Adenomas gigantes de hipófisis: análisis de variables relacionadas con resultados visuales, endocrinológicos y de resección en cirugía endoscópica transesfenoidal / GIANT PITUITARY ADENOMAS: ANALYSIS OF VARIABLES RELATED TO VISUAL, ENDOCRINOLOGICAL AND RESECTION RESULTS IN TRANSSPHENOIDAL ENDOSCOPIC SURGERY

Introducción. Los adenomas gigantes de hipófisis (AGHs) son aquellos tumores con un diámetro máximo ≥4 cm en cualquier dirección, representando del 5% al 14% del total de los adenomas que se tratan quirúrgicamente. Su manejo terapéutico es desafiante ya que, debido a su extensión hacia otras estructuras cerebrales,está asociado a un riesgo mayor de complicaciones quirúrgicas, con una menor tasa de resección total. El objetivo de este trabajo fue evaluar el impacto de la cirugía endoscópica transesfenoidal en AGHs, analizando las variables asociadas a resultados visuales, endocrinológicos y según el grado de resección. Pacientes y Métodos. Se evaluó en 44 pacientes con AGHs(diámetro ≥4 cm y/o volumen ≥10 ml) la presentación visual, endocrinológica e imágenes. Se analizaron estadísticamente resultados visuales, endocrinológicos, grado de resección y complicaciones quirúrgicas. Resultados. Edad promedio de 48.8 años, 24 mujeres y 20 hombres. Presentación: déficit del campo visual (93.1%), hipopituitarismo (61.3%), cefalea (54.5%). Diámetro, volumen y extensión supraselar promedios: 4.8 cm, 20.3 ml, 1.8 cm, respectivamente. Campo visual: mejoría: 83.3%, sin cambios: 9.5%, mayormente en síntomas bilaterales (p<0.0001). Desmejoríavisual: 0%. En resección total: mayor posibilidad de mejoría visual (p=0.040). Buenos resultados endocrinológicos: 85.7%. Tasa de resección total: 52.3%. Resección subtotal: más frecuente con invasión del seno cavernoso (p=0.014). Sin diferencias en el grado de resección según diámetro, volumen, extensión supraselar, forma ni aspecto. Hipopituitarismo: 4.2%. Diabetes insípida: 9.5%, asociada a mayor diámetro (p=0.038) o extensión supraselar (p=0.010) y aspecto sólido (p=0.023). Fístula de LCR: 7.1%. Conclusión. La resección total puede lograrse en la mitad de los casos, siendo la limitante principal el grado de invasión del seno cavernoso y no el aspecto morfológico del AGH per se. Aun así, los resultados visuales y endocrinológicos son muy buenos. En resecciones incompletas se logra el control de la enfermedad mediante tratamientos complementarios

Introduction. Giant pituitary adenomas (sGAs) are those tumors with a maximum diame- ter ≥4 cm in any direction, representing 5% to 14% of all adenomas that are treated surgi- cally. Its therapeutic management is challenging since, due to its extension to other brain structures, it is associated with a higher risk of surgical complications, with a lower rate of total resection. Te objective of this work was to evaluate the impact of transsphenoidal endoscopic surgery on AGHs, analyzing the variables associated with visual and endocri- nological results and according to the degree of resection. Patients and Methods. Visual, endocrinological and imaging presentation were evaluated in 44 patients with sHAA (dia- meter ≥4 cm and/or volume ≥10 ml). Visual and endocrinological results, degree of resection and surgical complications were statistically analyzed. Results. Average age of 48.8 years, 24 women and 20 men. Presentation: visual field deficit (93.1%), hypopituitarism (61.3%), headache (54.5%). Average diameter, volume and suprasellar extension: 4.8 cm, 20.3 ml, 1.8 cm, respectively. Visual field: improvement: 83.3%, no changes: 9.5%, mostly in bilate- ral symptoms (p<0.0001). Visual impairment: 0%. In total resection: greater possibility of visual improvement (p=0.040). Good endocrinological results: 85.7%. Total resection rate: 52.3%. Subtotal resection: more frequent with invasion of the cavernous sinus (p=0.014). No differences in the degree of resection according to diameter, volume, suprasellar exten- sion, shape or appearance. Hypopituitarism: 4.2%. Diabetes insipidus: 9.5%, associated with greater diameter (p=0.038) or suprasellar extension (p=0.010) and solid appearance (p=0.023). CSF fistula: 7.1%. Conclusion. Total resection can be achieved in half of the cases, the main limitation being the degree of invasion of the cavernous sinus and not the morphological appearance of the HGA per se. Even so, the visual and endocrinological results are very good. In incomplete resections, disease control is achieved through com- plementary treatments

Lithium and endocrine dysfunction / Litio y disfunción endocrina

Abstract Lithium carbonate is a commonly prescribed drug for bipolar disorders. In addition to its action on the central nervous system, lithium has systemic effects on multiple organs such as kidney, heart, motor end plate, thyroid and parathyroid glands. It can cause hypothyroidism, hyperthyroidism, goiter and oph thalmopathy by different mechanisms. It increases intrathyroid iodine content or compete for iodine transport, resulting in low iodine uptake by the thyroid. It also inhibits the coupling of iodotyrosine residues to form iodothy ronines and inhibits the release of T4 and T3. Lithium has direct actions on parathyroid glands by antagonizing the calcium sensing receptor, which may induce hypercalcemia or even hyperparathyroidism, requiring surgery in some cases. Furthermore, it inhibits the expression of aquaporins, mainly aquaporin 2, in the renal collecting tubule by unknown mechanisms leading to nephrogenic diabetes insipidus. This adverse effect is usually reversible after drug withdrawal. However, some patients may present irreversible kidney damage due to chronic interstitial nephropathy.

Resumen El carbonato de litio es un fármaco que se prescribe comúnmente para el tratamiento de trastornos bipolares. Además de su acción sobre el sistema nervioso central, el litio tiene repercusiones sistémicas, afectando a múltiples órganos como el riñón, el corazón, la placa motora terminal y glándulas tiroides y paratiroides. Puede causar hipotiroidismo, hipertiroidismo, bocio y oftalmopatía por diferentes mecanismos; también aumentar el contenido de yodo intratiroideo o competir por el transporte de yodo, lo que resulta en una baja captación tiroidea de yodo. Inhibe el acoplamiento de residuos de yodotirosina para formar yodotironinas e inhibe la liberación de T4 y T3. Tiene acciones directas sobre las glándulas paratiroides antagonizando el receptor sensor de calcio, lo que puede inducir hipercalcemia e incluso hiperparatiroidismo, y puede requerir cirugía en algunos casos. Inhibe la expresión de acuaporinas en el túbulo colector renal, prin cipalmente acuaporina 2, por mecanismos que aún no se conocen, produciendo diabetes insípida nefrogénica; este efecto adverso suele ser reversible tras la suspensión del fármaco. Sin embargo, algunos pacientes pueden presentar daño renal irreversible por nefropatía intersticial crónica.

Complex Fibroadenoma: a Cystic Neoplasia Report Case / Fibroadenoma Complexo: Relato de Caso de uma Neoplasia Cística

Abstract Fibroadenoma is the most common breast tumor in young woman. It is considered a non-malignant tumor, showing hyaline component and a biphasic stroma and epithelial process, thus, it is similar to phyllode tumor revealing intralobular stroma. The cystic changes in a complex fibroadenoma may mimic a carcinoma, therefore it may represent some problems in images interpretation, and it may enlarge the risk of cancer development. This is a description of a case report with literature review. A 21-year-old female patientwith no history of breast cancer in family, presented a palpable lump in her right breast and clinical examination revealed a mobile, firm, circumscribed lesion in the right inner quadrant, measuring around 8 x 7 cm. An excision had been done under a stereotactic surgery and the structure revealed a nodular surface, measuring 8 x 6.5x 5.5cm. Cut section revealed heterogeneous aspect: cysts with colloid content and white-gray compact fibroblastic areas. Histopathological examination shows hypocellular stroma and few hypercellular areas, without atypia. Epithelial components presenting proliferation of intracanalicular and pericanalicular pattern ducts. Cystic proliferation with epithelial lining and apocrine characteristics without atypia. Because of the variation may be present inside the lesion it is difficult to establish the diagnosis without a biopsy, and a histopathological analysis. Moreover, it is necessary to know the microscope difference between fibroadenoma and the other sort of lesions; furthermore, that heterogeneity represent why that tumor is considered complex. (AU)

Resumo Fibroadenoma é o tumor de mama mais comum em mulheres jovens. É considerado um tumor não-maligno, apresentando um componente hialino e um estroma bifásico, e processo epitelial, por isso, é similar ao tumor filoide, revelando estroma intralobular. As alterações císticas no fibroadenoma complexo pode mimetizar um carcinoma, isso acarreta alguns problemas na interpretação das imagens, e pode aumentar o risco de desenvolvimento de câncer. Trata-se de um relato de caso de paciente de 21 anos de idade, sem histórico de câncer de mama na família, apresenta uma massa palpável em seio direito. Exame clinico revelou lesão móvel, firme, circunscrita no quadrante interno do seio. Excisão por cirurgia estereotáctica e a estrutura se mostra com superfície multinodular, medindo 8 x 6,5 x 5,5 cm. com aspecto heterogêneo, cistos com conteúdo coloide, e áreas fibrobásticas branco-acinzentada. Exame histológico demonstra-se estroma hipercelular, com áreas hipocelularizadas, sem atipia. Componentes epiteliais apresentando proliferação intercanalicular e intracanicular dos ductos. Proliferação cística com revestimento epitelial e características apócrinas sem atipia. Por conta da variação presente na lesão, pode ser difícil a estabelecimento de um diagnóstico se biópsia e análise histopatológica. Além disso, é fundamental o conhecimento das diferenças microscópicas entre o fibroadenoma e outros tipos de lesões; além disso, a heterogeneidade representa o motivo do tumor ser considerado complexo. (AU)

Endocrine dysfunction induced by immune checkpoint inhibitors / Disfunción endocrina inducida por inhibidores de los puntos de control inmune

Abstract Since their approval in 2011, immune checkpoint inhibitors (ICPis) are increasingly used to treat several advanced cancers. ICPis target certain cellular molecules that regulate immune response resulting in antitumor activity. The use of these new agents needs careful monitoring since they brought a whole new spectrum of adverse events. In this review, we aim to describe different endocrine dysfunctions induced by ICPis and to underline the importance of diagnosing and managing these adverse effects. Immune-related endocrine toxicities include thyroid dysfunction, hypophysitis and, less frequently, type 1 diabetes, primary ad renal insufficiency and hypoparathyroidism. Diagnosis of endocrine adverse events related to ICPis therapy can be challenging due to nonspecific manifestations in an oncological scenario and difficulties in the biochemical evaluation. Despite the fact that these endocrine adverse events could lead to life-threatening consequences, the availability of effective replacement treatment enables continuing therapy and together with an interdisciplinary approach will impact positively on survival.

Resumen Desde su aprobación en 2011, el uso de los inhibidores de los puntos de control inmunes (ICPis) se ha ex tendido para el tratamiento de diversas neoplasias en estadios avanzados. Los ICPis tienen como blanco ciertas moléculas de las células que regulan la respuesta inmune favoreciendo una actividad antitumoral. El uso de estos nuevos agentes requiere un monitoreo específico, ya que se han vinculado con un amplio y nuevo espectro de efectos adversos. El objetivo de esta revisión es describir las diferentes disfunciones endocrinas inducidas por los ICPis y destacar la importancia del diagnóstico y manejo oportuno de estos efectos adversos. Los efectos adversos inmunes endocrinos incluyen disfunción tiroidea, hipofisitis y con menor frecuencia, diabetes tipo 1, insuficiencia suprarrenal primaria e hipoparatiroidismo. El diagnóstico de eventos adversos endocrinos relacionados con la terapia ICPis es un desafío debido a su presentación clínica inespecífica en un escenario oncológico y a las dificultades en la evaluación bioquímica. Estos eventos adversos endocrinos podrían tener consecuencias potencialmente letales, pero la disponibilidad de un tratamiento de reemplazo eficaz permite continuar la terapia y, junto con un enfoque interdisciplinario, generar un impacto positivo en la supervivencia.

Adrenal axis in critical illness / Eje adrenal en la enfermedad crítica

Abstract After a stressful event, adaptative mechanisms are carried out to support vital functions. Hypothalamic-pituitary-adrenal axis plays a key role in stress response regulating metabolism, cardiovascular function and immune system. This review addresses pathophysiological changes of the adrenal axis during critical illness, recognizing limitations of methods applied for its evaluation in this special context and defining indications for corticosteroid replacement in critically ill patients. The concept of relative adrenal insufficiency should be abandoned; cosyntropin stimulation test should not be performed for diagnosis of adrenal insufficiency in critical illness nor for establishing the need of treatment.

Resumen Diversos mecanismos adaptativos se ponen en marcha para sostener las funciones orgánicas vitales en el paciente crítico. El eje hipotálamo-hipófiso-adrenal tiene un papel clave en la respuesta al estrés al regular el metabolismo, la función cardiovascular y la respuesta inmune. Esta revisión tiene por objetivos analizar los cambios fisiopatológicos que se producen en el eje adrenal durante la enfermedad crítica, reconocer las limitaciones de los métodos diagnósticos y definir indicaciones de tratamiento de reemplazo corticoideo en este contexto. El concepto de insuficiencia adrenal relativa debe ser descartado y no se recomienda el test de estímulo con cosintropina para diagnóstico de insuficiencia adrenal durante enfermedad crítica ni para definir la necesidad de tratamiento.

Hyperprolactinemia associated with psychiatric disorders / Hiperprolactinemia asociada con trastornos psiquiátricos

Abstract Hyperprolactinemia may be associated with psychiatric disorders in the context of two scenarios: antipsychotic-induced hyperprolactinemia and psychiatric disorders arising from the medical treatment of hyperprolactinemia. Both situations are particularly common in psychiatric and endocrine clinical practice, albeit generally underestimated or unrecognized. The aim of this article is to provide tools for the diagnosis and treatment of hyperprolactinemia associated with psychiatric disorders to raise awareness, especially among psychiatrists and endocrinologists, so that these professionals can jointly focus on the appropriate management of this clinical entity.

Resumen La hiperprolactinemia puede asociarse con trastornos psiquiátricos en el contexto de dos escenarios: la hiperprolactinemia inducida por antipsicóticos y trastornos psiquiátricos surgidos por el tratamiento médico de la hiperprolactinemia. Ambas situaciones son particularmente comunes en la práctica clínica psiquiátrica y endocrinológica, aunque generalmente subestimadas o inadvertidas. El objetivo de este artículo es proporcionar herramientas de diagnóstico y tratamiento de la hiperprolactinemia asociada a trastornos psiquiátricos, para concientizar particularmente a psiquiatras y endocrinólogos a enfocar en conjunto el manejo apropiado de esta entidad.

Treatment of hypothyroidism in special situations / Tratamiento del hipotiroidismo en situaciones especiales

Abstract The treatment of hypothyroidism is aimed at restoring the euthyroid state. In most cases, the signs and symptoms of thyroid deficiency generally resolve, which is particularly gratifying for the treating physician and mainly, for patients. However, there may be coexisting special situations that can potentially hinder or interfere with a successful treatment, as in the case of the elderly, patients suffering from heart disease, hematological diseases or dyslipidemia, hypothyroid patients who will undergo an emergency surgery, those with chronic kidney failure, or adrenal insufficiency, among others. Besides management of hypothyroidism in time of COVID-19 is also included. Some patients may experience intolerance to treatment and others persistent symptoms of hypothyroidism even under adequate replacement therapy, requiring a special approach. Being aware of these special situations will provide benefits to the patient and will also prevent treatment failure or complications.

Resumen El tratamiento del hipotiroidismo tiene como objetivo restaurar el estado eutiroideo. En la mayoría de los casos los signos y síntomas del déficit tiroideo en general se resuelven, lo cual es muy gratificante para el médico tratante y en especial para los pacientes. Sin embargo, pueden coexistir situaciones especiales que potencialmente dificulten o interfieran con un tratamiento exitoso como en el caso de los pacientes ancianos, aquellos con cardiopatías, enfermedades hematológicas o dislipemia, pacientes hipotiroideos que requieran cirugía de urgencia, aquellos con insuficiencia renal crónica, o insuficiencia adrenal, entre otras. Además, se incluye el manejo del hipotiroidismo en la era del COVID-19. Algunos pacientes pueden manifestar intolerancia al tratamiento y otros, persistencia de síntomas de hipotiroidismo aun bajo un adecuado reemplazo hormonal, lo cual requerirá un abordaje especial. Estar advertido de estas situaciones especiales redundará en el beneficio del paciente y evitará fracasos o complicaciones terapéuticas.

Detección ecográfica de remanentes del conducto tirogloso luego de tiroidectomía por cáncer de tiroides / Thyroglossal duct remnants detected by ultrasonography after total thyroidectomy for thyroid carcinoma

Resumen Existen numerosas comunicaciones de hallazgo incidental de remanentes del conducto tirogloso (CTG) posteriores a una tiroidectomía total, pero se desconoce su implicancia en pacientes con cáncer diferenciado de tiroides (CDT). Nuestro objetivo fue determinar frecuencia de detección ecográfica de remanentes del CTG posterior a la tiroidectomía total en pacientes con CDT y evaluar el impacto del hallazgo en la respuesta al tratamiento. Se incluyeron 377 pacientes con CDT tratados con tiroidectomía total entre enero 1994 y enero 2017, con seguimiento de al menos un año posterior a la cirugía. Se detectó la presencia de remanente del CTG en 16/377 (4.2%): 15 de bajo riesgo de recurrencia y uno de riesgo intermedio. Trece recibieron radioyodo. Todos tuvieron un estado sin evidencia de enfermedad al final del seguimiento, excepto uno con riesgo intermedio que presentó una respuesta inicial estructural incompleta e indeterminada posterior al vaciamiento ganglionar. La mediana del tiempo de diagnóstico del remanente del CTG luego de la tiroidectomía fue de 5 años (rango 1-16). Dos pacientes con remanentes del CTG fueron intervenidos quirúrgicamente, ambos presentaron tumoraciones de aparición súbita en región suprahioidea, 2.4 y 4 cm, detectados a los 9 y 16 años luego de la tiroidectomía, respectivamente. La prevalencia de esta condición parece ser poco frecuente. Sin embargo, la aparición de una masa quística en el seguimiento de un paciente con CDT puede ser confundido con enfermedad metastásica y generar ansiedad. El hallazgo de remanentes del CTG parecería no tener ningún impacto en la respuesta al tratamiento.

Abstract There are numerous reports of incidental findings of thyroglossal duct remnants (TGDR) after total thyroidectomy, but its implication on the outcome of patients with differentiated thyroid cancer (DTC) is unknown. The aim of this study was to determine the frequency of TGDR detected by ultrasonography after total thyroidectomy in patients with DTC and to evaluate the impact of this finding on the response to treatment. A total of 377 records of patients with DTC who received total thyroidectomy between January 1994 and January 2017 were reviewed. Patients with less than one year of follow-up after surgery were excluded. TGDR was diagnosed in 16 out of 377 (4.2%). Fifteen had a low risk of recurrence DTC and 13 of them were treated with radioactive iodine. All low risk patients had an excellent response to treatment. Only one with an intermediate risk of recurrence DTC had an initial structural incomplete response which changed to an indeterminate response after a modified central lymph node dissection. The median time of TGDR diagnosis after thyroidectomy was 5 years (1-16). Two patients underwent TGDR surgery due to the presence of a rapidly growing neck mass, 2.4 and 4 cm in size, detected 9 and 16 years after thyroidectomy, respectively. The prevalence of this condition seems to be rare. However, the appearance of a cystic mass during the follow-up of a patient with DTC cancer could be confused with metastatic disease. The diagnosis of TGDR seems not to have an impact on the response to treatment.

Drug-induced hypothyroidism

The thyroid axis is particularly prone to interactions with a wide variety of drugs, whose list increases year by year. Hypothyroidism is the most frequent consequence of drug-induced thyroid dysfunction. The main mechanisms involved in the development of primary hypothyroidism are: inhibition of the synthesis and/or release of thyroid hormones, immune mechanisms related to the use of interferon and other cytokines, and the induction of thyroiditis associated with the use of tyrosine kinase inhibitors and drugs blocking the receptors for vascular endothelial growth factor. Central hypothyroidism may be induced by inhibition of thyroid-stimulating hormone (bexarotene or corticosteroids) or by immunological mechanisms (anti-CTLA4 or anti-PD-1 antibody drugs). It is also important to recognize those drugs that generate hypothyroidism by interaction in its treatment, either by reducing the absorption or by altering the transport and metabolism of levothyroxine. Thus, it is strongly recommended to evaluate thyroid function prior to the prescription of medications such as amiodarone, lithium, or interferon, and the new biological therapies that show important interaction with thyroid and endocrine function in general.

El eje tiroideo es particularmente proclive a sufrir interacciones con una amplia variedad de drogas, cuya lista se acrecienta año a año. El hipotiroidismo es la consecuencia más frecuente de disfunción tiroidea inducida por fármacos. Los principales mecanismos involucrados en el desarrollo de hipotiroidismo primario son: la inhibición de la síntesis y/o liberación de las hormonas tiroideas, mecanismos inmunes relacionados con el uso de interferón y otras citoquinas, y la inducción de tiroiditis asociada al uso de los inhibidores tirosina-kinasa y a drogas bloqueantes del receptor del factor de crecimiento del endotelio vascular. El hipotiroidismo central puede ser inducido por la inhibición de la tirotrofina (bexaroteno o corticoides) o por mecanismos inmunológicos (drogas anti-CTLA4 o anti PD-1). Es importante reconocer aquellas drogas que generan hipotiroidismo por interacción en su tratamiento, ya sea disminuyendo la absorción o alterando el transporte y metabolismo de la levotiroxina. Sería recomendable evaluar la función tiroidea previa a la prescripción de medicamentos como amiodarona, litio o interferón, y a las nuevas terapias biológicas que muestran importante interacción sobre la función tiroidea y endocrina en general.

Coma mixedematoso / Myxedema coma

El hipotiroidismo es una enfermedad frecuente, de diagnóstico y tratamiento simples. Si no es detectada a tiempo puede progresar a la forma más grave conocida como coma mixedematoso. El término "coma mixedematoso" es considerado generalmente engañoso, ya que la mayoría de los pacientes no se presenta inicialmente en estado de coma. La progresión típica es la letargia, evolucionando al estupor y eventualmente al coma, con insuficiencia respiratoria e hipotermia. Es relativamente infrecuente, afecta fundamentalmente a mujeres ancianas, y a menudo ocurre en invierno. Esta entidad debe ser considerada una forma de hipotiroidismo descompensado, desencadenada a partir de una variedad de enfermedades o condiciones no tiroideas que provocan un compromiso sistémico generalizado de extrema gravedad, con desenlace fatal de no mediar un diagnóstico precoz y un tratamiento intensivo.

Hypothyroidism is a frequently diagnosed and simply treated disease. If not recognised, however, in time it may develop into the most severe manifestation of hypothyroidism known as myxedema coma. The term "myxedema coma" is generally seen as misleading since most patients do not initially present in a coma. The typical progression is lethargy evolving into stupor and, eventually, into coma with respiratory failure and hypothermia. It mainly affects elderly women, often occurring in winter and is relatively rare. It can be considered a form of decompensated hypothyroidism often triggered by a variety of non-thyroid conditions or diseases provoking an extremely severe condition of multiple system failure with lethal consequences unless an early diagnosis is made and an aggressive treatment is administered.

Tiroiditis no-autoinmunes / Non-autoimmune thyroiditis

El término tiroiditis comprende un grupo de enfermedades de la glándula tiroides caracterizado por la presencia de inflamación, abarcando entidades autoinmunes y no-autoinmunes. Pueden manifestarse como enfermedades agudas con dolor tiroideo severo (tiroiditis subaguda y tiroiditis infecciosas), y condiciones en las cuales la inflamación no es clínicamente evidente, cursando sin dolor y presentando disfunción tiroidea y/o bocio (tiroiditis inducida por fármacos y tiroiditis de Riedel). El objetivo de esta revisión es aportar un enfoque actualizado sobre las tiroiditis no-autoinmunes cubriendo sus aspectos clínicos, diagnósticos y terapéuticos.

The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

Glucocorticoides: paradigma de medicina traslacional. De lo molecular al uso clínico / Glucocorticoids: examples of translational medicine; from molecular aspects to bedside

Los glucocorticoides o corticosteroides son fármacos antiinflamatorios, antialérgicos e inmunosupresores derivados del cortisol o hidrocortisona, hormona producida por la corteza adrenal. Su uso terapéutico fuera de la endocrinología data de la observación hecha por el reumatólogo Philip Hench quien, suponiendo que los pacientes con artritis reumatoidea tenían un déficit adrenal, inyectó en algunos cortisona, molécula de reciente producción industrial. El resultado obtenido fue tan contundente que se toma como ejemplo de la medicina traslacional. En la actualidad, los glucocorticoides figuran entre las drogas más usadas y, paralelamente, más temidas. Así, el objetivo de esta revisión es señalar los aspectos destacados de su farmacología para su uso racional en la práctica clínica.

Glucocorticoids are anti-inflammatory, immunosuppressant and anti-allergic drugs derived from hydrocortisone. Their widespread use was originated from Hench's observations in patients with rheumatoid arthritis. These drugs are examples of translational medicine and they can be envisaged as one of the most prescribed and feared drugs. The objective of this review is to highlight their pharmacological properties and thus, allow a more suitable prescription.

Low-dose glucocorticoids in hyperandrogenism / Efecto de bajas dosis de glucocorticoides en el hiperandrogenismo

To investigate the effect of low-doses of glucocorticoids on androgen and cortisol secretion during the course of the day, we evaluated clinical signs of hyperandrogenism and total, free and bioavailable testosterone, SHBG, and cortisol following two different protocols: A) fourteen patients received betamethasone 0.6 mg/day (n=8) or methylprednisolone 4 mg/day (n=6), as single daily oral dose at 11.00 PM, during 30 days, B) fourteen patients were evaluated under betamethasone 0.3 mg in a single daily dose at 11.00 PM during six months, 11 out of whom were re-evaluated six months later. Twenty eight women with hyperandrogenism were included and seven normal females were used as control. Blood samples were taken in follicular phase at 8 AM and 7 PM to determine SHBG, cortisol, total, free and bioavailable testosterone. In both protocols, a significant morning and evening decrease in cortisol and testosterone (p<0.05 to < 0.01), which was moremarked with betamethasone (p<0.05), was shown. In protocol B, morning SHBG levels showed a significant increase (p<0.05) and betamethasone also improved clinical hyperandrogenism along the trial. Although morning and evening cortisol significantly decreased during treatment, no side effects were reported. The 11 patients reevaluated after therapy withdrawal, showed a rise in serum total testosterone and its fractions to pre-treatment values and a normalization of cortisol levels. It is concluded that glucocorticoids in low-doses effectively normalize serum androgens, independently of their origin. They may be used therapeutically, mainly whenever a hyperandrogenic woman presents with cycle irregularities or seeking fertility.

Con el objetivo de investigar el efecto de bajas dosis de glucocorticoides sobre la secreción de andrógenos y cortisol en el curso del día, evaluamos signos de hiperandrogenismo, testosterona total, libre y biodisponible y cortisol según dos protocolos diferentes: A) catorce pacientes recibieron betametasona 0.6 mg/día (n= 8) o metilprednisolona 4 mg/día (n= 6) en dosis única cotidiana, a las 23 h, durante 30 días, B) catorce pacientes fueron evaluadas bajo betametasona 0.3 mg en dosis única cotidiana a la 23 h, administrada durante 6 meses; de ellas, 11 pacientes fueron re-evaluadas 6 meses más tarde. Se incluyeron 28 mujeres con hiperandrogenismo y 7 controles normales. Se obtuvieron muestras de sangre en fase folicular a las 08:00 y 9:00 h para determinar SHBG, cortisol, testosterona total, libre y biodisponible. En ambos protocolos se observó una disminución significativa de cortisol y testosterona (p<0.05 a <0.01), más importante con betametasona (p<0.05). En el protocolo B, los niveles matutinos de SHBG aumentaron significativamente (p<0.05) y se observó mejoría clínica con el tratamiento. Aunque los niveles matutinos y vespertinos de cortisol disminuyeron significativamente durante el tratamiento, no se observaron efectos secundarios. En las 11 pacientes reevaluadas luego de suspensión de glucocorticoides se observó un aumento de testosterona y sus fracciones a los niveles pre-tratamiento con normalización de las concentraciones de cortisol. Dosis bajas de glucocorticoides normalizaron eficazmente los andrógenos séricos elevados, independientemente de su causa. Pueden emplearse terapéuticamente, en especial cuando una mujer hiperandrogénica presenta alteraciones del ciclo menstrual o busca fertilidad.

Análise de 39 casos de pneumonia intersticial crônica idiopática / Analysis of 39 cases of idiopathic chronic interstitial pneumonia

OBJETIVO: Analisar de forma retrospectiva fragmentos de biópsias pulmonares que receberam o diagnóstico de pneumonia intersticial crônica idiopática, à luz da classificação da American Thoracic Society e European Respiratory Society, de 2000. MÉTODOS: A partir da revisão de 252 fragmentos de biópsias pulmonares a céu aberto de pacientes com doença intersticial pulmonar, no período de 1977 a 1999, 39 casos de doença pulmonar intersticial idiopática foram selecionados e reavaliados por dois patologistas, segundo a classificação da American Thoracic Society e European Respiratory Society, de 2000. RESULTADOS: Vinte e oito dos 39 diagnósticos foram mantidos (71,8 por cento). Uma nova entidade patológica, a pneumonia intersticial não específica, foi incluída na reclassificação e houve superposição de padrões em seis casos. Mantiveram o mesmo diagnóstico 28 casos, 4 casos apresentaram associação entre fibrose pulmonar idiopática e organização pneumônica criptogênica, 1 entre organização pneumônica criptogênica e pneumonia intersticial não específica, e 1 entre pneumonia intersticial descamativa e pneumonia intersticial não específica. Todos os casos de fibrose pulmonar idiopática foram confirmados, embora 3 deles estivessem associados a organização pneumônica criptogênica. Os diagnósticos anteriores foram quase todos mantidos na revisão dos espécimes (p > 0,05). CONCLUSÃO: A classificação das doenças pulmonares intersticiais da American Thoracic Society e European Respiratory Society é uma ferramenta útil aos patologistas que lidam com biópsias pulmonares.

OBJECTIVE: To make a retrospective analysis of lung biopsy samples obtained from patients diagnosed with chronic idiopathic interstitial pneumonia, as defined in the American Thoracic Society/European Respiratory Society classification system made public in 2000. METHODS: Samples from 252 open-lung biopsies of patients with interstitial lung disease, all performed between 1977 and 1999, were reviewed, and 39 cases of idiopathic interstitial lung disease were selected and re-evaluated by two pathologists in accordance with the American Thoracic Society/European Respiratory Society classification system. RESULTS: Among those 39 cases, the diagnoses were maintained in 28 (71.8 percent). A new pathologic entity, nonspecific interstitial pneumonia, was included in the reclassification, and overlapping patterns were observed in 6 cases. Of the 28 cases in which the diagnosis of chronic idiopathic interstitial pneumonia remained unchanged, idiopathic pulmonary fibrosis was accompanied by cryptogenic organizing pneumonia in 4, cryptogenic organizing pneumonia was accompanied by nonspecific interstitial pneumonia in 1, and desquamative interstitial pneumonia was accompanied by nonspecific interstitial pneumonia in 1. All cases of idiopathic pulmonary fibrosis were confirmed, although 3 of those were found to be accompanied by cryptogenic organizing pneumonia. Virtually all prior diagnoses were maintained in the review of the biopsy samples (p > 0,05). CONCLUSION: The American Thoracic Society/European Respiratory Society system of classifying interstitial lung disease is a useful tool for pathologists who deal with lung biopsies.