Changes of miRNA-138 and miRNA-26b before and after transsphenoidal surgery for pituitary tumors and their clinical significance / 中华内分泌外科杂志

Objective:To explore and analyze the changes of miRNA-138 and miRNA-26b before and after transsphenoidal surgery for pituitary tumors and their clinical significance.Methods:86 patients with functional pituitary tumors who underwent transsphenoidal surgery in Linyi People’s Hospital from Apr. 2020 to Apr. 2021 were retrospectively analyzed. The recurrence within 1 year after operation was followed up and the patients were divided into unrecovered group (24 cases) and cured group (62 cases) . Clinical data such as age, gender, tumor pathological type, Knosp grade, first operation, tumor diameter, intraoperative tumor residue, Ki-67 and adjuvant therapy were collected. Fasting venous blood was collected before surgery and the next morning after surgery. Quantitative real-time PCR was used to detect the serum levels of mircoRNA-138 (miRNA-138) and miRNA-26b (mirNA-26B) , and the changes of serum miRNA-138 and miRNA-26b levels before and after surgery. Univariate and multivariate logistic regression were used to analyze the relationship between serum miRNA-138 and miRNA-26b levels and postoperative prognosis, and ROC curve was drawn to analyze their predictive value for postoperative prognosis.Results:Univariate analysis showed that Knosp grade, tumor diameter, intraoperative tumor residual, Ki-67, and adjuvant therapy were associated with the recurrence of body tumor after transsphenoidal surgery ( P<0.05) . After operation, the expression of miRNA-138 in serum was higher than that before operation, and the expression of miRNA-138 in unhealed group (4.13±1.12) was higher than that in cured group (3.56±0.84) ( P<0.05) . The expression of miRNA-26b in serum after operation was lower than that before operation, and the expression of miRNA-26b in the unhealed group (2.34±0.62) was lower than that in the cured group (2.75±0.58) ( P<0.05) . Pituitary tumor hormone increased before operation and returned to normal after operation. Multivariate logistic regression analysis showed that tumor diameter ≥40cm (OR=3.476, 95%CI: 1.267-9.539) , postoperative tumor residual (OR=3.155, 95%CI: 1.236-8.052) , Ki-67≥3% (OR=3.885, 95%CI: 2.038-7.403) , postoperative serum miRNA-138 expression ≤3.62 (OR=2.323, 95%CI: 1.536-3.513) , postoperative serum miRNA-26b expression ≥2.59 (OR0.453, 95 %CI: 0.286-0.717) was an independent risk factor for the recurrence of pituitary tumors after transsphenoidal surgery ( P<0.05) . When the optimal cut-off value of serum miRNA-138 was 3.62, the area under the curve for predicting the recurrence of pituitary tumors after transsphenoidal surgery was 0.78, the sensitivity was 81.35%, and the specificity was 71.46%; the optimal cut-off value of serum miRNA-26b When it was 2.59, the area under the curve for predicting and predicting the recurrence of pituitary tumors after transsphenoidal surgery was 0.75, at this time, the sensitivity was 78.62%, and the specificity was 72.33%. The lower area was 0.83, the sensitivity was 85.47%, and the specificity was 72.38%. Conclusion:The expression of serum miRNA-138 was up-regulated and the expression of miRNA-26b was down-regulated after transsphenoidal surgery for pituitary tumors, and its abnormal expression was associated with postoperative recurrence, which has a good predictive value for predicting postoperative recurrence.

Acromegaly: a rare disease?

Acromegaly is generally considered a benign and uncommon disease. However, some recent data bring support to the idea that it is more frequent than previously thought. Besides, acromegaly can significantly shorten the length of life due to its cardiovascular and metabolic complications. Since its clinical signs are insidiously progressive for many years, there is a considerable delay in its detection. Usually, many different specialists have been consulted before reaching diagnosis of acromegaly. Those specialists include cardiologists, pulmonologists, dentists, rheumatologists, and diabetes specialists. Possible means to achieve earlier detection are based on increasing awareness of doctors and the public in general. In this paper, the author analyzes the factors related to delayed diagnosis and the potential ways to ameliorate awareness of the disease with particular attention to screening procedures.

Existe la idea generalizada de que la acromegalia es una enfermedad benigna e infrecuente. Sin embargo, el paciente acromegálico ve comprometida su vida a causa de complicaciones cardiovasculares y metabólicas. Por otra parte, trabajos recientes muestran que su frecuencia parece mucho mayor que lo supuesto previamente. Dado que los signos y síntomas de la enfermedad se instalan lenta e insidiosamente, existe una demora considerable en su diagnóstico. Habitualmente, los pacientes han consultado diversos especialistas antes de que el trastorno sea detectado. Los mismos incluyen cardiólogos, neumonólogos, odontólogos, reumatólogos y diabetólogos. Un camino posible para lograr una detección temprana es el incremento del grado de concientización de los médicos y de la comunidad. En este artículo se analizan los factores vinculados al retraso diagnóstico y los medios posibles para mejorar el conocimiento y detección precoz de la enfermedad.

Recent Progress in the Medical Therapy of Pituitary Tumors

Management of pituitary tumors is multidisciplinary, with medical therapy playing an increasingly important role. With the exception of prolactin-secreting tumors, surgery is still considered the first-line treatment for the majority of pituitary adenomas. However, medical/pharmacological therapy plays an important role in controlling hormone-producing pituitary adenomas, especially for patients with acromegaly and Cushing disease (CD). In the case of non-functioning pituitary adenomas (NFAs), pharmacological therapy plays a minor role, the main objective of which is to reduce tumor growth, but this role requires further studies. For pituitary carcinomas and atypical adenomas, medical therapy, including chemotherapy, acts as an adjuvant to surgery and radiation therapy, which is often required to control these aggressive tumors. In the last decade, knowledge about the pathophysiological mechanisms of various pituitary adenomas has increased, thus novel medical therapies that target specific pathways implicated in tumor synthesis and hormonal over secretion are now available. Advancement in patient selection and determination of prognostic factors has also helped to individualize therapy for patients with pituitary tumors. Improvements in biochemical and “tumor mass” disease control can positively affect patient quality of life, comorbidities and overall survival. In this review, the medical armamentarium for treating CD, acromegaly, prolactinomas, NFA, and carcinomas/aggressive atypical adenomas will be presented. Pharmacological therapies, including doses, mode of administration, efficacy, adverse effects, and use in special circumstances are provided. Medical therapies currently under clinical investigation are also briefly discussed.

Endoscopic Endonasal Transsphenoidal Pituitary Tumors Approach: Nuances of Neurosurgical Technique / Abordagem endoscópica endonasal transesfenoidal para tumores hipofisários: detalhes da técnica neurocirúrgica

Pituitary tumors are responsible for 7 to 17% of all intracranial lesions. Over the past decade, advances in endoscopic microsurgical techniques have resulted in an increasingly aggressive endonasal approach to tumors of the midline skull base. We present our series emphasizing technical nuances of endoscopic endonasal transsphenoidal approach to treat pituitary adenomas.

Tumores hipofisários são responsáveis por 7 a 17% de todas as lesões intracranianas. Durante a última década, avanços nas técnicas microcirúrgicas endoscópicas resultaram no aumento de acessos endonasais agressivos para tumores de base de crânio de linha média. Apresentamos nossa série de casos, com ênfase nos detalhes técnicos do acesso endoscópico endonasal transesfenoidal para o tratamento de tumores da hipófise.

Análisis de un registro de adenomas pituitarios / Analysis of a pituitary adenoma registry

Dada la complejidad que reviste el enfoque diagnóstico y terapéutico de los tumores pituitarios, el registro y análisis de la experiencia clínica acumulada es de gran ayuda en la toma de decisiones. En este trabajo se informan datos clínico-terapéuticos, extraídos de un registro computarizado, sobre 519 de un total de 670 pacientes con adenomas pituitarios. Trescientos cuarenta y cinco fueron mujeres (66%) y 174 varones (34%), de 14 a 80 años de edad. El diagnóstico final fue: acromegalia en 176, enfermedad de Cushing en 153, prolactinoma en 101 y adenoma clínicamente no-funcionante (ANF) en 89. La edad media al momento del diagnóstico de acromegalia fue 43.9 ± 13.5 (16-80), para enfermedad de Cushing 35.7 ± 12.9 (14-72), para prolactinomas 30.0 ± 13.4 (15-79) y para ANF 52.1 ± 15.2 (17-79) años. La creación de un registro institucional de tumores de hipófisis es un instrumento de gran utilidad para el análisis de la experiencia adquirida y constituye una herramienta valiosa para mejorar la estrategia terapéutica, optimizar la relación costo/beneficio y mejorar el cuidado del paciente. Contribuye a la docencia médica, tanto en el pre como en el posgrado y da base a la realización de trabajos de investigación clínica, aportando a la difusión y transferencia de conocimientos.

Collection and analysis of data obtained during the clinical treatment of pituitary tumours are of great utility in the decision making process, when facing clinical situations. We report here data on 519 from 670 patients with pituitary adenomas obtained from a computerized registry. Three hundred and forty five were females (66%) and 174 males (34%), aged 14-80. Final diagnosis was acromegaly in 176, Cushing's disease in 153, prolactinoma in 101 and clinically non-functioning adenoma in 89. Mean age at diagnosis was 43.9 ± 13.5 (16-80) for acromegalics, 35.7 ± 12.9 (14-72) for Cushing's, 30.0 ± 13.4 (15-79) for prolactinoma and 52.1 ± 15.2 (17-79), for non-functioning tumours. The setup of an institutional registry on pituitary tumours constitutes a useful tool to analyze clinical experience, optimize the cost/benefit ratio of procedures used for diagnosis and to ameliorate therapeutic strategies, improving patient's care. It greatly contributes to teaching medical students as well as to post-graduate physicians and provides a basis for developing clinical research.

Evolución del tratamiento neuroquirúrgico de la patología hipofisaria: Experiencia de 800 casos

Los tumores de hipófisis son las neoplasias intracraneales más frecuentes (10 %-15 %). El propósito del trabajo es presentar la experiencia del autor en el manejo neuroquirúrgico de 800 casos de tumores pituitarios, basado en el protocolo de estudio aplicado en las Unidades de Hipófisis de los Hospitales “Miguel Pérez Carreño” y Universitario de Caracas, y en el ejercicio privado del autor. Utilizando inicialmente abordaje trans-craneano y luego abordaje trans-esfenoidal en la mayoría de los casos.Se presentan los hallazgos más frecuentes del material de casos tratados y los procedimientos diagnósticos utilizados, resaltando el uso de resonancia magnética y angiografía cerebral. Se analizan los abordajes trans-craneano y trans-esfenoidal. Se enfatiza la ventaja de la microcirugía trans-esfenoidal y las mejoras introducidas en la técnica quirúrgica y el uso de neuro-endoscopia. Se argumenta la importancia del manejo inter-disciplinario. Estas experiencias permitieron reducir la morbi-mortalidad al acortar el tiempo quirúrgico y hacer el posoperatorio más benigno. Esto se tradujo en una reincorporación más temprana del paciente a su vida normal, mejor calidad de vida y mejor pronóstico.

Pituitary tumors are among the most common intracranial neoplasias (10 % to 15 %). The purpose of this study is to present the author’s experience in the surgical management of 800 pituitary tumors based on the study protocols applied in the Pituitary Units of the Miguel Pérez Carreño Hospital and University Hospital, and in the author’s private practice. The most frecuent findings and diagnostic techniques are presented, highlighting the role of magnetic resonance and cerebral angiography. Trans-sphenoidal and trans-cranial surgical techniques are analyzed. The advantage of the trans-sphenoidal technique, the improvements made to the surgical technique, and the use of neuro-endoscopy are presented. The importance of a multi-specialty team is stressed. This experience allowed to reduce the associated morbidity and mortality by shortening surgical time and improving recovery, quality of life, and prognosis.

Tumores hipofisários secretores de TSH: relato de dois casos e revisão da literatura / TSH-secreting pituitary tumors: two case reports and literature review

INTRODUÇÃO: Tumores hipofisários secretores de hormônio estimulante da tireoide (TSH), tireotropinomas, são raros e correspondem a menos de 2 por cento de todos os adenomas da hipófise. Manifestam-se clinicamente com sintomas e sinais de tireotoxicose, eventualmente associados a sintomas compressivos, sobretudo visuais, devido ao efeito de massa do tumor. Esses tumores se caracterizam pela presença de níveis séricos elevados de hormônios tireoidianos e níveis séricos elevados, ou inapropriadamente normais, de TSH. Frequentemente, ao diagnóstico, há relato de tratamento prévio cirúrgico, medicamentoso e/ou ablativo, por hipótese de hipertireoidismo primário por doença de Graves. OBJETIVO: Relatar dois casos de tireotropinomas acompanhados na Unidade de Neuroendocrinologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) e revisar a literatura visando ao manejo desta afecção. CONCLUSÃO: Na presença de hormônios tireoidianos elevados e níveis de TSH inapropriadamente normais ou elevados, a possibilidade de adenoma hipofisário produtor de TSH deve ser considerada com vistas à realização da terapia adequada.

INTRODUCTION: TSH-secreting pituitary adenomas are rare pituitary functioning tumors accounting for less than 2 percent of the pituitary adenomas. The clinical feature consists of thyrotoxicosis occasionally associated to tumoral symptoms due to mass effect. The biochemical feature consists of elevated thyroid hormones levels and normal or high TSH concentrations. This disease is often wrongly diagnosed as Grave's disease, and the ablative therapy is frequently conducted prior to the diagnosis. OBJECTIVE: To report two cases followed in the Neuroendocrine Unit of Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo and to review the literature aiming at the management of this affection. CONCLUSION: In the presence of elevated thyroid hormone levels associated with inappropriate normal or increased TSH levels, the possibility of a TSH-secreting pituitary adenoma should be considered for the proper medical treatment.

Gonadotrofinomas: análisis multicéntrico y retrospectivo de 66 pacientes / Gonadotrophinomas: multicenter and retrospective analysis of 66 patients

Objetivo: Analizar la presentación clínica, radiológica, bioquímica y el comportamiento posquirúrgico de una cohorte de pacientes portadores de gonadotrofinomas. Pacientes y Métodos: Se evaluaron pacientes con gonadotrofinomas estudiados en nueve centros endocrinológicos de la ciudad de Bs.As. durante el período 1983 a 2003. El criterio de inclusión fue la inmunohistoquímica (IH) positiva para hormona luteinizante (LH), folículoestimulante (FSH) y/o alfa subunidad (ASU). Los adenomas plurihormonales fueron excluidos. Resultados: Fueron analizados 66 pacientes de 51,8 ± 12,1 (X +/- DS) años (39 varones). Los síntomas mas frecuentemente observados fueron las alteraciones visuales (72,8%), seguidas por el hipogonadismo y las cefaleas. El 10,6% se diagnosticaron en forma incidental. El 98,5% fueron macroadenomas, 56,9% de los cuales correspondieron a un estadio Hardy (EH) 3 y 29,6% a un EH 4. El tiempo de seguimiento fue de 47,8 meses (r: 5-168). El hipogonadismo definido bioquímicamente se presentó en el 82,4% de los pacientes. En su mayoría presentaban niveles bajos o inapropiadamente normales de gonadotrofinas, pero 4 mujeres y 3 varones presentaron niveles séricos elevados y disociados de FSH y LH. La hiperprolactinemia por desconexión fue observada en 45,2% de la población (X: 65.6 ng/ml r: 30-172). El hipopituitarismo se detectó en 25,7% de los casos. La cirugía fue transeptoesfenoidal (TSE) en 80%; una segunda operación fue realizada en el 28% de la población. La IH fue positiva por orden de frecuencia para LH, FSH y ASU o las 3 combinaciones. La evolución posquirúrgica evidenció mejoría en el campo visual (CV) en el 41%. La presencia de restos tumorales y/o recidiva fue del 84%. Se indicó radioterapia en 37% y la sustitución hormonal fue necesaria en el 65% de los pacientes.

The aim of our study was to describe the clinical-biochemical and radiologic presentation and the post surgery outcome in a cohort of patients with gonadotrophinomas. Patients were selected from nine Endocrinology Units of the city of Buenos Aires from 1983 at 2003. The inclusion criteria was defined by nonfunctinoning pituitary adenomas with positive innmunohistochemical (IH) for luteinizing hormone (LH), follicle-stimulating hormone (FSH) and/or alpha subunit (ASU). Innmunohistochemically plurihormonal adenomas were excluded. Sixty six patients were analyzed, aged 51,8 ± 12,1 (X +/- DS) years; (39 men). More prevalent symptoms were visual alterations (72,8%), hypogonadism and headaches. Eleven percent was diagnosed as incidentalomas. Ninety eight percent were macroadenomas, 56,9% was Hardy stage (HS) 3 and 29,6% was HS 4. The patients were followed up for 47,8 months (r: 5-168). Hypogonadism was biochemically found in 82,4%. The majority showed low or inappropriately normal levels of gonadotrophins except for 4 women and 3 men that had high and dissociated levels. Hyperprolactinemia was observed in 45,2% and was interpreted as an interference with normal dopamine inhibition of prolactin secretion (X+/-DS: 65.6+/- ng/ml, r: 30-172). Hypopituitarism was found in 25,7% of the patients. Transsphenoidal surgery was carried out in 80% and in 28% a second surgery was needed. The IH was positive for LH, FSH and ASU in this order of frequency or its combinations. Tumor persistency and/or recurrency were found in 84% of the patients. Forty one percent showed improvement of visual defects. Radiotherapy was indicated in 37% and hormonal replacement was needed in 65% of the patients.

A non-functioning pituitary macroadenoma detected incidentally with PET-CT / 대한내과학회지

Whole-body positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (18F-FDG) is a tomographic imaging technique that uses a radiolabeled analog of glucose, 18F-FDG, to image relative glucose uptake rates in various tissues. Since the glucose uptake is increased in many malignancies, 18F-FDG PET is a sensitive method for detecting, staging, and monitoring the effects of therapy on many malignancies. However, it is uncommon to discover an asymptomatic non-functioning pituitary tumor unexpectedly as a hypermetabolic lesion in PET studies. Here, we report a pituitary tumor that was detected incidentally by FDG-PET and ultimately turned out to be a non-functioning pituitary macroadenoma.

Aspectos moleculares da tumorigênese hipofisária: [revisão] / Molecular aspects of pituitary tumorigenesis: [review]

Os tumores hipofisários, adenomas em sua quase totalidade, são de ocorrência freqüente, representando 10 por cento a 15 por cento de todas as neoplasias intracranianas. Estas lesões são classificadas em microadenomas (< 10 mm) ou macroadenomas (> 10 mm) e como secretoras ou quiescentes (não-funcionantes). Estes tumores são capazes de secretar, de maneira autônoma, os hormônios adenohipofisários, como o hormônio de crescimento (GH), a prolactina (PRL), o hormônio adrenocorticotrófico (ACTH), o hormônio tireotrófico (TSH), o hormônio folículo estimulante (FSH) e o hormônio luteinizante (LH). A ocorrência de metástase, caracterizando um carcinoma hipofisário, é bastante rara, mas são relativamente comuns tumores de comportamento agressivo que exibem sinais de invasão local. Embora a sua patogênese ainda não seja plenamente caracterizada, muitos mecanismos moleculares envolvidos na tumorigênese hipofisária já foram desvendados. Nesta revisão, serão descritos avanços consideráveis realizados na última década relativos à compreensão dos fatores envolvidos na progressão tumoral, incluindo a participação de oncogenes, supressores tumorais e fatores de crescimento.

Pituitary tumors, almost invariably adenomas, are of frequent occurrence, accounting for 10 percent to 15 percent of all the intracranial neoplasm. They are classified as microadenomas (< 10 mm) or macroadenomas (> 10 mm) and as secreting or clinically non-secreting (or not functioning) adenomas. These tumors are autonomously capable to release pituitary hormones such as the growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The occurrence of metastases, characterizing a pituitary carcinoma, is exceedingly rare. However tumors with aggressive behavior, leading to local invasion, are relatively common. Although the pathogenesis of pituitary tumors is fully characterized, many molecular mechanisms of pituitary tumorigenesis had already been revealed. This review intents to describe advances in the understanding of the involved advances that have been made in the last decade concerning pituitary tumors progression, including the participation of oncogenes, tumor suppressor genes and growth factors.

A Case of Acromegaly Caused by Double Pituitary Adenomas / 대한내분비학회지

Acromegaly is a clinical syndrome, which is caused by an excess of growth hormone (GH), most commonly secreted from a pituitary solitary adenoma. However, our patient had bilateral GH-secreting pituitary tumors, the incidence of which has been reported in only 1.3 to 1.69% of all acromegalic patients. A 59-year-old female, with no family history of pituitary adenomas, demonstrated an increased level of serum insulin-like growth factor-1 (IGF-1), and GH not suppressed after 75 g oral glucose loading. On a preoperative MRI, only one pituitary tumor, measuring 1.1 x 0.7 cm, could be observed using sellar MRI. After surgical resection of the tumor, her headache and myalgia were sustained, and the IGF-1 level was still in a high titer. Therefore, a follow-up sellar MRI was taken, and a 0.6 x 0.7 cm sized newly growing pituitary tumor was found on the other side. With a retrospective review of radiological examinations, the patient was found to have bilateral tumors. The 0.3 cm sized tumor on the left was too small to be detected on the preoperative MRI. As the patient preferred medical treatment after surgery, she was treated with sandostatin analogues. Acromegaly with bilateral GH-secreting pituitary tumors, is a very rare disease, with no previous case having been reported in Korea. Herein, we report the case with a review of the literature.

Endoscopic Surgery for Pituitary Tumor

OBJECTIVE: The purpose of this study is to assess the efficacy and advantages of an endoscopic endonasal approach for the treatment of pituitary tumors. METHODS: We retrospectively analyzed the records of 31 patients with pituitary tumors having endoscopic endonasal surgery between March 1999 and August 2003. RESULTS: Among 31 patients with pituitary adenomas, 25 (81%) patients exhibited gross total removal of tumor on postoperative MRI within 3 days after surgery. Among 6 patients removed subtotally, 2 had only radiosurgery, 3 have had periodic follow-up MRIs and one patient with large extended tumor (grade IV, Stage E) had secondary transcranial removal of tumor before radiosurgery. Postoperative complications included cerebrospinal fluid leak in 2 patients, sinusitis in 1 patient, and one patient died due to unexpected intracerebral hemorrhage on 5 days after surgery. Besides considerable experiences with this approach are needed because of narrow working channel to the sella turcica, the results of our study showed following advantages of this procedure: visualization of areas not seen with the operating microscope, elimination of oronasal complications, more functional and cosmetic outcome, and shortened operative time and hospital stay. CONCLUSION: The authors consider that endoscopic endonasal transsphenoidal approach provides good results with minimal invasion for patients with pituitary tumors.