Graves’ Disease in Children: A Comprehensive Review on Diagnosis, Treatment, and Long-Term Considerations
Main Article Content
Abstract
This comprehensive review of Graves’ Disease (GD) addresses some of the challenges in diagnosing the condition and with the techniques utilized. Focus is given to the relevant clinical manifestations, management options, complications and long-term effects, and future directions in treatment. It highlights the critical role of thyroid function tests (TFTs) in confirming thyrotoxicosis, and the role of thyroid autoantibodies in distinguishing GD from other thyroid disorders. It discusses the role of antithyroid medications, radioactive iodine therapy, and surgical interventions in the management of GD in children. It sheds light on the risks and benefits associated with each approach. The paper also studies the impact of GD on growth, development, and ophthalmic complications in the pediatric population. Promising advancements in treatment such as B-lymphocyte depletion, CD40 blockage, and small molecule TSH-receptor antagonists are also explored. Lastly, the importance of risk factor assessment, screening programs, and increased research are underscored with an attempt to enhance the understanding and management of GD in children.
Keywords:
thyrotoxicosis, Grave’s, children, thyroid, surgery
Article Details
How to Cite
RODRIGUEZ REYES, Derick et al.
Graves’ Disease in Children: A Comprehensive Review on Diagnosis, Treatment, and Long-Term Considerations.
Medical Research Archives, [S.l.], v. 11, n. 10, oct. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4549>. Date accessed: 15 may 2024.
doi: https://doi.org/10.18103/mra.v11i10.4549.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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7. Subekti I, Pramono LA. Current Diagnosis and Management of Graves' Disease. Acta Med Indones. 2018;50(2):177-182.
8. Drexhage HA. Are there more than antibodies to the thyroid-stimulating hormone receptor that meet the eye in Graves' disease?. Endocrinology. 2006;147(1):9-12. doi:10.1210/en.2005-1305
9. Grüters A. Ocular manifestations in children and adolescents with thyrotoxicosis. Exp Clin Endocrinol Diabetes. 1999;107 Suppl 5:S172-S174. doi:10.1055/s-0029-1212178
10. Fatourechi V. Thyroid dermopathy and acropachy. Best Pract Res Clin Endocrinol Metab. 2012;26(4):553-565. doi:10.1016/j.beem.2011.10.001
11. Xie H, Chen D, Zhang J, Yang R, Gu W, Wang X. Characteristics of Graves' disease in children and adolescents in Nanjing: A retrospective investigation study. Front Public Health. 2022;10:993733. Published 2022 Oct 11. doi:10.3389/fpubh.2022.993733
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13. Xie H, Chen D, Zhang J, Yang R, Gu W, Wang X. Characteristics of Graves' disease in children and adolescents in Nanjing: A retrospective investigation study. Front Public Health. 2022;10:993733. Published 2022 Oct 11. doi:10.3389/fpubh.2022.993733
14. Quintanilla-Dieck L, Khalatbari HK, Dinauer CA, et al. Management of Pediatric Graves Disease: A Review. JAMA Otolaryngol Head Neck Surg. 2021;147(12):1110-1118. doi:10.1001/jamaoto.2021.2715
15. Soh SB, Aw TC. Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility. Ann Lab Med. 2019;39(1):3-14. doi:10.3343/alm.2019.39.1.3
16. Staniforth JUL, Erdirimanne S, Eslick GD. Thyroid carcinoma in Graves' disease: A meta-analysis. Int J Surg. 2016;27:118-125. doi:10.1016/j.ijsu.2015.11.027
17. Smith JR, Oates E. Radionuclide imaging of the thyroid gland: patterns, pearls, and pitfalls. Clin Nucl Med. 2004;29(3):181-193. doi:10.1097/01.rlu.0000114530.12565.5b
18. Rivkees SA, Mattison DR. Propylthiouracil (PTU) Hepatoxicity in Children and Recommendations for Discontinuation of Use. Int J Pediatr Endocrinol. 2009;2009:132041. doi:10.1155/2009/132041
19. Mooij CF, Cheetham TD, Verburg FA, et al. 2022 European Thyroid Association Guideline for the management of pediatric Graves' disease. Eur Thyroid J. 2022;11(1):e210073. Published 2022 Jan 1. doi:10.1530/ETJ-21-0073
20. Palella M, Giustolisi FM, Modica Fiascaro A, et al. Risk and Prognosis of Thyroid Cancer in Patients with Graves' Disease: An Umbrella Review. Cancers (Basel). 2023;15(10):2724. Published 2023 May 11. doi:10.3390/cancers15102724
21. de Jong M, Nounou H, Rozalén García V, et al. Children are at a high risk of hypocalcaemia and hypoparathyroidism after total thyroidectomy. J Pediatr Surg. 2020;55(7):1260-1264. doi:10.1016/j.jpedsurg.2019.06.027
22. Edwards ER, Hazkani I, Stein E, et al. Total Thyroidectomy and Subsequent Weight Gain in Pediatric Populations. Laryngoscope. 2023;133(6):1518-1523. doi:10.1002/lary.30532
23. Sanabria A, Dominguez LC, Vega V, Osorio C, Duarte D. Routine postoperative administration of vitamin D and calcium after total thyroidectomy: a meta-analysis. Int J Surg. 2011;9(1):46-51. doi:10.1016/j.ijsu.2010.08.006
24. Azari S, Randolph J, Shi H, et al. Outcomes of pediatric thyroidectomy: a cross-sectional evaluation. World J Pediatr Surg. 2020;3(4):e000185. Published 2020 Dec 23. doi:10.1136/wjps-2020-000185
25. Smith TJ. Neck and Thyroid Examination. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 138. Available from: https://www.ncbi.nlm.nih.gov/books/NBK244/
26. Léger J, Carel JC. Hyperthyroidism in childhood: causes, when and how to treat. J Clin Res Pediatr Endocrinol. 2013;5 Suppl 1(Suppl 1):50-56. doi:10.4274/jcrpe.854
27. National Guideline Centre (UK). Thyroid function tests: Thyroid disease: assessment and management. London: National Institute for Health and Care Excellence (NICE); November 2019.
28. Koulouri O, Gurnell M. How to interpret thyroid function tests. Clin Med (Lond). 2013;13(3):282-286. doi:10.7861/clinmedicine.13-3-282
29. Williams GR, Bassett JHD. Thyroid diseases and bone health. J Endocrinol Invest. 2018;41(1):99-109. doi:10.1007/s40618-017-0753-4
30. Hamed SA, Attiah FA, Abdulhamid SK, Fawzy M. Behavioral assessment of children and adolescents with Graves' disease: A prospective study. PLoS One. 2021;16(4):e0248937. Published 2021 Apr 29. doi:10.1371/journal.pone.0248937
31. Krassas GE, Gogakos A. Thyroid-associated ophthalmopathy in juvenile Graves' disease--clinical, endocrine and therapeutic aspects. J Pediatr Endocrinol Metab. 2006;19(10):1193-1206. doi:10.1515/jpem.2006.19.10.1193
32. Ionescu IC, van Trotsenburg PAS, Paridaens D, et al. Pediatric Graves’ orbitopathy: a multicentre study. Acta Ophthalmol. 2022;100(6):e1340-e1348. doi:https://doi.org/10.1111/aos.15084
33. European Group on Graves' Orbitopathy (EUGOGO), Mourits MP, Bijl H, et al. Outcome of orbital decompression for disfiguring proptosis in patients with Graves' orbitopathy using various surgical procedures. Br J Ophthalmol. 2009;93(11):1518-1523. doi:10.1136/bjo.2008.149302
34. Struja T, Fehlberg H, Kutz A, et al. Can we predict relapse in Graves' disease? Results from a systematic review and meta-analysis. Eur J Endocrinol. 2017;176(1):87-97. doi:10.1530/EJE-16-0725
35. Zawadzka-Starczewska K, Tymoniuk B, Stasiak B, Lewiński A, Stasiak M. Actual Associations between HLA Haplotype and Graves' Disease Development. J Clin Med. 2022;11(9):2492. Published 2022 Apr 29. doi:10.3390/jcm11092492
36. Lane LC, Cheetham TD, Perros P, Pearce SHS. New Therapeutic Horizons for Graves’ Hyperthyroidism. Endocr Rev. 2020;41(6):873-884. doi:10.1210/endrev/bnaa022
37. Cheetham TD, Cole M, Abinun M, et al. Adjuvant Rituximab-Exploratory Trial in Young People With Graves Disease. J Clin Endocrinol Metab. 2022;107(3):743-754. doi:10.1210/clinem/dgab763
38. Kahaly GJ, Stan MN, Frommer L, et al. A Novel Anti-CD40 Monoclonal Antibody, Iscalimab, for Control of Graves Hyperthyroidism-A Proof-of-Concept Trial. J Clin Endocrinol Metab. 2020;105(3):dgz013. doi:10.1210/clinem/dgz013
39. Lane LC, Wood CL, Cheetham T. Graves' disease: moving forwards. Arch Dis Child. 2023;108(4):276-281. doi:10.1136/archdischild-2022-323905
40. Segni M. Disorders of the Thyroid Gland in Infancy, Childhood and Adolescence. In: Feingold KR, Anawalt B, Blackman MR, et al., eds. Endotext. South Dartmouth (MA): MDText.com, Inc.; March 18, 2017.
2. Mortara L, Coco G, Gatti L, Piantanida E, Gallo D. Analysis of Graves’ disease from the origins to the current historical evolution: The history of Graves’ disease discovery and treatment. Med Hist. 2022;5(3 SE-Original articles: History of Medicine):e2021030. https://mattioli1885journals.com/index.php/MedHistor/article/view/12121
3. Weetman AP. Grave's disease 1835-2002. Horm Res. 2003;59 Suppl 1:114-118. doi:10.1159/000067837
4. Volpé R. The pathogenesis of Graves' disease. Compr Ther. 1976;2(2):43-52.
5. Rydzewska M, Jaromin M, Pasierowska IE, Stożek K, Bossowski A. Role of the T and B lymphocytes in pathogenesis of autoimmune thyroid diseases. Thyroid Res. 2018;11:2. Published 2018 Feb 13. doi:10.1186/s13044-018-0046-9
6. Antonelli A, Fallahi P, Elia G, et al. Graves' disease: Clinical manifestations, immune pathogenesis (cytokines and chemokines) and therapy. Best Pract Res Clin Endocrinol Metab. 2020;34(1):101388. doi:10.1016/j.beem.2020.101388
7. Subekti I, Pramono LA. Current Diagnosis and Management of Graves' Disease. Acta Med Indones. 2018;50(2):177-182.
8. Drexhage HA. Are there more than antibodies to the thyroid-stimulating hormone receptor that meet the eye in Graves' disease?. Endocrinology. 2006;147(1):9-12. doi:10.1210/en.2005-1305
9. Grüters A. Ocular manifestations in children and adolescents with thyrotoxicosis. Exp Clin Endocrinol Diabetes. 1999;107 Suppl 5:S172-S174. doi:10.1055/s-0029-1212178
10. Fatourechi V. Thyroid dermopathy and acropachy. Best Pract Res Clin Endocrinol Metab. 2012;26(4):553-565. doi:10.1016/j.beem.2011.10.001
11. Xie H, Chen D, Zhang J, Yang R, Gu W, Wang X. Characteristics of Graves' disease in children and adolescents in Nanjing: A retrospective investigation study. Front Public Health. 2022;10:993733. Published 2022 Oct 11. doi:10.3389/fpubh.2022.993733
12. Bunevicius R, Prange AJ Jr. Psychiatric manifestations of Graves' hyperthyroidism: pathophysiology and treatment options. CNS Drugs. 2006;20(11):897-909. doi:10.2165/00023210-200620110-00003
13. Xie H, Chen D, Zhang J, Yang R, Gu W, Wang X. Characteristics of Graves' disease in children and adolescents in Nanjing: A retrospective investigation study. Front Public Health. 2022;10:993733. Published 2022 Oct 11. doi:10.3389/fpubh.2022.993733
14. Quintanilla-Dieck L, Khalatbari HK, Dinauer CA, et al. Management of Pediatric Graves Disease: A Review. JAMA Otolaryngol Head Neck Surg. 2021;147(12):1110-1118. doi:10.1001/jamaoto.2021.2715
15. Soh SB, Aw TC. Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility. Ann Lab Med. 2019;39(1):3-14. doi:10.3343/alm.2019.39.1.3
16. Staniforth JUL, Erdirimanne S, Eslick GD. Thyroid carcinoma in Graves' disease: A meta-analysis. Int J Surg. 2016;27:118-125. doi:10.1016/j.ijsu.2015.11.027
17. Smith JR, Oates E. Radionuclide imaging of the thyroid gland: patterns, pearls, and pitfalls. Clin Nucl Med. 2004;29(3):181-193. doi:10.1097/01.rlu.0000114530.12565.5b
18. Rivkees SA, Mattison DR. Propylthiouracil (PTU) Hepatoxicity in Children and Recommendations for Discontinuation of Use. Int J Pediatr Endocrinol. 2009;2009:132041. doi:10.1155/2009/132041
19. Mooij CF, Cheetham TD, Verburg FA, et al. 2022 European Thyroid Association Guideline for the management of pediatric Graves' disease. Eur Thyroid J. 2022;11(1):e210073. Published 2022 Jan 1. doi:10.1530/ETJ-21-0073
20. Palella M, Giustolisi FM, Modica Fiascaro A, et al. Risk and Prognosis of Thyroid Cancer in Patients with Graves' Disease: An Umbrella Review. Cancers (Basel). 2023;15(10):2724. Published 2023 May 11. doi:10.3390/cancers15102724
21. de Jong M, Nounou H, Rozalén García V, et al. Children are at a high risk of hypocalcaemia and hypoparathyroidism after total thyroidectomy. J Pediatr Surg. 2020;55(7):1260-1264. doi:10.1016/j.jpedsurg.2019.06.027
22. Edwards ER, Hazkani I, Stein E, et al. Total Thyroidectomy and Subsequent Weight Gain in Pediatric Populations. Laryngoscope. 2023;133(6):1518-1523. doi:10.1002/lary.30532
23. Sanabria A, Dominguez LC, Vega V, Osorio C, Duarte D. Routine postoperative administration of vitamin D and calcium after total thyroidectomy: a meta-analysis. Int J Surg. 2011;9(1):46-51. doi:10.1016/j.ijsu.2010.08.006
24. Azari S, Randolph J, Shi H, et al. Outcomes of pediatric thyroidectomy: a cross-sectional evaluation. World J Pediatr Surg. 2020;3(4):e000185. Published 2020 Dec 23. doi:10.1136/wjps-2020-000185
25. Smith TJ. Neck and Thyroid Examination. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 138. Available from: https://www.ncbi.nlm.nih.gov/books/NBK244/
26. Léger J, Carel JC. Hyperthyroidism in childhood: causes, when and how to treat. J Clin Res Pediatr Endocrinol. 2013;5 Suppl 1(Suppl 1):50-56. doi:10.4274/jcrpe.854
27. National Guideline Centre (UK). Thyroid function tests: Thyroid disease: assessment and management. London: National Institute for Health and Care Excellence (NICE); November 2019.
28. Koulouri O, Gurnell M. How to interpret thyroid function tests. Clin Med (Lond). 2013;13(3):282-286. doi:10.7861/clinmedicine.13-3-282
29. Williams GR, Bassett JHD. Thyroid diseases and bone health. J Endocrinol Invest. 2018;41(1):99-109. doi:10.1007/s40618-017-0753-4
30. Hamed SA, Attiah FA, Abdulhamid SK, Fawzy M. Behavioral assessment of children and adolescents with Graves' disease: A prospective study. PLoS One. 2021;16(4):e0248937. Published 2021 Apr 29. doi:10.1371/journal.pone.0248937
31. Krassas GE, Gogakos A. Thyroid-associated ophthalmopathy in juvenile Graves' disease--clinical, endocrine and therapeutic aspects. J Pediatr Endocrinol Metab. 2006;19(10):1193-1206. doi:10.1515/jpem.2006.19.10.1193
32. Ionescu IC, van Trotsenburg PAS, Paridaens D, et al. Pediatric Graves’ orbitopathy: a multicentre study. Acta Ophthalmol. 2022;100(6):e1340-e1348. doi:https://doi.org/10.1111/aos.15084
33. European Group on Graves' Orbitopathy (EUGOGO), Mourits MP, Bijl H, et al. Outcome of orbital decompression for disfiguring proptosis in patients with Graves' orbitopathy using various surgical procedures. Br J Ophthalmol. 2009;93(11):1518-1523. doi:10.1136/bjo.2008.149302
34. Struja T, Fehlberg H, Kutz A, et al. Can we predict relapse in Graves' disease? Results from a systematic review and meta-analysis. Eur J Endocrinol. 2017;176(1):87-97. doi:10.1530/EJE-16-0725
35. Zawadzka-Starczewska K, Tymoniuk B, Stasiak B, Lewiński A, Stasiak M. Actual Associations between HLA Haplotype and Graves' Disease Development. J Clin Med. 2022;11(9):2492. Published 2022 Apr 29. doi:10.3390/jcm11092492
36. Lane LC, Cheetham TD, Perros P, Pearce SHS. New Therapeutic Horizons for Graves’ Hyperthyroidism. Endocr Rev. 2020;41(6):873-884. doi:10.1210/endrev/bnaa022
37. Cheetham TD, Cole M, Abinun M, et al. Adjuvant Rituximab-Exploratory Trial in Young People With Graves Disease. J Clin Endocrinol Metab. 2022;107(3):743-754. doi:10.1210/clinem/dgab763
38. Kahaly GJ, Stan MN, Frommer L, et al. A Novel Anti-CD40 Monoclonal Antibody, Iscalimab, for Control of Graves Hyperthyroidism-A Proof-of-Concept Trial. J Clin Endocrinol Metab. 2020;105(3):dgz013. doi:10.1210/clinem/dgz013
39. Lane LC, Wood CL, Cheetham T. Graves' disease: moving forwards. Arch Dis Child. 2023;108(4):276-281. doi:10.1136/archdischild-2022-323905
40. Segni M. Disorders of the Thyroid Gland in Infancy, Childhood and Adolescence. In: Feingold KR, Anawalt B, Blackman MR, et al., eds. Endotext. South Dartmouth (MA): MDText.com, Inc.; March 18, 2017.