RESUMEN
Resistance to thyroid hormone beta (RTHß) caused by germline mutations in genes encoding thyroid hormone receptor beta (TRß) is a rare disorder. Little information is available regarding the clinical experience of this syndrome in Japan. We retrospectively reviewed the records of 34 patients with RTHß (21 adult females and 13 adult males) with positive TRß mutations identified at our division between 2000 and 2020. Of the 24 patients with available clinical history, 10 (41.7%) received inappropriate treatments such as antithyroid drugs, thyroidectomy, or radioactive iodine. Diagnostic delay and inappropriate management of RTHß are still present in Japan. Every patient except one demonstrated thyroid hormone profiles indicative of syndrome of inappropriate secretion of thyrotropin (SITSH), characterized by a hormonal profile of hyperthyroxinemia with a non-suppressed TSH concentration. Since the most common forms of hyperthyroidism including Graves' disease feature elevated thyroid hormone levels with suppressed TSH concentrations, early diagnosis of SITSH is critical for preventing inappropriate management. One patient positive for anti-thyroglobulin antibody (Tg-Ab) and anti-thyroperoxidase antibody (TPO-Ab) showed remarkably elevated TSH (>200 µIU/mL) despite thyroid hormone concentrations within the reference ranges. At least one thyroid autoantibody (Tg-Ab, TPO-Ab, or thyrotropin receptor antibodies) was identified in 37.9% (11/29) of the patients tested. One patient developed overt Graves' disease nine years after RTHß diagnosis. These findings suggest that RTHß is frequently comorbid with additional autoimmune thyroid disorders. Further research is required to identify the most appropriate treatments for RTHß patients who develop a second thyroid disorder.
Asunto(s)
Diagnóstico Tardío , Neoplasias de la Tiroides , Adulto , Femenino , Humanos , Radioisótopos de Yodo , Japón/epidemiología , Masculino , Estudios Retrospectivos , Hormonas Tiroideas , TirotropinaRESUMEN
A 74-year-old asymptomatic Japanese man with suspected thyroid dysfunction was referred to our hospital. He had an elevated TSH (53.8 mIU/L; reference interval: 0.5-5.0) despite a free T4 (FT4) level (1.4 ng/dL; reference interval: 0.9-1.6). Further analysis revealed macro-TSH. A notable finding was that a 500-µg TRH stimulation test revealed a blunted free T3 (FT3) response despite a prolonged TSH response. Macro-TSH typically presents with inappropriately marked elevation of serum TSH levels compared with other thyroid hormones, as exhibited in our case. However, the level of TSH elevation that might differentiate macro-TSH from subclinical hypothyroidism is poorly known. We retrospectively analyzed 8,183 concurrent measurements of TSH and FT4 in individuals previously examined in our hospital to define the cut-off value for screening cases of inappropriate TSH elevation. FT4 values were rounded off to one decimal place, and the 97.5th percentile of TSH against each FT4 value was calculated. The data of our patient and that of 30 cases of macro-TSH extracted from the English literature were then assessed. When the approximate curve obtained from the 97.5th percentile of TSH values was defined as the cut-off value [Log10TSH = 0.700 + 1.549/{1 + (FT4/0.844)6.854}], 25 of the 31 (80.6%) macro-TSH cases were identified. In conclusion, we report for the first time a case of macro-TSH demonstrating an abnormal FT3 response to TRH. A cut-off value of TSH adjusted to the FT4 level may be a good method of screening for inappropriate TSH elevation (or inappropriate hyperthyrotropinemia) including those caused by macro-TSH.
Asunto(s)
Complejo Antígeno-Anticuerpo/sangre , Pruebas de Función de la Tiroides , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangre , Anciano , Complejo Antígeno-Anticuerpo/inmunología , Humanos , Masculino , Pruebas de Función Hipofisaria , Valores de Referencia , Tirotropina/inmunología , Hormona Liberadora de TirotropinaRESUMEN
Subacute thyroiditis is a self-limited inflammatory disease and very few patients undergo ultrasonographic re-examination if no nodules are found at the initial examination. The objective of the study was to assess the diagnostic accuracy of ultrasonography in detecting nodular lesions in patients with subacute thyroiditis. We conducted a longitudinal study involving 710 patients with subacute thyroiditis who underwent ultrasonographic examinations in a single center between 2008 and 2018. These examinations were performed at initial diagnosis and during follow-up, with subsequent evaluation of nodules using fine needle aspiration cytology. Ultrasonographic examination used for the initial screening of thyroid nodules in patients with subacute thyroiditis showed a sensitivity of 72.4%, specificity of 89.0%, positive predictive value of 80.4%, and negative predictive value of 83.8%. Twenty-two patients (3.1%) had concomitant papillary thyroid carcinoma, 10 of whom underwent thyroidectomy while the remaining 12 opted for active surveillance owing to having low-risk microcarcinomas. Approximately 30% of papillary carcinomas (7/22) were identified during follow-up ultrasonography, but not during the initial scan. All tumors in this false-negative group were latently localized in the bilateral hypoechoic regions of the thyroid and showed no calcified components. Of the 15 tumors that were detected during both initial and follow-up examinations, 7 exhibited calcified components and 5 were located in unaffected areas apart from the inflammatory hypoechoic region. Subacute thyroiditis highly obscures any coexisting papillary carcinoma when inflammatory hypoechoic regions are present. Ultrasonographic re-examination after a sufficient interval is indispensable for patients with subacute thyroiditis.
Asunto(s)
Cáncer Papilar Tiroideo/diagnóstico por imagen , Neoplasias de la Tiroides/diagnóstico por imagen , Tiroiditis Subaguda/diagnóstico por imagen , Ultrasonografía , Adulto , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Cáncer Papilar Tiroideo/complicaciones , Neoplasias de la Tiroides/complicaciones , Tiroiditis Subaguda/complicacionesRESUMEN
While patients with large goitrous thyroid diseases often have a relatively high serum free triiodothyronine (FT3)/free thyroxine (FT4) ratio, athyreotic patients have a relatively low FT3/FT4 ratio. Here we investigated the relationship between thyroid hormone status and thyroid volume (TV) among a large number of euthyroid Hashimoto thyroiditis (HT) patients. We retrospectively enrolled 2,603 untreated HT patients who visited the Kuma hospital from 2012 to 2016, and divided them into four groups as per the TV: normal TV (<20 mL), slight goiter (20 ≤ TV < 50 mL), moderate goiter (50 ≤ TV < 80 mL), and the large goiter group (≥80 mL). Baseline characteristics and laboratory data of each group were compared to those of 1,554 control subjects. The association between FT3/FT4 ratio and TV among HT patients was then analyzed. We observed a change in laboratory parameters among 13 patients in the large goiter group who were prescribed levothyroxine (LT4) for reducing TV. Compared to normal subjects, the moderate and large goiter groups exhibited significantly higher serum FT3 levels, while all HT groups exhibited lower serum FT4 levels. Serum FT3/FT4 ratios showed a positive correlation with TV (r = 0.35, p < 0.01), which was independent of age, sex, body mass index, and TgAb and TSH levels. LT4 treatment lowered serum FT3 levels and FT3/FT4 ratios significantly. Our results indicated that HT patients with increased TV tended to present with high serum FT3, low FT4, and high FT3/FT4 ratios. The elevation of deiodinase activity may be an important factor affecting thyroid hormonal balance in such patients.
Asunto(s)
Enfermedad de Hashimoto/sangre , Enfermedad de Hashimoto/patología , Glándula Tiroides/patología , Hormonas Tiroideas/sangre , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Estudios Retrospectivos , Pruebas de Función de la Tiroides , Hormonas Tiroideas/análisis , Adulto JovenRESUMEN
Previous reports by us and other investigators showed that among athyreotic patients on levothyroxine (LT4) following total thyroidectomy patients with normal serum thyroid-stimulating hormone (TSH) levels had mildly low serum free triiodothyronine (FT3) levels, whereas patients with mildly suppressed serum TSH levels had normal serum FT3 levels and patients with strongly suppressed serum TSH had elevated serum FT3 levels. The objective of this study was to clarify which of these three patient groups are closer to their preoperative euthyroid condition based on reported subjective symptoms. We prospectively studied 148 consecutive euthyroid patients with papillary thyroid carcinoma who underwent a total thyroidectomy. Symptoms reflecting thyroid function documented preoperatively and following 12 months of LT4 after thyroidectomy were compared. In 65 patients with strongly suppressed TSH levels significant changes in symptoms with tendencies towards thyrotoxicosis were seen with regards to heat and cold tolerance (p < 0.01), bowel movements (p < 0.05), and hand tremors (p < 0.05). In 33 patients with normal TSH levels, significant changes in symptoms with tendencies towards hypothyroidism were seen with regards to heat and cold tolerance (p < 0.05) and activity (p < 0.05). Lastly, in 50 patients with mildly suppressed TSH levels and FT3 levels equivalent to preoperative levels, all symptom items remained equivalent to their preoperative levels. Symptoms reflecting thyroid function in patients on LT4 following total thyroidectomy suggested that patients with mildly suppressed TSH levels were closest to a euthyroid status. These data provide useful findings regarding the management of patients following total thyroidectomy.
Asunto(s)
Hipotiroidismo/metabolismo , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Tirotoxicosis/metabolismo , Tirotropina/metabolismo , Tiroxina/metabolismo , Triyodotironina/metabolismo , Adolescente , Adulto , Anciano , Apetito , Temperatura Corporal , Frío , Defecación , Femenino , Terapia de Reemplazo de Hormonas , Calor , Humanos , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tirotoxicosis/inducido químicamente , Tirotoxicosis/fisiopatología , Tiroxina/uso terapéutico , Temblor , Adulto JovenRESUMEN
It is generally believed that the detection of thyroid peroxidase antibodies (TPOAb) is superior to that of thyroglobulin antibodies (TgAb) for the diagnosis of Hashimoto's thyroiditis. However, limited data are available on the comparison of TgAb and TPOAb prevalence as a diagnostic measurement for Hashimoto's thyroiditis using sensitive immunoassays. We herein used five different current immunoassay kits (A-E) to compare the prevalence of TgAb and TPOAb in Hashimoto's thyroiditis (n = 70), Graves' disease (n = 70), painless thyroiditis (n = 50), and healthy control subjects (n = 100). In patients with Hashimoto's thyroiditis, positive TgAb was significantly more frequent than positive TPOAb in kits A-D (mean ± SD of the four kits: 98.6 ± 1.7 vs 81.4 ± 2.0%). In patients with Graves' disease, TgAb prevalence was almost equivalent to that of TPOAb in five kits. Patients with painless thyroiditis exhibited positive TgAb significantly more frequently than positive TPOAb in kits A-D (73.5 ± 4.1 vs 33.0 ± 3.4%). The prevalence of TgAb alone was significantly higher than that of TPOAb alone in both Hashimoto's thyroiditis and painless thyroiditis in kits A-D. In kit E, TgAb and TPOAb prevalence did not differ significantly for any disease, and TgAb distribution was different from other kits. In conclusion, the prevalence of TgAb was higher than that of TPOAb in patients with Hashimoto's thyroiditis and painless thyroiditis using commercially available kits. We suggest that TgAb immunoassay is the first choice of screening test for thyroid autoimmune abnormalities in Japan.
Asunto(s)
Autoanticuerpos/sangre , Enfermedad de Graves/sangre , Enfermedad de Hashimoto/sangre , Juego de Reactivos para Diagnóstico , Tiroiditis Subaguda/sangre , Adulto , Automatización de Laboratorios , Femenino , Enfermedad de Graves/inmunología , Enfermedad de Graves/fisiopatología , Enfermedad de Hashimoto/inmunología , Enfermedad de Hashimoto/fisiopatología , Hospitales Urbanos , Humanos , Inmunoensayo , Japón , Límite de Detección , Masculino , Ensayo de Materiales , Persona de Mediana Edad , Servicio Ambulatorio en Hospital , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Tiroiditis Subaguda/inmunología , Tiroiditis Subaguda/fisiopatologíaRESUMEN
Infertile women sometimes associated with subclinical hypothyroidism (SCH). The guidelines of the American Endocrine Society, and American Association of Clinical Endocrinologists and American Thyroid Association recommend treatment with thyroxine (T4) for patients with SCH who want to have children. We examined 69 female infertile patients with SCH and the effects of levothyroxine (l-T4) therapy on pregnancy rates and pregnancy outcomes were observed. Fifty-eight (84.1%) patients successfully conceived during the T4 treatment period (Group A), although 17 patients (29.3%) had miscarriage afterward. The remaining 11 patients continued to be infertile (Group B). The median TSH value in Group A before the T4 treatment was 5.46 µIU/mL (range 3.1-13.3) and this significantly decreased to 1.25 µIU/mL (range 0.02-3.75) during the treatment (p<0.001). The estimated duration of infertility before the T4 treatment was 2.8±1.7 years and the duration until pregnancy after the treatment was significantly shorter at 0.9±0.9 years (p<0.001). Shortening of the infertile period after the T4 therapy was observed not only in patients who were treated with assisted reproductive technology (ART) but also in patients who conceived spontaneously in Group A. Administered T4 dose was 54.3±14.2 µg before pregnancy and 68.5±22.8 µg during pregnancy (p<0.001). Anti-thyroid autoantibodies were identified in 42.0% of all patients and no significant difference was observed in positivity between Group A and Group B. High successful pregnancy rate and shorter duration of infertility until pregnancy after T4 treatment strongly suggest that T4 enhanced fertility in infertile patients with SCH.
Asunto(s)
Enfermedades Asintomáticas , Terapia de Reemplazo de Hormonas , Hipotiroidismo/tratamiento farmacológico , Infertilidad Femenina/prevención & control , Glándula Tiroides/efectos de los fármacos , Tiroxina/uso terapéutico , Aborto Espontáneo/etiología , Aborto Espontáneo/prevención & control , Adulto , Autoanticuerpos/análisis , Implantación Tardía del Embrión/efectos de los fármacos , Femenino , Humanos , Hipotiroidismo/sangre , Hipotiroidismo/inmunología , Hipotiroidismo/fisiopatología , Infertilidad Femenina/etiología , Infertilidad Femenina/terapia , Japón/epidemiología , Nacimiento Vivo , Embarazo , Índice de Embarazo , Estudios Prospectivos , Técnicas Reproductivas Asistidas , Glándula Tiroides/inmunología , Glándula Tiroides/metabolismo , Glándula Tiroides/fisiopatología , Tirotropina/sangre , Tiempo para Quedar EmbarazadaRESUMEN
The Japan Thyroid Association (JTA) recently published new guidelines for clinical management of thyroid nodules. This paper introduces their diagnostic system for reporting thyroid fine-needle aspiration cytology. There are two points where the new reporting system that differs from existing internationally-accepted ones. The first is the subclassification of the so-called indeterminate category, which is divided into 'follicular neoplasm' and 'others'. The second is the subclassification of follicular neoplasm into 'favor benign', 'borderline' and 'favor malignant'. It is characterized by self-explanatory terminologies as to histological type and probability of malignancy to establish further risk stratification as well as to facilitate communication between clinicians and cytopathologists. The different treatment strategies adopted for thyroid nodules is deeply influenced by the particular diagnostic system used for thyroid cytology. In Western countries all patients with follicular neoplasms are advised to have immediate diagnostic surgery while patients in Japan often undergo further risk stratification without immediate surgery. The JTA diagnostic system of reporting thyroid cytology is designed for further risk stratification of patients with indeterminate cytology. If a surgeon applies diagnostic lobectomy to all patients with follicular neoplasm unselectively, this subclassification of follicular neoplasm has no practical meaning and is unnecessary. Cytological risk stratification of follicular neoplasms is optional and cytopathologists can choose either a simple 6-tier system without stratification of follicular neoplasm or a complicated 8-tier system depending on their experience in thyroid cytology and clinical management.
Asunto(s)
Registros Médicos/normas , Guías de Práctica Clínica como Asunto , Glándula Tiroides/patología , Nódulo Tiroideo/clasificación , Nódulo Tiroideo/patología , Biopsia con Aguja Fina/normas , Grupos Diagnósticos Relacionados/normas , Humanos , Japón , Sociedades MédicasRESUMEN
Thyroid nodules that exhibit focal uptake of fluorine-18 ((18)F)-fluorodeoxyglucose (FDG) are relatively frequent. Although the clinical features and associated mechanisms of FDG-avid lesions in both thyroid cancer and cytologically indeterminate nodules have been extensively studied, not much information is available on benign nodules. Therefore, in this retrospective study, the clinical, serological, and sonographic features of 15 benign FDG-avid nodules were compared with those of 17 non-avid lesions. Univariate analysis indicated that the FDG-positive and -negative nodules were similar with regard to age, gender, thyroid stimulating hormone (TSH), anti-thyroglobulin antibodies, tumor size, 4 B-mode sonographic findings (i.e., shape, margin, texture, and echo level), and/or elasticity. The presence of intranodular blood flow and the absence of a cystic component were associated with a greater possibility of positive FDG uptake. Multivariate analysis showed that vascularity was the only independent factor predicting FDG uptake. Across a wide range of tumor types, the extent of FDG uptake is positively correlated with tumor perfusion; this observation is consistent with the results of this study, which shows that FDG uptake in benign thyroid nodules is associated with increased vascularity.
Asunto(s)
Fluorodesoxiglucosa F18 , Nódulo Tiroideo/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiofármacos , Estudios Retrospectivos , Nódulo Tiroideo/irrigación sanguínea , Nódulo Tiroideo/diagnóstico por imagen , Ultrasonografía Doppler en ColorRESUMEN
Lung dendritic cells (LDCs) are primary antigen-presenting cells that develop IgA-producing plasma cells in the lung through class switch recombination (CSR) in naive B cells. Recently, the major LDC subsets were found to comprise CD103(-)CD11b(high) LDCs (CD11b(high) LDCs) and CD103(+)CD11b(low or negative) LDCs (CD103(+) LDCs), but their abilities to induce IgA production have not been defined. Under T cell-dependent (T-D) and T cell-independent (T-ID) conditions, we compared the abilities of these two LDC populations to induce IgA. CD11b(high) or CD103(+) LDCs obtained from BALB/c mice were cocultured with naive IgD(+) B cells in the presence of LPS, with or without anti-CD40 monoclonal antibody (mAb) (i.e., T-D and T-ID coculture conditions, respectively). Under both T-D and T-ID conditions, CD11b(high) LDCs induced significantly greater amounts of IgA production, together with a significantly higher mRNA expression of activation-induced cytidine deaminase, than did CD103(+) LDCs. However, the protein expression of a proliferation-inducing ligand, B cell-activating factor of the tumor necrosis family, or retinaldehyde dehydrogenase-1 did not differ between the two LDC subsets. CD11b(high) LDCs displayed a significantly greater capacity to secrete IL-6 and IL-10 in response to LPS, with or without anti-CD40 mAb. Moreover, the IgA production induced by CD11b(high) LDCs in T-D coculture was attenuated by neutralizing both IL-6 and IL-10. These findings suggest that, of the two major LDCs, CD11b(high) LDCs more efficiently induce IgA than do CD103(+) LDCs, possibly through their potent capacity to produce IgA-inducing cytokines.
Asunto(s)
Antígenos CD/inmunología , Antígeno CD11b/inmunología , Células Dendríticas/inmunología , Inmunoglobulina A/biosíntesis , Cadenas alfa de Integrinas/inmunología , Pulmón/inmunología , Animales , Western Blotting , Células Dendríticas/citología , Pulmón/citología , Ratones , Reacción en Cadena de la PolimerasaRESUMEN
Mouse lung dendritic cells (LDCs) have been recently shown to contain two major subpopulations: CD103(+) CD11b(low or negative) (CD103(+) LDCs) and CD103(-) CD11b(high) LDCs (CD11b(high) LDCs). Although several studies have demonstrated functional differences between them, it is unclear whether the subpopulations induce distinct T helper (Th) cell responses. The present study was conducted to examine whether CD103(+) and CD11b(high) LDCs preferentially generate different Th responses. Naive DO11.10 CD4(+) T cells were primed with CD103(+) or CD11b(high) LDCs obtained from normal BALB/c mice. The primed CD4(+) T cells were restimulated, and their cytokine secretions were assessed. The expression of intracellular cytokines and the mRNA levels of chemokine receptors were also measured. We found that the CD4(+) T cells primed with CD103(+) LDCs secreted significantly larger amounts of IFN-γ and IL-17A, whereas those primed with CD11b(high) LDCs released significantly higher levels of IL-4, IL-6, and IL-10. Intracellular cytokine assay showed that CD103(+) LDCs induced greater frequencies of CD4(+) T cells producing IFN-γ and IL-17A, whereas CD11b(high) LDCs were more efficient at inducing CD4(+) T cells producing IL-4 and IL-10. The mRNA levels of CXCR3 and CCR5, which are expressed preferentially in Th1 cells, were significantly higher in CD4(+) T cells primed with CD103(+) LDCs. The mRNA levels of CXCR4 and CCR4, which are expressed primarily in Th2 cells, were significantly greater in those primed with CD11b(high) LDCs. These data suggest that mouse CD103(+) LDCs predominantly elicit Th1 and Th17 responses, whereas CD11b(high) LDCs primarily provoke a Th2 response under the steady state.
Asunto(s)
Antígenos CD/inmunología , Antígenos CD11/inmunología , Linfocitos T CD4-Positivos/inmunología , Células Dendríticas/inmunología , Cadenas alfa de Integrinas/inmunología , Pulmón/inmunología , Animales , Ensayo de Inmunoadsorción Enzimática , Ratones , Ratones Endogámicos BALB C , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
The syndrome of inappropriate secretion of thyrotropin (SITSH) is defined as the inappropriate non-suppression of serum TSH in the presence of elevated free thyroid hormone; TSH-secreting pituitary adenomas and the syndrome of resistance to thyroid hormone are the main etiologies of SITSH. In addition, erroneous thyroid function testing may result in the diagnosis of this syndrome. A 63-year-old woman was referred because of suspected SITSH. Laboratory tests showed a normal TSH (0.52 µIU/L; normal range: 0.5-5.0) measured by sandwich Elecsys, and elevated FT4 (3.8 ng/dL; normal range: 0.9-1.6) and FT3 (7.6 pg/mL; normal range: 2.3-4.0), determined by competitive Elecsys. To exclude possible assay interference, aliquots of the original samples were retested using a different method (ADVIA Centaur), which showed normal FT4 and FT3 levels. Eight hormone levels, other than thyroid function tests measured by competitive or sandwich Elecsys, were higher or lower than levels determined by an alternative analysis. Subsequent examinations, including gel filtration chromatography, suggested interference by substances against ruthenium, which reduced the excitation of ruthenium, and resulted in erroneous results. The frequency of similar cases, where the FT4 was higher than 3.2 ng/dL, in spite of a non-suppressed TSH, was examined; none of 10 such subjects appeared to have method-specific interference. Here, a patient with anti-ruthenium interference, whose initial thyroid function tests were consistent with SITSH, is presented. This type of interference should be considered when thyroid function is measured using the Elecsys technique, although the frequency of such findings is likely very low.
Asunto(s)
Errores Diagnósticos , Tirotropina/sangre , Artefactos , Femenino , Humanos , Inmunoensayo/efectos adversos , Mediciones Luminiscentes , Persona de Mediana Edad , Rutenio , Pruebas de Función de la Tiroides/efectos adversos , Tirotropina/metabolismo , Tiroxina/metabolismoRESUMEN
Neuropeptide W (NPW) was isolated as an endogenous ligand for NPBWR1, an orphan G protein-coupled receptor localized in the rat brain, including the paraventricular nucleus. It has been reported that central administration of NPW stimulates corticosterone secretion in rats. We hypothesized that NPW activates the hypothalamic-pituitary-adrenal (HPA) axis via corticotrophin-releasing factor (CRF) and/or arginine vasopressin (AVP). NPW at 1 pM to 10 nM did not affect basal or ACTH-induced corticosterone release from dispersed rat adrenocortical cells, or basal and CRF-induced ACTH release from dispersed rat anterior pituitary cells. In conscious and unrestrained male rats, intravenous administration of 2.5 and 25 nmol NPW did not affect plasma ACTH levels. However, intracerebroventricular (icv) administration of 2.5 and 5.0 nmol NPW increased plasma ACTH levels in a dose-dependent manner at 15 min after stimulation (5.0 vs. 2.5 nmol NPW vs. vehicle: 1802 ± 349 vs. 1170 ± 204 vs. 151 ± 28 pg/mL, respectively, mean ± SEM). Pretreatment with astressin, a CRF receptor antagonist, inhibited the increase in plasma ACTH levels induced by icv administration of 2.5 nmol NPW at 15 min (453 ± 176 vs. 1532 ± 343 pg/mL, p<0.05) and at 30 min (564 ± 147 vs. 1214 ± 139 pg/mL, p<0.05) versus pretreatment with vehicle alone. However, pretreatment with [1-(ß-mercapto-ß, ß-cyclopentamethylenepropionic acid), 2-(Ο-methyl)tyrosine]-arg-vasopressin, a V1a/V1b receptor antagonist, did not affect icv NPW-induced ACTH release at any time (p>0.05). In conclusion, we suggest that central NPW activates the HPA axis by activating hypothalamic CRF but not AVP.
Asunto(s)
Hormona Adrenocorticotrópica/metabolismo , Arginina Vasopresina/fisiología , Hormona Liberadora de Corticotropina/fisiología , Neuropéptidos/farmacología , Hormona Adrenocorticotrópica/sangre , Animales , Antagonistas de los Receptores de Hormonas Antidiuréticas , Células Cultivadas , Corticosterona/metabolismo , Evaluación Preclínica de Medicamentos , Antagonistas de Hormonas/administración & dosificación , Antagonistas de Hormonas/farmacología , Inyecciones Intravenosas , Masculino , Neuropéptidos/administración & dosificación , Adenohipófisis/citología , Adenohipófisis/efectos de los fármacos , Adenohipófisis/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Thyroid nodules are very common. Several articles suggest that thyroid nodules are detected by ultrasonography (US) in one of six males and one of 3.5 females in Japan. Thyroid cancer exists among these nodules and distinction between benign and malignant nodules is not always easy. Japan Thyroid Association (JTA) is currently preparing for guidelines for management of thyroid nodules. This article describes how to treat thyroid nodules according to the guidelines in progress. Ultrasonography and fine needle aspiration cytology (FNA) are critical to evaluate nodules. Every nodule should be examined by US, since it is safe, relatively cheap in Japan and can provide a lot of information about characteristics of nodules. Several findings suggesting benign and malignancy have been known. Regarding a FNA classification, the Bethesda system for reporting thyroid cytopathology published a few years ago is expected to become prevailing in the world. Currently the WHO classification of sixth version is used in Japan and the JTA guidelines will adopt a modified WHO classification: "Indeterminate" is divided into two categories; "Indeterminate A, considering follicular tumor" and "Indeterminate B, considering other than follicular tumor". Re-FNA is not recommended for the former subgroup, while re-FNA has a possibility to lead to a correct FNA diagnosis for the latter subgroup. This article discusses several issues regarding papillary thyroid cancer and follicular thyroid cancer also in brief.
Asunto(s)
Neoplasias de la Tiroides/diagnóstico , Nódulo Tiroideo/diagnóstico por imagen , Biopsia con Aguja Fina/métodos , Citodiagnóstico , Humanos , Japón , Guías de Práctica Clínica como Asunto , Neoplasias de la Tiroides/cirugía , Nódulo Tiroideo/patología , UltrasonografíaRESUMEN
The Japan Thyroid Association published the guidelines for the treatment of Graves disease with antithyroid drugs(ATD) in 2006 and has updated it in 2011. The revised guidelines includes radioisotope therapy also. This article describes several topics about how to treat a patient with Graves' disease according to the guidelines 2011, focusing the difference between the guidelines 2006 and the guidelines 2011.
Asunto(s)
Antitiroideos/efectos adversos , Antitiroideos/uso terapéutico , Esquema de Medicación , Enfermedad de Graves/tratamiento farmacológico , Guías de Práctica Clínica como Asunto/normas , Humanos , Japón , Glándula Tiroides/efectos de los fármacos , Resultado del TratamientoRESUMEN
Staphylococcal enterotoxins A (SEA) and B (SEB) are classical models of superantigens (SAg), which induce potent T-cell-stimulating activity by forming complexes with MHC class II molecules on antigen-presenting cells. This large-scale activation of T-cells is accompanied by increased production of cytokines such as interferon-γ (IFN-γ). Additionally, as we previously reported, IFN-γ-producing CD8(+) T cells act as "helper cells," supporting the ability of dendritic cells to produce interleukin-12 (IL-12)p70. Here, we show that DC pulsed with SAg promote the enhancement of anti-tumor immunity. Murine bone marrow-derived dendritic cells (DC) were pulsed with OVA(257-264) (SIINFEKL), which is an H-2Kb target epitope of EG7 [ovalbumin (OVA)-expressing EL4] cell lines, in the presence of SEA and SEB and were subcutaneously injected into naïve C57BL/6 mice. SAg plus OVA(257-264)-pulsed DC vaccine strongly enhanced peptide-specific CD8(+) T cells exhibiting OVA(257-264)-specific cytotoxic activity and IFN-γ production, leading to the induction of protective immunity against EG7 tumors. Furthermore, cyclophosphamide (CY) added to SAg plus tumor-antigens (OVA(257-264), tumor lysate, or TRP-2) pulsed DC immunization markedly enhanced tumor-specific T-cell expansion and had a significant therapeutic effect against various tumors (EG7, 2LL, and B16). Superantigens are potential candidates for enhancing tumor immunity in DC vaccines.
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Células Presentadoras de Antígenos/inmunología , Carcinoma Pulmonar de Lewis/inmunología , Células Dendríticas/inmunología , Linfoma/inmunología , Melanoma Experimental/inmunología , Superantígenos/inmunología , Linfocitos T Citotóxicos/inmunología , Animales , Antineoplásicos Alquilantes/uso terapéutico , Linfocitos T CD8-positivos , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Ciclofosfamida/uso terapéutico , Citocinas/metabolismo , Citometría de Flujo , Antígenos de Histocompatibilidad Clase II/metabolismo , Interferón gamma/metabolismo , Interleucina-12/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Activación de Linfocitos , Linfoma/tratamiento farmacológico , Linfoma/metabolismo , Masculino , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/metabolismo , Ratones , Ratones Endogámicos C57BL , Ovalbúmina/fisiología , Receptores Acoplados a Proteínas G/fisiología , Tasa de Supervivencia , Linfocitos T Colaboradores-Inductores/inmunología , Células Tumorales Cultivadas , Vacunas de Subunidad/uso terapéuticoRESUMEN
OBJECTIVE: To retrospectively analyze the prognostic implications of high-resolution computed tomography (HRCT) findings for patients with biopsy-proven nonspecific interstitial pneumonia (NSIP). METHODS: Fifty-nine patients with NSIP (25 idiopathic NSIP, 34 collagen-vascular disease-associated NSIP) were included. Two chest radiologists independently evaluated the extent, presence, and distribution of various HRCT findings. Cox hazards analysis was used to evaluate the relationship between HRCT findings and prognosis. RESULTS: The 5-year survival rate was 83% and the 10-year survival rate was 66%. Univariate analysis revealed that the extent of areas with ground-glass attenuation without traction bronchi-bronchiolectasis and that of airs-pace consolidation were associated with favorable outcome, whereas that of intralobular reticular opacities was associated with worse prognosis. Multivariate analysis showed that the extent of air-space consolidation was an independent factor of favorable outcome. CONCLUSION: In NSIP, the extent of areas with ground-glass attenuation without traction bronchi-bronchiolectasis, air-space consolidation, and intralobular reticular opacities correlate with survival.
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Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Biopsia , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Recently, the potential therapeutic effect of direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) has been reported for acute exacerbation of interstitial pneumonia (AE-IP), a highly morbid clinical event; however, there is no consensus on the appropriate procedure for PMX-DHP. We examined the appropriate perfusion duration of PMX-DHP for AE-IP. METHODS: AE-IP patients receiving PMX-DHP were divided into two groups: short-duration group (≤6 h) (n = 5) and long-duration group (12 h) (n = 12). RESULTS: ThePaO(2)/FiO(2) (P/F) ratio increased immediately after PMX-DHP in the two groups. In the long-duration group, the P/F ratio continued to increase over the following 7 days, while, in the short-duration group, the P/F ratio declined again 3 days after therapy. The survival rate 30 days after PMX-DHP was significantly higher in the long-duration group than in the short-duration group. CONCLUSIONS: A long perfusion duration of PMX-DHP is more efficacious for AE-IP than a short perfusion duration.
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Antibacterianos/metabolismo , Dicarbetoxidihidrocolidina/análogos & derivados , Hemoperfusión/métodos , Proteínas Inmovilizadas/metabolismo , Enfermedades Pulmonares Intersticiales/terapia , Polimixina B/metabolismo , Enfermedad Aguda , Corticoesteroides/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Antiinflamatorios/administración & dosificación , Dicarbetoxidihidrocolidina/química , Dicarbetoxidihidrocolidina/metabolismo , Femenino , Humanos , Proteínas Inmovilizadas/química , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Polimixina B/química , Polimixina B/uso terapéutico , Pruebas de Función Respiratoria , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Syndrome of inappropriate secretion of thyrotropin (SITSH) is a clinical state of inappropriately elevated secretion of thyrotropin (TSH) in the presence of elevated free thyroid hormones. Peripheral nerve hyperexcitability (PNH) is a rare disorder characterized by muscle twitching at rest. No relation between them is known. A 49-year-old man was referred to our hospital because of elevated serum free thyroxine (2.6 ng/dL; normal range, 0.9-1.7) and normal TSH (2.7 mIU/L; normal range, 0.5-5.0). Genetic analysis revealed no mutations of the thyroid hormone receptor ß gene. Magnetic resonance imaging visualized no pituitary adenoma. He complained of appetite loss, weight loss, myokymia, paraesthesia, hyperhydrosis and insomnia. Chest X ray and computed tomography (CT) scan showed a mediastinal tumor diagnosed as a thymoma by CT-guided biopsy. Electromyography disclosed fasciculations and myokymic discharges. Nerve conduction studies showed prolonged after-discharges following evoked compound muscle action potential. The patient was diagnosed with thymoma-associated PNH based on neurological manifestations and neurophysiological findings, and was treated with pulse therapy with methylprednisolone after thymectomy. Interestingly, the SITSH state became less prominent as his neurological manifestations improved. This is the first case of SITSH possibly caused by thymoma-associated PNH.
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Enfermedades del Sistema Nervioso Periférico/fisiopatología , Timoma/metabolismo , Neoplasias del Timo/metabolismo , Tirotropina/metabolismo , Humanos , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Fármacos Neuroprotectores/uso terapéutico , Enfermedades del Sistema Nervioso Periférico/terapia , Timectomía , Timoma/terapia , Neoplasias del Timo/terapiaRESUMEN
We report the case of a common type papillary thyroid carcinoma (PTC) patient who developed early recurrence and persistent disease even after ablation therapy. The patient was an 80-year-old man that was incidentally found to have a mass lesion in the left lower lobe of his thyroid. A total thyroidectomy and a left side modified radical neck dissection were performed; histological examination revealed a common type PTC. The patient underwent lymph node dissection twice for recurrence and (131)I-Na ablations for fluctuated elevation of serum thyroglobulin. The resected tumor and recurrence in lymph nodes revealed non-solid type papillary carcinoma with mixed features of less well-differentiated morphology, which we suggest included loss of cellular polarity/cohesiveness, tall cells and columnar cells. Immunohistochemistry revealed high a MIB-1 labeling index (15-20%) in both the primary tumor and the metastatic tumor in the lymph nodes. p53 immunoreaction was found positive at very low level (<5%). E-cadherin was faintly positive in a few cells of the primary tumor and negative in the metastatic site. We recently proposed a new classification for follicular cell tumors of the thyroid gland, and this case is an example of moderately-differentiated adenocarcinoma according to our classification.