Orbitopatía tiroidea, una visión global con atención especial al papel de la radioterapia / Thyroid orbitopathy, an overview with special attention to the role of radiotherapy

La orbitopatía tiroidea es el síntoma no tiroideo más prevalente en el síndrome de Graves. Presenta una alta incidencia, afectando especialmente a mujeres jóvenes. Existe una clara relación causal con el tabaco, que se halla implicado tanto en su desarrollo como en su evolución y en la respuesta a los diferentes tratamientos. Se trata de un proceso autoinmune que suele evolucionar de manera benigna e independiente del hipertiroidismo, aunque cuando es grave y progresiva representa un gran reto terapéutico. Su evaluación clínica presenta grandes dificultades al no existir una escala de valoración realmente objetiva y representativa de la actividad de la enfermedad. En esta línea pueden ser útiles nuevos marcadores moleculares o de inflamación. En la presente revisión se describen nuevos hallazgos sobre su fisiopatología, así como las diferentes técnicas utilizadas para su tratamiento a lo largo del tiempo. La discusión se centra especialemente en el papel inmunomodulador de la radioterapia, así como en su papel junto con los corticoides

Thyroid orbitopathy is the most prevalent non-thyroid symptom in Graves’ syndrome. It has a high incidence and particularly affects young women. Smoking is clearly involved in its development and progress, and in its response to different treatments. This autoimmune condition usually has a benign course, independent from hyperthyroidism, but its severe, progressive forms represent a major therapeutic challenge. Clinical evaluation poses great difficulties, as there is no truly objective rating scale representing disease activity. New molecular or inflammation markers may prove to be useful in this regard. This review reports new findings about its pathophysiology and the different techniques used for treatment over time. Discussion particularly focuses on the immunomodulatory role of radiotherapy, as well as on its role together with corticosteroids

[Thyroid orbitopathy, an overview with special attention to the role of radiotherapy]. / Orbitopatía tiroidea, una visión global con atención especial al papel de la radioterapia.

Thyroid orbitopathy is the most prevalent non-thyroid symptom in Graves' syndrome. It has a high incidence and particularly affects young women. Smoking is clearly involved in its development and progress, and in its response to different treatments. This autoimmune condition usually has a benign course, independent from hyperthyroidism, but its severe, progressive forms represent a major therapeutic challenge. Clinical evaluation poses great difficulties, as there is no truly objective rating scale representing disease activity. New molecular or inflammation markers may prove to be useful in this regard. This review reports new findings about its pathophysiology and the different techniques used for treatment over time. Discussion particularly focuses on the immunomodulatory role of radiotherapy, as well as on its role together with corticosteroids.

Compresión medular: aproximación multidisciplinar a una auténtica urgencia neurooncológica. Réplica / Spinal cord compression: a multidisciplinary approach to an authentic neuro-oncological emergency

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[Spinal cord compression: a multidisciplinary approach to a real neuro-oncological emergency. Reply]. / Compresion medular: aproximacion multidisciplinar a una autentica urgencia neurooncologica. Replica.

TITLE: Compresion medular: aproximacion multidisciplinar a una autentica urgencia neurooncologica. Replica.

Compresión medular: aproximación multidisciplinar a una auténtica urgencia neurooncológica / Spinal cord compression: a multidisciplinary approach to a real neuro-oncological emergency

La compresión medular debe ser considerada una urgencia neurooncológica de primera magnitud. Bajo este planteamiento, la aproximación multidisciplinar y la rapidez en la instauración de las medidas terapéuticas que procedan son cruciales para optimizar el pronóstico funcional (y quizás vital) de los pacientes afectos. Las actitudes nihilistas hasta ahora imperantes en algunos sectores profesionales, posiblemente derivadas de una percepción de mal pronóstico a corto plazo, deben ser completamente desterradas. La mejora de la supervivencia global de los pacientes oncológicos en su conjunto, la disponibilidad de nuevas técnicas neuroquirúrgicas accesibles a una gran mayoría de nuestros hospitales, y las mejoras evidentes en los equipos y técnicas de radioterapia permiten abordar esta patología con mejores perspectivas de éxito, no sólo en lo que al control de la progresión tumoral propiamente dicha se refiere, sino también en el control del dolor, el mantenimiento de la funcionalidad de la médula espinal y la supervivencia global del paciente. En este contexto, consideramos obligado que todos los hospitales dispongan de protocolos de actuación específicos para la compresión medular aguda. La puesta en marcha en el Centro Médico de Asturias de un protocolo de estas características ha animado a realizar una revisión y actualización sobre el tema, con especial énfasis en las evidencias disponibles para cada una de las modalidades terapéuticas comentadas

Spinal cord compression must be considered a top-priority neuro-oncological emergency. Hence, a multidisciplinary approach and swiftness in establishing appropriate therapeutic measures are crucial to optimise the functional (and perhaps vital) prognosis of these patients. The nihilistic attitudes that have prevailed up until now in some professional sectors, possibly stemming from the perception of a poor short-term prognosis, must be completely eradicated. The overall improvement in survival rates among cancer patients in general, the availability of new neurosurgical techniques in the vast majority of our hospitals and the obvious improvements in radiotherapy equipment and techniques all this pathology to be addressed with greater chances of success. This greater likelihood of accomplishing a better outcome refers not only to the control of the development of the tumour itself, but also to pain control, maintenance of the functioning of the spinal cord and the overall survival of the patient. In this context, we consider it essential for all hospitals to have specific protocols on how to proceed in cases of acute spinal cord compression. The fact that this kind of protocol has been introduced in the Centro Médico de Asturias has prompted us to conduct a review of the current state-of-the-art in this field, with special emphasis on the evidence available for each of the modes of therapy that are discussed

[Spinal cord compression: a multidisciplinary approach to a real neuro-oncological emergency]. / Compresion medular: aproximacion multidisciplinar a una autentica urgencia neurooncologica.

Spinal cord compression must be considered a top-priority neuro-oncological emergency. Hence, a multi-disciplinary approach and swiftness in establishing appropriate therapeutic measures are crucial to optimise the functional (and perhaps vital) prognosis of these patients. The nihilistic attitudes that have prevailed up until now in some professional sectors, possibly stemming from the perception of a poor short-term prognosis, must be completely eradicated. The overall improvement in survival rates among cancer patients in general, the availability of new neurosurgical techniques in the vast majority of our hospitals and the obvious improvements in radiotherapy equipment and techniques all this pathology to be addressed with greater chances of success. This greater likelihood of accomplishing a better outcome refers not only to the control of the development of the tumour itself, but also to pain control, maintenance of the functioning of the spinal cord and the overall survival of the patient. In this context, we consider it essential for all hospitals to have specific protocols on how to proceed in cases of acute spinal cord compression. The fact that this kind of protocol has been introduced in the Centro Medico de Asturias has prompted us to conduct a review of the current state-of-the-art in this field, with special emphasis on the evidence available for each of the modes of therapy that are discussed.

Mechanism of hot flashes.

Hot flashes are a common and disturbing adverse effect of hormonal therapy for cancer. Their pathophysiology is poorly understood. At present, the leading mechanistic hypothesis rests on the assumption that abrupt hormone deprivation will result in loss of negative feedback over hypothalamic noradrenaline synthesis. In this article we critically review the different theories used to explain this phenomenon. A better understanding of the pathophysiology of hot flashes may facilitate the development of new therapeutic approaches.

[Review of current treatment for hot flushes induced by androgen deprivation in prostate carcinoma]. / Revisión del tratamiento actual de los sofocos inducidos por deprivación androgénica en el carcinoma prostático.

Considering the currently increased incidence, prevalence and survival of prostate cancer, the management of hot flushes associated with LH-RH analog treatment must be taken into account. The most widely used and effective treatment is hormone replacement, though the latter is not without risks. It is presently possible to address hot flushes in these patients based on a broad range of treatment options in which hormone therapy may constitute a last option, due to the risk of tumor relapse or progression -- since prostate cancer is hormone sensitive. The present study reviews the currently used treatments and hygiene-dietary measures that may help reduce the symptoms. A review is made of both hormone and non-hormone therapies, based on the existing scientific evidence. Drugs such as the new antidepressants, gabapentin and clonidine may play an important role in the management of hot flushes. While the underlying mechanisms of action are varied, they are related to the complex feedback exerted by the sexual hormones upon the hypothalamic secretion of noradrenalin -- this being the principal etiological factor of hot flushes.

[Physiopathological mechanism of hot flushes-perspiration induced by androgen deprivation in prostate carcinoma]. / Mecanismo fisiopatológico de los sofocos-sudores inducidos por deprivación androgénica en el carcinoma prostático.

Hot flushes and perspiration are common problems during androgen deprivation therapy for prostate carcinoma, and largely contribute to worsen patient quality of life. Different hypotheses have been proposed to explain the underlying physiopathological mechanisms, though all are very complex, basically because of the multiple causal factors involved. The present review offers a pondered and updated perspective of the origin of hot flushes-perspiration in such patients. Negative feedback of the plasma sexual hormones upon the hypothalamic secretion of noradrenalin and serotonin appears to be the main cause. Likewise, the direct action of such mechanisms upon the LH-RH producing hypothalamic center located close to the thermoregulatory center, together with shortening of the thermoneutral interval, would also play a role. Improved understanding of the causal mechanism may help improve the treatment of such symptoms.

Trazodona: ¿Nuevo enfoque selectivo para el tratamiento de los sofocos generados por la deprivación androgénica en el carcinoma prostático? / Trazodone: A new selective approach to the treatment of hot flashes induced by androgen deprivation in prostate carcinoma?

El protagonismo creciente del carcinoma prostático en las sociedades desarrolladas hace que tenga que ser muy tenido en cuenta el balance beneficio-perjuicio de los tratamientos prestados. Dado el enfoque terapéutico cada vez más complejo del carcinoma prostático, hoy en día se requiere de una suma de conocimientos extensos. La deprivación androgénica juega un papel principal en esta patología. El tratamiento de la toxicidad derivada en forma de sofocos, síndrome metabólico, osteoporosis, trastornos cognitivos, etc., adquiere cada vez mayor interés. El tratamiento farmacológico de los sofocos pasa por un manejo hormonal no exento de riesgo oncológico a la par que de una toxicidad nada despreciable. Dentro del tratamiento no hormonal de esta patología juegan un papel destacado los antidepresivos. La trazodona, un antidepresivo SARI (inhibidores de la recaptación de serotonina/antagonista de la 2A), con un perfil de actuación más selectivo sobre los receptores implicados en los sofocos; podría ser de gran interés. Trazodona muestra una gran afinidad por los receptores 5-HT2A y una moderada afinidad por los receptores 5-HT1A. Como es conocido los niveles de serotonina (5-hidroxitriptamina o 5-HT) en mujeres postmenopáusicas están disminuidos, normalizándose con las terapias sustitutivas. Todo ello sugiere que la de privación abrupta de hormonas sexuales da lugar a una reducción en la circulación de serotonina, con el consiguiente aumento de sus receptores 5-HT2A hipotalámicos. Estos receptores estarían implicados en la patogénesis de los sofocos siendo su bloqueo una de las principales medidas terapéuticas. El uso de trazodona elevando las concentraciones de serotonina y bloqueando a los receptores 5-HT2A y 5-HT1A podría plantearse como un nuevo enfoque más de acorde con la fisiopatología de los sofocos. Estudios comparativos bien dirigidos son necesarios para dar respuesta en cuanto a su efectividad. Otras cuestiones pendientes serían las dosis y el tiempo de tratamiento más eficaz para el control de los sofocos (AU)

The growing relevance of prostate carcinoma in the developed world requires serious attention to focus on the risk-benefit relationships of the treatments used. Given the increasingly complex therapeutic approach to prostate carcinoma, an extensive range of knowledge is required. Androgen deprivation plays a central role in this disease. The management of androgen deprivation-derived toxicity in the form of hot flashes, metabolic syndrome, osteoporosis, cognitive disorders, etc., is of growing interest. The drug treatment of hot flashes involves hormone management that is not without oncological risk and moreover generates considerable toxicity. Antidepressants in turn play an important role in the non-hormone treatment of this disorder. Trazodone, a serotonin reuptake inhibitor/5-HT2A receptor antagonist affording more selective action upon the receptors implicated in hot flashes, could be of great interest. Trazodone shows great affinity for the 5-HT2A receptors and moderate affinity for the 5-HT1A receptors. Serotonin (5-hydroxytryptamine, or 5-HT) levels are known to be lowered in postmenopausal women, and normalize when replacement therapy is provided. This suggests that abrupt sexual hormone deprivation gives rise to a reduction in blood serotonin –with a subsequent increase in its hypothalamic 5-HT2A receptors. These receptors would be implicated in the physiopathology of hot flashes; as a result, the blocking of such receptors is one of the principal therapeutic measures. The use of trazodone, increasing the serotonin concentrations and blocking the 5-HT2A and 5-HT1A receptors, could be viewed as a novel management approach more in line with the physiopathology of hot flashes. Well designed comparative studies are needed to establish the efficacy of such treatment. Other issues pending clarification would be the most effective dose and duration of treatment for controlling hot flashes (AU)

Revisión del tratamiento actual de los sofocos inducidos por deprivación androgénica en el carcinoma prostático / Review of current treatment for hot flushes induced by androgen deprivation in prostate carcinoma

Dada la mayor incidencia, prevalencia y supervivencia del carcinoma prostático en la actualidad, el manejo de los sofocos derivados de su tratamiento con análogos LH-RH ha de ser muy tenido en cuenta. El tratamiento más utilizado y a la vez el más eficaz, es la sustitución hormonal pero este tipo de terapia no esta exenta de riesgos. Hoy por hoy es factible el abordaje de los sofocos de estos pacientes mediante un variado arsenal terapéutico en el cual el tratamiento hormonal puede quedar relegado al último lugar, dado el riesgo de recidiva o progresión tumora lal tratarse de un tumor hormonosensible. El objetivo de este trabajo es revisar los tratamientos utilizados actualmente y las medidas higiénico-dietéticas que pueden ayudar a disminuir la sintomatología. Se revisarán tanto los tratamientos hormonales como los no hormonales basados en su evidencia científica. Fármacos como los nuevos antidepresivos, la gabapentina y la clonidina podrían jugar un papel destacado en el manejo. Sus mecanismos de actuación aunque dispares, se enmarcan en el complejo sistema de retroalimentación ejercido por los niveles de hormonas sexuales sobre la secreción hipotalámica de noradrenalina, causa principal en la génesis de los sofocos (AU)

Considering the currently increased incidence, prevalence and survival of prostate cancer, the management of hot flushes associated with LH-RH analog treatment must be taken into account. The most widely used and effective treatment is hormone replacement, though the latter is not without risks. It is presently possible to address hot flushes in these patients based on a broad range of treatment options in which hormone therapy may constitute a last option, due to the risk of tumor relapse or progression – since prostate cancer is hormone sensitive. The present study reviews the currently used treatments and hygiene-dietary measures that may help reduce the symptoms. A review is made of both hormone and non-hormone therapies, based on the existing scientific evidence. Drugs such as the new antidepressants, gabapentin and clonidine may play an important role in the management of hot flushes. While the underlying mechanisms of action are varied, they are related to the complex feedback exerted by the sexual hormones upon the hypothalamic secretion of noradrenalin – this being the principal etiological factor of hot flushes (AU)

Mecanismo fisiopatológico de los sofocos-sudores inducidos por deprivación androgénica en el carcinoma prostático / Physiopathological mechanism of hot flushes-perspiration induced by androgen deprivation in prostate carcinoma

Los sofocos-sudores son problemas frecuentes durante el tratamiento con de privación androgénica en pacientes afectos de carcinoma prostático. Estos efectos secundarios contribuyen en gran medida al deterioro de la calidad de vida. Se han postulado diferentes hipótesis sobre los mecanismos fisiopatogénicos implicados, todos ellos de una alta complejidad debida básicamente a su multicausalidad. El objetivo de esta revisión es aportar una visión meditada y actualizada de su génesis. La retroalimentación negativa de las hormonas sexuales plasmáticas sobre la secreción hipotalámica de noradrenalina y serotonina serían la causa principal. Asimismo la acción directa de estos mecanismos sobre el centro hipotalámico productor de LH-RH cercano al centro termorregulador, junto al acortamiento del intervalo termo neutral también estarían implicados. La mejor comprensión de su mecanismo de producción nos puede hacer enfocar mas correctamente su tratamiento (AU)

Hot flushes and perspiration are common problems during androgen deprivation therapy for prostate carcinoma, and largely contribute to worsen patient quality of life. Different hypotheses have been proposed to explain the underlying physiopathological mechanisms, though all are very complex, basically because of the multiple causal factors involved. The present review offers a pondered and updated perspective of the origin of hot flushes-perspiration in such patients. Negative feedback of the plasma sexual hormones upon the hypothalamic secretion of noradrenalin and serotonin appears to be the main cause. Likewise, the direct action of such mechanisms upon the LH-RH producing hypothalamic centerlocated close to the thermoregulatory center, together with shortening of the thermo neutral interval, would also play a role. Improved understanding of the causal mechanism may help improve the treatment of such symptoms (AU)