Skip to main content
SpringerLink
Log in

Betreuung von Kindern und Jugendlichen mit M. Basedow in einem endokrinologischen Zentrum

Care of children and adolescents with Graves’ disease in an endocrinological center

  • Originalien
  • Published:
Monatsschrift Kinderheilkunde Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Der M. Basedow ist im Kindes- und Jugendalter selten. Die Diagnosekriterien sind klar definiert; die Therapiemodalitäten werden kontrovers diskutiert.

Fragestellung

Retrospektive Analyse von Therapie und Langzeitverlauf der Patienten, die in der endokrinologischen Ambulanz der Kinderklinik des Universitätsklinikums Erlangen zwischen 2000 und 2015 betreut wurden.

Patienten und Methoden

Die Daten von 50 Kindern und Jugendlichen (40 w, 10 m) im Alter von 4,5 bis 17,6 Jahren mit der Diagnose M. Basedow wurden anhand der Krankenakten ausgewertet. Erfasst wurden Anamnese, klinische Symptome, Körpergröße, Gewicht und Laborwerte bei Erstvorstellung sowie bei jeder ambulanten Vorstellung. Ebenso wurden die Dauer bis zum Erreichen der euthyreoten Stoffwechsellage (Remission), der Zeitpunkt des Auslassversuchs, die Dauer der Remission, der Zeitpunkt des Rezidivs und der Zeitpunkt und die Art einer etwaigen endgültigen Therapie erfasst. Körperhöhe und BMI wurden in Standard Deviation Score (SDS) anhand der Referenzen von Kromeyer-Hauschild et al. und das sonographische Volumen der Schilddrüse (SD) in SDS mit den Daten der KiGGS-Studie berechnet.

Ergebnisse (Medianwerte)

Die Diagnose wurde 6 Monate nach Symptombeginn im Alter von 12,4 Jahren gestellt. Serum-TSH (thyreoidstimulierendes Hormon) war supprimiert, die freien Hormone fT3 (freies Trijodthyronin) und fT4 (freies Thyroxin) mit 21,6 pmol/l (Norm: 3,5–8,1) bzw. 48,3 pmol/l (Norm: 7,6–17,7) sowie die TRAK (TSH-Rezeptor-Antikörper) mit 9,4 U/l (Norm <1,5) waren erhöht. Bei Diagnose hatten 28 Patienten ein erhöhtes SD-Volumen (+5,9 SDS); im Verlauf zusätzlich 15. Die Therapie erfolgte primär mit Thiamazol (n = 34) bzw. Carbimazol (n = 16), 18 Pat. bekamen initial einen β‑Blocker. Im Verlauf erhielten 96 % eine duale Therapie (Thyreostatikum plus L‑T4). Der Langzeitverlauf konnte bei 41 Patienten beurteilt werden. Bei 8 Patienten erfolgte unter der Initialtherapie bei massiver Struma eine Thyreoidektomie, bei 33 wurde nach 32 Monaten ein Auslassversuch durchgeführt. Davon blieben 17 in Remission (51 %), und 16 bekamen ein Rezidiv. Unter der medikamentösen Rezidivtherapie wurden 9 Patienten thyreoidektomiert.

Schlussfolgerungen

Die Remissionsrate ist nach Primärtherapie hoch und korreliert positiv mit der Behandlungsdauer. Möglichweise hat die duale Therapie die Remissionsrate beeinflusst. Die Therapie hatte keinen Effekt auf das SD-Volumen. Bei zunehmender Struma sollte bei Euthyreose unter der thyreostatischen Therapie als definitive Lösung eine Thyreoidektomie erfolgen.

Abstract

Background

Graves’ disease is rare in childhood and adolescence. While the criteria for diagnosis are clearly defined, there are controversial discussions in the literature regarding the optimal treatment modality.

Objective

The aim of the study was to retrospectively analyze the treatment and long-term course of patients with Graves’ disease who were under the care of this outpatient department of pediatric endocrinology between 2000 and 2015.

Material and methods

The data of 50 children and adolescents (40 female, 10 male) aged between 4.5 and 17.6 years (median 12.4 years) were evaluated. The patient history, height, weight and laboratory values were documented at the initial presentation and at every outpatient visit. The duration to achievement of euthyroidism (remission), the time until attempted withdrawal, the duration of remission, the time of recurrence and the time and type of a final treatment were also documented. To calculate thyroid volume (SDS) values, the data of Kromeyer-Hauschild et al. were used as references for height and BMI and for the sonographically measured thyroid volume the data of the German National Health Examination Survey for Children and Adolescents (KiGGS) were used.

Results (median values)

The diagnosis was made 6 months after the onset of symptoms at the age of 12.4 years. Serum thyroid-stimulating hormone (TSH) levels were suppressed, free tri-iodothyronine (fT3, 21.6 pmol/l; normal range 3.5–8.1), free thyroxine (fT4, 48.3 pmol/l; 7.6–17.7), and TSH-receptor antibody (TRAB, 9.4 U/l; <1.5) were elevated. At diagnosis 28 children had goiter (+5.9 SDS) and 15 patients developed a goiter during the further course. All patients primarily received thiamazole (n = 34) or carbimazole (n = 16) and 18 patients a beta blocker. During the course 96% received dual therapy (antithyroid drug plus L‑T4) and 9 patients are still receiving primary treatment. Thus, 41 patients could be assessed with respect to the long-term course. The treatment did not affect the size of the thyroid gland. A withdrawal trial was performed in 33 patients at 32 months, including 6 patients receiving treatment for <24 months and 11 patients receiving treatment for more than 36 months. Thyroidectomy was performed in 8 patients on drug treatment without a withdrawal trial due to the increasing goiter. After the end of the thyrostatic therapy, 17 patients achieved full remission (no recurrence of hyperthyroidism after completion of drug treatment) and 8 patients currently have a remission duration ≥12 months. Recurrence treatment was initiated in 7 patients after the first remission and 9 patients underwent thyroidectomy.

Conclusion

The high remission rate was positively correlated with the treatment duration. The dual therapy regimen might also affect the outcome. The size of the thyroid gland was unchanged during treatment. The extent of TRAB levels at the time of the withdrawal trial did not affect the long-term outcome. In all cases with a rapid goiter progression, an early thyroidectomy should be performed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2

Literatur

  1. Abraham P, Avenell A, Mcgeoch SC et al (2010) Antithyroid drug regimen for treating Graves’ hyperthyroidism. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD14003420.pub14651854

    Article  PubMed  PubMed Central  Google Scholar 

  2. Bahn Chair RS, Burch HB, Cooper DS et al (2011) Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 21:593–646

    Article  PubMed  Google Scholar 

  3. Bartalena L, Chiovato L, Vitti P (2016) Management of hyperthyroidism due to Graves’ disease: frequently asked questions and answers (if any). J Endocrinol Invest 39:1105–1114

    Article  CAS  PubMed  Google Scholar 

  4. Bergman P, Auldist AW, Cameron F (2001) Review of the outcome of management of Graves’ disease in children and adolescents. J Paediatr Child Health 37:176–182

    Article  CAS  PubMed  Google Scholar 

  5. Bettendorf M (2001) S1-Leitlinie Hyperthyreose (Registernummer 027 - 041). https://www.awmf.org/leitlinien/detail/ll/027-041.html Stand: Januar 2019

    Google Scholar 

  6. Cohen RZ, Felner EI, Heiss KF et al (2016) Outcomes analysis of radioactive iodine and total thyroidectomy for pediatric Graves’ disease. J Pediatr Endocrinol Metab 29:319–325

    Article  CAS  PubMed  Google Scholar 

  7. Collen RJ, Landaw EM, Kaplan SA et al (1980) Remission rates of children and adolescents with thyrotoxicosis treated with antithyroid drugs. Pediatr Electron Pages 65:550–556

    CAS  Google Scholar 

  8. Dietlein M, Grünwald F, Schmidt M et al (2015) S1-Leitlinie Radioiodtherapie bei benignen Schilddrüsenerkrankungen (Registernummer: 031-003). https://www.awmf.org/leitlinien/detail/ll/031-003.htmlStand: Januar 2019

    Google Scholar 

  9. Dötsch J, Siebler T, Hauffa BP et al (2000) Diagnosis and management of juvenile hyperthyroidism in Germany: a retrospective multicenter study. J Pediatr Endocrinol Metab 13:879–885

    Article  PubMed  Google Scholar 

  10. Gastaldi R, Poggi E, Mussa A et al (2014) Graves disease in children: thyroid-stimulating hormone receptor antibodies as remission markers. J Pediatr 164(181):1189–1194.e1

    Article  CAS  PubMed  Google Scholar 

  11. Glaser NS, Styne DM (1997) Predictors of early remission of hyperthyroidism in children. J Clin Endocrinol Metab 82:1719–1726

    CAS  PubMed  Google Scholar 

  12. Grüters A (1998) Treatment of Graves’ disease in children and adolescents. Horm Res 49:255–257

    PubMed  Google Scholar 

  13. Harvengt J, Boizeau P, Chevenne D et al (2015) Triiodothyronine-predominant Graves’ disease in childhood: detection and therapeutic implications. Eur J Endocrinol 172:715–723

    Article  CAS  PubMed  Google Scholar 

  14. Jevalikar G, Solis J, Zacharin M (2014) Long-term outcomes of pediatric Graves’ disease. J Pediatr Endocrinol Metab 27:1131–1136

    CAS  PubMed  Google Scholar 

  15. Kaguelidou F, Alberti C, Castanet M et al (2008) Predictors of autoimmune hyperthyroidism relapse in children after discontinuation of antithyroid drug treatment. J Clin Endocrinol Metab 93:3817–3826

    Article  CAS  PubMed  Google Scholar 

  16. Kaguelidou F, Carel JC, Leger J (2009) Graves’ disease in childhood: advances in management with antithyroid drug therapy. Horm Res 71:310–317

    CAS  PubMed  Google Scholar 

  17. Kahaly GJ, Bartalena L, Hegedus L et al (2018) 2018 European thyroid association guideline for the management of graves’ hyperthyroidism. Eur Thyroid J 7:167–186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kromeyer-Hauschild K, Wabitsch M, Kunze D, Geller F, Geiß HC, Hesse V, Von Hippel A, Jaeger U, Johnsen D, Korte W, Menner K, Müller G, Müller JM, Niemann-Pilatus A, Remer T, Schaefer F, Wittchen H‑U, Zabransky S, Zellner K, Ziegler A, Hebebrand J (2001) Perzentile für den Body-mass-Index für das Kindes- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben. Monatsschr Kinderheilkd 149:11

    Article  Google Scholar 

  19. Krude H (2015) Schilddrüsenerkrankungen im Kindes- und Jugendalter. Monatsschr Kinderheilkd 163:601–615

    Article  Google Scholar 

  20. Leger J, Carel JC (2013) Hyperthyroidism in childhood: causes, when and how to treat. J Clin Res Pediatr Endocrinol 5(Suppl 1):50–56

    PubMed  PubMed Central  Google Scholar 

  21. Leger J, Gelwane G, Kaguelidou F et al (2012) Positive impact of long-term antithyroid drug treatment on the outcome of children with Graves’ disease: national long-term cohort study. J Clin Endocrinol Metab 97:110–119

    Article  CAS  PubMed  Google Scholar 

  22. Lippe BM, Landaw EM, Kaplan SA (1987) Hyperthyroidism in children treated with long term medical therapy: twenty-five percent remission every two years. J Clin Endocrinol Metab 64:1241–1245

    Article  CAS  PubMed  Google Scholar 

  23. Mciver B, Rae P, Beckett G et al (1996) Lack of effect of thyroxine in patients with Graves’ hyperthyroidism who are treated with an antithyroid drug. N Engl J Med 334:220–224

    Article  CAS  PubMed  Google Scholar 

  24. Minamitani K, Sato H, Ohye H et al (2017) Guidelines for the treatment of childhood-onset Graves’ disease in Japan, 2016. Clin Pediatr Endocrinol 26:29–62

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ohye H, Minagawa A, Noh JY et al (2014) Antithyroid drug treatment for graves’ disease in children: a long-term retrospective study at a single institution. Thyroid 24:200–207

    Article  CAS  PubMed  Google Scholar 

  26. Okawa ER, Grant FD, Smith JR (2015) Pediatric Graves’ disease: decisions regarding therapy. Curr Opin Pediatr 27:442–447

    Article  CAS  PubMed  Google Scholar 

  27. Rabon S, Burton AM, White PC (2016) Graves’ disease in children: long-term outcomes of medical therapy. Clin Endocrinol 85:632–635

    Article  CAS  Google Scholar 

  28. Rivkees SA (2016) Controversies in the management of Graves’ disease in children. J Endocrinol Invest 39:1247–1257

    Article  CAS  PubMed  Google Scholar 

  29. Rivkees SA (2003) The management of hyperthyroidism in children with emphasis on the use of radioactive iodine. Pediatr Endocrinol Rev 1(Suppl 2):212–221 (discussion 221–212)

    PubMed  Google Scholar 

  30. Rivkees SA (2010) Pediatric Graves’ disease: controversies in management. Horm Res Paediatr 74:305–311

    Article  CAS  PubMed  Google Scholar 

  31. Ross DS, Burch HB, Cooper DS et al (2016) 2016 American thyroid association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 26:1343–1421

    Article  PubMed  Google Scholar 

  32. Thamm M, Karaolis-Dankert N, Kroke A et al (2007) Jod-Monitoring im Rahmen des bundesweiten Kinder- und Jugendgesundheitssurveys, S 30–40

    Google Scholar 

  33. Vaidya B, Wright A, Shuttleworth J et al (2014) Block & replace regime versus titration regime of antithyroid drugs for the treatment of Graves’ disease: a retrospective observational study. Clin Endocrinol (oxf) 81:610–613

    Article  CAS  Google Scholar 

  34. Van Veenendaal NR, Rivkees SA (2011) Treatment of pediatric Graves’ disease is associated with excessive weight gain. J Clin Endocrinol Metab 96:3257–3263

    Article  PubMed  PubMed Central  Google Scholar 

  35. Volkan-Salancı B, Özgen Kıratlı P (2015) Nuclear medicine in thyroid diseases in pediatric and adolescent patients. Mol Imaging Radionucl Ther 24:47–59

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zimmerman D, Lteif AN (1998) Thyrotoxicosis in children. Endocrinol Metab Clin North Am 27:109–126

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Kinderendokrinologie und -Diabetologie, Kinder- und Jugendklinik, Universitätsklinikum Erlangen, Loschgestraße 15, 91054, Erlangen, Deutschland

    T. Penger, A. Albrecht, M. Marx &  H. G. Dörr

  2. Abteilung für Sonographie, Kinder- und Jugendklinik, Universitätsklinikum Erlangen, Erlangen, Deutschland

    J. Jüngert

  3. Nuklearmedizinische Klinik, Universitätsklinikum Erlangen, Erlangen, Deutschland

    T. Kuwert

Authors
  1. T. Penger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Albrecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Marx
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Jüngert
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. Kuwert
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H. G. Dörr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. G. Dörr.

Ethics declarations

Interessenkonflikt

T. Penger, A. Albrecht, M. Marx, J. Jüngert, T. Kuwert und H.G. Dörr geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Additional information

Redaktion

B. Koletzko, München

T. Lücke, Bochum

E. Mayatepek, Düsseldorf

N. Wagner, Aachen

S. Wirth, Wuppertal

F. Zepp, Mainz

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Penger, T., Albrecht, A., Marx, M. et al. Betreuung von Kindern und Jugendlichen mit M. Basedow in einem endokrinologischen Zentrum. Monatsschr Kinderheilkd 169, 639–644 (2021). https://doi.org/10.1007/s00112-019-0650-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00112-019-0650-3

Schlüsselwörter

Keywords

Search

Navigation