RESUMEN
Calcitonin (CT) is an important tumor marker for medullary thyroid carcinoma (MTC). Recent CT assays chiefly recognize the monomeric form of CT (mCT). It was the objective of this study to examine the consequences of the higher specificity of the assay for interpretation of the postoperative CT values in MTC patients. The postoperative mCT concentration was measured in 214 patients with differentiated thyroid carcinoma (MTC excepted; non-MTC patients) to determine a reference range of mCT in totally thyroidectomized patients. Monomeric CT was also determined with a two-site chemiluminescence immunoassay (Nichols) in 94 healthy subjects and in 68 MTC patients. The mCT concentrations were below the detection limit in all examined completely thyroidectomized non-MTC patients. Basal and stimulated mCT values were also below the detection limit in 32 of the 68 MTC patients. The biochemical and imaging diagnosis of the latter patients did not give any indication of tumor recurrence. We conclude that completely thyroidectomized patients with non-MTC do not show any measurable mCT concentrations. In comparison with an unspecific CT-RIA, the more specific mCT determination by immunoluminometric assay permits a more precise differentiation between postoperative normal and pathological values and an earlier diagnosis of recurrent MTC.
Asunto(s)
Biomarcadores de Tumor/sangre , Calcitonina/sangre , Carcinoma Medular/diagnóstico , Carcinoma Medular/cirugía , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Valores de Referencia , Sensibilidad y Especificidad , Caracteres SexualesRESUMEN
BACKGROUND AND OBJECTIVE: When multiple endocrine neoplasia type 2 (MEN2) is suspected, genetic tests are at the centre of screening procedures. It was the aim of this study to compare the diagnostic value of molecular biological investigations with that of conventional biochemical tests. PATIENTS AND METHODS: The study cohort consisted of all 144 patients cared for in our department since 1990 with the suspected diagnosis of MEN2 (evidence of a medullary thyroid carcinoma [MTC]), coexistence of two MEN2 tumours or a family history of MEN2. 14 of the 144 patients (from 12 families) were already known to have an hereditary MTC, while the remaining 130 had been referred for further diagnostic investigations. RESULTS: An hereditary MTC was diagnosed in 22 of the 130 patients, a sporadic MTC in 32, while no definitive classification was possible in 20 MTC patients without a positive family history and on whom no mutation analysis had been performed. MEN2 was excluded in 56 family members. All 22 patients with newly diagnosed MTC had abnormally high calcitonin levels. A germ-line mutation in the RET proto-oncogene was found in 8 of the 9 families who had undergone molecular biological tests. The investigate results led to a thyroidectomy in 19 of the 22 patients with hereditary MTC; in all of them the surgical specimen showed C-cell hyperplasia and/o MTC. CONCLUSION: These results emphasize the importance of genetic tests in family screening. Preoperative measurement of calcitonin remains essential in MEN2 families in whom a germ-line mutation is not known. The choice of the appropriate diagnostic test must be individualized to the particular patients so that optimal results are obtained.
Asunto(s)
Carcinoma Medular/cirugía , Pruebas Genéticas , Neoplasia Endocrina Múltiple Tipo 2a/genética , Neoplasia Endocrina Múltiple Tipo 2a/terapia , Neoplasias de la Tiroides/cirugía , Adolescente , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/cirugía , Adulto , Carcinoma Medular/genética , Niño , Preescolar , Estudios de Cohortes , Familia , Femenino , Humanos , Masculino , Anamnesis , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 2a/diagnóstico , Feocromocitoma/genética , Feocromocitoma/cirugía , Valor Predictivo de las Pruebas , Proto-Oncogenes Mas , Proto-Oncogenes , Neoplasias de la Tiroides/genética , TiroidectomíaRESUMEN
The MEN1 tumor predisposition syndrome is caused by mutations in the MEN1 gene on human chromosome 11q13. We screened MEN1 gene exons 1-10 and flanking intron sequences from four different MEN1 families for mutations. In three families, heterozygous germline mutations within the exons were found, two of these representing novel mutations. In another family, all clinically affected members were heterozygous for a point mutation Gright curved arrow A within intron 4. Sequence analysis of cDNA from lymphocytes of the affected patients revealed that the intron mutation created a new acceptor splice site, leading to the inclusion of 7 bp of intronic sequence into the mRNA. The resulting frameshift generates a premature stop in codon 271. Intron borders should thus be screened for mutations in MEN1 diagnostics and cDNA sequence analysis is helpful in identifying pathophysiological consequences of intron mutations.
Asunto(s)
Empalme Alternativo/genética , Mutación de Línea Germinal/genética , Intrones/genética , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogénicas , ARN Mensajero/genética , Secuencia de Bases , Cromosomas Humanos Par 11/genética , Análisis Mutacional de ADN , ADN Complementario/aislamiento & purificación , Humanos , Datos de Secuencia MolecularRESUMEN
INTRODUCTION: Persistent detectable calcitonin (CT) values can be frequently observed after treatment of medullary thyroid carcinomas (MTCs). Apart from residual C cells or incomplete tumor extirpation, ectopic CT production should be taken into account. CT determination in patients without MTC and after total thyroidectomy should reveal to what extent, apart from the C cells, other neuroendocrine cells show a relevant CT production. OBJECTIVES: The objective of this study was to find out whether ectopic CT production can be detected using an assay specifically recognizing the monomeric form of CT. METHODS: The CT serum values were obtained from 94 healthy individuals and 64 patients who had undergone total thyroidectomy and radioiodine therapy because of follicular or papillary carcinoma. RESULTS: In the group of thyroidectomized patients, the CT values were below the detection limit of the assay. In the tested patients, there was neither a physiological (C cell) nor a pathological (MTC cell) secretion of monomeric CT. CONCLUSION: A relevant ectopic monomeric CT production could be excluded because the patients were without detectable CT concentration. For this reason, postoperative CT concentrations of the monomeric form in MTC patients can be traced either to remaining C cells or to tumor cells. For a differentiation of these two possibilities further diagnostics is necessary.