Hipertensión arterial secundaria a enfermedad de Cushing. Reporte de Caso / Hypertension secondary to Cushing´s Disease. Report of a clinical case

INTRODUCCIÓN: La Enfermedad de Cushing es una de las causas menos prevalentes de hipertensión arterial secundaria (HTA) (0,7 a 2,4 casos por millón de personas), sin embargo conlleva un aumento de la morbi-mortalidad que se relaciona con el tiempo de exposición al exceso de corticoides 6, lo cual representa un problema debido a que la inespecificidad de los síntomas y su baja prevalencia, llevan a un retraso diagnóstico de 2 a 4 años 6, generando un incremento del riesgo cardiovascular pese a una resolución completa de la enfermedad 6-9. Este artículo tiene como objetivo describir la presentación clínica de la Enfermedad de Cushing como causa de HTA secundaria. CASO CLÍNICO: Paciente femenina de 36 años con HTA de 7 años de evolución, a quien se identificó adenoma hipofisario productor de ACTH, con posterior exéresis transesfenoidal parcial, presentando enfermedad persistente, en quien se optó manejo farmacológico a base de inhibidor de la esteroidogénesis para control de la enfermedad. DISCUSIÓN: La HTA es un problema de salud pública considerado el principal factor de riesgo para discapacidad y muerte prematura 2, con las causas secundarias como responsables de gran afectación en la calidad de vida, tomando en cuenta que estas son potencialmente curables. El manejo de la enfermedad de Cushing (EC) es principalmente quirúrgico 6,13-14, pero en caso de enfermedad persistente existen alternativas para control de la enfermedad 6,15-16, siendo los fármacos inhibidores de la esteroidogénesis los más usados. CONCLUSIONES: La EC es una causa poco frecuente hipertensión arterial secundaria, pero implica un importante compromiso de la calidad de vida, al igual que otras etiologías secundarias, por lo que es fundamental tener en cuenta las características clínicas y bioquímicas que sugieran una etiología secundaria que lleven a un diagnóstico y tratamiento oportunos.

INTRODUCTION: Cushing's Disease is one of the least prevalent causes of secondary hypertension (0.7 to 2.4 cases per million people), however it entails an increase in morbidity and mortality that is related to the chronic exposure of corticosteroids 6, which represents a problem because the no specificity of the symptoms and their low prevalence lead to a diagnostic delay of 2 to 4 years 6, increasing the cardiovascular risk despite complete resolution of the disease 6 -9. The purpose of this article aims to describe the clinical presentation of Cushing Disease (CD) as a cause of secondary hypertension. CLINICAL CASE: 36-year-old female patient with hypertension of 7 years of evolution, in whom an ACTH-producing pituitary adenoma was identified, with subsequent partial transsphenoidal excision, presenting persistent disease, in whom pharmacological management based on a steroidogenesis inhibitor was chosen. for disease control. DISCUSSION: Hypertension is a public health problem, considered the main risk factor for disability and premature death 2, with secondary causes responsible for great impact on quality of life, considering that these are potentially curative. The management of CD is mainly surgical 6,13-14, but in cases of persistent disease there are alternatives to control the disease 6,15-16, with steroidogenesis inhibitor drugs being the most used. CONCLUSIONS: CD is a rare cause of secondary hypertension, but it implies a significant compromise in quality of life, like other secondary etiologies, so it is essential to consider the clinical and biochemical characteristics that suggest a secondary etiology, which can lead to timely diagnosis and treatment.

From Knee Pain Consultation to Pituitary Surgery: The Challenge of Cushing Disease Diagnosis.

Cushing syndrome (CS) is a rare endocrinological disorder resulting from chronic exposure to excessive cortisol. The term Cushing disease is used specifically when this is caused by excessive secretion of adrenocorticotropic hormone (ACTH) by a pituitary tumor, usually an adenoma. This disease is associated with a poor prognosis, and if left untreated, it has an estimated 5-year survival rate of 50%. We present the case of a 66-year-old female patient who received a referral to endocrinology for an evaluation of obesity due to right knee arthropathy. Taking into consideration her age, she was screened for osteoporosis, with results that showed diminished bone density. Considering this, combined with other clinical features of the patient, suspicion turned toward hypercortisolism. Laboratory findings suggested that the CS was ACTH-dependent and originated in the pituitary gland. After a second look at the magnetic resonance imaging results, a 4-mm lesion was identified on the pituitary gland, prompting a transsphenoidal resection of the pituitary adenoma.

Role of the Fungus Pneumocystis in IL1ß Pathway Activation and Airways Collagen Deposition in Elastase-Induced COPD Animals.

Inflammation and mucus production are prevalent characteristics of chronic respiratory conditions, such as asthma and chronic chronic obstructive pulmonary disease (COPD). Biological co-factors, including bacteria, viruses, and fungi, may exacerbate these diseases by activating various pathways associated with airway diseases. An example is the fungus Pneumocystis, which is linked to severe COPD in human patients. Recent evidence has demonstrated that Pneumocystis significantly enhanced inflammation and mucus hypersecretion in a rat model of elastase-induced COPD. The present study specifically aims to investigate two additional aspects associated with the pathology induced by Pneumocystis infection: inflammation and collagen deposition around airways. To this end, the focus was to investigate the role of the IL-1ß pro-inflammatory pathway during Pneumocystis infection in COPD rats. Several airway pathology-related features, such as inflammation, mucus hypersecretion, and fibrosis, were evaluated using histological and molecular techniques. COPD animals infected with Pneumocystis exhibited elevated inflammation levels, including a synergistic increase in IL-1ß and Cox-2. Furthermore, protein levels of the IL-1ß-dependent transcription factor cAMP response element-binding (CREB) showed a synergistic elevation of their phosphorylated version in the lungs of COPD animals infected with Pneumocystis, while mucus levels were notably higher in the airways of COPD-infected animals. Interestingly, a CREB responsive element (CRE) was identified in the Muc5b promoter. The presence of CREB in the Muc5b promoter was synergistically increased in COPD animals infected with Pneumocystis compared to other experimental groups. Finally, an increment of deposited collagen was identified surrounding the airways of COPD animals infected with Pneumocystis compared with the other experimental animal groups and correlated with the increase of Tgfß1 mRNA levels. These findings emphasize the role of Pneumocystis as a potential biological co-factor in chronic respiratory diseases like COPD or asthma, warranting new perspectives in the treatment of chronic respiratory diseases.

Clinical and Pathological Predictors of Death for Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare and lethal disease with a poor prognosis. This study aims to share our 41-year experience as a referral center, focusing on identifying risk factors associated with ACC mortality. Our retrospective analysis included a cohort of 150 adult patients with ACC in all stage categories, treated between 1981 and 2022. Tumor hormonal hypersecretion was observed in 78.6% of the patients, and the median age of diagnosis was 40 years. The majority presented as European Network for the Study of Adrenal Tumors (ENSAT) III or IV (22.9% and 31.2%, respectively), and the overall mortality rate was 54.6%. Independent predictors of death were elevated secretion of cortisol (HR = 2.0), androstenedione (HR = 2.2), estradiol (HR = 2.8), 17-OH progesterone (HR = 2.0), and 11-deoxycortisol (HR = 5.1), higher Weiss (HR = 4.3), modified Weiss (HR = 4.4), and Helsinki scores (HR = 12.0), advanced ENSAT stage (HR = 27.1), larger tumor size (HR = 2.7), higher Ki-67 percentage (HR = 2.3), and incomplete surgical resection (HR = 2.5). Mitosis greater than 5/50 high-power field (HR = 5.6), atypical mitosis (HR = 2.3), confluent necrosis (HR = 15.4), venous invasion (HR = 2.8), and capsular invasion (HR = 2.4) were also identified as independent predictors of death. Knowing the risk factors for ACC's mortality may help determine the best treatment option.

Neurosurgical aspects and clinical outcomes on the treatment of Cushing disease in pediatric patients: Case series and literature review.

Background: Cushing disease (CD) is a state of hypercortisolism caused by an adrenocorticotropic hormone-(ACTH) producing pituitary adenoma which rarely occurs in pediatric patients. The outstanding features are weight gain and growth retardation. However, the insidious onset and rarity of the disease in children and adolescents often result in delayed diagnosis. Case Description: We present five patients <14 years of age who underwent neurosurgical treatment for CD at the Department of Neurosurgery of a public referral hospital in Lima, Peru. Age at diagnosis ranged from 5.5 to 12.5 years with a history of disease from 9 months to 3.5 years of moderate to severe stunting and obesity, among other features of Cushing syndrome (CS). Although biochemical tests and cerebral imaging were crucial for the diagnosis, confirmation was made by bilateral petrosal sinuous sampling. Regarding treatment, three patients underwent transcranial surgery, one patient underwent endoscopic transsphenoidal surgery, and one patient underwent microscopic transsphenoidal surgery. None of the patients underwent radiotherapy or pharmacological treatment. Only one patient had a recurrence and achieved remission until an endoscopic transsphenoidal approach was performed. Short- and long-term endocrinologic follow-up is also described in detail. Conclusion: CD is a heterogeneous disorder that requires multidisciplinary diagnosis and management. Transsphenoidal selective adenomectomy is the optimal treatment because of its higher remission rates. However, technical and anatomic aspects should be considered in pediatric patients.

Pneumocystis Exacerbates Inflammation and Mucus Hypersecretion in a Murine, Elastase-Induced-COPD Model.

Inflammation and mucus hypersecretion are frequent pathology features of chronic respiratory diseases such as asthma and COPD. Selected bacteria, viruses and fungi may synergize as co-factors in aggravating disease by activating pathways that are able to induce airway pathology. Pneumocystis infection induces inflammation and mucus hypersecretion in immune competent and compromised humans and animals. This fungus is a frequent colonizer in patients with COPD. Therefore, it becomes essential to identify whether it has a role in aggravating COPD severity. This work used an elastase-induced COPD model to evaluate the role of Pneumocystis in the exacerbation of pathology, including COPD-like lung lesions, inflammation and mucus hypersecretion. Animals infected with Pneumocystis developed increased histology features of COPD, inflammatory cuffs around airways and lung vasculature plus mucus hypersecretion. Pneumocystis induced a synergic increment in levels of inflammation markers (Cxcl2, IL6, IL8 and IL10) and mucins (Muc5ac/Muc5b). Levels of STAT6-dependent transcription factors Gata3, FoxA3 and Spdef were also synergically increased in Pneumocystis infected animals and elastase-induced COPD, while the levels of the mucous cell-hyperplasia transcription factor FoxA2 were decreased compared to the other groups. Results document that Pneumocystis is a co-factor for disease severity in this elastase-induced-COPD model and highlight the relevance of STAT6 pathway in Pneumocystis pathogenesis.

Hipercortisolismo severo e hipocalemia recurrente / Severe hypercortisolism and recurring hypocalemia

RESUMEN El síndrome de Cushing endógeno deriva de un aumento crónico, inapropiado y sostenido de glucocorticoides principalmente como respuesta al exceso en las concentraciones séricas elevadas de la hormona adrenocorticotropa (ACTH) desde un tumor adenohipofisiario, enfermedad de Cushing; o producida de forma ectópica por tumores neuroendocrinos. El Cushing suprarrenal se origina por tumores de la corteza adrenal que producen de forma autónoma cortisol y es independiente de ACTH. El curso clínico, tratamiento, pronóstico y posibles complicaciones dependen de identificar de forma correcta la lesión desencadenante; situación que en múltiples ocasiones resulta en una experiencia retadora para los clínicos. Se presenta el caso de una mujer de 62 años, ingresada por síntomas constitucionales con hipocaliemia severa de difícil corrección e hipercortisolismo severo.

ABSTRACT Endogenous Cushing syndrome derives from a chronic, inappropriate, and sustained increase in glucocorticoids, mainly in response to remarkably high serum concentrations of adrenocorticotropic hormone (ACTH) secreted from an adenohypophyseal tumor, Cushing's disease, or due to ectopic production by neuroendocrine tumors. Adrenal Cushing's disease is caused by tumors of the adrenal cortex that autonomously produce cortisol and this is independent from ACTH action. Clinical course, treatment, prognosis, and possible complications depend on correctly identifying the triggering lesion; this situation frequently becomes a challenging experience for clinicians. We present the case of a 62-year-old woman, admitted for constitutional symptoms with severe hypokalemia that was difficult to correct and severe hypercortisolism.

Diagnostic Power of Bilateral Inferior Petrosal Sinus Sampling with Desmopressin in Paediatric Cushing's Disease

Objective: The aim of this study was to evaluate the diagnostic accuracy of bilateral inferior petrosal sinus sampling (BIPSS) with desmopressin for pediatric Cushing's disease (CD). Methods: We reviewed studies performed in children that evaluated the accuracy of BIPSS with desmopressin. Results: All included studies were case series of children with adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome. The overall accuracy of BIPSS before stimulation was 84.1% (37/44), and after stimulation it was 92.3% (36/39). The overall lateralizing accuracy of BIPSS was 50.0%. Conclusion: Considering that available evidence is limited, it appears that BIPSS with desmopressin stimulation is accurate for the diagnosis of pediatric CD, but its lateralizing accuracy is probably not suitable for pediatric clinical practice.

Sampling of the petrosal sinuses. Indications, results and usefulness / Muestreo de senos petrosos. Indicaciones, resultados y utilidad

Abstract Objectives: to analyze, evaluate and describe the usefulness of petrosal sinus sampling for diagnosing central Cushing's syndrome. Materials and methods: the technical aspects and results of bilateral venous sampling of the petrosal sinuses at the Hospital Universitario San Vicente de Paul in Medellín, Colombia, from January 1, 2012 to December 31, 2018, were analyzed. Results: the average age was 43.3 years, with a range from 19 to 69 years. Laterality could be shown in 68.2% of cases, with a tendency to be located on the left in 53.3%. The central source of ACTH production could be shown in 95.4% of cases, with a basal average central/peripheral ratio of 21.7, and 70.8 after stimulation. All samples at 3, 5 and 10 minutes were confirmatory following stimulation. Conclusion: in our retrospective study, petrosal sinus catheterization provided laboratory confirmation of the central source of ACTH production in a high percentage of patients, with no immediate complications.

Resumen Objetivos: analizar, evaluar y describir la utilidad del muestreo de senos petrosos para diagnóstico del síndrome de Cushing de origen central. Material y métodos: se analizaron los aspectos técnicos y resultados del muestreo bilateral venoso de senos petrosos, desde el 1° de enero de 2012 a 31 de diciembre de 2018 en el Hospital Universitario San Vicente de Paúl en Medellín, Colombia. Resultados: el promedio de edad fue 43.3 años con un rango de edad desde los 19 hasta los 69 años. La lateralidad pudo ser demostrada en 68.2% de los casos con una tendencia a la localización en el lado izquierdo en 53.3%. El origen central de producción de ACTH logró ser demostrado en 95.4% de los casos, con una relación central/periferia basal promedio de 21.7 y postestimulación de 70.8. Todas las muestras a los 3, 5 y 10 minutos fueron confirmatorias tras la estimulación. Conclusión: en nuestro estudio retrospectivo el cateterismo de senos petrosos confirmó la fuente central de producción de ACTH por laboratorio en un alto porcentaje de pacientes sin ninguna complicación inmediata.

Comparative analysis of rhinologic outcomes in Cushing disease and non-functioning pituitary adenoma in patients submitted to endoscopic endonasal transsphenoidal surgery.

PURPOSE: Adrenocorticotropic hormone (ACTH) secreted by pituitary tumors lead to changes in nasal cavity anatomy and physiology. As a consequence of hormonal alteration, there is an abnormal soft tissue and an increased capillary fragility, inducting to a thinner mucosa that acts in the healing process. We compared post-operative nasal alterations in patients with Cushing's disease versus patients with non-functioning macroadenomas who underwent endoscopic endonasal transsphenoidal surgery. METHODS: A retrospective study with 14 patients with Cushing's disease who underwent initial transsphenoidal endonasal surgery for an ACTH-secreting adenoma was conducted. Forty-two patients who underwent the same surgery for non-functioning adenomas were selected as controls. The following data were collected: operative technique, endoscopic alterations in late post-operative period and post-operative nasal complaints. RESULTS: There were 13/14 (92.9%) females with Cushing disease versus 23/42 (54.8%) in the non-functioning adenoma group. Surgical approach was similar in both groups, with no differences in flap usage, turbinectomies or ethmoidectomies. No difference occurred concerning endoscopic alterations or nasal complaints in post-operative period. CONCLUSIONS: Post-operative results are similar, and healing could be expected to be equal.

Long Term Follow-up after Endoscopic Endonasal Approach for the Treatment of Cushing's Disease.

Introduction Surgery has been the standard treatment for Cushing's disease. Currently, the endoscopic endonasal approach (EEA) is the most widely used technique. However, among some endocrinologists and neurosurgeons used to the microscope assisted technique, there are still questions about the effectiveness and safety of transitioning to the EEA. We aim to show our initial experience with such transition. Method Retrospective review of medical records of patients, who underwent EEA in our center as a first treatment for Cushing's disease, and with a minimum 18 months of follow-up, from March 2004 to March 2014 Results Our cohort had 16 patients (14 females and 2 males), with a mean age of 33.7 years. The mean follow-up was 52.0 months. Magnetic resonance imaging (MRI) identified an adenoma in 93.8% of the patients (56.2% microadenomas and 37.5% macroadenomas). Postoperative cerebrospinal fluid (CSF) leak was observed in two patients (12.5%). No new neurological deficits were present after surgery. The early remission and sustained remission rates after a single procedure were 87.5 and 68.75%, respectively. Weight reduction, improved control of blood pressure, and lower serum glucose levels were documented in 68.75, 60, and 55.5% of patients, respectively, after remission. Conclusion Despite the need for specialized training, equipment and team building by ENT (Ear, Nose and Throat) and neurosurgery, the transition from microscope assisted pituitary surgery to endoscopic endonasal approach is possible and safe. The clinical outcomes, even in the early years, are similar to the previous microscope assisted treatment, and over time, with greater experience and knowledge, there is a tendency for improvement.

Remisión espontánea de acromegalia y enfermedad de Cushing en adultos mayores: casos clínicos / Spontaneous remission of acromegaly and Cushing's disease in older patients: report of two cases

Pituitary diseases such as acromegaly and Cushing's disease require surgical or medical therapy. In some functioning pituitary tumors, a spontaneous remission of hormonal hypersecretion is observed, mainly associated to apoplexy or pituitary infarction. We report the evolution of two female patients older than 70 years at the time of diagnosis, with multiple comorbidities. In case 1, acromegaly was diagnosed at 74 years of age. Sellar CT scan showed a 10-mm adenoma. During her follow-up, IGF1 levels remained normal. Nine years later, a magnetic resonance (MR) showed a 7-mm adenoma. In case 2, clinical and biochemical diagnosis of Cushing's disease was done being 71 years old. Sellar MR showed a 6-mm adenoma. Three years later, urinary cortisol normalized with no changes in adenoma at MR. Seven years later, she remains without clinical or biochemical signs of hypercortisolism. In both cases, no signs of hemorrhage were observed at MR.

Encephalitis associated with inappropriate antidiuretic hormone secretion due to chikungunya infection in Recife, State of Pernambuco, Brazil

Abstract The symptoms of chikungunya virus (CHIKV) infection include fever, headache, muscle aches, skin rash, and polyarthralgia, characterized by intense pain, edema, and temporary functional impairment. This is the first report of encephalitis caused by CHIKV infection associated with an atypical presentation of syndrome of inappropriate antidiuretic hormone secretion, evolving to cognitive impairment and apraxia of speech.

Efeitos do cetoconazol e seus mecanismos de ação in vitro sobre linhagens hipofisárias tumorais imortalizadas / Effects of ketoconazole and its mechanisms of action in pituitary tumoral immortalizaded cell lines

O cetoconazol, inicialmente descrito como um agente antifúngico, revelou-se um potente inibidor da esteroidogênese adrenal, podendo, assim, ser utilizado no manejo da doença de Cushing, como terapia primária ou após insucesso cirúrgico, enquanto aguarda o efeito da radioterapia. Durante o tratamento com cetoconazol, uma redução dos níveis de cortisol é observada, usualmente não acompanhada por uma elevação do ACTH plasmático, como poderia ser esperada. Este fenômeno paradoxal, caracterizado pela redução do cortisol com níveis de ACTH inadequadamente normais ou não elevados, pode estar relacionado a uma ação adicional do cetoconazol nas células hipofisárias produtoras de ACTH. Para se testar essa hipótese, alguns estudos in vitro realizados na década de 80, avaliando a secreção de ACTH na vigência do cetoconazol, sugeriram a sua ação em células adenohipofisárias. Em adição, foi evidenciado que o cetoconazol ativou vias de apoptose em linhagens tumorais não hipofisárias. O presente estudo tem como objetivo avaliar o efeito in vitro do cetoconazol na viabilidade celular e na expressão de genes envolvidos na apoptose e replicação do DNA em linhagens tumorais hipofisárias imortalizadas corticotróficas (AtT-20), gonadotróficas (alfaT3.1), mamossomatotróficas (GH3) e mamotróficas (MMQ), utilizando-se a técnica de RT-qPCR. Os resultados mostraram que, na presença do cetoconazol, ocorreu uma redução da viabilidade celular nas linhagens hipofisárias, de forma concentração-dependente, às custas do estímulo da via extrínseca e intrínseca da apoptose, com aumento da expressão dos receptores de morte celular (ex.: Fas, TNFR) e/ou caspases (ex.: -2, -3, -6 ,-7 ,-9). Estes resultados foram associados a um aumento da expressão gênica dos inibidores do ciclo celular p21 (nas linhagens GH3 e alfaT3.1) e p27 (nas linhagens GH3 e MMQ), com uma redução acentuada da expressão destes genes após retirada do cetoconazol do meio de cultura...

Ketoconazole, initially described as an antifungal agent, proved to be a potent inhibitor of steroidogenesis, allowing its use in the management of Cushing's disease as primary or after unsuccessfully surgery and waiting the effect of radiotherapy. During treatment with ketoconazole, there a reduction in the cortisol levels is observed, usually not accompanied by an elevation of plasmatic ACTH, as could be expected. This paradoxical phenomenon, characterized by reduced cortisol with ACTH levels inappropriately normal or not elevated, could be related to an additional action of ketoconazole on ACTH-producing pituitary cells. In agreement with this hypothesis, some in vitro studies in the 80's, evaluating ACTH secretion in the presence of ketoconazole, suggested its action in pituitary cells. In addition, ketoconazole activated apoptosis pathways in non-pituitary tumor cell lines. Therefore, the present study aims to revisit this topic and evaluate the in vitro effect of ketoconazole on cell viability and expression of genes involved in apoptosis and DNA replication by RT-qPCR in immortalized pituitary tumoral corticotroph (AtT-20), gonadotroph (alphaT3.1), mammosomatotroph (GH3), mammotroph (MMQ) cell line. As a result, there was a reduction in pituitary cell viability with ketoconazole, in a concentration-dependent manner, due to stimulation of the extrinsic and intrinsic pathway of apoptosis, with increased expression of cell death receptors (eg. Fas, TNFR) and/or caspases (eg. -2, -3, -6, -7, -9). These results were associated with an increased gene expression of the cell cycle inhibitors p21 (in GH3 and alphaT3.1 cell line), and also p27 (in GH3 and MMQ cell line), with a significant reduction in the expression of these genes after removal of ketoconazole in the media. In conclusion, the ketoconazole have the potential of reduce cell viability in pituitary tumoral lineages possibly due to a cytotoxic effect (by increasing...

Muestreo de senos petrosos inferiores en el diagnóstico de pacientes con síndrome de Cushing dependiente de hormona adrenocorticotrópica / Inferior petrosal sinus sampling in the diagnosis of patients with adrenocorticotropic hormone-dependent Cushing’s syndrome

Resumen: El síndrome de Cushing endógeno es una de las enfermedades más difíciles de estudiar, dado que sus diferentes etiologías requieren una cuidadosa valoración diagnóstica desde el punto de vista clínico, bioquímico y radiológico. Con frecuencia, las características clínicas se solapan con las de enfermedades comunes y algunos pacientes tienen una presentación atípica. Una vez se establece la sospecha clínica, las pruebas bioquímicas de tamizaje permiten definir si existe un estado de hipercor-tisolismo endógeno; en caso afirmativo, el estudio prosigue con pruebas de laboratorio que ayudan a localizar la causa de la hipercortisolemia. En este punto es fundamental determinar si se trata de un síndrome de Cushing dependiente o no dependiente de hormona adrenocorticotrópica (ACTH) y en caso que sea dependiente, diferenciar entre origen hipofisario y un origen ectópico de la enfermedad. Dicha situación se puede resolver mediante el cateterismo y muestreo de los senos petrosos inferiores, el cual es un procedimiento invasivo y sensible para el diagnóstico diferencial entre el tumor hipofisario y el tumor ectópico secretor de ACTH...

Abstract: Endogenous Cushing’s syndrome is one of the most difficult diseases to study. It has different etiologies and requires a careful clinical, biochemical, and radiological diagnosis. Often, its signs and symptoms overlap those of common diseases and some patients have atypical presentations. Once the clinical suspicion is established, screening biochemical tests allow identifying of endogenous hypercortisolism.After identification, it is necessary to use the appropriate diagnostic approach that helps to recognize the source of hypercortisolism. It then becomes imperative to differentiate between an adrenocorticotropic hormone (ACTH)-dependent or ACTH-independent Cushing’s syndrome. In the case of an ACTH-dependent Cushing’s syndrome, one must further distinguish between pituitary and ectopic etiology. This diagnostic challenge can be solved with inferior petrosal sinus sampling, an invasive but sensitive procedure used to discriminate between ACTH-producing pituitary or ectopic ACTH-producing tumors...

Características clínicas y epidemiológicas del síndrome de cushing. Medellín, 1986-2010 / Clinical and epidemiological features of cushing’s syndrome. Medellín, 1986-2010

Introducción: El síndrome de Cushing, aunque poco frecuente, se asocia a una morbimortalidad significativa.En nuestro medio, no se cuenta aún con estudios que reporten las características clínicas y epidemiológicas de esta entidad. Por esta razón, en este estudio se describen los datos recopilados durante 24 años en 30 pacientes con síndrome de Cushing en la ciudad de Medellín, Colombia. Métodos:Estudio descriptivo retrospectivo, donde se evaluó el diagnóstico, tratamiento y desenlaces de pacientes con síndrome de Cushing, atendidos entre mayo de 1986 y enero de 2010 en los servicios de Endocrinología de la Universidad de Antioquia, Hospital Universitario de San Vicente Fundación. Resultados:Se encontraron seis casos de síndrome de Cushing independiente de la hormona adrenocorticotropa (ACTH), cuatro de origen ectópico y 20 de origen hipofisario. En las pruebas bioquímicas, solo hubo diferencias significativas en la prueba de supresión con dosis altas de dexametasona en la enfermedadde Cushing.

Introduction: Although Cushing’s syndrome is an uncommon disease, it is associated with significant morbidity and mortality. Thus far, there are no reports of the clinical and epidemiological characteristicsof this entity in our country. Consequently, this study was conducted to analyze data collected over 24 years in 30 patients with Cushing’s syndrome in the city of Medellin, Colombia. Methods: A retrospective descriptive study was conducted to evaluate the diagnostic approach, treatment and outcomes of patients with Cushing’s syndrome between May, 1986 and January, 2010 in the Endocrinology Service at the University of Antioquia and in the Hospital Universitario San Vicente Fundación. Results: We found six cases of ACTH-independent Cushing’s syndrome, four ectopic tumors and 20 tumors of pituitaryorigin. Regarding biochemical tests, there was statistically significant difference in suppression test with high-dose dexamethasone in Cushing’s disease.

The morphological effects of asthma, as well as conventional and alternative asthma therapies on parietal and chief cells in the stomach of BALB/c Mice / Los efectos morfológicos del asma, así como de las terapias convencionales y alternativas del asma sobre las células parietales y principales en el estómago de ratones Balb/c

Scientific literature, although limited in this area, supports the hypothesis that asthma, by means of selective leukocyte trafficking between the various mucosal and glandular sites of the body, can have the same pathophysiological effects on the stomach as the airways. This study aimed to determine if asthma, in the absence and presence of various asthma therapies (Hydrocortisone and Modul8TM), imparted any morphological alteration on the stomach parietal and chief cells. The BALB/c murine asthmatic mouse model was the model of choice in this study. The asthma induction protocol as well as the asthma therapies were proved to be effective with the aid of bronchial lavage fluid leukocyte quantification. Fundic and pyloric biopsies were extracted at termination and assessed by means of transmission electron, scanning electron and light microscopy. The extracted fundic and pyloric biopsies revealed asthma alone induced parietal cell hypertrophy (increase in parietal cell size P < 0.000100 in both stomach regions) and chief cell hyper functioning. The use of Hydrocortisone and Modul8TM, as a therapy to correct the perceived gastric alterations were dismal; only in the case of fundic parietal cells were both treatments able to compensate for the hypertrophic effect caused by asthma, while in the pylorus parietal cell asthma- induced hypertrophy was only compensated for by Modul8TM.

La literatura científica, aunque limitada en esta área, apoya la hipótesis de que el asma, por medio del tráfico selectivo de leucocitos entre los diferentes sitios y la mucosa glandular del cuerpo, puede tener los mismos efectos fisiopatológicos en el estómago y las vías respiratorias. Este estudio tuvo como objetivo determinar si el asma, en ausencia y presencia de diversos tratamientos para el asma (hidrocortisona y Modul8 TM), generó alguna alteración morfológica en las céluals parietales y principales del estómago. El modelo murino BALB/c del ratón asmático fue el modelo de elección en este estudio. El protocolo de inducción de asma, así como el tratamiento del asma demostró ser eficaz con la ayuda de lavado bronquial y cuantificación leucocitaria del fluido. Biopsias de las regiones fúndica y pilórica fueron extraídas y evaluadas por medio de microscopía electrónica de transmisión, de barrido y de luz. Las biopsias extraídas de la región fúndica y pilórica revelaron que el asma solamente induce hipertrofia de las células parietales (aumento del tamaño de las células parietales P <0,00001 en ambas regiones del estómago) e hiperfuncionamiento de las células principales. El uso de hidrocortisona y Modul8 TM, como una terapia para corregir las alteraciones gástricas fue disimil, sólo en el caso de las células parietales fúndicas ambos tratamientos fueron capaces de compensar el efecto hipertrófico causado por el asma, mientras que en la célula parietal pílorica la hipertrofia inducida por el asma solamente se vio compensada por Modul8TM.

La hipersecreción ácida en la práctica médica: un reto al médico práctico: [revisión] / The acid hypersecretion in the medical practice: a challenge to the general practitioner: [review]

La hipersecreción ácida del estómago ha sido vista en numerosos procesos, incluyendo la úlcera duodenal, el síndrome de Zollinger Ellison, las gastritis asociadas al helicobacter pylori, síndrome pilórico, síndrome del intestino corto, la exclusión antral, la hiperfunción de las células G gástricas, la mástocitosis sistémica, leucemia basofílica, el síndrome carcinoide con toma gástrica, y los tumores pancreáticos no productores de gástrica. La gran mayoría de los estádos hipersecretores gástricos son ideopáticos y como la medición de está secreción no se lleva rutinariamente, el diagnóstico de estos estádos generalmente se pierde.

Gastric acid hypersecretion is seen in several disorders, including duodenal ulcers, Zollinger-Ellison Syndrome (ZES), Helicobacter pylori–associated gastritis, gastric outlet obstruction, short gut syndrome, antral exclusion, gastric G-cell hyperfunction, systemic mastocytosis, basophilic leukemia, gastric carcinoids with carcinoid syndrome, and non–gastrin producing pancreatic tumors. Most incidences of gastric acid hypersecretion are idiopathic. As gastric acid secretion is not routinely measured, the diagnosis of a gastric acid hypersecretory state can often be missed in many cases.