Schilddrüse: Hypo- und Hyperthyreose im Kindes- und Jugendalter

Zusammenfassung

Funktionsstörungen der Schilddrüse (SD) gehören zu den häufigsten endokrinen Erkrankungen im Kindes- und Jugendalter. Ihre Erkennung und frühzeitige Behandlung ist notwendig, um ein altersentsprechendes Wachstum und eine normale psychomotorische Entwicklung zu gewährleisten. Während die angeborene primäre Hypothyreose durch das Neugeborenen-TSH-Screening entdeckt wird, bleibt die Erkennung der zentralen Hypothyreose eine klinische Herausforderung. Die häufigste Ursache der erworbenen Hypothyreose ist die Autoimmunthyreoiditis, die durch den Nachweis von SD-Autoantikörpern und ihr typisches Ultraschallbild diagnostiziert wird. Auch die Hyperthyreose im Kindes- und Jugendalter entsteht vorwiegend durch autoimmune Mechanismen (Basedow-Erkrankung) mit TSHRezeptor-Antikörpern (TRAK) und einem oft chronisch-rezidivierenden Verlauf. Bei fehlendem Antikörpernachweis kann hingegen eine konstitutive Aktivierung des TSH-Rezeptors vorliegen. Die Identifizierung dieser und anderer genetischer Defekte hat in den letzten Jahren wesentlich zum molekularen Verständnis von Entwicklung und Funktion der SD beigetragen.

Summary

Functional thyroid disorders are among the most frequent endocrine diseases in childhood and adolescence. Early detection and treatment is mandatory to ensure normal growth and psychomotor development of affected children. While congenital primary hypothyroidism is readily identified by TSH-based neonatal screening, the detection of central hypothyroidism remains a clinical challenge. Autoimmune thyroiditis is the most frequent cause of acquired hypothyroidism in infancy. The diagnosis is based on detection of thyroid autoantibodies and typical ultrasonographic findings. Hyperthyroidism in infancy is predominantly caused by autoimmune mechanisms (Graves’ disease) characterized by antibodies against the TSH-receptor and a chronic-relapsing clinical course. Antibody-negative hyperthyroidism may be caused by activating TSH-receptor mutations. The identification of this and other genetic defects in recent years has improved the molecular understanding of thyroid development and function.

Schlüsselwörter

Schilddrüse - Hypothyreose - Hyperthyreose - Autoimmunthyreoiditis - Basedow-Erkrankung

Keywords

Thyroid - hypothyroidism - hyperthyroidism - autoimmune thyroiditis - Graves’ disease

• Literatur

• 1 Aghini-Lombardi F, Antonangeli L, Martino E, Vitti P, Maccherini D, Leoli F, Rago T, Grasso L, Valeriano R, Balestrieri A, Pinchera A. The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano survey. J Clin Endocrinol Metab 1999; 84 (02) 561-6.
• 2 Bongers-Schokking JJ, Koot HM, Wiersma D, Verkerk PH, de-Muinck-Keizer-Schrama SM. Influence of timing and dose of thyroid hormone replacement on development in infants with congenital hypothyroidism. J Pediatr 2000; 136 (03) 292-7.
• 3 Brix TH, Hansen PS, Kyvik KO, Hegedus L. Cigarette smoking and risk of clinically overt thyroid disease: a population-based twin case-control study. Arch Intern Med 2000; 160 (05) 661-6.
• 4 Buckler JM, Willgerodt H, Keller E. Growth in thyrotoxicosis. Arch Dis Child 1986; 61 (05) 464-71.
• 5 Corvilain B, Van-Sande J, Dumont JE, Vassart G. Somatic and germline mutations of the TSH receptor and thyroid diseases. Clin Endocrinol (Oxf) 2001; 55 (02) 143-58.
• 6 Cushman LJ, Showalter AD, Rhodes SJ. Genetic defects in the development and function of the anterior pituitary gland. Ann Med 2002; 34 (03) 179-91.
• 7 Doeker B, Andler W. Hyperthyreose im Kindesund Jugendalter: Klinik, Therapie und Verlauf bei 16 Patienten. Monatsschr Kinderheilkd 1998; 146: 673-7.
• 8 Doeker B, Reinehr T, Andler W. Die Autoimmunthyreoiditis bei Kindern und Jugendlichen: Klinische und biochemische Befunde bei 34 Patienten. Klin Padiatr 2000; 212 (03) 103-7.
• 9 Doeker BM, Pfäffle RW, Pohlenz J, Andler W. Congenital central hypothyroidism due to a homozygous mutation in the thyrotropin beta-subunit gene follows an autosomal recessive inheritance. J Clin Endocrinol Metab 1998; 83 (05) 1762-5.
• 10 Dotsch J, Siebler T, Hauffa BP, Doeker B, Andler W, Bettendorf M, Heinrich U, Gohlke B, Albers N, Willgerodt H, Kiess W. Diagnosis and management of juvenile hyperthyroidism in Germany: a retrospective multicenter study. J Pediatr Endocrinol Metab 2000; 13 (07) 879-85.
• 11 Eckstein A, Quadbeck B, Mueller G, Rettenmeier AW, Hoermann R, Mann K, Steuhl P, Esser J. Impact of smoking on the response to treatment of thyroid associated ophthalmopathy. Br J Ophthalmol 2003; 87 (06) 773-6.
• 12 Eisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. N Engl J Med 2004; 350 (20) 2068-79.
• 13 Gruneiro-Papendieck L, Chiesa A, Finkielstain G, Heinrich JJ. Pediatric Graves’ disease: outcome and treatment. J Pediatr Endocrinol Metab 2003; 16 (09) 1249-55.
• 14 Grüters A. Diagnostic tests of thyroid function in children and adolescents. In: Ranke MB. (ed). Diagnostics of endocrine function in children and adolescents. Basel: Karger; 2003: 93-106.
• 15 Gruters A, Krude H, Biebermann H. Molecular genetic defects in congenital hypothyroidism. Eur J Endocrinol 2004; 151 (Suppl. 03) U39-44.
• 16 Hampel R, Beyersdorf-Radeck B, Below H, Demuth M, Seelig K. Jodidurie bei Schulkindern in Deutschland 1999 im Normbereich. Med Klin (Munich) 2001; 96 (03) 125-8.
• 17 Hanna CE, Krainz PL, Skeels MR, Miyahira RS, Sesser DE, LaFranchi SH. Detection of congenital hypopituitary hypothyroidism: ten-year experience in the Northwest Regional Screening Program. J Pediatr 1986; 109 (06) 959-64.
• 18 Hunter I, Greene SA, MacDonald TM, Morris AD. Prevalence and aetiology of hypothyroidism in the young. Arch Dis Child 2000; 83 (03) 207-10.
• 19 Kabelitz M, Liesenkotter KP, Stach B, Willgerodt H, Stablein W, Singendonk W, Jager-Roman E, Litzenborger H, Ehnert B, Gruters A. The prevalence of anti-thyroid peroxidase antibodies and autoimmune thyroiditis in children and adolescents in an iodine replete area. Eur J Endocrinol 2003; 148 (03) 301-7.
• 20 Karges B, LeHeup B, Schoenle E, Castro-Correira C, Fontoura M, Pfaffle R, Andler W, Debatin KM, Karges W. Compound heterozygous and homozygous mutations of the TSHbeta gene as a cause of congenital central hypothyroidism in Europe. Horm Res 2004; 62: 149-55.
• 21 Krassas GE. Treatment of juvenile Graves’ disease and its ophthalmic complication: the ‘European way’. Eur J Endocrinol 2004; 150 (04) 407-14.
• 22 Leclere J, Bene MC, Aubert V, Klein M, Pascal-Vigneron V, Weryha G, Faure G. Clinical consequences of activating germline mutations of TSH receptor, the concept of toxic hyperplasia. Horm Res 1997; 47 (4–6): 158-62.
• 23 Mastorakos G, Mitsiades NS, Doufas AG, Koutras DA. Hyperthyroidism in McCune-Albright syndrome with a review of thyroid abnormalities sixty years after the first report. Thyroid 1997; 7 (03) 433-9.
• 24 Parma J, Duprez L, Van-Sande J, Hermans J, Rocmans P, Van-Vliet G, Costagliola S, Rodien P, Dumont JE, Vassart G. Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas. J Clin Endocrinol Metab 1997; 82 (08) 2695-701.
• 25 Pfäffle RW, Blankenstein O, Wuller S, Kentrup H. Combined pituitary hormone deficiency: role of Pit-1 and Prop-1. Acta Paediatr Suppl 1999; 88 (433): 33-41.
• 26 Pfeilschifter J, Ziegler R. Suppression of serum thyrotropin with thyroxine in patients with Graves’ disease: effects on recurrence of hyperthyroidism and thyroid volume. Eur J Endocrinol 1997; 136 (01) 81-6.
• 27 Polak M, Le-Gac I, Vuillard E, Guibourdenche J, Leger J, Toubert ME, Madec AM, Oury JF, Czernichow P, Luton D. Fetal and neonatal thyroid function in relation to maternal Graves’ disease. Best Pract Res Clin Endocrinol Metab 2004; 18 (02) 289-302.
• 28 Polak M, Sura-Trueba S, Chauty A, Szinnai G, Carre A, Castanet M. Molecular mechanisms of thyroid dysgenesis. Horm Res 2004; 62: 14-21.
• 29 Prummel MF, Strieder T, Wiersinga WM. The environment and autoimmune thyroid diseases. Eur J Endocrinol 2004; 150 (05) 605-18.
• 30 Reinhardt W, Luster M, Rudorff KH, Heckmann C, Petrasch S, Lederbogen S, Haase R, Saller B, Reiners C, Reinwein D, Mann K. Effect of small doses of iodine on thyroid function in patients with Hashimoto’s thyroiditis residing in an area of mild iodine deficiency. Eur J Endocrinol 1998; 139 (01) 23-8.
• 31 Rittmaster RS, Abbott EC, Douglas R, Givner ML, Lehmann L, Reddy S, Salisbury SR, Shlossberg AH, Tan MH, York SE. Effect of methimazole, with or without L-thyroxine, on remission rates in Graves’ disease. J Clin Endocrinol Metab 1998; 83 (03) 814-8.
• 32 Shalitin S, Phillip M. Autoimmune thyroiditis in infants with Down’s syndrome. J Pediatr Endocrinol Metab 2002; 15 (05) 649-52.
• 33 Weetman AP. Cellular immune responses in autoimmune thyroid disease. Clin Endocrinol (Oxf) 2004; 61: 405-13.
• 34 Zois C, Stavrou I, Kalogera C, Svarna E, Dimoliatis I, Seferiadis K, Tsatsoulis A. High prevalence of autoimmune thyroiditis in schoolchildren after elimination of iodine deficiency in northwestern Greece. Thyroid 2003; 13 (05) 485-9.