Nariz en silla de montar poscirugía transesfenoidal de hipófisis. Reconstrucción con cartílago costal / Saddle nose after transsphenoidal pituitary surgery. Reconstruction with rib cartilage

Durante los últimos años, la cirugía endoscópica transesfenoidal se ha convertido en el procedimiento quirúrgico de elección para el tratamiento de tumores hipofisarios. La técnica de abordaje actual es el resultado de una evolución histórica de vía por craneotomía a vía endonasal con ingreso a través del seno esfenoidal. Aunque la cirugía de tumores hipofisarios vía transesfenoidal endoscópica ha permitido disminuir las complicaciones graves asociadas a los abordajes externos, no está exenta de complicaciones, como la fístula de líquido cefalorraquídeo. A nivel del abordaje nasal, hay escasas descripciones de complicaciones y el compromiso del cartílago septal con deformidad en silla de montar no es una complicación documentada. Se presenta un caso de rinodeformidad en silla de montar poscirugía transesfenoidal de hipófisis en una paciente de 32 años a quien se le practicó una reconstrucción nasal con cartílago costal autólogo. En nuestra búsqueda bibliográfica es el primer caso registrado en Iberolatinoamérica

In recent years, transsphenoidal endoscopic surgery has become the surgical procedure of choice for the treatment of pituitary tumors. The current approach technique is the result of an historical evolution from craniotomy surgery to an endonasal procedure with entry through the sphenoid sinus. Although endoscopic transsphenoidal surgery has made it possible to reduce serious complications associated with external approaches, it is not without complications, such as cerebrospinal fluid fistula. At the level of the nasal approach, there are few descriptions of complications and involvement of the septal cartilage with saddle deformity is not a documented complication. We present a case of saddle rhinodeformity after transsphenoidal pituitary surgery in a 32-year-old patient who underwent nasal reconstruction with autologous costal cartilage. In our bibliographic search, it is the first case registered in IberoLatin America.

Proteína moduladora de la actividad del receptor de aril hidrocarburos (AIP): genética, bioquímica e impacto clínico / Aryl hydrocarbon receptor interacting protein (AIP): genetics, biochemistry and clinical impact

El gen AIP (proteína moduladora de la actividad del receptor de aril hidrocarburos) se localiza en la región 11q13.2 y codifica para una proteína de 330 aminoácidos que interactúa con el factor de transcripción AhR (receptor para aril hidrocarburos). Las mutaciones en este gen se han asociado con adenomas pituitarios aislados de tipo familiar (APAF). Se caracterizan por una presentación temprana (alrededor de 20 años), por lo regular producen hormona de crecimiento y/o prolactina, tienen un comportamiento clínico agresivo y poca respuesta a análogos de somatostatina.

The AIP gene (aryl hydrocarbon receptor interacting protein) is located on chromosome 11q13.2 and encodes a 330 amino acid protein which interacts with the aryl hydrocarbon receptor (AHR) transcription factor. Mutations in the AIP gene have been associated with familial isolated pituitary adenomas (FIPA). They characterize by an early-onset (around the age of 20 years old) and for being aggressive, growth hormone and/or prolactin-secreting tumors, with poor response to somatostatin analogues.

Hipopituitarismo postraumatismo encefalocraneano: revisión de la literatura y algoritmo de estudio y abordaje terapéutico

Hypopituitarism after moderate or severe traumatic brain injury (TBI) is usually underdiagnosed and therefore undertreated. Its course can be divided in an acute phase during the first 14 days after TBI with 50 to 80% risk of hypopituitarism, and a chronic phase, beginning three months after the event, with a prevalence of hypopituitarism that ranges from 2 to 70%. Its pathophysiology has been addressed in several studies, suggesting that a vascular injury to the pituitary tissue is the most important mechanism during the acute phase, and an autoimmune one during chronic stages. In the acute phase, there are difficulties to correctly interpret pituitary axes. Hence, we propose a simple and cost-effective algorithm to detect and treat a potential hypothalamic-pituitary-adrenal axis impairment and alterations of sodium homeostasis, both of which can be life-threatening. In the chronic phase, post-concussion syndrome is the most important differential diagnosis. Given the high prevalence of hypopituitarism, we suggest that all pituitary axes should be assessed in all patients with moderate to severe TBI, between 3 to 6 months after the event, and then repeated at 12 months after trauma by a specialized team in pituitary disease.

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.

Comparison of a combination test (1 µg ACTH test plus glucagon test) versus 1 µg ACTH test and glucagon test in the evaluation of the hypothalamic-pituitary-adrenal axis in patients with pituitary disorders

ABSTRACT Objective To investigate whether a combination of the low-dose (1 µg) adrenocorticotropin (ACTH) stimulation test and glucagon stimulation test (GST) could overcome the problem of equivocal results with the GST or ACTH test alone in patients with pituitary disorders. Subjects and methods The study included 41 adult patients with pituitary disorders and 20 healthy subjects who underwent evaluation of cortisol response to ACTH, GST, and a combination of both tests. Blood samples for cortisol measurement were obtained at baseline and 30, 60, 90, and 120 minutes after intravenous administration of ACTH 1 μg and 90, 120, 150, 180, 210, and 240 minutes after subcutaneous injection of glucagon 1 mg. The combination test was performed by injecting ACTH 1 µg at the 180-minute time point of the GST, with blood samples for cortisol measurement obtained at 210 and 240 minutes. Results Overall, 28 patients with normal cortisol response to both tests also had a normal cortisol response to the combination test. Ten patients with adrenal insufficiency in both tests also had adrenal insufficiency in the combination test, including a patient who had a peak cortisol value of 12.4 µg/dL (which is the cutoff value for the combination test). Two patients with adrenal insufficiency in the ACTH stimulation test and one patient with adrenal insufficiency in the GST had normal cortisol responses to the combination test. Conclusion By using an appropriate cutoff value, the combination test may offer additional information in patients with equivocal results in the GST and ACTH stimulation test.

Hipofisitis linfocitaria primaria. Caso clínico / Primary lymphocytic hypophysitis. Report of one case

Primary lymphocytic hypophysitis is an autoimmune disease characterized by lymphocytic infiltration of the pituitary gland, with a higher incidence during late pregnancy and the postpartum period. It causes glandular destruction, mass effect and symptoms such headache, visual field defects, ophthalmoplegia and symptoms of hypopituitarism. We report a 38-year-old postpartum woman who, after giving birth presented decreased left visual acuity associated with a non ictal headache. Magnetic resonance imaging demonstrated a sellar mass associated with decreased free thyroxine and cortisol levels. Suspecting a primary lymphocytic hypophysitis, she was treated with prednisone 60 mg/day and hormonal replacement therapy. One month later, size of the pituitary gland decreased, and the visual field defect improved. Steroidal treatment was maintained for 36 months and progressively tapered. After two years of follow-up, the imaging studies show a normal sized pituitary gland.

Quiste de la bolsa de Rathke / Rathke pouch cyst

Es una lesión quística que surge del remanente epitelial de la bolsa de Rathke, casi siempre su diagnóstico es un hallazgo incidental ya que en la mayoría de los casos es asintomático. Cuando se manifiesta se debe a que ha aumentado lo suficiente su volumen hasta comprimir estructuras vecinas causando cefalea, alteraciones visuales y disfunción pituitaria. En su mayoría ocurre en adultos entre la cuarta y quinta década de vida. Presentamos el caso de una paciente femenina de 9 años de edad que consultó por talla baja al servicio de endocrinología, por lo cual se inició tratamiento con hormona de crecimiento y se solicitó una resonancia magnética nuclear (RMN) la cual reportó quiste de la bolsa de Rathke versus adenoma hipofisario.

Rathke pouch cysts are epithelium-lined cysts arising from the embryological remnants of Rathke ́s pouch. They are usually incidentally identified since the majority are asymptomatic. They become symptomatic when they enlarge enough to compress neighbor structures causing headache, visual disturbances and pituitary dysfunction. They occur mostly in adults in the fourth to fifth decades of life. A case is presented in a 9-year-old female patient who consulted for growth retardation to the endocrinology service. She was treated with growth hormone and a magnetic resonance imaging (MRI) scan reported Rathke ́s pouch cyst versus pituitary adenoma.

Quiste de la bolsa de Rathke / Rathke pouch cyst

Es una lesión quística que surge del remanente epitelial de la bolsa de Rathke, casi siempre su diagnóstico es un hallazgo incidental ya que en la mayoría de los casos es asintomático. Cuando se manifiesta se debe a que ha aumentado lo suficiente su volumen hasta comprimir estructuras vecinas causando cefalea, alteraciones visuales y disfunción pituitaria. En su mayoría ocurre en adultos entre la cuarta y quinta década de vida. Presentamos el caso de una paciente femenina de 9 años de edad que consultó por talla baja al servicio de endocrinología, por lo cual se inició tratamiento con hormona de crecimiento y se solicitó una resonancia magnética nuclear (RMN) la cual reportó quiste de la bolsa de Rathke versus adenoma hipofisario.

Rathke pouch cysts are epithelium-lined cysts arising from the embryological remnants of Rathke ́s pouch. They are usually incidentally identified since the majority are asymptomatic. They become symptomatic when they enlarge enough to compress neighbor structures causing headache, visual disturbances and pituitary dysfunction. They occur mostly in adults in the fourth to fifth decades of life. A case is presented in a 9-year-old female patient who consulted for growth retardation to the endocrinology service. She was treated with growth hormone and a magnetic resonance imaging (MRI) scan reported Rathke ́s pouch cyst versus pituitary adenoma.

Lista de chequeo preoperatorio para la cirugía endoscópica de hipófisis / Preoperative checklist for endoscopic pituitary surgery

Introducción: las listas de chequeo son herramientas que buscan evitar errores y complicaciones al momento de realizar un procedimiento. El adenoma hipofisiario es la primera causa de cirugía endoscópica transnasal de la región selar, y se estima que ocurren hasta un 20 % de complicaciones derivadas de esta cirugía. Objetivo: desarrollar una lista de chequeo preoperatoria que sirva como una guía para la evaluación prequirúrgica de los pacientes a quienes se les realicen cirugías de la región selar. Metodología: se realizó una revisión de la literatura para desarrollar una lista de chequeo preliminar y una serie de declaraciones que resumían los puntos importantes de la lista. Se construyó un comité de expertos en cirugía endoscópica de la base de cráneo conformado por neurocirujanos y otorrinolaringólogos de hospitales de Bogotá. Utilizando la metodología Delphi modificada, se llegó a un consenso para la realización de la lista de chequeo final. Resultados: se describieron 15 declaraciones; de estas, hubo una discrepancia en 6 declaraciones. Por esta razón, se realizaron modificaciones en 5 declaraciones, y se llegó a un consenso entre los expertos participantes. La lista de chequeo final aprobada está compuesta por 4 ítems. Discusión/conclusiones: la cirugía para el manejo de la patología de la región selar es compleja y requiere de un equipo quirúrgico entrenado y disciplinado para lograr los mejores desenlaces posibles. Consideramos que nuestra lista de chequeo es una herramienta que permitirá a los equipos que realizan estas cirugías en Colombia tener una visión más completa del paciente y, eventualmente, ayudar a evitar errores y posibles complicaciones.

Introduction: checklists that seek to avoid errors are very useful tools for any surgical practice. Pituitary adenomas are the leading indication to perform a transnasal endoscopic surgery in the sellar region and up to 20 % complications have been reported related to this procedure. Objetive: develop a preoperative checklist, based on an expert consensus, to serve as a guide for the skull base teams to consistently evaluate preoperatively all patients with pathologies in the sellar region. Methods: a literature review was conducted to develop a preliminary checklist and a series of statements summarizing the most important items on the list. A committee of experts in endoscopic skull base surgery was summoned, made up of neurosurgeons and otolaryngologists from hospitals in Bogotá. Using the modified Delphi methodology, a consensus was reached for the completion of the final checklist. Results: fifteen statements were developed. A discrepancy was seen in six statements. Modifications were made for five statements, thus reaching a consensus among the participating experts. The final approved checklist is made up of 4 items. Conclusion: surgery for treating different pathologies in the sellar region is complex and requires a welltrained and disciplined surgical team to achieve the best possible outcomes. We consider that our preoperative checklist is a valuable resource for skull base surgical teams performing transnasal endoscopic surgery of the sellar region. This tool will allow skull base surgical teams in Colombia to have a more comprehensive view of the patient and eventually help to avoid errors and possible complications.

Síndromes de neoplasia endocrina múltiple: revisión radiológica / Multiple Endocrine Neoplasia Syndromes: Radiological Review

Los síndromes de neoplasia endocrina múltiple (MEN), incluyen una serie de enfermedades con alteraciones genéticas que se caracterizan por la presencia de tumores que afectan a dos o más glándulas endocrinas. Son síndromes con una herencia autosómica dominante e incluyen tres patrones: MEN 1 (síndrome de Wermer), MEN 2 (que incluye MEN 2A o síndrome de Sipple y MEN 2B o síndrome de Wagenmann-Froboese) y MEN 4. Los adenomas paratiroideos y el carcinoma medular tiroideo, son los tumores más frecuentes del MEN tipo 1 y 2 respectivamente. Esos síndromes son más comunes en pacientes jóvenes, con patología de afectación bilateral, múltiple o multifocal y, sobre todo, en pacientes con antecedentes familiares. Es necesario el trabajo en equipo de endocrinólogos, cirujanos, oncólogos y radiólogos para optimizar el tratamiento de esos pacientes.

Multiple endocrine neoplasia (MEN) encompasses a serial of familial genetically disorders in wich tumors simultaneusly occur in two or more endocrine organs. MEN síndromes are autosomal-dominant disorders categorized into three main patterns: MEN 1 (Wermer syndrome), MEN 2 (includes MEN 2A o Sipple syndrome and MEN 2B o Wagenmann-Froboese syndrome) and MEN 4. Parathyroid adenomas and medullary thyroid carcinoma are the most frecuent tumors in MEN 1 and MEN 2 respectively. These entities will be suspected in younger patients, bilateral, multiple or multifocal disease and, specially, in patients with family background. Cooperation between endocrinologist, surgeons, oncologists and radiologists is pivotal for optimizing patient treatment.

Infundibuloneurohipofisitis: caso clínico y revisión de la literatura / Infundibuloneurohypophysitis: clinical report and literature review

Infundibuloneurohypophysitis is a rare condition, which is part of the group of hypophysitis, of relatively recent description (1993). The main clinical manifestation is diabetes insipidus, whose natural evolution is towards chronicity. The differential diagnosis with other thickening of the hypophysial stem is very important, where the clinic, imaging, laboratory and eventually biopsy are a main support for a correct diagnosis. We present a clinical case that shows the usual picture of infundibuloneurohypophysitis, and illustrates the imaging evolution in a female patient, with diabetes insipidus as the main clinical manifestation

Histopathological features of post-mortem pituitaries: A retrospective analysis / Características histopatológicas de hipófises post mortem: análise retrospectiva

SUMMARY Objective: As a result of the use of neuroimaging techniques, silent pituitary lesions are diagnosed more and more frequently; however, there are few published post-mortem studies about this gland. Incidence data of pituitary lesions are rare and in Portugal they are outdated or even non-existent. The aim of this study is to determine the prevalence of normal patterns and incidental post-mortem pituitary pathology at Centro Hospitalar Lisboa Norte, analyzing the associations with clinical data and assessing the clinical relevance of the findings. Method: We reviewed retrospectively and histologically 167 pituitaries of a consecutive series of autopsies from the Department of Pathology of this centre. They were done between 2012 and 2014, and in all cases medical records were reviewed. The morphological patterns observed, were classified into three major groups: 1) Normal histological patterns and variants; 2) Infectious-inflammatory pathology, metabolic and vascular disorders; 3) Incidental primary proliferation and secondary to systemic diseases. Results: The subjects included in this study were of all age groups (from 1 day to 91 years old), 71 were female and 96 male. Fifty-seven of these glands didn’t show any alteration; 51 showed colloid cysts arising from Rathke cleft; 44 presented hyperplasia in adenohypophysis and we identified 20 adenomas in 19 glands (immunohistochemically, eight PRL-producing and five ACTH-producing tumors), ten of which associated with obesity, 11 to hypertension and six to diabetes mellitus. There were two cases with metastasis. Conclusion: Subclinical pathology in our country is similar to that seen in other parts of the world, but at older ages.

RESUMO Objetivo: como resultado da utilização de técnicas de neuroimagem, cada vez se diagnosticam mais lesões hipofisárias silentes; porém, há poucos estudos post mortem publicados sobre essa glândula. Os dados de incidência existentes sobre lesões hipofisárias são raros, sendo em Portugal desatualizados ou inexistentes. O objetivo é determinar a prevalência dos padrões normais e da patologia hipofisária incidental post mortem no Centro Hospitalar Lisboa Norte, analisando as associações com dados clínicos e avaliando a relevância clínica dos achados. Método: revisaram-se histologicamente de forma retrospectiva 167 hipófises de uma série consecutiva de autópsias do Serviço de Anatomia Patológica desse centro, realizadas entre 2012 e 2014, sendo revisadas em todos os casos as histórias clínicas. Os padrões morfológicos observados classificaram-se em três grandes grupos: 1) padrões histológicos de normalidade e variantes; 2) patologia infeccioso-inflamatória, distúrbios metabólicos e transtornos vasculares; 3) proliferação primária incidental e secundária a doenças sistêmicas. Resultados: os doentes incluíam todas as faixas etárias (de 1 dia a 91 anos), sendo 71 do sexo feminino e 96 do masculino. Cinquenta e sete das glândulas não apresentaram qualquer alteração; 51 mostraram cistos coloides derivados da fissura de Rathke; em 44, observou-se hiperplasia da adeno-hipófise e identificaram-se 20 adenomas em 19 glândulas (oito imuno-histoquimicamente produtores de PRL e cinco de ACTH), dos quais dez associados à obesidade, 11 à hipertensão arterial e seis a diabetes mellitus. Houve dois casos com metástases. Conclusão: a patologia subclínica em nosso meio é similar à observada em outras partes do mundo, mas em idades mais avançadas.

Absceso hipofisiario como causa de meningitis crónica / Pituitary abscess as cause of chronicle meningitis

Se presenta el caso clínico de una paciente con un cuadro de Meningitis crónica recurrente en que el diagnóstico de absceso selar sólo se logró al operarla con el diagnóstico de Adenoma Hipofisiario. Siendo el absceso hipofisiario una patología de muy baja frecuencia, la presencia de una Meningitis crónica recurrente como forma de presentación es aún más infrecuente. La literatura en general presenta muy pocas series de abscesos hipofisiarios, siendo la mayoría sólo comunicaciones de casos clínicos.

We present the case of a patient with a history of Recurrent Chronic Meningitis, in which the diagnosis of Pituitary abscess was only made after surgery under the diagnosis of Pituitary Adenoma. Given the low frequency of the Pituitary Abscess, the presence of a Recurrent Chronic Meningitis as its presentation is even more infrequent. The common literature presents only a few series of pituitary abscess, which, in most cases, are only case reports.

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...

Reappraisal of serum insulin-like growth factor-I (IGF-1) measurement in the detection of isolated and combined growth hormone deficiency (GHD) during the transition period / Reavaliação da dosagem sérica do fator de crescimento insulina-símile-1 (IGF-1) para o diagnóstico da deficiência isolada e combinada de hormônio de crescimento no período de transição

OBJECTIVE: To evaluate the accuracy of serum IGF-1 in the detection of isolated (IGHD) or combined growth hormone deficiency (CGHD) at the transition phase. SUBJECTS AND METHODS: Forty nine patients with GHD during childhood [16 with IGHD (10 men) and 33 with CGHD (24 men); age 23.2 ± 3.5 yrs.] were submitted to an insulin tolerance test (ITT) with a GH peak < 5 µg/L used for the diagnosis of GHD at the transition phase. Pituitary function and IGF-1 measurements were evaluated in the basal sample of the ITT. Transition patients were reclassified as GH-sufficient (SGH; n = 12), IGHD (n = 7), or CGHD (n = 30). RESULTS: Five (31%) patients with IGHD and 32 (97%) with CGHD at childhood persisted with GHD at retesting. One patient with IGHD was reclassified as CGHD, whereas 3 patients with CGHD were reclassified as IGHD. Mean GH peak was 0.2 ± 0.3 µg/L in the CGHD, 1.3 ± 1.5 µg/L in the IGHD, and 18.1 ± 13.1 µg/L in the SGH group. Serum IGF-1 level was significantly higher in the SGH (272 ± 107 ng/mL) compared to IGHD (100.2 ± 110) and CGHD (48.7 ± 32.8) (p < 0.01). All patients reclassified as CGHD, 86% reclassified as IGHD, and 8.3% reclassified as SGH had low IGF-1 level, resulting in 97.3% sensitivity and 91.6% specificity in the detection of GHD at the transition period; the cutoff value of 110 ng/mL showed 94.5% sensitivity and 100% specificity. Mean IGF-1 values did not differ in IGHD or CGHD associated with one, two, three, or four additional pituitary deficiencies. CONCLUSION: IGF-1 measurement is accurate to replace ITT as initial diagnostic test for IGHD and CGHD detection at the transition phase.

OBJETIVO: Avaliar a acurácia da dosagem sérica de IGF-1 no diagnóstico da deficiência de hormônio de crescimento isolada (DGHI) ou combinada (DGHC) na fase de transição. SUJEITOS E MÉTODOS: Quarenta e nove pacientes com DGH na infância [16 DGHI (10 homens) e 33 DGHC (24 homens); idade 23,2 ± 3,5 anos] realizaram teste de tolerância à insulina (TTI), com pico de GH < 5 µg/L considerado diagnóstico de DGH na transição. Função hipofisária e níveis de IGF-1 foram determinados na amostra basal do TTI e os pacientes foram reclassificados em GH suficientes (SGH; n = 12), DGHI (n = 7) ou DGHC (n = 30). RESULTADOS: Cinco (31%) pacientes com DGHI e 32 (97%) com DGHC na infância persistiram com DGH no reteste. Um paciente com DGHI foi reclassificado como DGHC e três com DGHC como DGHI. Os picos médios de GH foram 0,2 ± 0,3 µg/L (DGHC), 1,3 ± 1,5 µg/L (DGHI) e 18,1 ± 13,1 µg/L (SGH). O nível médio de IGF-1 foi maior no grupo SGH (272 ± 107 ng/mL) comparado com DGHI (100,2 ± 110) e DGHC (48,7 ± 32,8) (p < 0,01). IGF-1 baixo foi observado em todos os pacientes reclassificados como DGHC, 86% dos DGHI e 8,3% dos SGH, resultando em sensibilidade de 97,3% e especificidade de 91,6% para detecção de DGH na transição; valor de corte de 110 ng/mL mostrou 94,5% sensibilidade e 100% especificidade. O nível médio de IGF-1 foi similar nos pacientes com DGHI ou DGHC com uma, duas, três ou quatro deficiências hipofisárias associadas. CONCLUSÃO: A dosagem sérica de IGF-1 mostrou-se acurada para substituir o TTI na detecção tanto de DGHI como DGHC na transição.

Alterações neuroendócrinas em pacientes com traumatismo cranioencefálico / Neuroendocrine disorders in traumatic brain injury patients

O traumatismo cranioencefálico (TCE) corresponde a uma das principais causas de morte em adultos jovens. Alguns pacientes com TCE podem ser vítimas de várias alterações hormonais decorrentes do trauma. Algumas são facilmente reconhecíveis, como diabetes insipidus, enquanto outras podem passar despercebidas inicialmente, como a deficiência do hormônio do crescimento (GH). As alterações neuroendócrinas após a ocorrência de trauma podem cursar com deficiências da hipófise anterior, da posterior ou de ambas, acometer apenas um eixo hormonal ou vários e, ainda, ser transitórias ou permanentes. A grande maioria dos pacientes que apresentam disfunção neuroendócrina foi vítima de traumas considerados moderados ou graves pela escala de Glasgow. No entanto, a maioria dos estudos não evidenciou relação entre a gravidade da lesão e a ocorrência de alteração hipofisária pósTCE. As deficiências hipofisárias devem ser tratadas precocemente, uma vez que déficits hormonais hipofisários dificultam a recuperação dos pacientes traumatizados, constituindo-se em fator de pior prognóstico. Apesar da frequência com que ocorrem os TCE, existem poucos estudos a respeito das complicações neuroendócrinas decorrentes...

Traumatic brain injury (TBI) is one of the main causes of death in young adults. Some cases of TBI could lead to the development of easily recognizable diabetes insipidus. In other cases it can lead to alterations in the endocrine axis that are more difficult to notice at the beginning and that can occur together with other hormone deficiencies. The majority of patients with neuroendrocrine dysfunction were TBI victims with a Glasgow Coma Scale scores of 3-13 (moderate and severe trauma). However, previous studies did not show correlationships between the severity of injury and pan-hypopituitarism after TBI. The pituitary disorders have to be treated as soon as possible because it makes the recovery of TBI patients more difficult and lead to a worse prognosis. Despite the number of studies about TBI, actually there are only a few studies concerning the secondary neuroendocrine complications...