Copyright© AE&M all rights reserved. of InternalMedicine, Ankara, Turkey Department Medicine (Kastamonu), Ankara, TurkeyCenter, Diagnostic of StemCellandGenetic and Research Department Hospital, Ankara, Turkey Metabolism, and Department ofEndocrinology Training andResearch Hospital, Accepted onNov/24/2014 Received onMay/16/2014 [email protected] Ankara, Turkey I Diskapi Hospital, Melia Karakose Correspondence to: 3 2 1 DOI: 10.1590/2359-3997000000091 364 the toprevent inorder TSH release is usedtosuppress (8).Afterthanlevothyroxine the riskoftumorrecurrence asameansofreducing dine (RAI)isoftenadministered However, ofradioactiveio adjuvanttherapy intheform ofthesepatients. isappliedinthetreatment thyroidectomy (DTC)(7).Total carcinoma thyroid of differentiated form (5,6).PTCisthemostcommon (PTC) intheliterature carcinoma thyroid thatdescribeRTH withpapillary ports fewcasere are diseases(4).There autoimmune thyroid excess. hormone and metabolicconsequencesofthyroid butabsenceof the usual symptoms goitre are features thecommoncharacteristicclinical clinical presentation, Despiteavariable TSHsecretion. with nonsuppressed (fT3)concentrations triiodothyronine (fT4) andfree thyroxine free Patients with RTH have elevated serum equallybyRTH (3). unknown andbothsexesaffected tor beta(THRβ recep hormone is causedbymutationsinthethyroid (1,2). RTH hormone peripheral target tissues to thyroid and of the pituitary responsiveness rized by a reduced R INTRODUCTION case report rfan Bastug Caddesi, - Hacettepe University, School of Beyazit TrainingDiskapi Yildirim Diskapi Yildirim Beyazit Patients with RTH have an increased risk of developing Patients withRTH riskof developing haveanincreased tosomal dominant hereditary disorder characte disorder tosomal dominanthereditary (RTH) au hormone isarare esistance tothyroid ) gene(1,2).TheincidenceofRTH is BRAFV600E mutation status thyroid microcarcinoma andtheir in two patientswithpapillary Thyroid resistance hormone ment ofthesepatients. are neededtoexplaintherelationshipbetweenRTH andDTCwhich mightbehelpfulforthetreat high the persistently TSH inpatientswithRTH anddifferentiated thyroid cancer (DTC).Further studies were negative.RTH isveryrareandmightbeoverlooked. There isnoconsensusonhowtoovercome mutationanalysisresults dings wereconsistentwithpapillarythyroid microcarcinoma.BRAFV600E showed multiple nodules in both lobes. Total thyroidectomy was performed. The pathological fin and clinical datas. Thyroid nodule was palpated on physical examination. Thyroid ultrasonography unsuppressed TSH. We consideredthissituation thyroid hormoneresistanceinthelightoflaboratory were admitted toourclinicandtheirlaboratoryresultswereelevatedthyroid hormonelevelswith report twopatientswithRTH inwhomdifferentiated thyroid cancerwas diagnosed. Two patients Resistance tothyroid hormone(RTH) isarareautosomaldominanthereditarydisorder. Herein,we SUMMARY Melia Karakose Erman CakalErman 1 ,Ahmet Yesilyurt 1 , Mustafa Caliskan Arch EndocrinolMetab. 2015;59(4):364-6 - - - - - patients withRTH inwhomDTCwasdiagnosed. in patientswithRTH wedescribetwo andDTC.Herein thepersistently highTSH consensus onhowtoovercome inapatientwithRTH. isno doses oflevothyroxine There maynotbeobtaineddespite increasing TSH suppression cancer(9). thyroid oftheresidual orprogression relapse ppressed followingT3administration. Thea ppressed andwassu hormone to thyrotropin-releasing response tumor. ofa pituitary TSHshowedexaggerated presence MRIscandid notdetectthe of typicalthyrotoxicosis. negative.Shehadnosignsorsymptoms antibody were (anti-TPO) antibody (anti-TG)andanti-thyroperoxidase T3 (fT3):6.2pg/mL(range,2.3-4.2),anti-thyroglobulin T4(fT4):2.45ng/dL(range,0.74-1.52),free 4.78), free detected asfollows;TSH:2.81mUI/mL(range,0.55- were results was admittedtoourclinicandherlaboratory becauseofmultinodulargoiterformed wasper in physicalexamination.Subtotalthyroidectomy medicine becauseofthedetectionmultinodulargoiter A 56-year-old Turkish tointernal womenwasreferred Case 1 CASE REPORTS 2 ,Delibasi Tuncay 1 , Muyesser Sayki Arslan 1,3 Arch Metab. Endocrinol 2015;59/4 1 , 20 years ago. She 20 yearsago.She -subunit of -subunit of - - - - Arch Metab. Endocrinol 2015;59/4 A234D; c.701C>A) that was detected in the first case. A234D; c.701C>A) thatwasdetectedinthe firstcase. oftheTHRβ mutation intheregions wassame following T3administration.There supressed stimulation testandTSHwas hormone tropin-releasing of TSHtoathyro gland,anexaggeratedresponse tary (0.36 IU/L,range,0-1.6),anegativeMRIofthepitui leveloftheα the patienthadanormal outbecause adenomawasruled pituitary TSH secreting RTH. excessTSHshouldbeexcludedfrom secreting tumor(TSHoma)that xicosis. Insuchcases,apituitary tive. Hehadnosignsorsymptomsoftypicalthyroto nega mUI/L). Anti-TGandanti-TPOantibodywere and TSH(fT4:1.95ng/dL,fT3:7.2pg/mL,TSH:5.52 functiontestsshowedelevatedfT4,fT3 thyroid Serum because ofhermother’sRTH andMGdisease(case1). A 33-year-old Turkish manwasadmittedtoourclinic Case 2 respectively. 23.6mUI/Land1.11ng/dL, level andfT4were to 150m was reduced 50 wasdisappeared. her symptomsofhyperthyroidism level was98.76mUI/L,fT41.06ng/dLand to175m vothyroxine thedoseofle wedecreased therefore, hyperthyroidism; 2.33 ng/dLandshecomplainedforthesymptomsof the fT4levelwas TSH levelwas84mUI/L,whereas upto200m ally increased therapywasadjustedandthedosegradu thyroxine Levo not administered. ses ofradioactive iodine were cancer,adverse clinicalcourseofherthyroid ablativedo lowrisk”foran at“very As thepatientwasconsidered small sothattheBRAFmutationcouldnotbeanalyzed. very lobe). Histologic sections of the tumor tissue are tumorsizewas 0.2 cm(right microcarcinoma, thyroid ry papilla Pathologicexaminationrevealed was performed. significance’. pical ofundetermined Total thyroidectomy andcytologicalexaminationshowed‘aty was performed in bothlobes.Afine-needleaspirationbiopsy(FNAB) ultrasonography showed multiple nodules tion. Thyroid and clinicaldatas. patient wasdiagnosedasRTH inthelightoflaboratory missense mutationinexon8(A234D;c.701C>A).The testingforTHRβ also underwent (0.76IU/L,range,0-1.6). The patient TSH was normal For to ensure the TSH suppression triiodotironin triiodotironin theTSHsuppression For toensure nodule waspalpatedonphysicalexamina Thyroid m g/day was added to treatment and levothyroxine andlevothyroxine g/day wasaddedtotreatment g/day. AftertwomonthsherTSH g/day. After two monthsTSH g/day. Aftertwomonths,her gene, which showed a gene,whichshoweda -subunit of TSH -subunit ofTSH gene (exon 8; gene(exon8; ------control appointment arranged fortwomonthslater. appointmentarranged control to150m thedoseoflevothyroxine increased 150mUI/Land1.26ng/dL respectively.level were We 100 upto was initiatedandthedosegraduallyincreased therapy andafterthatlevothyroxine tion wasperformed histopathologicalsections.I from negative were BRAFV600E mutationanalysisresults meters of0.4cmintheleftlobeandisthmus. detectedintwofocuswithdia were microcarcinoma thyroid andpapillary totalthyroidectomy underwent asnon-diagnostic.Thepatient cal examinationresulted echogenicity. andcytologi Two FNABwasperformed withmixed left lobe andhadfociof macrocalcification dominant nodulewas27x4251mminsizethe detected multiple nodules in both lobes. The were gland tion. Ultrasonographic evaluation of the thyroid pillary thyroid cancers (14). Our in the first case, we cancers(14). Ourinthefirstcase, we thyroid pillary cancer,tion inthyroid andfoundinabout45%ofpa FV600E mutationisthemost commongeneticaltera in codon334THRβgene(11 cer whichhaveasinglenucleotidesubstitution(T>C) acaseofRTH Turkey can from withthyroid reported byourclinic.AlsoÜnlütürk tation discovered missensemu Thisisanovelheterozygous literature. as beingassociated with RTH inthe viously reported A234D; c.701C>A).Thismutationhadnotbeenpre oftheTHRβgene(exon8; mutations intheregions in about90%ofRTH cases.Ourtwocaseshavesame afterT3administrationfavour theRTH. suppression stimulation test and TSH hormone thyrotropin-releasing ofTSHtoa gland,anexaggeratedresponse the pituitary leveloftheTSHa The normal tumour(TSHoma). apituitary from priate TSHsecretion diagnosistobeexcludedisinappro The maindifferential TSH must be investigated for RTH. with unsuppressed levels hormone withgoiterandelevatedthyroid present RTH isautosomaldominant(1,2).Thosepatientswho cause is mostlymutations in TRβ in1967(10).The RTH hasbeendescribedbyRefetoff DISCUSSION PTC, particularly the small micro PTC (12,13). BRA the small micro PTC, particularly diagnosis of cancer ismainlyattributedto theincreased malignancyandtherisingincidence ofthyroid thyroid Thyroid nodules were detectedonphysicalexamina nodules were Thyroid gene are found The pointmutationsintheTHRβgeneare PTC is the most common histological type of PTC isthemostcommonhistologicaltypeof m g/day. After two months her TSH level and fT4 A caseofresistance to thyroid hormone -subunit, a normal MRI of MRIof -subunit, anormal gene and inheritance of gene and inheritance of ). 131 radio remnant abla radio remnant g/day and g/day and and cols. 365 ------
Copyright© AE&M all rights reserved. Copyright© AE&M all rights reserved. 366 2. 1. REFERENCES was reported. relevant tothisarticle nopotentialconflictofinterest Disclosure: ofthesepatients. might behelpfulforthetreatment betweenRTHplain therelationship and DTCwhich neededtoex studiesare with RTH andDTC.Further thepersistentlyhighTSHinpatients how toovercome L-T4 in a patient with RTH. is no consensus on There doses of maynotbeobtaineddespiteincreasing pression andradioactiveiodinetherapy.thyroidectomy TSHsup aftertotal asthekeystepofDTCtreatment considered hasbeen TSHconcentration.suppression serum in suppressing tients withRTH because ofthedifficulty inpa aggressive cancerismore one iswhetherthyroid cancerandtheother riskforthyroid atanincreased are be explained;oneofthemiswhetherpatientswithRTH TSHsomuchperipheraltissueeffect. ppress inRTH withDTCtosu drug might beanalternative acid(TRIAC)inRTHdothyroacetic (19,20).TRIAC analogs,suchastriio hormone of TSHwiththyroid withsuppression alsopapersrelated are (17,18). There range to the normal TSHlevels decreased treatment Intwocases,withtheadditionofT3to decreased. dosewas solevothroxine anxiety)occurred, chycardia, symptoms (ta sed, inthosepatientshyperthyroidism wasincrea When thedoseoflevothyroxine occured. wasnot ment hasbeenachivedbutTSHsuppression replace withlevothyroxine cases, clinicaleuthyroidism of theRTH (5,6).Inthese andPTCintheliterature cancer(16). thyroid indifferentiated tive treatment asadjunc recommended ofTSHlevelsare suppression malignancy(15).Whereas riskofthyroid with increased TSH levels,typicallydescribedinRTH, associated are case BRAFV600Emutationwasnegative.Highserum butinthesecond small histopathologiccross-sections did notevaluateBRAFV600Emutationbecauseofthe A caseofresistance to thyroid hormone
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