Dokument: Retrospektive Analyse zur Serum-Calcitonin-Bestimmung zur Diagnosesicherung eines medullären Schilddrüsenkarzinoms
| Titel: | Retrospektive Analyse zur Serum-Calcitonin-Bestimmung zur Diagnosesicherung eines medullären Schilddrüsenkarzinoms | |||||||
| Weiterer Titel: | Retrospective analysis of serum-calcitonin measurement for the diagnosis of medullary thyroid cancer | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=64135 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20231114-100656-8 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Dr. med. Bratengeier, Corinna [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Matthias Schott [Gutachter] Prof.Dr. Goretzki, Peter [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Calcitonin (CT) gilt als hochsensitiver Tumormarker für das medulläre Schilddrüsenkarzinom (MTC). Unklar ist jedoch, ab welchem CT-Wert eine operative Therapie empfohlen werden sollte. Um die Aussagekraft zu erhöhen, können Stimulationstests mit Pentagastrin oder Calcium eingesetzt werden. Da Pentagastrin kommerziell nicht mehr erhältlich ist und der Calciumstimulationstest aufgrund unzureichender Standardisierung umstritten ist, wird aktuell empfohlen, sich beim präoperativen Screening auf die Bestimmung des basalen Calcitonins im Serum (bCT) zu beschränken.
Ziel dieser Arbeit war es, optimale bCT Cut-offs zur Abgrenzung eines MTC von einer C-Zell Hyperplasie (CCH) und Struma nodosa zu ermitteln, die für die Primärdiagnostik des MTC und die Indikation zur Thyreoidektomie genutzt werden können. Im Rahmen der retrospektiven multizentrischen Studie erfüllten 114 Patienten (63♀/ 51♂) die Kriterien eines erhöhten präoperativen bCT-Spiegels (> 10 pg/ml) bei gleichzeitigem Vorliegen eines postoperativen Histologiebefundes. Basierend auf einer ROC Plot Analyse konnten die bCT Cut-offs zur Abgrenzung eines MTC von einer CCH bzw. Struma ermittelt werden. Der optimale bCT Cut-off ist bei Männern ≥ 46 pg/ml (Sensitivität: 93.6%, Spezifität: 95.0%, PPV: 97%, NPV: 90%) und bei Frauen ≥ 35 pg/ml (Sensitivität: 87.3%, Spezifität: 87.5%, PPV: 98%, NPV: 50%). Bei Anwendung dieser Cut-offs wurde in 6% der männlichen MTC- Patienten kein MTC nachgewiesen (falsch negativ), während 5% ein falsch positives Ergebnis aufwiesen (Vorliegen einer CCH). 13% der MTC-Patientinnen wiesen ein falsch negatives und 13% ein falsch positives Ergebnis auf (Vorliegen einer CCH). Abweichende sCT-Spiegel können aufgrund potenzieller analytischer, physiologischer, pharmakologischer und krankheitsbedingter Einflussfaktoren, wie z.B. einer CCH oder Niereninsuffizienz, nicht ausgeschlossen werden. Um den Einfluss genetischer Faktoren zu reduzieren, wurden alle Patienten mit familiärem MTC oder multipler endokriner Neoplasie des Typs 2 (MEN 2) ausgeschlossen sowie Patienten mit anderen Tumorerkrankungen. Die Berechnungen basieren auf einzelnen sCT-Messungen, sodass nicht ausgeschlossen werden kann, dass zusätzliche sCT-Messungen zu geringfügig abweichenden Ergebnissen geführt hätten. Durch das Fehlen weiblicher Struma Patientinnen gab es keine weiblichen Kontrollen. Unter der geringen Anzahl an Frauen mit CCH hatte eine Frau einen sehr hohen sCT-Spiegel. Ein weiterer Nachteil ist die Verwendung vier verschiedener Assays mit unterschiedlichen Referenzwerten. Trotzdem ergab diese Studie mit einer größeren Patientenkohorte nahezu identische bCT Cut-offs für die Abgrenzung eines MTC im Vergleich zu anderen Assay- abhängigen Studien mit geringeren Patientenzahlen. Ein Vorteil ist, dass die bCT Cut-offs für verschiedene Assay-Typen angewendet werden können, zumindest für die in dieser Studie verwendeten Assays. Geschlechterspezifische bCT Cut-offs für die präoperative Diagnose des MTC wurden ermittelt, wobei die Zuverlässigkeit der Vorhersage bei Männern höher ist als bei Frauen. Die Ergebnisse sind mit bisher veröffentlichten Daten vergleichbar und können zur Früherkennung eines sporadischen MTC dienen und dabei helfen die Indikation zur Thyreoidektomie zu stellen. Die Ergebnisse dieser Studie hatten bereits Einfluss auf die neuen Empfehlungen zum Calcitonin Screening bei Struma nodosa der Sektion Schilddrüse (Deutsche Gesellschaft für Endokrinologie).Calcitonin (CT) is a highly sensitive tumor marker for medullary thyroid carcinoma (MTC), though it is still uncertain above which CT-value a thyroid operation should be recommended. To increase the accuracy of the tumor prediction, CT can be stimulated with pentagastrin or calcium. Because of the unavailability of pentagastrin in most countries and insufficient standardization of the calcium stimulation test, the determination of basal calcitonin in the serum (bCT) for preoperative screening is currently recommended. The aim of this study was to determine the most accurate gender-specific bCT cut-off thresholds for the distinction between MTC, C cell hyperplasia (CCH) and nodular goiter, which can be used for the early detection of sporadic MTC and the indication for thyroidectomy. Within a retrospective multicenter study, 114 patients (63 ♀/ 51 ♂) fulfilled the criteria of an increased preoperative bCT (> 10 pg/ml) and an available postoperative histological report. The bCT cut-offs for the distinction between MTC, CCH and nodular goiter were determined based on a ROC plot analysis. The most precise bCT cut-offs were ≥ 46 pg/ml for males (sensitivity: 93.6 %, specificity: 95.0 %, PPV: 97 %, NPV: 90 %) and ≥ 35 pg/ml for females (sensitivity: 87.3 %, specificity: 87.5 %, PPV: 98 %, NPV: 50 %). By applying these bCT cut-offs, only 6% of male patients were not identified of having MTC (false negative), while 5% were false positive (having CCH instead). We could observe a higher discrepancy in females, as 13 % of female MTC patients were false negative and 13 % false positive (having CCH instead). Deviated sCT levels cannot be ruled out due to potential analytical, physiological, pharmacological, and disease-related influencing factors such as CCH or renal failure. To reduce the influence of genetic factors, patients with familial MTC or multiple endocrine neoplasia Type 2 (MEN 2) were excluded as well as patients with other tumor diseases. The calculations are based on single sCT measurements. Therefore, it cannot be ruled out that further sCT measurements would have led to slightly different bCT cut-offs. Due to a lack of female goiter patients, there were no female controls. Among the small number of women with CCH, one had an extremely high level of sCT. Another disadvantage is the usage of four distinct assays with different reference ranges. However, this study with a larger patient cohort yielded almost identical bCT cut-offs for the identification of MTC compared to other assay-dependent studies with a smaller number of patients. One advantage is that the bCT cut-offs can be applied to different assays, at least to the assays used in this study. Gender-specific bCT cut-offs for the preoperative diagnosis of MTC were determined, the accuracy being higher in men than in women. The results are comparable with data published so far. The cut-offs can be used in the clinical routine for the early detection of sporadic MTC and help to establish the indication for a thyroidectomy. The results of this study already had an impact on the new recommendations for calcitonin screening for nodular goiter of the Thyroid Section (German Society for Endocrinology). | |||||||
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| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 14.11.2023 | |||||||
| Dateien geändert am: | 14.11.2023 | |||||||
| Promotionsantrag am: | 21.10.2022 | |||||||
| Datum der Promotion: | 24.10.2023 |
