Prospective evaluation of autoimmune and non-autoimmune subclinical hypothyroidism in Down syndrome children

in European Journal of Endocrinology

Correspondence should be addressed to G Pepe; Email: giorgiapepe23@gmail.com
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Objective

To evaluate the prevalence and natural course of autoimmune and non-autoimmune subclinical hypothyroidism (SH) in Down syndrome (DS) children and adolescents.

Design

Prospective multicenter study.

Methods

For the study, 101 DS patients with SH (TSH 5–10 mIU/L; FT4 12–22 pmol/L), aged 2–17 years at SH diagnosis were enrolled. Annual monitoring of TSH, FT4, BMI, height, and L-thyroxine dose was recorded for 5 years. Thyroid autoimmunity was tested at diagnosis and at the end of follow-up.

Results

Thirty-seven out of 101 patients displayed autoantibody positivity (group A); the remaining 64 were classified as non-autoimmune SH (group B). Group A was characterized by higher median age at SH diagnosis and by more frequent family history of thyroid disease (6.6 vs 4.7 years, P = 0.001; 32.4% vs 7.8%, P = 0.001 respectively), whereas congenital heart defects were more common in group B (65.6% vs 43.2%, P = 0.028). Gender, median BMI (SDS), height (SDS), FT4, and TSH were similar in both groups. At the end of follow-up: 35.1% of group A patients developed overt hypothyroidism (OH) vs 17.2% of group B (P = 0.041); 31.25% of group B vs 10.8% of group A became biochemically euthyroid (P = 0.02); and 37.8% of group A vs 51.5% of group B still had SH condition (P = 0.183). Logistic regression suggested autoimmunity (OR = 3.2) and baseline TSH values (OR = 1.13) as predictive factors of the evolution from SH to OH.

Conclusions

In DS children, non-autoimmune SH showed higher prevalence and earlier onset. The risk of thyroid function deterioration over time seems to be influenced by thyroid autoimmunity and higher baseline TSH values.

 

     European Society of Endocrinology

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  • 1

    WasniewskaMSalernoMCassioACorriasAAversaTZirilliGCapalboDBalMMussaADe LucaF. Prospective evaluation of the natural course of idiopathic subclinical hypothyroidism in childhood and adolescence. European Journal of Endocrinology 2009 160 417421. (https://doi.org/10.1530/EJE-08-0625)

    • Search Google Scholar
    • Export Citation
  • 2

    WuTFlowersJWTudiverFWilsonJLPunyasavatsutN. Subclinical thyroid disorders and cognitive performance among adolescents in the United States. BMC Pediatrics 2006 6 12. (https://doi.org/10.1186/1471-2431-6-12)

    • Search Google Scholar
    • Export Citation
  • 3

    LazarLFrumkinRBBattatELebenthalYPhillipMMeyerovitchJ. Natural history of thyroid function tests over 5 years in a large pediatric cohort. Journal of Clinical Endocrinology and Metabolism 2009 94 16781682. (https://doi.org/10.1210/jc.2008-2615)

    • Search Google Scholar
    • Export Citation
  • 4

    WasniewskaMAversaTSalernoMCorriasAMessinaMFMussaACapalboDDe LucaFValenziseM. Five-year prospective evaluation of thyroid function in girls with subclinical mild hypothyroidism of different etiology. European Journal of Endocrinology 2015 173 801808. (https://doi.org/10.1530/EJE-15-0484)

    • Search Google Scholar
    • Export Citation
  • 5

    AversaTValenziseMCorriasASalernoMDe LucaFMussaARezzutoMLombardoFWasniewskaM. Underlying Hashimoto’s thyroiditis negatively affects the evolution of subclinical hypothyroidism in children irrespective of other concomitant risk factors. Thyroid 2015 25 183187. (https://doi.org/10.1089/thy.2014.0235)

    • Search Google Scholar
    • Export Citation
  • 6

    RadettiGMaselliMBuziFCorriasAMussaACambiasoPSalernoMCappaMBaiocchiMGastaldiR et al. The natural history of the normal/mild elevated TSH serum levels in children and adolescents with Hashimoto’s thyroiditis and isolated hyperthyrotropinaemia: a 3-year follow-up. Clinical Endocrinology 2012 76 394398. (https://doi.org/10.1111/j.1365-2265.2011.04251.x)

    • Search Google Scholar
    • Export Citation
  • 7

    VigoneMCCapalboDWeberGSalernoM. Mild hypothyroidism in childhood: who, when, and how should be treated? Journal of the Endocrine Society 2018 2 10241039. (https://doi.org/10.1210/js.2017-00471)

    • Search Google Scholar
    • Export Citation
  • 8

    PierceMJLaFranchiSHPinterJD. Characterization of thyroid abnormalities in a large cohort of children with Down syndrome. Hormone Research in Paediatrics 2017 87 170178. (https://doi.org/10.1159/000457952)

    • Search Google Scholar
    • Export Citation
  • 9

    ClaretCGodayABenaigesDChillarónJJFloresJAHernandezECorretgerJMCanoJF. Subclinical hypothyroidism in the first years of life in patients with Down syndrome. Pediatric Research 2013 73 674678. (https://doi.org/10.1038/pr.2013.26)

    • Search Google Scholar
    • Export Citation
  • 10

    WhootenRSchmittJSchwartzA. Endocrine Manifestations of Down syndrome. Current Opinion in Endocrinology Diabetes and Obesity 2018 25 6166. (https://doi.org/10.1097/MED.0000000000000382)

    • Search Google Scholar
    • Export Citation
  • 11

    van TrotsenburgASVulsmaTvan Rozenburg-MarresSLvan BaarALRidderJCHeymansHSTijssenJGde VijlderJJ. The effect of thyroxine treatment started in the neonatal period on development and growth of two-year-old Down syndrome children: a randomized clinical trial. Journal of Clinical Endocrinology and Metabolism 2005 90 33043311. (https://doi.org/10.1210/jc.2005-0130)

    • Search Google Scholar
    • Export Citation
  • 12

    van TrotsenburgASKempersMJEndertETijssenJGde VijlderJJVulsmaT. Trisomy 21 causes persistent congenital hypothyroidism presumably of thyroidal origin. Thyroid 2006 16 671680. (https://doi.org/10.1089/thy.2006.16.671)

    • Search Google Scholar
    • Export Citation
  • 13

    MeyerovitchJAntebiFGreenberg-DotanSBar-TalOHochbergZ. Hyperthyrotropinaemia in untreated subjects with Down’s syndrome aged 6 months to 64 years: a comparative analysis.Archives of Disease in Childhood 2012 97 595598. (https://doi.org/10.1136/archdischild-2011-300806)

    • Search Google Scholar
    • Export Citation
  • 14

    GibsonPANewtonRWSelbyKPriceDALeylandKAddisonGM. Longitudinal study of thyroid function in Down’s syndrome in the first two decades. Archives of Disease in Childhood 2005 90 574578. (https://doi.org/10.1136/adc.2004.049536)

    • Search Google Scholar
    • Export Citation
  • 15

    IughettiLLucaccioniLFugettoFMasonAPredieriB. Thyroid function in Down syndrome. Expert Review of Endocrinology and Metabolism 2015 10 525532. (https://doi.org/10.1586/17446651.2015.1063995)

    • Search Google Scholar
    • Export Citation
  • 16

    KarlssonBGustafssonJHedovGIvarssonSAAnnerénG. Thyroid dysfunction in Down’s syndrome: relation to age and thyroid autoimmunity. Archives of Disease in Childhood 1998 79 242245. (https://doi.org/10.1136/adc.79.3.242)

    • Search Google Scholar
    • Export Citation
  • 17

    AversaTSalernoMRadettiGFaienzaMFIughettiLCorriasAPredieriBMussaAMirabelliSDe LucaF et al. Peculiarities of presentation and evolution over time of Hashimoto’s thyroiditis in children and adolescents with Down’s syndrome. Hormones 2015 14 410416. (https://doi.org/10.14310/horm.2002.1574)

    • Search Google Scholar
    • Export Citation
  • 18

    AversaTCrisafulliGZirilliGDe LucaFGallizziRValenziseM. Epidemiological and clinical aspects of autoimmune thyroid diseases in children with Down’s syndrome. Italian Journal of Pediatrics 2018 44 39. (https://doi.org/10.1186/s13052-018-0478-9)

    • Search Google Scholar
    • Export Citation
  • 19

    AmrNH. Thyroid disorders in subjects with Down syndrome an update. Acta Bio-Medica 2018 89 132139. (https://doi.org/10.23750/abm.v89i1.7120)

    • Search Google Scholar
    • Export Citation
  • 20

    BullMJ & Committee on Genetics. Health supervision for children with Down syndrome. Pediatrics 2011 128 393406. (https://doi.org/10.1542/peds.2011-1605)

    • Search Google Scholar
    • Export Citation
  • 21

    LavigneJSharrCElsharkawiIOzonoffABaumerNBrasingtonCCannonSCrissmanBDavidsonEFlorezJC et al. Thyroid dysfunction in patients with Down syndrome: results from a multi-institutional registry study. American Journal of Medical Genetics: Part A 2017 173 15391545. (https://doi.org/10.1002/ajmg.a.38219)

    • Search Google Scholar
    • Export Citation
  • 22

    IughettiLPredieriBBruzziPPredieriFVellaniGMadeoSFGaravelliLBiagioniOBedogniGBozzolaM. Ten-year longitudinal study of thyroid function in children with Down’s syndrome. Hormone Research in Paediatrics 2014 82 113121. (https://doi.org/10.1159/000362450)

    • Search Google Scholar
    • Export Citation
  • 23

    ArrigoTWasniewskaMCrisafulliGLombardoFMessinaMFRulliISalzanoGValenziseMZirilliGDe LucaF. Subclinical hypothyroidism: the state of the art. Journal of Endocrinological Investigation 2008 31 7984. (https://doi.org/10.1007/BF03345571)

    • Search Google Scholar
    • Export Citation
  • 24

    CooperDS. Clinical practice. Subclinical hypothyroidism. New England Journal of Medicine 2001 345 260265. (https://doi.org/10.1056/NEJM200107263450406)

    • Search Google Scholar
    • Export Citation
  • 25

    LazarusJBrownRSDaumerieCHubalewska-DydejczykANegroRVaidyaB. 2014 European Thyroid Association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. European Thyroid Journal 2014 3 7694. (https://doi.org/10.1159/000362597)

    • Search Google Scholar
    • Export Citation
  • 26

    WasniewskaMCorriasASalernoMMussaACapalboDMessinaMFAversaTBombaciSDe LucaFValenziseM. Thyroid function patterns at Hashimoto’s thyroiditis presentation in childhood and adolescence are mainly conditioned by patients’ age. Hormone Research in Paediatrics 2012 78 232236. (https://doi.org/10.1159/000343815)

    • Search Google Scholar
    • Export Citation
  • 27

    WasniewskaMCorriasASalernoMLombardoFAversaTMussaACapalboDDe LucaFValenziseM. Outcomes of children with hashitoxicosis. Hormone Research in Paediatrics 2012 77 3640. (https://doi.org/10.1159/000334640)

    • Search Google Scholar
    • Export Citation
  • 28

    CacciariEMilaniSBalsamoASpadaEBonaGCavalloLCeruttiFGargantiniLGreggioNToniniG et al. Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). Journal of Endocrinological Investigation 2006 29 581593. (https://doi.org/10.1007/BF03344156)

    • Search Google Scholar
    • Export Citation
  • 29

    KariyawasamDCarréALutonDPolakM. Down syndrome and nonautoimmune hypothyroidisms in neonates and infants. Hormone Research in Paediatrics 2015 83 126131. (https://doi.org/10.1159/000370004)

    • Search Google Scholar
    • Export Citation
  • 30

    OlivieriAStaziMAMastroiacovoPFazziniCMeddaESpagnoloADe AngelisSGrandolfoMETaruscioDCordedduV et al. A population-based study on the frequency of additional congenital malformations in infants with congenital hypothyroidism: data from the Italian Registry for Congenital Hypothyroidism (1991–1998). Journal of Clinical Endocrinology and Metabolism 2002 87 557562. (https://doi.org/10.1210/jcem.87.2.8235)

    • Search Google Scholar
    • Export Citation
  • 31

    AversaTValenziseMSalernoMCorriasAIughettiLRadettiGDe LucaFWasniewskaM. Metamorphic thyroid autoimmunity in Down syndrome: from Hashimoto’s thyroiditis to Graves’ disease and beyond. Italian Journal of Pediatrics 2015 41 87. (https://doi.org/10.1186/s13052-015-0197-4)

    • Search Google Scholar
    • Export Citation
  • 32

    RubelloDPozzanGBCasaraDGirelliMEBoccatoSRigonFBaccichettiCPiccoloMBetterleCBusnardoB. Natural course of subclinical hypothyroidism in Down’s syndrome: prospective study results and therapeutic considerations. Journal of Endocrinological Investigation 1995 18 3540. (https://doi.org/10.1007/BF03349694)

    • Search Google Scholar
    • Export Citation