Carcinoma medular de tiroides: estudio multicéntrico. Presentación y evolución en 219 pacientes / Medullary Thyroid Carcinoma: Clinical Presentation and Outcome in 219 Patients

Ante la baja frecuencia del carcinoma medular de tiroides (CMT), en el Departamento de Tiroides de SAEM nos propusimos realizar un estudio de cohorte, observacional, retrospectivo y multicéntrico. Se incluyeron 219 pacientes con diagnóstico histológico de CMT. El 65 % fueron mujeres, la edad promedio fue de 39 ± 20 años (1 a 84 años); 44-% de los casos fueron familiares. Las formas de presentación más frecuentes fueron nódulo tiroideo (58 %) y pesquisa genética por antecedente familiar (22 %). Si bien la citología tiroidea fue diagnóstica de CMT en el 39 % de los casos, fue determinante de indicación quirúrgica en el 79 %. En el 47 % de los pacientes el diagnóstico de CMT se obtuvo previamente al tratamiento quirúrgico inicial por punción aspiración con aguja fina (PAAF), estudio genético o nivel de calcitonina (CT)). El 65 % se presentó en estadios avanzados (TNM III y IV). El estudio del protoncogen RET se realizó en 162 pacientes (74 %). En el 49 % se observó mutación siendo la más frecuente (76 %) en el codón 634. La forma hereditaria más frecuentemente observada fue el síndrome de neoplasia endocrina múltiple (NEM) 2A (57 % de los casos familiares), seguida por carcinoma medular familiar (25 %) y NEM 2B (13 %). Los casos familiares tuvieron menor edad al diagnóstico y mayor frecuencia de diagnóstico prequirúrgico. Los casos índice tuvieron mayor edad al momento del diagnóstico, mayores niveles de antígeno carcinoembrionario (CEA) y CT prequirúrgicos, mayor proporción de estadios III y IV y mayor porcentaje de evidencia de enfermedad al momento de la última consulta que aquellos detectados por pesquisa. En 143 pacientes (65 %) se obtuvieron registros completos de seguimiento en los que se analizaron los factores relacionados con la evolución. La mediana de seguimiento fue de 44 meses: fallecieron 21 pacientes (14,6 %) y 122 (86 %) viven; 76 de estos (54 %) se encuentran libres de enfermedad. El grupo con evidencia de enfermedad se presentó en estadios más avanzados. Resultaron factores de mayor riesgo para evidencia de enfermedad: sexo masculino, CMT esporádico, niveles elevados de CT prequirúrgicos, estadio IV y presencia de metástasis. Los niveles de CT posquirúrgicos fueron menores en aquellos pacientes que en la evolución final no presentaron evidencia de enfermedad. El principal factor pronóstico de la evolución de los pacientes con CMT fue el estadio de presentación, determinando la importancia del diagnóstico precoz con el fin de poder implementar un tratamiento quirúrgico curativo en estadios menos avanzados.

Due to the low frequency of medullary thyroid cancer (MTC), an observational, cohort, retrospective multicenter study was conducted at the Thyroid Department of the Endocrine and Metabolism Argentine Society (SAEM). We included 219 patients with histologically proven MTC, with a mean age of 39 ± 20 yr (range 1-84 years). Sixty five percent were women and 44% were familial cases. The most common presentations were thyroid nodule (58 %) and genetic screening due to family history (22 %). In 39 % of patients, diagnosis of MTC was made by fine needle aspiration, but cytology led to surgery in 79 %. In 47 % of patients, MTC was diagnosed by cytology, calcitonin (CT) levels or genetic studies prior to initial surgery. Sixty five percent of patients had advanced stages of the disease (TNM III or IV) at diagnosis. Proto-oncogene RET was studied in 162 patients (74 %). In 49% a mutation was reported, most frequently in codon 634 (76 %). Regarding hereditary forms of MTC, MEN 2A was the most frequent (57%), followed by familial MTC in 25 % and MEN 2B in 13 % of cases. Familial cases were younger subjects and had more frequently a pre-surgery diagnosis. Index cases were older, with higher CEA and CT levels, presented in more advanced stages and had more frequently evidence of disease at final assessment than patients who were diagnosed by genetic screening. Follow-up records of 143 patients were analyzed (65%); median time was 44 months; 21 patients died (14.6 %) and 122 survived (86 %), 76 showed no evidence of disease (NED) (54 %). High risk factors for evidence of disease at the final evaluation were: male gender, sporadic MTC, higher CT pre-surgery levels, stage IV and metastasis. Post surgery CT levels were lower in patients with NED. Stage at initial diagnosis was the main prognostic factor in patients with MTC, determining the importance of early detection for performing curative surgery in less advanced stages.

Programa nacional de bocio nodular (PRONBONO): Estudio multicéntrico de bocio nodular único palpable / National Program for Nodular Goiter (PRONBONO): Multicenter study of single palpable thyroid nodules

Introducción: La presencia de nódulos tiroideos palpables en la población general, es uno de los signos clínicos tiroideos más frecuentes en la práctica diaria. Objetivos: 1) establecer la prevalencia de las distintas patologías en bocio nodular único palpable y analizar sus características y su relación con los resultados citológicos. 2) analizar la existencia de diferencias regionales en Argentina. Pacientes y Métodos: Estudio prospectivo de 739 pacientes con bocio nodular único palpable evaluados entre el 1/1/2000 y el 31/12/2001 en Centros de Buenos Aires, Bahía Blanca, Mendoza y La Pampa. Se recabaron datos de examen clínico, ecografía tiroidea, TSH, ATPO y citología por punción con aguja fina. (PAAF). Fue utilizado para el análisis estadístico Correlación de Pearson, X2 y Test de Fisher. Resultados: la edad (X ± DS) fue 46,3 ± 14 años, 93,1 % eran de sexo femenino. El 1,6 % tenía historia de radiación en cuello y el 29,9 % antecedentes familiares de patología tiroidea. Hallazgos clínicos: disfagia en el 7,9 %, disfonía 3,5 %, crecimiento nodular en los últimos 6 meses 19,2 %, consistencia dura el 24,7 %, fijeza a estructuras adyacentes 1,5 % y adenopatías en el 3 %. Hallazgos bioquímicos: TSH normal en el 81,2 % y ATPO positivos en el 30,3 % de los casos. Características Ecográficas: nódulos sólidos: 53,1 %, hipoecoicos: 63,8 %, microcalcificaciones 10,3 %, halo incompleto: 15 %, multinodular: 30,5 %, tiroides heterogénea: 60,2 % y adenopatías: 3,8 %. Hallazgos citológicos: En el 86,8 % de los casos fue necesario solo una punción para llegar al diagnóstico. Insatisfactorio (excluyendo quiste): 3,2 %: benignos: 77,3 %; sospechosos: 12,6 % y cáncer: 7 % (42 papilar, 2 medular y 3 sin especificar). Una correlación significativa (p<0,02) fue observada entre citología maligna y crecimiento rápido, dureza, fijeza a estructuras vecinas, nódulo sólido, halo incompleto y adenopatías aunque estos parámetros son más frecuentes en números absolutos en nódulos benignos. La mayoría de las cirugías fueron indicadas en base al hallazgo citológico. El diagnóstico histológico de los 96 pacientes que fueron operados mostró 51 carcinomas, de los cuales solo dos tenían citología benigna y 31 adenomas. Conclusión: Los nódulos palpables únicos fueron más frecuentes en mujeres eutiroideas en la edad media de la vida. Un tercio tenía historia familiar de patología tiroidea, similar al porcentaje hallado de ATPO positivos. Por ecografía los nódulos fueron predominantemente sólidos, hipoecoicos, únicos con resto de la glándula tiroides heterogénea. La PAAF fue predominantemente benigna. El crecimiento rápido, la dureza, la fijeza a estructuras adyacentes, el halo incompleto y la presencia de adenopatías fueron relacionados con malignidad, pero la benignidad fue más frecuente. En la mayoría de los pacientes la cirugía fue recomendada por los hallazgos citológicos. Nuestros resultados son similares a los reportados en otras áreas geográficas.

Introduction: the presence of palpable thyroid nodules in the general population is one of the most common clinical signs of thyroid disease in daily practice. Objectives: 1) To assess the prevalence of pathologies, clinical and cytological findings of single palpable thyroid nodules (SPTN) in Argentina. 2) Analyze the regional differences in Argentina. Methods: Prospective study of 739 patients with STPN were evaluated at centres in Buenos Aires, Bahía Blanca, Mendoza, and La Pampa between 1/1/00 and 12/31/01. Clinical examination, thyroid ultrasound scan (US), TSH, TPOAb and fine needle aspirations (FNA) were performed. Statistics: Pearson Correlation, X2 & Fisher Tests. Results: Age (X ± SD) 46 ± 14ys: 93.1 % were women. Previous history of neck radiation & familial thyroid disease were found in 1.6 and 29.9 % respectively. Clinical findings: dysphagia: 7.9 %; dysphonia: 3.5%; nodule growth: 19.2 %; hard consistence: 24.7 %; fixation to adjacent structure: 1.5 % and lymphadenopathies (ADP): 3 %. Biochemical findings: TSH was normal in 81.2 % & TPOAb+ in 30.3 %. US features: solid: 53.1 %; hypoechoic: 63.8 %; microcalcifications: 10.3 %; incomplete halo: 15 %; more than 1 nodule: 30.5 %; thyroid heterogeneity: 60.2 % and ADP: 3.8 %. Cytology: Only 1 FNA was needed in 86.8%. Unsatisfactory (excluding cysts): 3.2 %; benign: 77.2%; suspicious: 12.6 % and cancer: 7 % (42 papillary, 2 medullary and 3 non specified). A significant correlation (p<0.02) was established between malignant nodules and rapid growth, hard, fixed, solid nodule, incomplete halo and ADP, though these parameters were more frequent (in absolute number) in benign nodules. Surgery was mainly indicated based on FNA results. Histological diagnosis of 96 patients who underwent surgery showed 51 carcinomas, of which only 2 were cytologically benign and 31 adenomas. Conclusion: Palpable single nodules were more frequent in middle aged euthyroid women. One third had familial thyroid pathology, similar to the presence of TPOAb. On US, nodules were predominantly solid, hypoechoic, single with heterogeneous thyroid gland. FNA was predominantly benign. Rapid growth, hard, fixed, solid nodule, incomplete halo and ADP were associated with malignancy, but benignity was more common. In most of the patients surgery was recommended based on cytological findings. Our results are similar to those reported in other geographic areas.

Ascites due to hypothyroidism in a patient with alcoholic cirrhosis.

Myxedema is the cause of ascites in less than 1% of new-onset ascites cases, where as only 4% of patients with hypothyroidism present ascites. When ascites is the first manifestation of thyroid insufficiency, there is usually a delay in diagnosis. We report here a case of myxedema ascites occurring in a patient with alcoholic cirrhosis, that was first thought to be the cause of the ascites, and review the features of 48 cases previously reported. Some clinic and analytical findings that have been commonly reported, are the long duration of the ascites before diagnosis, the prompt response (with resolution of ascites) to thyroid replacement treatment, a high total protein concentration in ascites fluid, white moderate white blood cell counts and a lymphocyte predominance. Serum-ascites albumin gradient has been postulated to be high in myxedema ascites, but we believe this has been studied in too few cases thus far, to be conclusive.

[Molecular diagnosis in an Argentinian family with multiple endocrine neoplasia type-1 (MEN-1)]. / Diagnóstico molecular de neoplasia endocrina múltiple tipo 1 (MEN-1) en una familia Argentina afectada.

MEN-1 is a hereditary autosomal dominant syndrome characterized by the involvement of parathyroid glands, pancreatic islet cells and anterior pituitary gland. Today molecular genetics permit gene carrier analysis to compare the data obtained with the clinical biochemical tests. The twenty living members of the first, second and third generation of a family with MEN-1 were studied to determine the presence of genetic markers in MEN-1 loci 11q13, by linkage analysis and in affected individuals by biochemical tests and clinical examination. Two very informative polymorphic markers immediately flanking the MEN-1 gene on chromosome 11 band q13 were detected: PYGM and D11S987, haplotypes segregated by two members of the second generation, inherited from their father and two of the third generation: the affected one and one presymptomatic. The third generation had the affected member with renal stones and elevated PTH, PRL and glucagon. The presymptomatic carrier of MEN-1 allele showed elevated PTH. Among the members who inherited the normal allele we found one with elevated gastrin, one with elevated glucagon and one with elevated PTH, all asymptomatic. Of one Argentine family studied, molecular diagnosis allowed us to detect one presymptomatic carrier in the members at risk. As suggested by the available literature, accuracy of molecular diagnosis seems to make it the test of choice to exclude those members at risk for MEN-1 inheriting the normal allele.

Ionic conductances in cultured pre-infundibular cells from the hypothalamic arcuate region.

The hypothalamic arcuate nucleus plays an important role in the gating system controlling the secretion of hypothalamic neurons. In order to analyze this gating mechanism, arcuate neurons from rats aged 21-22 days were cultured in a chemically defined medium. Addition of nerve growth factor to this medium increased the survival of the arcuate neurons. Neuron characterization was done with the Lucifer Yellow liposome technique and neurofilament immunocytochemistry. Electrophysiological information was obtained with the patch-clamp technique by whole-cell recordings and single-channel measurements. This qualitative inventory demonstrated the presence of at least five types of conductances: a sodium conductance, two potassium conductances, a calcium-activated conductance, presumably determined by potassium, and a leakage conductance.

Properties of cultured suprachiasmatic nucleus cells.

A method to culture neurons from various hypothalamic brain area of young and fetal rats is described. Hypothalamic slabs will survive for several months, and they are able to make interslab connections. Identification of the cultured cells was done by means of immunocytochemical and Lucifer Yellow liposome techniques.