[20] S T Chen and J I Chuang ldquoThe antioxidantmelatonin reducescortical neuronal death after intrastriatal injection of kainate inthe ratrdquoExperimental Brain Research vol 124 no 2 pp 241ndash2471999

[21] M A Beck H K Nelson Q Shi et al ldquoSelenium deficiencyincreases the pathology of an influenza virus infectionrdquo TheFASEB Journal vol 15 no 8 pp 1481ndash1483 2001

[22] L Flohe J R Andreesen R Brigelius-Flohe M Maiorino andF Ursini ldquoSelenium the element of the moon in life on earthrdquoIUBMB Life vol 49 no 5 pp 411ndash420 2000

[23] M P Rayman ldquoThe importance of selenium to human healthrdquoThe Lancet vol 356 no 9225 pp 233ndash241 2000

[24] P J Schmidt L KNiemanMADanaceau L F Adams andDR Rubinow ldquoDifferential behavioral effects of gonadal steroids


in women with and in those without premenstrual syndromerdquoThe New England Journal of Medicine vol 338 no 4 pp 209ndash216 1998

[25] A Peretz J Neve J Duchateau and J P Famaey ldquoAdjuvanttreatment of recent onset rheumatoid arthritis by seleniumsupplementation preliminary observationsrdquo British Journal ofRheumatology vol 31 no 4 pp 281ndash282 1992

[26] L Hasselmark R Malmgren O Zetterstrom and G UngeldquoSelenium supplementation in intrinsic asthmardquo Allergy vol48 no 1 pp 30ndash36 1993

[27] J-M Reimund C Hirth C Koehl R Baumann and B DuclosldquoAntioxidant and immune status in active Crohnrsquos disease Apossible relationshiprdquo Clinical Nutrition vol 19 no 1 pp 43ndash48 2000

[28] P Gerwins ldquoModification of a competitive protein bindingassay for determination of inositol 145-trisphosphaterdquo Analyt-ical Biochemistry vol 210 no 1 pp 45ndash49 1993

[29] J Aaseth H Frey E Glattre G Norheim J Ringstad and YThomassen ldquoSelenium concentrations in the human thyroidglandrdquo Biological Trace Element Research vol 24 no 2 pp 147ndash152 1990

[30] U B Ericsson E M Erfurth and A Schutz ldquoSerum seleniumconcentrations in patients with autoimmune thyroiditis andnon-toxic nodular goiterrdquo Thyroidology vol 5 no 1 pp 21ndash241993

[31] A J Duffield C D Thomson K E Hill and S WilliamsldquoAn estimation of selenium requirements for New ZealandersrdquoAmerican Journal of Clinical Nutrition vol 70 no 5 pp 896ndash903 1999

[32] W C Hawkes and L Hornbostel ldquoEffects of dietary seleniumon mood in healthy men living in a metabolic research unitrdquoBiological Psychiatry vol 39 no 2 pp 121ndash128 1996

[33] HD Foster ldquoThe iodine-seleniumconnection its possible rolesin intelligence cretinism sudden infant death syndrome breastcancer and multiple sclerosisrdquo Medical Hypotheses vol 40 no1 pp 61ndash65 1993

[34] A Castano A Ayala J A Rodrıguez-Gomez A J HerreraJ Cano and A Machado ldquoLow selenium diet increases thedopamine turnover in prefrontal cortex of the ratrdquoNeurochem-istry International vol 30 no 6 pp 549ndash555 1997

[35] C Bert B Balansard J Arnaud A-M Roussel and A Alper-ovitch ldquoCognitive decline is associated with systemic oxidativestress the EVA studyrdquo Journal of theAmericanGeriatrics Societyvol 48 no 10 pp 1285ndash1291 2000

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


regulates H2O2-mediated iodination [4] In particular it has

been shown that relatively lowTSH concentrations are able tostimulate cAMPmediated signal cascade while only 100-foldhigher TSH concentrations are able to stimulate the inositol-mediated signal cascade [6]

The aim of this study was to evaluate whether the as-sociation betweenMyo-Inositol and Selenium can ensure eu-thyroidism in subclinical hypothyroidism patients withautoimmune thyroiditis

2 Materials and Methods

The present study was performed as a prospective ran-domized double-blinded controlled study in women (119899 =48 mean age 38 years) with autoimmune thyroiditis andTPOAb inclusion criteria were TgAb and or TPOAb above350 IUmL TSH levels between 401mIUL and 999mIULand a normal free-thyroxine level (06ndash18 ngdL) as well astypical hypoechogenicity of the thyroid in high-resolutionsonography The primary endpoint of the study was restora-tion of TSH levels (lower than 4mIUL) Secondary endpoints were decreased in serum TPOAb and TgAb concen-trations free thyroid hormone levels and improvement of thethyroid and quality of life estimation All patients enrolledsigned an informed consent Patients were randomized into2 groups according to their initial TPOAb concentrationsgroup A consisted of 24 patients who received orally 83 120583gselenomethionineday in a soft gel capsule group B consistedof 24 patients who received a combined treatment plus Myo-Inositol 600mg also in a 83 120583g selenomethionine soft gelcapsule orally for 6 months The patients were asked totake the medication with water about 2 h before or aftera meal They were not given further treatment such asover-the-counter vitamins or trace elements All patientswere otherwise healthy No patients were substituted with L-T4 TPOAb TgAb TSH and free thyroid hormones weredetermined by commercial assays The echogenicity of thethyroid was monitored with high-resolution ultrasound

21 Laboratory and Technical Investigations A total of 48patients were enrolled in the study two were excludedbecause they become pregnant during the study periodTwenty-four patients received combined treatment withMyo-Inositol 600mg plus 83120583g selenomethioninedie softgel capsule twenty-two received soft gel capsule of 83 120583gselenomethioninedie The mean age in both groups wasidentical

Blood samples were drawn at the beginning and at theend of the treatment Free T4 and T3 concentrations andTSH were measured by an enzyme immunometric assay(Byk-Sangtec Dietzenbach Germany) Plasma total TPOAband TgAb concentrations were measured by a commer-cial chemiluminescence assay (Byk-Sangtec) The specificityfor autoimmune thyroiditis in these assays is greater than90 when antibody concentrations are above 350 IUmLPlasma seleniumwas determined by atomic absorption spec-trometry Plasma Myo-Inositol was determined using GasChromatography-Mass Spectrometry (GC-MS) analysis after

Table 1 Values are listed as mean plusmn SD

MI-SEL (GROUP B) SEL (GROUP A) 119875 valueAge 3795 plusmn 216 3803 plusmn 163 NSTSH 443 plusmn 089 433 plusmn 091 NSFree T4 1887 plusmn 402 1875 plusmn 389 NSFree T3 649 plusmn 236 660 plusmn 166 NSTgAb 101974 plusmn 37421 108080 plusmn 4851 NSTPOAb 9139 plusmn 5439 9056 plusmn 4016 NS

extraction with organic solvents and derivatization Injection(10 120583L) was performed on splitless mode at 270∘C and a cap-illary column Agilent 122ndash5532 DB-5ms (025mm times 30m times025 120583m) was used Total run time was 15 minutes ovenat 70∘C from 0 to 1min 20∘Cmin to 150∘C 10∘Cmin to240∘C 4min at 320∘C in postrun The flow rate was fixed to12mLmin and results were analyzed by anMS 5973NetworkSeries detector in sim mode High-resolution ultrasound(75MHz SONOLINE Elegra Siemens Erlangen Germany)of the thyroid gland was performed and echogenicity as wellas perfusion by Doppler sonography was documented andcompared at the beginning and end of the study by an inde-pendent experienced investigator The subjective wellbeingwas evaluated using the standardized SF 12 protocol beforeand after the studyThe SF 12 protocol is a 12-item short formto survey health status in medical outcome studies

22 Statistics The relative changes in antibody concentra-tions as well as thyroid hormone concentrations in bothgroups were compared using Wilcoxonrsquos matched pairssigned-ranks test In addition the differences in antibodyconcentrations at the beginning and end of the study weredetermined by 119905-test for paired samples The 119875 values werecorrected for the numbers of tests performed

3 Results

At study entry mean TSH levels concentrations free T4 freeT3 TgAb and TPOAb concentrations were not statisticallydifferent in both groups (Table 1) The ultrasound pattern inall patients revealed the typical hypoechoic thyroid tissueNone of the patients had thyroid nodules

Improvement of ultrasound echogenicity was observedin all patients in group B versus ten patients in group A(119875 lt 001) Evaluation of subjective wellbeing revealed animprovement in 18 patients in group B compared with 8 ingroupA no change in 6 patients in group B versus 14 in groupA (119875 lt 005)

Plasma selenium values were identical in both groupsat study entry (1274 plusmn 153 120583gL group A 1292 plusmn 151 120583gLgroup B) In both groups plasma selenium concentrationincreased after treatment by than 75 precisely in theselenomethionine-treated group selenium levels reached2235 plusmn 153 120583gL (119875 lt 001 versus baseline) while in thecombined therapy selenium levels reached 2254 plusmn 125 120583gL(119875 lt 001 versus baseline)






4 Discussion














References











































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















4 Discussion














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
















research article combined treatment with myo-inositol and

Documents