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RESUMEN La Endotelina-1 (ET1) y Proteína C Reactiva ultrasensible (PCRus) como marcadores de disfunción endotelial (DE) e inflamación vascular en hipotiroidismo subclínico (HS) han mostrado resultados controvertidos. El rol del estrés oxidativo y defensa antioxidante (TRAP) es motivo de discusión. Objetivos Establecer si el HS y la autoinmunidad tiroidea (AIT), excluyendo otros factores de riesgo cardiovascular, pueden causar DE e inflamación vascular, evaluadas a través de ET1 y PCRus, respectivamente. Establecer si TRAP juega algún rol. Evaluar cambios en ET1 y PCRus luego del tratamiento con levotiroxina (LT4). Material y métodos Se evaluaron prospectivamente 70 pacientes divididos en 3 grupos: HS: 41 pacientes (T4 normal,TSH >4,2 y <10 mUI/L), AIT: 10 pacientes eutiroideos (TSH <4,2 mUI/L) con aTPO y/o aTg (+) y Control: 19 pacientes eutiroideos sin AIT. Se excluyeron otros factores de riesgo cardiovascular. Se midió basalmente ET1, PCRus y TRAP plasmáticos, y en HS bajo LT4 (n = 24): ET1 y PCRus. Resultados No hubo diferencias significativas en edad, IMC, perfil lipídico y TRAP. ET1 y PCRus fueron significativamente mayores en pacientes con HS (media ± DS 1,77 ± 0,85 pg/ml y 1,5 ± 0,6 mg/l vs. controles (0,8 ± 0,3 pg/ml y 0,5 ± 0,2 mg/l) p <0,0001 y <0,008 respectivamente. Del mismo modo en AIT (1,4 ± 0.4 pg/ml y 2,3 ± 1,3 mg/l) vs controles p <0,0001 y <0,034, respectivamente. La TSH fue mayor en el grupo AIT vs. Control 2,57 ± 0,88 vs. 1,64 ± 0,5 mUI/L; p = 0,002. En HS bajo LT4 (8,7 ± 3,8 meses) se observó descenso de ET1 (p <0,001). ET1 correlacionó con TSH (r = 0,5 p <0,0001). El punto de corte de ET1 mediante curva ROC fue 1,32 pg/ml (Sensibilidad 81,6%-Especificidad 75%). Conclusiones ET1 y PCRus resultaron marcadores útiles para evaluar DE e inflamación vascular asociadas a HS. La defensa antioxidante no ejercería un rol en estos mecanismos. El tratamiento con LT4 produjo una significativa caída de ET1, pudiendo necesitarse un período más largo de eutiroidismo para normalizarla. En AIT, niveles de TSH >2,5 mUI/L podrían sugerir un mínimo grado de hipotiroidismo justificando la elevación en ET1 y PCR, sin descartar el rol de la AIT "per se".
ABSTRACT The measurement of endothelin-1 (ET1) and high sensitivity C-reactive protein (hsCRP) as markers of endothelial dysfunction (ED) and vascular inflammation in subclinical hypothyroidism (SH) has shown controversial results. The role of oxidative stress and antioxidant defense (TRAP) is a matter of discussion. Objectives To establish if SH and thyroid autoimmunity (TAI), excluding other cardiovascular risk factors, may cause ED and vascular inflammation, evaluated through the measurement of ET1 and hsCRP respectively. To determine if TRAP could have some role. Additionally, changes in these parameters after treatment with levothyroxine (LT4) will be evaluated. Material and methods: 70 patients were prospectively evaluated. They were classified into: SH Group: 41 patients (normal T4, TSH> 4.2 and <10 mIU/L), TAI Group: 10 euthyroid patients (TSH <4.2 mUI/L) with positive aTPO and/or aTg and Control Group: 19 euthyroid patients without TAI. Other cardiovascular risk factors were excluded in patients and controls. Plasma ET1, hsCRP and TRAP were measured basally, and ET1 and hsCRP under LT4 therapy in the HS Group. Results There were no significant differences between the 3 groups in age, BMI, lipids and TRAP. ET1 and hsCRP were significantly higher in patients with SH (mean ± SD 1.77 ± 0.85 pg/ml and 1.5 ± 0.6 mg/l) vs. controls (0.8 ± 0.3 pg/ml y 0.5 ± 0.2 mg/l) p <0.0001 y <0.008 respectively. Similarly, in TAI patients (1.4 ± 0.4 pg/ml y 2.3 ± 1.3 mg/l) vs controls, p <0.0001 and <0.034, respectively. TSH was higher in the TAI patients versus control group (2.5 ± 0.88 versus 1.64 ± 0.5 mIU/L, p = 0.002). Twenty-four patients with SH showed a significant decrease in ET1 (p <0.001) under treatment with LT4 (8.7 ± 3.8 months). ET1 had a highly significant correlation (p <0.0001) with TSH (r = 0.5). The cut-off level of ET1 established by ROC curve was 1.32 pg/ml (Sensitivity 81.6%-Specificity 75%). Conclusions ET1 and hsCRP were useful markers to evaluate ED and vascular inflammation associated with SH. There were no differences in TRAP levels between patients and controls, so it does not appear that oxidative stress would have played any role. Treatment with LT4 produced a significant drop in ET1. Probably, a longer period of euthyroidism might be necessary to normalize ET1 levels. In TAI Group, TSH levels >2.5 mUI/L could suggest a "minimal degree" of hypothyroidism justifying the elevation in ET1 and hs CRP. The role of the TAI "per se" couldn't be completely ruled out.
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Proteína C-Reactiva/efectos de los fármacos , Endotelina-1/efectos de los fármacos , Hipotiroidismo/complicaciones , Tiroxina/uso terapéutico , Proteína C-Reactiva/análisis , Autoinmunidad/efectos de los fármacos , Estudios de Casos y Controles , Endotelina-1/análisis , Antioxidantes/metabolismoRESUMEN
BACKGROUND: We report a case of interference in thyroglobulin (Tg) measurement in a woman with differentiated thyroid cancer and rheumatoid arthritis history. Due to discordant Tg in relation to TSH concentrations and negative images, we investigated possible interference in the measurement of Tg. METHODS: During the follow-up we measured Tg by chemiluminescence (TgQL) using Immulite 2000 immunoassay system. To investigate possible interference in Tg measurement, we made serial dilutions, re-testing of Tg by an alternative method: electrochemiluminescence, Cobas 6000 analyzer (TgEQL), recovery test of Tg and polyethylene glycol (PEG) 6000 precipitation. RESULTS: During the patient follow-up, the TgQL ranged between <0.3 and 16.1ng/ml. In the evaluated serum samples very high titers of rheumatoid factor (RF) were found. When RF titers were lowered post PEG precipitation, Tg QL concentrations became undetectable. CONCLUSION: We describe an unusual case of interference in Tg assay due to RF. When disagreement among Tg concentrations, images and clinical features is observed, we suggest taking into account the evaluation of possible Tg interference to avoid unnecessary complementary exams and inappropriate treatment.
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Análisis Químico de la Sangre/métodos , Factor Reumatoide/inmunología , Tiroglobulina/sangre , Adulto , Reacciones Falso Positivas , Femenino , Humanos , Inmunoensayo , Mediciones Luminiscentes , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/inmunologíaRESUMEN
Las metástasis a distancia ocurren en el 10 % de los pacientes con carcinoma diferenciado de tiroides (CDT). Las metástasis óseas (MO) son las segundas en frecuencia, luego de las pulmonares. Son causa de morbilidad significativa y su manejo es complejo. Objetivo: Revisar la experiencia en el diagnóstico y tratamiento de pacientes con MO evaluados en 10 centros asistenciales. Material y métodos: Estudio retrospectivo multicéntrico. Criterio de inclusión: presencia de MO en pacientes con CDT, diagnosticada por a) biopsia de la lesión, b) lesión estructural ósea con captación de 131I asociada a Tiroglobulina (Tg) elevada o c) lesión estructural ósea captante de (fluor-deoxi-glucosa) 18FDG en (Tomografía por emisión de positrones) PET-TC y Tg elevada. Se evaluaron datos extraídos de la revisión de historias clínicas. Resultados: Se incluyeron 47 pacientes, 55 % mujeres; edad: mediana 55 años (rango 15-84). La histología fue carcinoma papilar en 55 %, folicular en 32 % y otros tipos en 13 %. El diagnóstico de las MO fue sincrónico en 47 % y metacrónico en 53 %, estas últimas detectadas en promedio a los 72 meses (7-240) luego del diagnóstico inicial. Las MO fueron sintomáticas en 64 %. El síntoma más frecuente fue el dolor (70 %). La localización más frecuente fue la vertebral (36 %), con compromiso de múltiples sitios en el 68% de los casos. Dieciséis pacientes (34 %) tuvieron además persistencia/recurrencia locorregional y 68 % metástasis en otras localizaciones, siendo la más frecuente la pulmonar (90 %). Los niveles de Tg estimulada se obtuvieron en 38 pacientes; fueron > 100 ng/ml en 87 % y <100 ng/ml en 13 %. La calcemia fue normal en todos los casos. Los marcadores de remodelado óseo estuvieron elevados en 9 de 31 pacientes (29 %). Los tratamientos efectuados fueron 131I (78 %), bifosfonatos (64 %), cirugía (53 %), radioterapia externa (55 %) y otras modalidades (23 %). La mediana de seguimiento fue de 24 meses (1-228). La sobrevida fue de 41 %. Un paciente fue considerado sin evidencia de enfermedad. Veintiocho pacientes (59 %) murieron con enfermedad. La causa de muerte se conoció en 27 casos, relacionándose con las MO en 8 casos (30 %). Conclusiones: Las MO se observaron predominantemente en pacientes >45 años, con una distribución similar por sexo. Fueron múltiples a predomino axial, ocasionando morbilidad en la mayoría de los pacientes. Los marcadores de remodelado óseo estuvieron elevados en un tercio de los casos evaluados. Ningún paciente presentó hipercalcemia. El tratamiento incluyó múltiples modalidades, lo que demuestra la importancia del enfoque multidisciplinario en estos pacientes. Aunque las MO se asociaron a enfermedad incurable, la mortalidad se relacionó principalmente con la diseminación en otras localizaciones del CDT. Rev Argent Endocrinol Metab 51:51-58, 2014 Los autores declaran no poseer conflicto de interés.
Distant metastasis is an infrequent event in patients with differentiated thyroid cancer (DTC) and it occurs approximately in 10 % of cases. Bone is the second metastatic site in patients with DTC. The aim of this multicenter retrospective study was to describe the diagnosis and treatment of bone metastases (BMs) in patients followed up in ten different hospitals from Argentina. Diagnosis of BMs was made when: a) BM was confirmed by biopsy, b) a structural bone lesion was found following 131I uptake associated with elevated levels of serum thyroglobulin (Tg) or c) a structural bone lesion was demonstrated by 18FDG uptake on PET/CT, also associated with high levels of serum Tg. Demographical, clinical, pathological and outcome data were obtained from hospital charts. We included 47 patients: 55 % were women, with a median age of 55 years old. Histology of DTC was as follows: 55 % had papillary thyroid cancer, 32 % had follicular thyroid cancer and 13 % had other variants. Diagnosis of BMs were synchronous in 47 % of patients (at the same time as DTC diagnosis) and metachronous in 53 %, occurring within a mean period of 72 months after initial diagnosis. In 64 % of patients, BMs were symptomatic: pain was referred in 70 % of these cases. In 68 % of cases, there were multiple sites of BMs, with the spine being the most frequent localization (36 %). In 68 % of patients, other distant metastases were observed, mainly in the lungs. Stimulated Tg levels were known in 38 patients at diagnosis: > 100 ng/ml in 87 % and <100ng/ml in 13 %. Serum calcium level was normal in all subjects in whom it was measured (n = 41). In 9 (29 %) of the 31 patients studied, serum bone turnover markers were elevated. At least one modality of treatment was prescribed in 96 % of patients with BMs. Radioiodine was indicated in 78 % of cases, bisphophonates were prescribed in 64 % of patients, while surgery was performed in 53 %. In 55 % of cases, external beam radiotherapy was also indicated and 23 % of individuals received other therapeutic approaches. Median follow-up was 24 months (range 1-228 months). The survival rate at the end of follow-up was 41 %. One patient (3 %) was considered to have no evidence of disease, 28 patients (59 %) died as a consequence of the DTC. The cause of death was known in 27 cases and it was related to BMs in only 8 patients (30 %). In conclusion, BMs were mainly observed in patients >45 years old, with similar gender distribution. BMs were multiple and had mainly an axial skeletal localization, causing high morbidity in most patients. Although bone turnover markers were elevated in one third of cases, no patient had hypercalcemia. Multiple modalities of treatment were used in the majority of cases, which indicates the importance of a multidisciplinary approach. Finally, although BMs were associated with incurable disease, mortality was mainly related to the spread of DTC to other sites, and not specifically to BM. Rev Argent Endocrinol Metab 51:51-58, 2014 No financial conflicts of interest exist.
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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.
RESUMEN
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.
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El carcinoma diferenciado de tiroides en quiste tirogloso (CaQT) es una rara entidad. En diferentes series de pacientes operados por quistes tiroglosos su incidencia fue del 0.7 al 1.07%. Luego de la extirpación del quiste por el procedimiento de Sistrunk, no hay consenso sobre la indicación de tiroidectomía total, radioablación y/o terapéutica supresiva con levotiroxina. El objetivo del Departamento de tiroides de SAEM, fue evaluar: formas de presentación, evolución clínica, métodos diagnósticos de utilidad y tratamiento para consensuar futuras conductas. Material y Métodos: Estudio multicéntrico, retrospectivo en 22 pacientes entre 10 a 69 años, 15 mujeres y 7 varones. Resultados: El tamaño de los quistes osciló entre 1 y 8 cm (Mediana= 3.0 cm, Χ ± DS= 3.7 ± 2.2 cm). La mitad de los pacientes presentó crecimiento del quiste en los 6 meses previos a la cirugía. La punción resultó sospechosa en 2/5 quistes y positiva en uno. La ecografía tiroidea evidenció nódulos en 4/13 casos (30%). Se realizó tiroidectomía en 17/22 pacientes (total: 15 y subtotal: 2). La histología del CaQT demostró carcinoma papilar en 21 y carcinoma folicular en uno. Hubo coexistencia de cáncer intratiroideo en el 23.5% de los casos, ninguno multicéntrico. Dos pacientes presentaron metástasis ganglionares y otro tuvo compromiso muscular (ninguno de ellos coexistió con cáncer intratiroideo). Se radioablacionó a 13 pacientes. En 9/11 pacientes la tiroglobulina permaneció indetectable durante el seguimiento (1 a 14 años). Conclusiones: 1) Realizar ecografía de cuello y punción ecoguiada a todo paciente con quiste tirogloso. 2) En caso de CaQT combinar simultáneamente tiroidectomía total y procedimiento de Sistrunk. 3) Evaluar radioablación complementaria y tratamiento supresivo con levotiroxina en cada caso. 4) Efectuar el seguimiento tal como en los carcinomas ortotópicos.
Differentiated thyroid carcinoma (DTC) in thyroglosal duct cyst (TGDC) is rare, ranging from 0.7 to 1.07% in different series. After the surgery of choice (Sistrunk procedure) the other alternative treatments such as thyroidectomy (Tx), radioiodine and L-T4 therapy are controversial. OBJECTIVE: to evaluate several and controversial aspects in the largest series of DTC in TGDC reported in the literature. Subjects and methods: retrospective multicentric study: n= 22, aged 10-69 yrs. (15 females and 7 men) who underwent the Sistrunk procedure for TGDC. Results: none of the TGDC was less than 1 cm (median 3.0 cm, Χ±SD= 3.7 ± 2.2cm). In half of them there was an increased cystic size in the last 6 months before surgery. Cyst FNA was suspicious in 2/5 and positive in one, whereas the histological diagnosis of the operated TGCD was papillary cancer in 21 and 1 follicular carcinoma. Thyroid ultrasound (US) (n=13) showed nodules in 30% of the cases. Tx was performed in 17/22 (total: 15, subtotal: 2). Thyroid DTC coexisted in 4/17 (23.5%), and was unilateral in all of them. Lymph node metastases were present in 2 adults and muscle involvement was found in the 10-year old girl. None of these 3 patients had overt thyroid lesions. 131-I therapy was performed in 10 patients. In 9 out of 11 subjects Tg remained undetectable during follow-up (1-14yrs.). Persistent high Tg was present in one case without thyroid DTC. Conclusions: 1) Ultrasonography and FNAB should be performed to every patient with thyroglossal duct cyst 2) In case of TGDC, total Tx and Sistrunk's procedure should be simultaneously combined 3) 131-I therapy and L-T4 suppressive treatment should be evaluated in every case 4) Follow-up as in the DTC.
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Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Quiste Tirogloso/cirugía , Quiste Tirogloso/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/terapia , Terapia Recuperativa/métodosRESUMEN
Langerhans cell histiocytosis (LCH) is a rare granulomatous disease of unknown etiology. We retrospectively reviewed data from four patients (3 males and 1 female), mean age 33.5 years old (range: 21-40), with histopathological diagnosis of LCH. All of them presented with symptoms suggestive of endocrine involvement. The main complaint was goiter in two patients and polyuria and polydipsia in three. Before the LCH diagnosis, two patients had unevaluated symptoms of diabetes insipidus (DI) and hypogonadism. The mean time from symptoms onset to diagnosis was 6.25 years (range: 2-13). Histopathological diagnosis was established by total thyroidectomy (TT) biopsy in two patients, skin lesion biopsy in one, and pituitary stalk biopsy in the other. In the two-first patients, surgery was indicated after the fine-needle aspiration biopsy (FNAB) showed a false positive result of differentiated thyroid carcinoma and immunohistochemistry was used for diagnosis confirmation. Three cases were treated with chemotherapy; one of them had already received radiation therapy on the hypothalamic-pituitary region, developing post-radiation hypopituitarism.
Asunto(s)
Enfermedades del Sistema Endocrino/etiología , Histiocitosis de Células de Langerhans/complicaciones , Histiocitosis de Células de Langerhans/diagnóstico , Adulto , Enfermedades del Sistema Endocrino/diagnóstico , Enfermedades del Sistema Endocrino/patología , Femenino , Histiocitosis de Células de Langerhans/patología , Humanos , Enfermedades Hipotalámicas/diagnóstico , Enfermedades Hipotalámicas/etiología , Enfermedades Hipotalámicas/patología , Masculino , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/etiología , Enfermedades de la Tiroides/patología , Adulto JovenRESUMEN
BACKGROUND: Increased oxidative stress, with elevated levels of free radicals, together with diminished antioxidation have been described previously in models of hyperthyroidism and in patients with Graves' disease. However, controversial results have been found about the antioxidant status and its response to treatment. AIM: To evaluate the antioxidant/oxidant balance in active Graves' disease and the effects of treatment with methimazole (MMI) and 131 iodine (131I). PATIENTS AND METHODS: We studied 69 hyperthyroid (H) patients, 58 female and 11 male, 16-50 years old; total T3: 8 +/- 2 nmol/l, total T4: 264 +/- 65 nmol/l (all mean +/- SD), TSH: 0.1 +/- 0.1 mIU/l, TSH receptor antibody 41 +/- 21%, highest 131Iodine uptake: 67 +/- 16%. As a control group (C), 19 normal adults were studied. DESIGN: Parameters evaluated were: tert-butyl hydroperoxide initiated chemiluminiscence (CL), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and total reactive antioxidant potential (TRAP). RESULTS: In patients vs. controls there was an increase in CL levels (6207 +/- 1434 vs. 3000 +/- 851 cpm/mg of haemoglobin, P < 0.001), decrease in SOD (0.4 +/- 0.1 vs. 0.7 +/- 0.2 U/mg prot, P < 0.05; corresponding to 0.15 micro g/ml), CAT (2.8 +/- 0.6 vs. 3.8 +/- 0.7 pmol/mg prot, P < 0.001) and GSH (1.2 +/- 0.4 vs. 2 +/- 0.7 mmol/l erythrocytes, P < 0.05). The decrease in GPx and TRAP did not show significant differences. The parameters were also recorded in 30 patients who became euthyroid after treatment: 20 of them under MMI therapy (2-12 months) and the rest 3-6 months after 131Iodine administration. All the parameters evaluated were normalized after MMI; however, CL levels stayed high after 131I and only CAT and GSH levels returned to normal values. CONCLUSION: Our results confirm the imbalance of the antioxidant/oxidant status in hyperthyroid patients. MMI treatment was more effective than 131I therapy to improve that balance. We speculate on the benefits of antioxidant therapy administrated together with the habitual treatment of hyperthyroidism, especially in patients after 131I therapy.
Asunto(s)
Antitiroideos/uso terapéutico , Enfermedad de Graves/sangre , Radioisótopos de Yodo/uso terapéutico , Metimazol/uso terapéutico , Estrés Oxidativo , Adolescente , Adulto , Biomarcadores/sangre , Catalasa/sangre , Eritrocitos/metabolismo , Femenino , Glutatión/sangre , Glutatión Peroxidasa/sangre , Enfermedad de Graves/tratamiento farmacológico , Humanos , Mediciones Luminiscentes , Masculino , Persona de Mediana Edad , Superóxido Dismutasa/sangreRESUMEN
We studied the evolution of 150 pregnancies corresponding to 114 women (16-39 years old) with primary hypothyroidism. Fifty-one pregnancies (34%) were conceived under hypothyroidism: 16 overt (X +/- standard deviation [SD], thyroxine [T4]: 2.44 +/- 0.7 microg/dL; thyrotropin [TSH]: 33.4 +/- 8.82 mIU/L), and 35 subclinical hypothyroidism (T4: 6.93 +/- 1.88 microg/dL; TSH: 12.87 +/- 8.43 mIU/L); 99 pregnancies were conceived under euthyroidism while undergoing thyroid therapy. When treatment with levothyroxine was inadequate, the outcome of pregnancy was abortion in 60% of overtly hypothyroid patients and in 71.4% of subclinically hypothyroid patients, premature delivery in 20% and 7.2% respectively, and term delivery in 20% and 21.4%, respectively. When treatment was adequate, 100% of overtly hypothyroid patients and 90.5% of subclinically hypothyroid patients carried pregnancies to term; there were no abortions in any of the groups. Abortions, premature and term deliveries in patients who were euthyroid on levothyroxine at the time of conception were 4%, 11.1% and 84.9% respectively. Of the patients receiving levothyroxine therapy before conception, 69.5% had to increase the dose (mean increase 46.2 +/- 29.6 microg/d). Of 126 evaluated newborns, 110 were delivered at term while 16 were premature. Eight newborns, 4 were premature, had congenital malformations (6.3%), and 4 died. Our results show that the evolution of pregnancies did not depend on whether the hypothyroidism was overt or subclinical but mainly on the treatment received. The adequate treatment of hypothyroidism during gestation minimizes risks and generally, makes it possible for pregnancies to be carried to term without complications.
Asunto(s)
Hipotiroidismo/complicaciones , Complicaciones del Embarazo , Aborto Espontáneo/epidemiología , Adolescente , Adulto , Anomalías Congénitas/epidemiología , Hipotiroidismo Congénito , Femenino , Edad Gestacional , Humanos , Hipertiroidismo/epidemiología , Hipotiroidismo/tratamiento farmacológico , Recién Nacido , Recien Nacido Prematuro , Embarazo , Resultado del Embarazo , Tirotropina/sangre , Tiroxina/administración & dosificación , Tiroxina/sangre , Tiroxina/uso terapéuticoRESUMEN
Information on the effect of abnormal thyroid function on male reproduction is less available than that for the female. To assess the effects of hyperthyroidism on hypothalamic-pituitary-testicular axis and on spermogram parameters, 25 male patients (19-47 years old) suffering from active Graves' disease were studied. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL) were measured before and after administration of 100 microg GnRH plus 200 microg thyrotropin-releasing hormone (TRH). Testosterone (T), estradiol (E2), and 17-hydroxyprogesterone (17-OHP) were determined before and after 5000 IU human chorionic gonadotropin (HCG) administration. Serum sex hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), androstenedione and bioavailable testosterone (bioT), and bioavailable estradiol (bioE2) were also measured. Spermograms according to World Health Organization (WHO) criteria were determined in 21 patients. Hormonal and seminal studies were repeated in six patients after 7 to 19 months of euthyroidism achieved after treatment for hyperthyroidism. As a control group, 10 normal men were evaluated. Impaired sexual function, gynecomastia, and low testicular volume were found in 12, 6, and 3 hyperthyroid patients. Mean basal LH was significantly higher than the control group (7.8 +/- 4.7 vs. 5.0 +/- 1.9 mIU/mL, respectively, p < 0.02), with hyperresponse to GnRH. The response of PRL to TRH was lower in patients versus control group (30 minutes: 3.9 +/- 3.4 and 12.0 +/- 2.8 ng/mL, p < 0.01). Basal levels of steroids and SHBG were significantly higher in patients than in normal men (T: 9.3 +/- 3.3 vs. 5.4 +/- 1.6 ng/mL, p < 0.005; E2: 62.2 +/- 25.2 vs. 32.1 +/- 11.0 pg/mL, p < 0.005; 17-OHP: 2.4 +/- 0.9 vs. 1.1 +/- 0.5 ng/mL, p < 0.001; SHBG: 102.3 +/- 37.3 vs. 19.0 +/- 5.0 nmol/L, p < 0.01). The maximal increment of T and 17-OHP after HCG was lower in hyperthyroid patients than in normal men (p < 0.019 and p < 0.001, respectively). Basal bioT was lower in patients than controls (1.7 +/- 0.8 and 3.1 +/- 1.9 ng/mL, p < 0.02). The following incidence of abnormal semen parameters was found: asthenospermia 85.7%, hypospermia 61.9%, oligospermia 42.9%, necrospermia 42.9% and teratospermia 19.0%. In euthyroidism, a normalization of 85% of seminal alterations was observed in the limited number of patients evaluated. Our results confirm that hyperthyroidism causes marked alterations of the gonadotropic and PRL axis and dramatically affects spermatic function. BioT measurement was useful to identify hypoandrogenism in these patients in spite of the high concentration of total testosterone. The restoration of most semen parameters when euthyroidism was achieved suggests that the alterations were induced by the Graves' disease.
Asunto(s)
Enfermedad de Graves/fisiopatología , Sistema Hipotálamo-Hipofisario/fisiopatología , Semen/citología , Testículo/fisiopatología , Adulto , Estudios de Casos y Controles , Femenino , Hormonas Esteroides Gonadales/sangre , Enfermedad de Graves/complicaciones , Enfermedad de Graves/terapia , Humanos , Masculino , Persona de Mediana Edad , Oligospermia/etiología , Hormonas Hipofisarias/sangre , Prolactina/sangre , Recuento de Espermatozoides , Motilidad Espermática , Espermatozoides/anomalías , Testosterona/sangreAsunto(s)
Amiodarona/efectos adversos , Hipertiroidismo/inducido químicamente , Hipotiroidismo/inducido químicamente , Adulto , Femenino , Humanos , Imidazoles/uso terapéutico , Masculino , Persona de Mediana Edad , Propranolol/uso terapéutico , Enfermedades de la Tiroides/tratamiento farmacológico , Enfermedades de la Tiroides/metabolismo , Pruebas de Función de la Tiroides , Hormonas Tiroideas/metabolismoRESUMEN
Se evaluaron 8 hipertiroidismos y 4 hipotiroidismos inducidos por amiodarona desde el punto de vista clínico y bioquímico a través de dosajes hormonales de tiroxina (T4), triiodotironina (T3), tiroxina libre (T4L) y tirotrofina (TSH), medición de anticuerpos antitiroideos y prueba de TRH en los hipertiroideos luego de la remisión del cuadro. El hipertiroidismo se presentó en una relación mujer: varón 1:1, en mujeres con tiroideopatía previa y en varones sin ella; bajo la ingesta del fármaco o luego de su supensión, con clínica leve o florida. Aunque la elevación de T4 resultó más constante, la de T3 adquiró mayor jerarquía por cuanto la primera situación podría deberse a un mero bloqueo de T4 a T3. En los cuadros leves sólo se suspendió la amiodarona, en los francos se agregó, además, ß bloqueantes y antitiroides, observándose tendencia a requerimientos mayores en tiempo y dosis para alcanzar el eutiroidismo. La prueba de TRH permitió inferir integridad previa del eje en 6 casos. El hipotiroidismo se presentó en mujeres, 3 de ellas con tiroideopatía previa y clínica franca. En los casos factibles se suspendió la amiodarona, agregándose hormona tiroidea cuando el cuadro clínico resultó relevante