Hashimoto's thyroiditis in childhood: presentation modes and evolution over time.

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by  De Luca, Filippo

DeLucaetal.ItalianJournalofPediatrics2013,39:8
http://www.ijponline.net/content/39/1/8 ITALIAN JOURNAL
OF PEDIATRICS
COMMENTARY Open Access
Hashimoto's thyroiditis in childhood: presentation
modes and evolution over time
Filippo De Luca*, Simona Santucci, Domenico Corica, Elda Pitrolo, Marika Romeo and Tommaso Aversa
Abstract
Aim ofthis survey is to report themost recent views about Hashimoto’sthyroiditis (HT) natural history according to
thedifferent presentations. Inchildrenpresentingwith either euthyroidism or subclinical hypothyroidism HT
spontaneous course is frequently characterizedby a trend towards deterioration ofthyroid function,whereas in
thosepresenting with overt hyperthyroidism a definitive resolution ofhyperthyroid phase is to be expected.
Another possibleeven though unusualoutcome of HT is the conversion to Graves’disease.
Keywords: Autoimmune thyroid disease, Hashitoxicosis, Subclinical hypothyroidism,Thyroidautoantibodies
Introduction
HTpresentation
Autoimmune thyroid disease (AITD) manifests itself in Atthetimeofdiagnosis,childrenandadolescentwithHT
various clinical forms such as classical Hashimoto' s may be asymptomatic, and the main reasons for referral
thyroiditis (HT) and Graves' disease (GD). Although GD are goiter, hypothyroid symptoms, and findings which
and HT have different phenotypes and the mechanisms occur while working on unrelated problems or for high-
leading to their dichotomy are unknown, they are gener- riskgroups[11].Thyroidfunctionatpresentationmaysig-
ally believed to share a number of common etiological nificantly vary in the different pediatric reports [12-16],
factors. In fact, there have been reports on monozygotic ranging from euthyroidism to overt hypothyroidism or,
twins in whom one twin had GD and the other one had occasionally, hyperthyroidism [12]. Further complaints of
HT [1-3]. Moreover, both conditions may aggregate in thyroid function reported in children and adolescent at
the same families [4] or may even coexist in the same HTpresentationincludeeithersubclinicalhypothyroidism
thyroid gland [5], and some individuals may progress [13-15], or more rarely, subclinical hyperthyroidism [16].
from one form to the other. It is more frequent that GD In a very recent study, we respectively evaluated clinical
may spontaneously culminate in hypothyroidism due to andlaboratorycharacteristicsatHTdiagnosisin608chil-
HT [6], while the development of GD from HT has only dren and adolescent from three pediatric endocrinology
occasionallybeenreporteduntilnow[7-9]. centers in Northern and Southern Italy. The aims of our
HT is the most common form of thyroiditis in child- investigationweretoassessthefrequencyofthyroidfunc-
hood [10] and the most frequent cause of pediatric thy- tion patterns at HT diagnosis and to analyze the factors
roiddiseaseiniodine-repleteareasoftheworld. that may affect the status of thyroid at time of diagnosis
Nevertheless, in spite of this high frequency, there [17].Ourtestresultsatpresentationshowedeuthyroidism
are still several concerns and controversies concerning in 52.1% of patients, overt or subclinical hypothyroidism
the spontaneous evolution of this condition, at least in in 41.4%, and overt or subclinical hyperthyroidism in
childhood. 6.5%. The mean age of patients with thyroid dysfunctions
Aim of the present review is to report the most recent was significantly lower than that found in euthyroid chil-
views about HT natural history according to the differ- dren. Other variables related to thyroid function patterns
entpresentations. were prepubertal status, association with either Down or
Turner syndromes, which correlated with increased risk
of thyroid dysfunctions, and association with other auto-
immune disease, which correlated with decreased risk of
*Correspondence:[email protected]
DepartmentofPediatrics,UniversityofMessina,PadiglioneNIPoliclinico thyroid dysfunctions [17]. On overall, thyroid function
Universitario,ViaConsolareValeria,98125,Messina,Italy
©2013DeLucaetal.;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsoftheCreative
CommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,and
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DeLucaetal.ItalianJournalofPediatrics2013,39:8 Page2of3
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patterns at HT presentation seem to be mainly condi- developing overt hypothyroidism after 3 years in the SH
tioned by children age, with an increased risk of severe children with HT. Thus, at presentation an increased
glanddysfunctionsinthecaseswithearlyHTpresentation TSH can be considered as the best predictor of future
[17].Otherfactorsthatmayalsobeinvolvedaretheasso- hypothyroidism from SH, as also suggested by our group
ciation with either chromosomopathies or other auto- [26] and by others [27]. On overall, on the basis of the
immunedisease[17]andenvironmentalfactors[18]. most recent literature data we can argue that the risk of
The transient hyperthyroid phase of HT is known as developing overt hypothyroidism over time is higher in
hashitoxicosis (Htx), and is believed to result from un- the SH children with an underlying HT than in those
regulated release of stored thyroid hormones during withno underlying thyroid disease [28,29].This inference
inflammatory-mediated destruction of the thyroid gland is strongly supported by the most recent surveys on SH
[19]. Htx has been reported as the second commonest [30-33].
cause of thyrotoxicosis in childhood, after GD [20]. Pre- Finally,anotherpossibleeventhoughunusualoutcome
senting signs and symptoms of Htxcanbe very similarto of HT is the conversion to GD [7,34,35]. In fact, accord-
those generally observed in GD, as previously reported in ing to a recent retrospective epidemiological study, in at
a retrospective study on clinical presentation of Htx in least 3,7% of children and adolescents with GD, the
children[21].Therefore,differentialdiagnosisofHtxfrom onset of hyperthyroidism may be preceded by an HT
GD can be particularly challenging when the diagnosis is diagnosis, with either hypothyroidism or euthyroidism
onlybasedonclinicalandbiochemicalfeatures[22]. [9]. Amechanismthat mightbehypothesized to account
for the change from HT to GD is the alteration in the
HTevolutionovertime biological activity of TSH receptor Abs from predomin-
According to a very recent prospective study aiming to antly thyroid-blocking antibodies during the hypothyroid
investigate long-term outcome of HT in the children phase to thyroid-stimulating antibodies when GD mani-
presenting with overt hyperthyroidism, a definitive reso- fests itself [8]. However, blocking Abs [8] as a cause of
lution of hyperthyroidism is generally observed on aver- HT are very rare and, therefore, this remains a contro-
age eight months after Htx diagnosis, even though there versial point, with no good evidence that the change
is a wide variability between subjects [23]. According to from one disorder to the other really reflects changes in
thatreport,managementofchildrenwithHtxmayrequire the biological activity of TSH receptor Abs. To sum up,
a prolonged clinical and biochemical follow-up, but these studies altogether confirm the existence of a pos-
pharmacological treatment is only required in selected sible continuum between HT and GD within the broad
casesandnon-pharmacologicaltherapiesareneverneeded spectrumofAITD[7,9,34,35].
[23]. Hyperthyroid phase in children with Htx is always
followedbydefinitiveresolution,withnorelapsesandper-
Conclusions
sistentandeuthyroidismorhypothyroidism[23].
In children presenting withbiochemical and/orclinical a) In childhood euthyroidism is the most frequent thy-
euthyroidism, natural history of HTseems to be charac- roid pattern at HT presentation, followed by either overt
terized by a trend towards progressively deteriorating or subclinical hypothyroidism and by either overt or
thyroid function in around 50% of cases, whereas at subclinical hyperthyroidism; b) presenting thyroid func-
5 years of follow-up the remaining 50% of cases were tion patterns are mainly conditioned by patients’ age;
reported to remain or become euthyroid [24]. The pres- c) a trend towards progressively deteriorating thyroid
ence of goiter and elevated thyroglobulin autoantibodies function is frequently observed both in the initially eu-
(Abs) at presentation, together with progressive increase thyroid children and in those presenting with SH; d) the
in both thyroid peroxydase Abs and TSH may be con- risk of developing overt hypothyroidism over time is
sidered as predictive factors for the future development higher in the SH children with an underlying HT than
of hypothyroidism [24]. inthose withnounderlying thyroid disease.
A similar trend towards a spontaneous deterioration of
thyroid function over time has been recently reported in
Abbreviations
a series of children with HT initially presenting with SH, AITD:Autoimmunethyroiddisease;HT:Hashimoto'sthyroiditis;GD:Graves’
even though the process is very slow and not predictable disease;Htx:Hashitoxicosis;Abs:Autoantibodies;SH:Subclinical
hypothyroidism.
in the single case [25]. Therefore, although surveillance is
mandatory, it may take a very long time to see whether
treatment with L-T4 should be implemented or not [25]. Competinginterests
The presence of additional risk factors such as celiac Theauthorsdeclarethattheyhavenocompetinginterests.
disease or elevated TSH and thyroid peroxidase Abs at
Received:18January2013Accepted:23January2013
presentation seems to significantly increase the risk of Published:30January2013
DeLucaetal.ItalianJournalofPediatrics2013,39:8 Page3of3
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References 23. WasniewskaM,CorriasA,SalernoM,LombardoF,AversaT,MussaA,
1. IlickiA,MarcusC,KarlssonFA:Hyperthyroidismandhypothyroidismin CapalboD,DeLucaF,ValenziseM:Outcomesofchildrenwith
monozygotictwins:detectionofstimulatingandblockingTHSreceptor hashitoxicosis.HormResPaediatr2012,77:36–40.
antibodiesusingtheFRTL5-cellline.JEndocrinolInvest1990,13:327–331. 24. RadettiG,GottardiE,BonaG,CorriasA,SalardiS,LocheS:Studygroupfor
2. TaniJ,YoshidaK,FukazawaH,KisoY,SayamaN,MoriK,AlzawaY,HoriH, thyroiddiseasesoftheItaliansocietyforpediatricendocrinologyand
NakasatoN,AbeK:HyperthyroidGraves'diseaseandprimary diabetes(SIEDP/ISPED):thenaturalhistoryofeuthyroidHashimoto's
hypothyroidismcausedbyTSHreceptorantibodiesinmonozygotic thyroiditisinchildren.JPediatr2006,149:827–832.
twins:casereports.EndocrJ1998,45:117–121. 25. RadettiG,MaselliM,BuzitF,CorriasA,MussaA,CambiasoP,SalernoM,
3. AustG,KrohnK,MorgenthalerNG,SchröderS,EdelmannJ,BryllaE:Graves' CappaM,BaiocchiM,GastaldiR,MinerbaL,LocheS:Thenaturalhistoryof
diseaseandHashimoto'sthyroiditisinmonozygotictwins:casestudyas thenormal/mildelevatedTSHserumlevelsinchildrenandadolescents
wellastranscriptomicandimmunohistologicalanalysisofthyroid withHashimoto'sthyroiditisandisolatedhyperthyrotropinaemia:a
tissues.EurJEndocrinol2006,154:13–20. 3-yearfollow-up.ClinEndocrinol2012,76:394–398.
4. DesaiMP,KarandikarS:Autoimmunethyroiddiseaseinchildhood:a 26. WasniewskaM,CorriasA,AversaT,ValenziseM,MussaA,DeMartinoL,
studyofchildrenandtheirfamilies.IndianPediatr1999,36:659–668. LombardoF,DeLucaF,SalernoM:Comparativeevaluationoftherapy
5. DoniachD:Humoralandgeneticaspectsofthyroidautoimmunity. withL-thyroxineversusnotreatmentinchildrenwithidiopathicand
ClinEndocrinolMetab1975,4:267–285. mildsubclinicalhypothyroidism.HormResPaediatr2012,77:376–381.
6. WoodLC,IngbarSH:HypothyroidismasalatesequelainpatientwithGraves' 27. DíezJJ,IglesiasP,BurmanKD:Spontaneousnormalizationofthyrotropin
diseasetreatedwithantithyroidagents.JClinInvest1979,64:1429–1436. concentrationsinpatientswithsubclinicalhypothyroidism.JClin
7. leBerreJP,RousseauC,DupuyO,BordierL,MayaudonH,BauduceauB: EndocrinolMetab2005,90:4124–4127.
Unusualevolutionofautoimmunehypothyroidism:occurrenceof 28. WasniewskaM,SalernoM,CassioA,CorriasA,AversaT,ZirilliG,CapalboD,
Grave'sdisease.(inFrench).RevMedInterne2004,25:841–843. BalM,MussaA,DeLucaF:Prospectiveevaluationofthenaturalcourseof
8. LudgateM,EmersonCH:Metamorphicthyroidautoimmunity.Thyroid idiopathicsubclinicalhypothyroidisminchildhoodandadolescence.Eur
2008,18:1035–1037. JEndocrinol2009,160:417–421.
9. WasniewskaM,CorriasA,ArrigoT,LombardoF,SalernoM,MussaA,Vigone 29. CerboneM,BravaccioC,CapalboD,PolizziM,WasniewskaM,CioffiD,
MC,DeLucaF:FrequencyofHashimoto'sthyroiditisantecedentsinthe ImprodaN,ValenziseM,BruzzeseD,DeLucaF,SalernoM:Lineargrowth
historyofchildrenandadolescentswithgraves'disease.HormRes andintellectualoutcomeinchildrenwithlong-termidiopathic
Paediatr2010,73:473–476. subclinicalhypothyroidism.EurJEndocrinol2011,164:591–597.
10. WasniewskaM,VigoneMC,CappaM,AversaT,RubinoM,DeLucaF:Study 30. ArrigoT,WasniewskaM,CrisafulliG,LombardoF,MessinaMF,RulliI,
GroupforThyroiddiseasesofItalianSocietyforPediatricEndocrinology: SalzanoG,ValenziseM,ZirilliG,DeLucaF:Subclinicalhypothyroidism:the
Acutesuppurativethyroiditisinchildhood:relativefrequencyamong stateoftheart.JEndocrinolInvest2008,31:79–84.
thyroidinflammatorydiseases.JEndocrinolInvest2007,30:346–347. 31. DeLucaF,WasniewskaM,ZirilliG,AversaT,ArrigoT:Attheendofatwo-
yearfollow-upelevatedTSHlevelsnormalizeorremainunchangedin
11. deVriesL,BulvikS,PhillipM:Chronicautoimmunethyroiditisinchildren
andadolescents:atpresentationandduringlong-termfollow-up.Arch mostthechildrenwithsubclinicalhypothyroidism.ItalJPediatr2010,
DisChild2009,94:33–37. 36:11.
12. ZakT,NoczyńskaA,WasikowaR,Zaleska-DorobiszU,GolenkoA:Chronic 32. MonzaniA,ProdamF,RapaA,MoiaS,AgarlaV,BelloneS,BonaG:Natural
historyofsubclinicalhypothyroidisminchildrenandadolescentsand
autoimmunethyroiddiseaseinchildrenandadolescentsintheyears
1999-2004inLowerSilesia.Poland.Hormones.2005,4:45–48. potentialeffectsofreplacementtherapy:areview.EurJEndocrinol2012,
168:R1–R11.
13. GopalakrishnanS,ChughPK,ChhillarM,AmbardarVK,SahooM,SankarR:
33. BonaG,ProdamF,MonzaniA:Subclinicalhypothyroidisminchildren:
Goitrousautoimmunethyroiditisinapediatricpopulation:alongitudinal
study.Pediatrics2008,122:e670–e674. naturalhistoryandwhentotreat.JClinResPediatrEndocrinol2012,
doi:10.4274/jcrpe.851.Nov15[Epubaheadofprint].
14. DemirbilekH,KandemirN,GoncEN,OzonA,AlikasifogluA:Assessmentof
34. OhyeH,NishiharaE,SasakiI,KubotaS,FukataS,AminoN,KumaK,
thyroidfunctionduringthelongcourseofHashimoto'sthyroiditisin
childrenandadolescents.ClinEndocrinol2009,71:451–454. MiyauchiA:FourcasesofGraves'diseasewhichdevelopedafterpainful
Hashimoto'sthyroiditis.InternMed2006,45:385–389.
15. SkarpaV,KappaoustaE,TertipiA,AnyfandakisK,VakakiM,DolianitiM,
35. ChampionB,GopinathB,MaG,El-KaissiS,WallJR:ConversiontoGraves'
FotinouA,PapathanasiouA:Epidemiologicalcharacteristicsofchildren
withautoimmunethyroiddisease.Hormones2011,10:207–214. hyperthyroidisminapatientwithhypothyroidismduetoHashimoto's
16. ÖzenS,BerkÖ,ŞimşekDG,DarcanS:ClinicalcourseofHashimoto's thyroiditisdocumentedbyreal-timethyroidultrasonography.Thyroid
2008,18:1135–1137.
thyroiditisandeffectsoflevothyroxinetherapyontheclinicalcourseof
thediseaseinchildrenandadolescents.JClinResPediatrEndocrinol2011,
3:192–197. doi:10.1186/1824-7288-39-8
Citethisarticleas:DeLucaetal.:Hashimoto'sthyroiditisinchildhood:
17. WasniewskaM,CorriasA,SalernoM,MussaA,CapalboD,MessinaMF,
presentationmodesandevolutionovertime.ItalianJournalofPediatrics
AversaT,BombaciS,DeLucaF,ValenziseM:ThyroidFunctionPatternsat
201339:8.
Hashimoto'sThyroiditisPresentationinChildhoodandAdolescenceAre
MainlyConditionedbyPatients'Age.HormResPaediatr2012,78:232–236.
18. CorriasA,CassioA,WeberG,MussaA,WasniewskaM,RapaA,GastaldiR,
EinaudiS,BaronioF,VigoneMC,MessinaMF,BalM,BonaG,DeSanctisC:
StudygroupforthyroiddiseasesofItaliansocietyforpediatric
endocrinologyanddiabetology(SIEDP/ISPED):thyroidnodulesand Submit your next manuscript to BioMed Central
cancerinchildrenandadolescentsaffectedbyautoimmunethyroiditis. and take full advantage of:
ArchPediatrAdolescMed2008,162:526–531.
19. RallisonML,DobynsBM,KeatingFR,RallJE,TylerFH:Occurrenceand
naturalhistoryofchroniclymphocyticthyroiditisinchildhood.JPediatr • Convenient online submission
1975,86:675–82. • Thorough peer review
20. WilliamsonS,GreeneSA:Incidenceofthyrotoxicosisinchildhood:a • No space constraints or color figure charges
nationalpopulationbasedstudyintheUKandIreland.ClinEndocrinol
2010,72:358–363. • Immediate publication on acceptance
21. NabhanZM,KreherNC,EugsterEA:Hashitoxicosisinchildren:clinical • Inclusion in PubMed, CAS, Scopus and Google Scholar
featuresandnaturalhistory.JPediatr2005,146:533–536.
• Research which is freely available for redistribution
22. ReinweinD,BenkerG,KönigMP,PincheraA,SchatzH,SchleusenerA:The
differenttypesofhyperthyroidisminEurope.Resultsofaprospective
surveyof924patients.JEndocrinolInvest1988,11:193–200. Submit your manuscript at
www.biomedcentral.com/submit