Malignant thyroid teratoma: report of an aggressive tumor in a 64-year-old man.

Malignant teratoma of the thyroid is a rare and aggressive tumor, frequent in children than in adults. Histologically, thyroid teratomas usually show a predominance of a neuroectodermal component. Mature cartilage and bone may be present. We present the case of primary malignant teratoma of the thyroid in a 64-year-old man. Histologically, the tumor displayed a predominant neuroectodermal component. The diagnosis was confirmed by immunohistochemistry. The patient underwent a radical thyroidectomy with central neck dissection as primary treatment and radioiodine treatment afterwards. The patient had local and distant recurrence. A second surgery was performed with poor results and the patient died 3 months afterwards.

Clinical significance of RET/PTC and p53 protein expression in sporadic papillary thyroid carcinoma.

AIMS: Rearranged during Transfection (RET)/papillary thyroid carcinoma (PTC) and p53 are two genes involved in the pathogenesis of PTC. It has been suggested that RET/PTC expression is associated with higher rates of local extension and lymph node involvement, whereas p53 mutations are more frequent in poorly differentiated and anaplastic carcinomas. In addition, experimental studies have shown that p53 activity can modify the behaviour of PTC carrying RET/PTC. The aim of this study was to investigate the expression of both RET/PTC and p53 in order to evaluate their usefulness as prognostic factors. METHODS AND RESULTS: Resected specimens of 61 cases of PTC were studied immunohistochemically using a polyclonal antibody to RET and a monoclonal antibody to p53 protein. RET/PTC expression was associated with extrathyroid extension of PTC, at diagnosis (P < 0.05). In contrast, no relationship between p53 immunoreactivity and clinical status was found. In addition, p53 expression was more prevalent among RET/PTC+ patients, and significantly influenced the relationship observed between RET/PTC and extrathyroid extension of the disease. CONCLUSION: Our results suggest that immunohistochemistry for both PTC/RET and p53 could be useful in the clinical evaluation of patients with PTC.

Valor predictivo de la clasificación de Knosp en el grado de resección quirúrgica de los macroadenomas invasivos. Estudio prospectivo de una serie de 23 casos / Predicitve value of the Knosp classification in the staging of invasive pituitary macroadenomas. A Prospective study of 23 cases

Objetivos. Analizar y valorar el grado de resección y las complicaciones de la cirugía transesfenoidal en una serie de 23 casos de macroadenomas con invasión del seno cavernoso evaluados mediante la clasificación de Knosp. Material, métodos y resultados. Estudio prospectivo de 22 pacientes (23 operaciones) intervenidos en nuestro centro entre Mayo del 2002 y Diciembre del 2004 de macroadenomas hipofisarios con diferentes grados de invasión del seno cavernoso según la clasificación de Knosp15. Entre las variables del estudio se incluyeron los grados de invasión y de resección postoperatoria con un seguimiento radiológico medio a largo plazo de 15 meses. Nuestra serie consta de 15 varones y 7 mujeres, con una edad media de 48 años (27 - 75 años). Todos ellos presentaban macroadenomas con afectación de uno o ambos senos cavernosos. De acuerdo con la clasificación de Knosp 4 pacientes fueron grado 1, 2 grado 2, 1 grado 3 y 16 grado 4. En 20 casos se utilizó una vía transesfenoidal clásica y en tres casos se hizo un abordaje transesfenoidal endoscópico. Según la RMN postoperatoria los grados de resección fueron: completo o total en todos los pacientes con grados 1 y 2 y en sólo 2 pacientes con grado 4; subtotal (>80%) en 1 paciente con grado 3 y en 6 pacientes con grado 4 y parcial (<80%) en 7 pacientes con grado 4 de Knosp. Se compararon los grados de resección versus los grados de invasión mediante el Test exacto de Fsiher y las diferencias no fueron estadísticamente significativas (p=0,12). Discusión y conclusiones. Si bien únicamente la clasificación radiológica de Knosp por si sola no puede predecir el comportamiento biológico del tumor o si la pared medial del seno cavernoso está infiltrado o desplazada, en nuestra serie los tumores de grado 4 han sido los que han presentado un peor resultado de acuerdo al grado de resección. En los tumores que invaden el seno cavernoso, incluso en los caos donde la carótida está englobada en posible realizar resecciones completas con una morbimortalidad aceptable (AU)

Objective. To evaluate our experience regarding the treatment of pituitary macroadenomas with cavernous sinus invasion in a series of 23 cases of transphenoidal resection. Materials, methods and results. Twenty two patients, fifteen males and seven females, with ages ranging from 27 to 75 (mean of 48), were operated under protocol by a single surgeon between May of 2002 and December of 2004. Preoperatively all lesions were diagnosed by MRI and staged according to the Knosp classification. All tumors had extension to one or both cavernous sinuses. Four patients were considered to be grade 1, two grade 2, one grade 3 and sixteen grade 4. Twenty three operations were performed on twenty-two patients. Twenty cases were the standard transsphenoidal approach, and three were endoscopic. Postoperatively, the excision was classified as Complete or Total, Subtotal or Partial. Mean follow up was 15 months. The variables considered for analysis include invasion and resection grades. All six patients with graded 1 and 2 lesions and two patients with grade 4 lesions underwent a complete resection. Subtotal (greater than 80%) excision was achieved in one patient with a grade 3 tumor and six patients with grade 4 tumors. The remaining seven patients with grade 4 adenomas had a Partial (less than 80%) excision. We compare de resection grade versus invasion grade with exact Fisher test. And there is not estadistical difference (p=0.12). Conclusion. The Knosp classification alone cannot predict the behavior of these tumors. In our experience, despite tumor extension to the cavernous sinus, pituitary macroadenomas can be safely resected with low morbidity and mortality (AU)

[Predictive value of the Knosp classification in grading the surgical resection of invasive pituitary macroadenomas. A prospective study of 23 cases]. / Valor predictivo de la clasificación de Knosp en el grado de resección quirúrgica de los macroadenomas invasivos. Estudio prospectivo de una serie de 23 casos.

OBJECTIVE: To evaluate our experience regarding the treatment of pituitary macroadenomas with cavernous sinus invasion in a series of 23 cases of transphenoidal resection. MATERIALS, METHODS AND RESULTS: Twenty two patients, fifteen males and seven females, with ages ranging from 27 to 75 (mean of 48), were operated under protocol by a single surgeon between May of 2002 and December of 2004. Preoperatively all lesions were diagnosed by MRI and staged according to the Knosp classification. All tumors had extension to one or both cavernous sinuses. Four patients were considered to be grade 1, two grade 2, one grade 3 and sixteen grade 4. Twenty three operations were performed on twenty-two patients. Twenty cases were the standard transsphenoidal approach, and three were endoscopic. Postoperatively, the excision was classified as Complete or Total, Subtotal or Partial. Mean follow up was 15 months. The variables considered for analysis include invasion and resection grades. All six patients with graded 1 and 2 lesions and two patients with grade 4 lesions underwent a complete resection. Subtotal (greater than 80%) excision was achieved in one patient with a grade 3 tumor and six patients with grade 4 tumors. The remaining seven patients with grade 4 adenomas had a Partial (less than 80%) excision. We compare de resection grade versus invasion grade with exact Fisher test. And there is not estadistical difference (p=0.12). CONCLUSION: The Knosp classification alone cannot predict the behavior of these tumors. In our experience, despite tumor extension to the cavernous sinus, pituitary macroadenomas can be safely resected with low morbidity and mortality.

Guía clínica del manejo del prolactinoma y otros estados de hiperprolactinemia / Clinical guidelinesfor the management of prolactinoma and other hyperprolactinemia states

No disponible

Guía clínica del manejo del prolactinoma y otros estados de hiperprolactinemia / Clinical guidelines for the management of prolactinoma and other hyperprolactinemia states

No disponible

Acromegaly Quality of Life Questionnaire (ACROQOL) a new health-related quality of life questionnaire for patients with acromegaly: development and psychometric properties.

OBJECTIVE: To develop a disease-specific questionnaire suitable to measure health-related quality of life (HRQOL) in acromegaly (ACROQOL). DESIGN, PATIENTS AND MEASUREMENTS: For the development of the ACROQOL questionnaire different sources of information were used: First, a literature search was performed to identify relevant papers describing the impact of acromegaly in HRQOL. Second, 10 endocrinologists identified the main domains of impact on HRQOL in patients with acromegaly. Third, 10 in-depth, semistructured interviews were conducted in acromegalic patients to identify domains and items related to the self-perceived impact of acromegaly in patients' life. Qualitative analyses of the information were performed identifying domains and items to be included in the questionnaire. Those items considered ambiguous, complicated to read, double-barrelled, with jargon terms, too long, or negatively worded were excluded. Each remaining item was subsequently rated by the same panel of endocrinologists and experts in HRQOL evaluation, and assessed according to clarity of wording, frequency of occurrence and importance among patients with acromegaly. Analysis of internal consistency of the questionnaire was evaluated with a Cronbach's Alpha. A preliminary questionnaire was administered to 72 patients with acromegaly. Rasch analysis (dichotomous logistic response model) of the answers given by these patients allowed parameter estimates and model data fit indices to be computed and misfitting items deleted. Frequency of occurrence and degree of agreement with the statements were selected as response choices in a 5-point Likert type scale. RESULTS: The following domains related to HRQOL in acromegaly were identified: physical and psychological functions, social, daily activities, symptoms, cognition, general health perception, sleep, sexual function, pain, energy and body image. An initial set of 204 expressions were identified from the initial transcripts of the patient interviews. After elimination of ambiguous or unclear expressions, 142 items remained drafted in question form. From the quantitative analysis of the item rank position within each of the three areas of clarity, frequency and importance, the 38-item questionnaire was produced, with satisfactory internal consistency (Cronbach's Alpha 0.94). Rasch analysis produced a further reduction to the final 22-item questionnaire (Cronbach's Alpha 0.91) containing two scales that evaluate physical (eight questions) and psychological aspects related to appearance and personal relations (seven items each). The evaluation of the item parameters confirmed the construct validity of the new instrument. The substantial reliability of the questionnaire suggested the sample was well targeted by the questionnaire. The initial Spanish version was translated into English and presented to five English-speaking Australian patients with acromegaly to assess and correct for comprehension, clarity, cultural relevance and suitable wording. CONCLUSIONS: We present the ACROQOL questionnaire, developed and preliminarily validated to specifically assess HRQOL in patients with acromegaly.

nm23-H1 immunoreactivity as a prognostic factor in differentiated thyroid carcinoma.

Several prognostic factors have been proposed to identify the patients at risk to develop metastases in differentiated thyroid carcinoma. Reduced nm23-H1 expression (a metastatic suppressor gene) has been correlated with high tumor metastatic potential in various human carcinomas, but the results obtained in differentiated thyroid carcinoma remain controversial. To elucidate the usefulness of nm23-H1 as a differentiated thyroid carcinoma prognosis factor, we evaluate the relationship between nm23-H1 immunoreactivity as well as both clinical status and patient outcome. For this purpose, thyroid resected specimens obtained from 94 differentiated thyroid carcinoma consecutive patients (64 papillary and 30 follicular) with at least 5 yr of follow-up were stained using monoclonal antibody to nm23-H1. We did not observe any relationship between nm23-H1 immunoreactivity and age, gender, initial differentiated thyroid carcinoma stage, local recurrence, or distant metastases in patients with papillary carcinoma. However, in patients with follicular carcinoma, a significant inverse association between metastatic disease and the expression of nm23-H1 product was obtained (P < 0.05). In addition, significant differences were found in the survival curves according to nm23-H1 immunoreactivity (log-rank P < 0.01). Finally, nm-23-H1 immunoreactivity was more specific but less sensitive than AMES score to predict metastases. In conclusion, our results suggest that nm23-H1 immunostaining could be added to the classic prognostic factors currently used to predict the outcome of patients with follicular thyroid carcinoma.

Proteasome subunits, low-molecular-mass polypeptides 2 and 7 are hyperexpressed by target cells in autoimmune thyroid disease but not in insulin-dependent diabetes mellitus: implications for autoimmunity.

Autoimmune thyroid diseases (AITD) and insulin-dependent diabetes mellitus (IDDM) are two autoimmune syndromes of unknown etiology with common immune features. One is that the target cells, thyrocytes and pancreatic islet beta cells respectively, hyperexpress several proteins encoded in the HLA region: HLA class I, HLA class II and transporter associated with antigen processing (TAP-1): the clinical course and many aspects of the immunopathology are, however, quite different. Low-molecular-mass polypeptides 2 and 7 (LMP2 and LMP7) are proteasome subunits that increase the efficiency of endogenous antigen processing and are encoded in close vicinity to the TAP genes. We investigated whether LMP2 and LMP7 are hyperexpressed in thyrocytes and islet cells in AITD and IDDM. Thyroid tissue from Graves' disease patients (GD, n = 8) and Hashimoto thyroiditis (HT, n = 1) and pancreatic tissue from IDDM patients (n = 4) as well as control tissues were examined by the two-color indirect immunofluorescence technique. The results demonstrate that, in normal glands, thyrocytes and pancreatic islet cells express comparable moderate to low levels of LMP2 and LMP7. In AITD and IDDM, expression of LMP2/7 in the endocrine cells was disparate: while in AITD glands there was hyperexpression of LMP2 and 7 parallel to that of HLA class I and TAP-1, in the islet cells of recent onset diabetic pancreases (n = 2) the level of LMP2 and 7 expression was totally normal, including islets that were infiltrated by lymphocytes and hyperexpressed HLA class I and TAP-1. These observations suggest different mechanisms of endogenous peptides generation at the target cells in AITD from IDDM. Since this is a key step for the maintenance of peripheral tolerance, it may help to understand some of the different clinical features of the two autoimmune diseases.

[Differentiated thyroid carcinoma, 1972-1992. Follow-up, detection of recurrences and prognostic factors]. / Carcinoma diferenciado de tiroides, 1972-1992. Estudio evolutivo, detección de recurrencias y factores pronósticos.

BACKGROUND: There is no consensus about the treatment and the follow-up of differentiated thyroid carcinoma (DTC), because in some patients, currently known prognostic factors cannot predict the course of the disease. The aim of this work has been to review the results of the treatment of our patients with DTC and to assess the prognostic factors. PATIENTS AND METHODS: We include, retrospectively, 204 patients with DTC (54 males and 150 women) with a men (SD) age of 38 (23) years, attending to a terciary university hospital. The follow-up is 9.2 (6) years (range, 2-22 years). They all underwent near total thyroidectomy, ablative doses of radioactive iodine (131INa) and L-thyroxine to suppress thyroid stimulating hormone (TSH) levels. At least once a year, a clinical examination, a whole-body scan (WBS) with 131INa and serum thyroglobulin (Tg) measurements were performed in hypothyroid state. In the statistics, chi 2 test, univariate analysis, Student's t test, Kaplan-Meier method, Mantel-Cox test and multiple regression analysis were employed. RESULTS: The survival rate was 89.05%. Twenty patients died of DTC (9.8%) (papillary 8 [6%], follicular 12[17%]). Surgical complications (recurrent nerve palsy or permanent hypoparathyroidism) were seen in 5% of the patients. The sensitivity of WBS to detect distant metastases or local (neck) involvement was 71% (initial 100%, late 71%). Tg sensitivity was 85% (initial 95%, late 73%). Factors associated to a poor prognosis were age > 40 years (p < 0.0001), follicular carcinoma (p < 0.02) and initial stages III and IV (p < 0.0001). CONCLUSIONS: The mortality and complications rates in our patients with differentiated thyroid carcinoma validate our management schedule. Tg measurements are more sensitive than WBS to detect distant or local metastases; however, sensitivity of both techniques was lower in the detection of late metastases. Age below 40 years, papillary carcinoma and initial stages I and II are factors of better prognosis.

Hyperinducibility of HLA class II expression of thyroid follicular cells from Graves' disease. A primary defect?

Thyroid follicular cells (thyrocytes) from Graves' disease (GD) patients' thyroid glands express HLA class II molecules "ectopically." This phenomenon has been attributed to induction by locally produced cytokines and may be relevant to disease pathogenesis. We have compared IFN-gamma-mediated induction of HLA class II in thyrocytes from glands affected with GD and a nonautoimmune disease (MNG), to investigate a possible differential regulation of HLA expression between these two pathologies. HLA induction has been measured in primary thyrocyte cultures and control autologous macrophages stimulated or not stimulated with IFN-gamma. Comparison of flow cytometric data using an improved algorithm demonstrated that expression of HLA class II molecules is more readily induced in thyrocytes from GD than from MNG thyroid glands. This higher inducibility was parallel to a faster and stronger induction of HLA class II message in GD thyrocytes but did not correlate with the levels of HLA class II or class I originally expressed by thyrocytes in the tissue or with the degree of lymphocytic infiltration of the gland. There was no association with a particular HLA class II allele or with the presence of IFN-gamma and IL-2 in the tissue, as assessed by reverse transcription-PCR. No differences in the induction of class II were found in macrophages from each group of patients. These results suggest that an intrinsic feature of thyrocytes from GD patients is an up-regulation of HLA class II expression and that this is a characteristic that may facilitate the triggering of autoimmunity to "hyperinducible" thyroid glands.

Characterization of neural cell adhesion molecule (NCAM) expression in thyroid follicular cells: induction by cytokines and over-expression in autoimmune glands.

NCAM (CD56) is a cell surface glycoprotein of the immunoglobulin superfamily expressed on neuroendocrine and natural killer (NK) cells which has considerable molecular heterogeneity due to differential splicing and post-translational modifications. NCAM has been detected in the thyroid follicular cells (thyrocytes) immunohistologically. We report here the molecular form, the modulation by cytokines and the levels of expression in thyroid pathology. By using a panel of MoAbs to NCAM on Western blots from thyrocyte extract we have determined that these cells express the 140- and 180-kD forms of NCAM. Exposure of primary cultures of thyrocytes to interferon-gamma (IFN-gamma), and even more, to the combination of IFN-gamma plus tumour necrosis factor-alpha (TNF-alpha) induced a clear increase in the expression of NCAM as assessed by FACS analysis. NCAM expression in thyrocytes was assessed by immunofluorescence in 59 surgical specimens of thyroid glands, and was found increased in 11/17 (64%) of Graves', in 5/25 (20%) of multinodular goitre (MNG) and in occasional adenoma glands. No correlation was found with the expression of HLA class I, class II or the degree of lymphocytic infiltration scored in adjacent sections, but it was often seen in areas infiltrated by macrophages. In conclusion, NCAM is an adhesion molecule whose expression is clearly increased in thyrocytes in autoimmune glands, probably as a consequence of exposure to cytokines locally released. Since one of the forms of NCAM expressed by thyrocytes has the capability to generate intracellular signal it may play a role in normal thyroid function. In addition, NCAM may facilitate the recognition of thyrocytes by lymphocytes, particularly by NK CD56+ lymphocytes.

Gamma delta lymphocytes in endocrine autoimmunity: evidence of expansion in Graves' disease but not in type 1 diabetes.

Endocrine autoimmune disorders are mediated by T cell-dependent responses to organ-specific antigens, but the mechanisms initiating the process remain unknown. Lymphocytes which use the gamma delta heterodimer as T cell receptor (TCR) for antigen constitute a distinct subset of T cells whose function remains elusive. In order to investigate their possible involvement in endocrine autoimmunity we have determined the proportion of gamma delta T cells in the peripheral blood of 23 patients with type 1 (insulin-dependent) diabetes mellitus (type-1 DM) and 30 patients with autoimmune thyrotoxicosis (Graves' disease). T lymphocyte TCR expression was assessed by fluorescence-activated flow cytometry on peripheral blood mononuclear cells using MoAbs UCHT1 (CD3), TCR delta 1 (gamma delta TCR), WT31 and beta F1 (alpha beta TCR) and both the percentage of T cells expressing gamma delta and the ratio gamma delta/alpha beta were calculated. In the diabetic patients gamma delta cells were not significantly different from the control group (7.7 +/- 54% versus 8.0 +/- 5.5% of T cells, P NS). There was no relation between the proportion of gamma delta lymphocytes and the presence of islet cell antibodies (ICA) in the sera. The Graves' patients showed a tendency towards a higher proportion of gamma delta T lymphocytes than the controls (gamma delta/alpha beta ratios: 0.095 +/- 0.047 versus 0.063 +/- 0.022, P = 0.03). In 14 Graves' patients the number of gamma delta were measured in paired samples of peripheral and intrathyroidal lymphocytes, demonstrating an expansion of gamma delta within the thyroid glands (0.21 +/- 0.3 versus 0.095 +/- 0.047, P = 0.032). Immunohistochemical studies showed that gamma delta cells were scattered among the predominant alpha beta lymphocytes infiltrating the thyroid gland and that they account for 10% of intraepithelial lymphocytes. No relation was found between the increase of gamma delta lymphocytes and any clinical features.

Expression of intercellular adhesion molecule-1 in thyroid follicular cells in autoimmune, non-autoimmune and neoplastic diseases of the thyroid gland: discordance with HLA.

The presence of intercellular adhesion molecule-1 (ICAM-1) on epithelial cells facilitates their recognition by specific T lymphocytes. To assess the possible role of ICAM-1 in the recognition of thyroid follicular cells by T cells in thyroid autoimmune disease, we investigated the expression of ICAM-1 in thyrocytes from thyroid glands affected by Graves' disease, in glands with non-autoimmune pathology and normal glands using immunofluorescence staining on cryostat sections and on dispersed cell preparations. Sequential tissue sections from glands affected by Graves' disease (n = 15), multinodular goitre (MNG, n = 26), benign nodules (n = 11), primary carcinomas (n = 12) and control thyroid glands (n = 5) were stained for ICAM-1, HLA class I, HLA class II, CD3 and thyroid peroxidase (TPO). Weak and patchy ICAM-1 expression was found in the thyrocytes of 4/15 (27%) Graves' disease and of 1/26 (4%) multinodular goitre glands. In contrast, ICAM-1 expression was detected in the thyrocytes of 5/11 (45%) benign nodules and of 8/12 (67%) thyroid carcinomas in which it was sometimes strong. Thyrocytes in the five control glands were negative. These results correlated well with flow cytometry data from 23 of these glands which showed that ICAM-1 expression in thyrocytes from Graves' patients was, when present, 'dull', while in some malignant thyrocytes it was 'bright'. In preparations of thyrocytes from Graves' disease glands we found a striking discordance between the high levels of expression of HLA class I and HLA class II and the low expression of ICAM-1. This is surprising since in vitro the expression of these three molecules is equally induced by IFN-gamma and TNF-alpha. These results suggest that additional factors are involved in the induction of the inappropriate HLA class II expression observed in the thyrocytes of glands affected by Graves' disease.