Dysfunktion der Hypothalamus-Hypophysen-Schilddrüsenachse bei Menschen mit Down-Syndrom

Abstract

Menschen mit Down-Syndrom (DS; Synonyme: Morbus Down, Trisomie 21) sind prädisponiert für die Entwicklung thyroidaler Erkrankungen (Iughetti et al., 2014). Das zusätzliche Chromosom 21 scheint mit einer Dysfunktion der Hypothalamus-Hypophysen-Schilddrüsenachse assoziiert zu sein. Hierbei stehen vor allem zwei Probleme im Vordergrund. Dazu zählt zum einen das vermehrte Vorkommen autoimmuner Schilddrüsenerkrankungen und zum anderen die erhöhte Prävalenz für Schilddrüsenunterfunktionen, insbesondere für kongenitale (Synonyme: konnatale, angeborene) Hypothyreosen (Claret et al., 2013; Pierce et al., 2017; Van Trotsenburg et al., 2005). Ziel dieser Studie ist es, den Verlauf dieser Schilddrüsenerkrankungen hinsichtlich ihres Timings und der Prävalenz für die verschiedenen Funktionsstörungen besser erfassen und charakterisieren zu können. Auf der Basis dieser Ergebnisse wird die Reevaluation der Screening-Empfehlungen ermöglicht und ein Leitfaden für Therapiemaßnahmen erarbeitet. Außerdem soll die Ätiologie der Schilddrüsenerkrankungen bei Menschen mit Down-Syndrom genauer beleuchtet werden. Als Ursache wird eine milde Form der Schilddrüsen-Hypoplasie diskutiert (Fort et al., 1984).

1.2 Summary 1.2.1 Introduction People with Down's syndrome have a predisposition to develop thyroid diseases (Iughetti et al., 2014). The additional chromosome 21 appears to be associated with a dysfunction of the hypothalamic-pituitary-thyroid axis. The focus is on two problems here; namely, the increased incidence of autoimmune thyroid diseases and the increased prevalence of hypothyroidism, especially congenital hypothyroidism (Claret et al., 2013; Pierce et al., 2017; Van Trotsenburg et al., 2005). The aim of this study is to better understand and characterize the course of these thyroid diseases in terms of their timing and prevalence for the different functional disorders. On the basis of these results, the re-evaluation of the screening recommendations will be made possible and a guideline for therapeutic measures will be developed. In addition, the etiology of thyroid diseases in people with Down's syndrome will be examined in more detail. A moderate form of thyroid hypoplasia is discussed as the cause (Fort et al., 1984). 1.2.2 Methods A retrospective analysis of thyroid-specific data from a cohort of 274 patients was performed. The patient collective comprised 134 male (49%) and 140 female (51%) volunteers who came to the Down's syndrome consultation hours of Saarland University Hospital between 2012 and 2018 with a confirmed diagnosis of trisomy 21. Among other things, data on the thyroid hormones TSH, fT3 and fT4 and the thyroid autoantibodies (thyroid peroxidase antibodies, thyroglobulin antibodies, TSH receptor antibodies) were collected. The diagnosed thyroid diseases were categorized under epidemiological and etiological aspects. Where available, the sonographic findings were also recorded and evaluated. The longitudinal data collection was followed by the evaluation and analysis of the data. 1.2.3 Results Thyroid dysfunction was detected in 127 patients (46%), of which 34 patients had congenital hypothyroidism. An autoimmune etiology was found in 24 patients. A high proportion of subclinical hypothyroidism was also found. This moderate form of hypothyroidism was diagnosed in 27 patients. With regard to timescale, it was noticed that thyroid diseases were manifested at an earlier age. About half of the diagnoses were made by the age of two. These results illustrate the extremely high proportion of connatal hypothyroidism. A further manifestation peak was emerging for young people between eleven and fifteen years. In addition, a strikingly high proportion of autoimmune thyroid diseases was found. These began at an earlier age and with increasing age, the proportion of thyroid peroxidase positive patients increased parallel to the thyroid peroxidase mean. These results formed the basis for the screening and treatment recommendations. Thyroid hypoplasia could not be excluded as a potential cause for the tendency to thyroid diseases. 1.2.4 Conclusion The predisposition for children with Down's syndrome to develop thyroid hormone disorders was clearly demonstrated and confirmed in this study. Regular screening measures are therefore absolutely necessary and should be intensified, especially in the first two years of the child's life (Luton et al., 2012). An additional control of the TSH values four to five weeks postnatally, as part of the U3 examination, is recommended in order not to overlook later forms of connatal hypothyroidism. Hormone replacement therapy proved to be useful under observation of TSH value normalization. Further studies are required to conclusively assess the protective effect of the therapy. Sensitization to thyroid dysfunction in children with Down's syndrome is extremely important in order to ensure adequate care of the children in everyday clinical practice. The establishment of the screening and therapy recommendations should enable an optimal functional adjustment of the thyroid gland and thus offer the children the best conditions for their quality of life.