Çocuklarda Hipertiroidi Tanı ve Tedavisi
Özet
Çocukluk çağında tirotoksikozun en sık nedeni, TSH reseptör antikorlarının tiroid bezini uyarmasıyla karakterize Graves hastalığıdır. Hastalık özellikle adolesan dönemindeki kız çocuklarında görülmekle birlikte sinsi bir klinik başlangıca sahiptir. Çocuklarda davranış değişiklikleri, hiperaktivite, uykusuzluk, çarpıntı, terleme, iştah artışına rağmen kilo kaybı ve ileri kemik yaşı gibi belirtilerle kendini gösterir. Tanıda serum fT4 düzeyinde artış ve baskılanmış TSH seviyesi ile birlikte tiroid antikorları ve ultrasonografiden yararlanılır. Tedavide ilk seçenek genellikle medikal olup, yarılanma ömrü uzun olan metimazol (MMI) en sık kullanılan antitiroid ilaçtır. Propiltiourasil (PTU) ise karaciğer toksisitesi riski nedeniyle yalnızca gebeliğin ilk trimesterı veya tiroid fırtınası gibi sınırlı durumlarda tercih edilir. İlaç tedavisine yanıt vermeyen, ciddi yan etki geliştiren veya büyük guatrı olan hastalarda radyoaktif iyot (RAI) tedavisi ya da total/subtotal tiroidektomi gibi cerrahi seçenekler uygulanır. Nadir görülen neonatal Graves hastalığı ise anneden plasenta yoluyla geçen antikorlardan kaynaklanır ve genellikle doğumdan sonraki 3-12 hafta içinde kendiliğinden düzelir.
The most common cause of thyrotoxicosis in childhood is Graves' disease, characterized by the stimulation of the thyroid gland by TSH receptor antibodies. The disease is predominantly observed in adolescent girls and often presents with an insidious clinical onset. Key manifestations in children include behavioral changes, hyperactivity, insomnia, palpitations, sweating, weight loss despite increased appetite, and advanced bone age. Diagnosis relies on elevated serum fT4 levels, suppressed TSH, thyroid autoantibodies, and ultrasonography. Medical management is the first-line treatment, with methimazole (MMI) being the preferred antithyroid drug due to its long half-life. Propylthiouracil (PTU) is restricted to specific cases like the first trimester of pregnancy or thyroid storm due to severe hepatotoxicity risks. For patients unresponsive to medication, those with severe side effects, or large goiters, definitive therapies such as radioactive iodine (RAI) or total/subtotal thyroidectomy are implemented. Neonatal Graves' disease, a rare entity caused by the transplacental transfer of maternal antibodies, typically resolves spontaneously within 3 to 12 weeks after birth.
Referanslar
Minamitani, Kanshi, et al. "Guidelines for the treatment of childhood-onset Graves’ disease in Japan, 2016." Clinical Pediatric Endocrinology 26.2 (2017): 29-62.
De Leo S,Lee SY, Braverman LE, Hyperthyroiidism. Lancet, 2016;388:906-18.
Zimmerman D, Lteif AN. Thyrotoxicosis in children. Endocrinol Metab Clin North Am. 1998;27:109-126.
Williamson, S.,& Greene, S. A. (2010). Incidence of thyrotoxicosis in childhood: a national population based study in the UK and Ireland. Clinical endocrinology, 72(3), 358-363.
Kjær, R. H., Andersen, M. S., & Hansen, D. (2015). Increasing incidence of juvenile thyrotoxicosis in Denmark: a nationwide study, 1998-2012. Hormone research in paediatrics, 84(2), 102-107.
Darendeliler F, Aycan Z, Kara C, Özen S, Eren E. Çocuk Endokrinolojisi ve Diyabet. Bölüm 11.6-Tirotoksikoz. 1. Baskı/2021, Sayfa 1170-1181.
Smith, T. J., & Hegedüs, L. (2016). Graves’ disease. New England Journal of Medicine, 375(16), 1552-1565.
Brix, T. H., Kyvik, K. O., Christensen, K., & Hegedüs, L. (2001). Evidence for a major role of heredity in Graves’ disease: a population-based study of two Danish twin cohorts. The Journal of Clinical Endocrinology & Metabolism, 86(2), 930-934.
Weetman AP. Graves disease. N Engl J Med 2000;343:12361247.
Foley TP. Mediators of thyroid disease in children. J Pediatr 1998;132:569-570.
Srinivasan, S.,& Misra, M. (2015). Hyperthyroidism in children. Pediatrics in Review, 36(6), 239-248.
Congedo, V.,& Celi, F. S. (2007). Thyroid disease in patients with McCune-Albright syndrome. Pediatric endocrinology reviews: PER, 4, 429-433.)
Ferraz, C.,& Paschke, R. (2017). Inheritable and sporadic non-autoimmune hyperthyroidism. Best Practice & Research Clinical Endocrinology & Metabolism, 31(2), 265-275.
Bauer AJ. Approach to the pediatric patient with Graves’ disease: when is definitive therapy warranted? J Clin Endocrinol Metab. 2011;96(3):580-588.).
Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., & Walter, M. A. (2016). 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid, 26(10), 1343-1421.
Cinaz P, Darendeliler F, Akıncı A, Özkan B, Dündar BN, Abacı A, Akçay T. Temel Çocuk Endokrinoloji. 2013. Bölüm 19.3: Hipertiroidizm. Sayfa 331-340.
Léger, J., Gelwane, G., Kaguelidou, F., Benmerad, M., Alberti, C., & French Childhood Graves' Disease Study Group. (2012). Positive impact of long-term antithyroid drug treatment on the outcome of children with Graves' disease: national long-term cohort study. The Journal of Clinical Endocrinology & Metabolism, 97(1), 110-119.).
Rivkees SA, Sklar C, Freemark M: Clinical Review 99: The management of Graves’ disease in children, with special emphasis on radioiodine treatment. J Clin Endocrinol Metab 83:3767, 1998
Rivkees SA. Pediatric Graves’ Disease: Controversies in management. Horm Res Paediatr. 2010;74:305-311
Safa AM, Schumacher OP, Rodriguez-Antunez A. Long-term follow-up results in children and adolescents treated with radioactive iodine (131I) for hyperthyroidism. N Engl J Med. 1975; 292:167– 171.
Miccoli P, Vitti P, Rago T, et al. Surgical treatment of Graves’ disease: subtotal or total thyroidectomy? Surgery. 1996;120:1020–1024
Altman RP. Total thyroidectomy for the treatment of Graves’ disease in children. J Pediatr Surg. 1973; 8:295–300
Rivkees SA. Thyroid disorders in children and adolescent. In: Sperling MA., (editor). Pediatric Endocrinology. 4 ed: Elsevier Saunders, USA; 2014. p. 444-70.
Gozu HI, Lublinghoff J, Bircan R, Paschke R. Genetics and phenomics of inherited and sporadic non-autoimmune hyperthyroidism. Mol Cell Endocrinol 2010;322(1-2):125-34.
Duprez L, Parma J, Van Sande J, Allgeier A, Leclère J, Schvartz C, Delisle MJ, Decoulx M, Orgiazzi J, Dumont J, et al. Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism. Nat Genet 1994;7(3):396-401.
Wasniewska M, Corrias A, Salerno M, Lombardo F, Aversa T, Mussa A, Capalbo D, De Luca F, Valenzise M. Outcomes of children with hashitoxicosis. Horm Res Paediatr 2012;77(1):36-40.
Ogawa E, Katsushima Y, Fujiwara I, Iinuma K. Subacute thyroiditis in children: patient report and review of the literature. J Pediatr Endocrinol Metab 2003;16(6):897-900.
Beck-Peccoz P, Lania A, Beckers A, Chatterjee K, Wemeau JL. 2013 European thyroid association guidelines for the diagnosis and treatment of thyrotropin-secreting pituitary tumors. Eur Thyroid J 2013;2(2):76-82.
Hauser, P, Zametkin, AJ, Martinez, P, et al. Attention deficit-hyperactivity disorder in people with generalized resistance to thyroid hormone. N Engl J Med 1993; 328:997.
Blair JC, Mohan U, Larcher VF, Rajanayagam O, Burrin JM, Perry LA, Grossman AB, Chatterjee VK, Savage MO. Neonatal thyrotoxicosis and maternal infertility in thyroid hormone resistance due to a mutation in the TRbeta gene (M313T). Clin Endocrinol (Oxf ) 2002;57(3):405-9.).
Dallas JS. Hyperthyroidism. In: Pediatric Endocrinology: Informa Healtcare, Lifshitz F, (editor). USA; 2007. p.415-42.
Samuels, S. L., Namoc, S. M., & Bauer, A. J. (2018). Neonatal thyrotoxicosis. Clinics in perinatology, 45(1), 31-40
Kurtoğlu S, Özdemir A. Fetal neonatal hyperthyroidism: diagnostic and therapeutic approachment. Turk Pediatri Ars 2017;52(1):1-9.
