RESUMO
Cushing's disease (CD) is a life-threatening condition with a challenging diagnostic process and scarce treatment options. CD is caused by usually benign adrenocorticotrophic hormone (ACTH)-secreting pituitary neuroendocrine tumors (PitNETs), known as corticotropinomas. These tumors are predominantly of sporadic origin, and usually derive from the monoclonal expansion of a mutated cell. Somatic activating variants located within a hotspot of the USP8 gene are present in 11-62% of corticotropinomas, making USP8 the most frequent genetic driver of corticotroph neoplasia. In contrast, other somatic defects such as those affecting the glucocorticoid receptor gene (NR3C1), the BRAF oncogene, the deubiquitinase-encoding gene USP48, and TP53 are infrequent. Moreover, patients with familial tumor syndromes, such as multiple endocrine neoplasia, familial isolated pituitary adenoma, and DICER1 rarely develop corticotropinomas. One of the main molecular alterations in USP8-driven tumors is an overactivation of the epidermal growth factor receptor (EGFR) signaling pathway, which induces ACTH production. Hotspot USP8 variants lead to persistent EGFR overexpression, thereby perpetuating the hyper-synthesis of ACTH. More importantly, they condition a characteristic transcriptomic signature that might be useful for the clinical prognosis of patients with CD. Nevertheless, the clinical phenotype associated with USP8 variants is less well defined. Hereby we discuss the current knowledge on the molecular pathogenesis and clinical picture associated with USP8 hotspot variants. We focus on the potential significance of the USP8 mutational status for the design of tailored clinical strategies in CD.
Assuntos
Adenoma Hipofisário Secretor de ACT , Adenoma , Hipersecreção Hipofisária de ACTH , Humanos , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/genética , Hipersecreção Hipofisária de ACTH/metabolismo , Endopeptidases/genética , Endopeptidases/metabolismo , Adenoma Hipofisário Secretor de ACT/genética , Adenoma Hipofisário Secretor de ACT/metabolismo , Hormônio Adrenocorticotrópico , Adenoma/genética , Receptores ErbB/metabolismo , Ribonuclease III , RNA Helicases DEAD-box , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismoRESUMO
INTRODUCTION: Pituitary neuroendocrine tumors (PitNETs) represent 15-18.2% of all intracranial tumors. Their clinical presentation can range from chronic headache, visual defects, hypopituitarism to hormone excess syndromes. PitNETS are commonly classified as functioning neuroendocrine tumors (F-PitNETs) and non-functioning neuroendocrine tumors (NF-PitNETs). At the moment, new classification has emerged based on cell lineages. Almost 50% of all patients with PitNETs require surgical intervention, and about 25% of these have residual and persistent disease that may require additional management. SUBJECTS AND METHODS: A retrospective cohort of medical records of patients with PitNETs, aiming to describe the incidence of recurrence of patients who received surgical treatment over a 12 month follow up period at San Jose Hospital (SJH) in Bogotá, Colombia, over an observation period of 10 years. Furthermore, clinical presentation, biochemical characteristics and immunohistochemistry, postoperative complications are detailed. RESULTS: Eight hundred and eighty-seven patients with pituitary tumors were included in the cohort; 83% (737/887) had a diagnosis of PitNET. Of these, 18.9% (140) received surgical management. The majority 58% (98/140) had nonfunctional-PitNETs (NF-PitNETs), followed by growth-hormone-secreting pituitary adenoma (22.1%; 33/140), adrenocorticotropic- hormone-secreting pituitary adenoma (9.3%; 13/140), and prolactinomas (9.3%; 13/140). A recurrence was found in 45.71% (64/140), subclassified as biochemical in 15.71% (22/140), controlled with medications in 20% (28/140), and remission occurred in 18.57% (26/140). CONCLUSION: Clinical presentation and incidence of recurrence in patients with PitNETs in a referral center in Colombia are similar to other surgical cohorts with low cure rates and high recurrence.
Assuntos
Adenoma Hipofisário Secretor de ACT , Adenoma , Tumores Neuroendócrinos , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/terapia , Colômbia/epidemiologia , Estudos Retrospectivos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/cirurgia , Adenoma Hipofisário Secretor de ACT/cirurgia , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/terapia , HormôniosRESUMO
OBJECTIVE: To explore pituitary tumors by methylome and transcriptome signatures in a heterogeneous ethnic population. METHODS: In this retrospective cross-sectional study, clinicopathological features, methylome, and transcriptome were evaluated in pituitary tumors from 77 patients (61% women, age 12-72 years) followed due to functioning (FPT: GH-secreting n = 18, ACTH-secreting n = 14) and nonfunctioning pituitary tumors (NFPT, n = 45) at Ribeirao Preto Medical School, University of São Paulo. RESULTS: Unsupervised hierarchical clustering analysis (UHCA) of methylome (n = 77) and transcriptome (n = 65 out of 77) revealed 3 clusters each: one enriched by FPT, one by NFPT, and a third by ACTH-secreting and NFPT. Comparison between each omics-derived clusters identified 3568 and 5994 differentially methylated and expressed genes, respectively, which were associated with each other, with tumor clinical presentation, and with 2017 and 2022 WHO classifications. UHCA considering 11 transcripts related to pituitary development/differentiation also supported 3 clusters: POU1F1-driven somatotroph, TBX19-driven corticotroph, and NR5A1-driven gonadotroph adenomas, with rare exceptions (NR5A1 expressed in few GH-secreting and corticotroph silent adenomas; POU1F1 in few ACTH-secreting adenomas; and TBX19 in few NFPTs). CONCLUSION: This large heterogenic ethnic Brazilian cohort confirms that integrated methylome and transcriptome signatures classify FPT and NFPT, which are associated with clinical presentation and tumor invasiveness. Moreover, the cluster NFPT/ACTH-secreting adenomas raises interest regarding tumor heterogeneity, supporting the challenge raised by the 2017 and 2022 WHO definition regarding the discrepancy, in rare cases, between clinical presentation and pituitary lineage markers. Finally, making our data publicly available enables further studies to validate genes/pathways involved in pituitary tumor pathogenesis and prognosis.
Assuntos
Adenoma Hipofisário Secretor de ACT , Adenoma , Neoplasias Hipofisárias , Humanos , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Adenoma/genética , Adenoma/patologia , Epigenoma , Transcriptoma , Estudos Retrospectivos , Estudos Transversais , Adenoma Hipofisário Secretor de ACT/genética , Hormônio Adrenocorticotrópico/genéticaRESUMO
Resumen: Presentamos un caso de una paciente femenina de 27 años, con síndrome de Cushing ACTH dependiente con hipercortisolismo severo, causado por un macroadenoma hipofisario recurrente y resistente pese a dos cirugías transesfenoidales, radioterapia y terapia médica. Dada la falla en las diferentes terapias se realiza una adrenalectomía bilateral como tratamiento definitivo. La paciente fallece en el posoperatorio por causa no clara. Si bien la adrenalectomía bilateral ha sido reportada como un tratamiento efectivo en pacientes con enfermedad de Cushing, se ha relacionado con una mortalidad significativa vinculada con la severidad del hipercortisolismo y las comorbilidades presentes. En este caso la adrenalectomía izquierda se tuvo que convertir a cielo abierto, asociada con mayor morbimortalidad.
Abstract: The study presents the case of a 27-year-old female patient with adrenocorticotropic hormone (ACTH) dependent Cushing's disease and severe hypercortisolism caused by recurrent pituitary macroadenoma that was resistant to treatment despite two transsphenoidal surgeries, radiotherapy and medical treatment. Upon failure of the different therapies a bilateral adrenalectomy was performed as the final treatment. The patient died in after surgery although the case of death was not clear. Despite bilateral adrenalectomy having been reports as an effective treatment in patients with Cushing's disease, it has been related to significant mortality rates in connection with the severity of hypercortisolism and existing comorbilities. In this case the left adrenalectomy ended up being an open surgery, which is associated to a higher mortality rate.
Resumo: Apresentamos o caso de uma paciente de 27 anos com síndrome de Cushing ACTH-dependente com hipercortisolismo grave causado por macroadenoma hipofisário, recorrente e resistente, apesar de haver sido submetida a duas cirurgias transesfenoidal, radioterapia e terapia medicamentosa. Diante do fracasso das diferentes terapias, foi realizada adrenalectomia bilateral como tratamento definitivo. A paciente faleceu no pós-operatório por causa não esclarecida. Embora a adrenalectomia bilateral tenha sido relatada como tratamento eficaz em pacientes com doença de Cushing, ela tem sido associada a mortalidade significativa relacionada à gravidade do hipercortisolismo e às comorbidades presentes. Neste caso, a adrenalectomia esquerda teve que ser convertida para cirurgia aberta, associada a maior morbimortalidade.
Assuntos
Humanos , Feminino , Adulto , Adenoma/complicações , Síndrome de Cushing/complicações , Síndrome de Cushing/terapia , Adenoma Hipofisário Secretor de ACT/complicações , Recidiva , Doença Catastrófica , Evolução Fatal , Adrenalectomia , Síndrome de Cushing/cirurgiaRESUMO
Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH adenomas (SCA), Crooke cell adenomas (CCA) and ACTH-producing carcinomas (CA). The molecular pathogenesis of these tumors is still poorly understood. To better understand the genomic landscape of all the lesions of the corticotroph lineage, we sequenced the whole exome of three SCA, one CCA, four ACTH-secreting PA causing CD, one corticotrophinoma occurring in a CD patient who developed Nelson syndrome after adrenalectomy and one patient with an ACTH-producing CA. The ACTH-producing CA was the lesion with the highest number of single nucleotide variants (SNV) in genes such as USP8, TP53, AURKA, EGFR, HSD3B1 and CDKN1A. The USP8 variant was found only in the ACTH-CA and in the corticotrophinoma occurring in a patient with Nelson syndrome. In CCA, SNV in TP53, EGFR, HSD3B1 and CDKN1A SNV were present. HSD3B1 and CDKN1A SNVs were present in all three SCA, whereas in two of these tumors SNV in TP53, AURKA and EGFR were found. None of the analyzed tumors showed SNV in USP48, BRAF, BRG1 or CABLES1. The amplification of 17q12 was found in all tumors, except for the ACTH-producing carcinoma. The four clinically functioning ACTH adenomas and the ACTH-CA shared the amplification of 10q11.22 and showed more copy-number variation (CNV) gains and single-nucleotide variations than the nonfunctioning tumors.
Assuntos
Adenoma Hipofisário Secretor de ACT , Adenoma , Carcinoma , Genômica , Síndrome de Nelson , Neoplasias Hipofisárias , Adenoma Hipofisário Secretor de ACT/genética , Adenoma/genética , Adenoma/patologia , Hormônio Adrenocorticotrópico , Aurora Quinase A , Carcinoma/genética , Corticotrofos/patologia , Receptores ErbB , Humanos , Melanocortinas , Complexos Multienzimáticos , Nucleotídeos , Neoplasias Hipofisárias/genéticaRESUMO
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.
Assuntos
Humanos , Masculino , Feminino , Adulto , Idoso , Síndrome de Cushing , Doenças da Hipófise , Flebografia , Amostragem do Seio Petroso , Hipersecreção Hipofisária de ACTH , Adenoma Hipofisário Secretor de ACTRESUMO
Corticotroph adenomas frequently harbor somatic USP8 mutations. These adenomas also commonly exhibit underexpression of P27, a cell cycle regulator. The present study aimed to determine the influence of USP8 mutations on clinical features of Cushing's disease and to elucidate the relationship between USP8 mutations and P27 underexpression in these tumors. Retrospective study with 32 patients with Cushing's disease was followed at the Ribeirao Preto Medical School University Hospital. We evaluated the patients' clinical data, the USP8 mutation status and the gene expression of cell cycle regulators P27/CDKN1B, CCNE1, CCND1, CDK2, CDK4, and CDK6 in tumor tissue in addition to the protein expression of P27/CDKN1B. We observed somatic mutations in the exon 14 of USP8 in 31.3% of the patients. Larger tumor size was observed in patients harboring USP8 mutations (p=0.04), with similar rates of remission, age of presentation, salivary cortisol at 23:00 h and after 1 mg dexamethasone, ACTH levels, and early postoperative plasma cortisol. We observed no differences regarding the gene or protein expression of the cell cycle regulators according to USP8 mutation status. In this Brazilian series, the observed frequency of USP8 somatic mutations was similar to that reported in European ancestry populations. Although it was reasonable that USP8 mutations could contribute to cell cycle dysregulation and P27 underexpression in corticotroph adenomas, our data did not confirm this hypothesis. It is possible that increased deubiquitinase activity observed in mutated USP8 might influence other pathways related to cell growth and proliferation.
Assuntos
Adenoma Hipofisário Secretor de ACT/genética , Ciclo Celular , Endopeptidases/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Hipersecreção Hipofisária de ACTH/genética , Ubiquitina Tiolesterase/genética , Adenoma Hipofisário Secretor de ACT/fisiopatologia , Adolescente , Hormônio Adrenocorticotrópico/sangue , Adulto , Brasil , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Criança , Endopeptidases/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Éxons , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Hipersecreção Hipofisária de ACTH/metabolismo , Hipersecreção Hipofisária de ACTH/fisiopatologia , Estudos Retrospectivos , Ubiquitina Tiolesterase/metabolismo , Adulto JovemRESUMO
INTRODUCTION: A single study suggested that silent corticotropinomas (SCAs) have a different imaging phenotype, with microcystic aspect on T2-weighted sequence of magnetic resonance imaging (T2-MRI). This study only analysed manifest and silent corticotropinomas and nonfunctioning gonadotroph adenomas. Therefore, the prevalence of microcystic patterns of other tumours is not known. AIM: To analyse frequency of microcystic patterns on T2-MRI in all subtypes of pituitary adenomas and determine accuracy of this radiological finding for diagnosing SCA. METHODS: Consecutive pituitary adenoma patients who underwent surgery between 2013 and 2016 at a single centre were included. T2-MRIs were evaluated by a radiologist and an endocrinologist blinded to histological diagnosis. RESULTS: A total of 143 patients (52% female) with median age of 49 years (14-80) were included. Clinically, there were 90 nonfunctioning pituitary adenomas (NFPAs), 32 somatotropinomas, 13 corticotropinomas, five prolactinomas and three TSH-secreting adenomas. Of the patients with NFPA, 12 (13%) were SCAs, 73 (79%) were gonadotropinomas and five (6%) were positive for prolactin (three) or TSH (two). A microcystic pattern was observed in 16 tumours (11%): one somatotropinoma, one corticotropinoma, seven SCAs and seven gonadotropinomas, and in no prolactinomas or TSH-secreting adenomas. It was more common in SCAs than in other tumours (58.3% vs 6.9%, respectively, P < .001) and had a sensitivity of 58%, a specificity of 93% and an accuracy of 90% to define an SCA. CONCLUSION: Microcystic aspect on T2-MRI is able to define SCA with a good accuracy and can be a useful tool, considering the more aggressive behaviour of these tumours.
Assuntos
Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma/diagnóstico , Imageamento por Ressonância Magnética/métodos , Adenoma Hipofisário Secretor de ACT/patologia , Adenoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Carga Tumoral , Adulto JovemRESUMO
BACKGROUND: Double pituitary adenomas are a rare occurrence. Synchronous clinical manifestation is extremely rare. CASE DESCRIPTION: We report a case of a 51-year-old female with symptoms of both hypercortisolism and acromegaly during the past 2 years. Endocrine evaluation confirmed active acromegaly and revealed adrenocorticotropin hormone-dependent hypercortisolemia. Preoperative magnetic resonance imaging of the pituitary demonstrated separated double microadenomas with different intensity. Immunohistochemical analysis of each separate adenoma confirmed an exact diagnosis. The diagnosis of acromegaly and adrenocorticotropin hormone-dependent Cushing's disease was confirmed. CONCLUSIONS: This is the third reported case in the literature of synchronous clinical manifestation of acromegaly and Cushing's disease. Extensive surgical exploration of the sella must be performed to avoid surgical failures from residual tumor. Immunohistochemical analysis is required to confirm an exact diagnosis for each of the double pituitary adenomas.
Assuntos
Adenoma Hipofisário Secretor de ACT/diagnóstico por imagem , Adenoma Hipofisário Secretor de ACT/cirurgia , Acromegalia/diagnóstico por imagem , Acromegalia/etiologia , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Hipersecreção Hipofisária de ACTH/etiologia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Corticotrofos/metabolismo , Feminino , Humanos , Hidrocortisona/metabolismo , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Somatotrofos/metabolismo , Resultado do TratamentoAssuntos
Humanos , Masculino , Adolescente , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Síndrome de Cushing/fisiopatologia , Adenoma Hipofisário Secretor de ACT/cirurgia , Adenoma Hipofisário Secretor de ACT/diagnóstico , Osso Esfenoide/cirurgia , Resultado do Tratamento , Diagnóstico Diferencial , Endoscopia/métodos , Transtornos do Crescimento/complicações , ObesidadeRESUMO
PURPOSE: Filamin A (FLNA) expression is related to dopamine receptor type 2 (DRD2) expression in prolactinomas. Nevertheless, in corticotrophinomas, there are few studies about DRD2 expression and no data on FLNA. Therefore, we evaluated FLNA and DRD2 expression in corticotrophinomas and their association with tumor characteristics. METHODS: DRD2 and FLNA expression by immunohistochemistry, using H-score, based on the percentage of positive cells in a continuous scale of 0-300, were evaluated in 23 corticotrophinomas samples from patients submitted to neurosurgery. In six patients, treatment with cabergoline was indicated after non curative surgery. RESULTS: Twenty-two patients were female and one male. Regarding tumor size, 10 were micro and 12 were macroadenomas. DRD2 expression was found in 89% of cases and did not correlate with FLNA expression. Moreover, the response to cabergoline, observed in 33% of the cases, did not correlate with DRD2 nor FLNA expression. FLNA expression was not associated with clinical and tumor characteristics, except for sphenoid sinus invasion. CONCLUSIONS: In our cohort of corticotrophinomas, DRD2 expression was not associated with FLNA expression nor to the response to CAB. Nonetheless, FLNA expression could be related to tumor invasiveness.
Assuntos
Adenoma Hipofisário Secretor de ACT/metabolismo , Filaminas/metabolismo , Receptores de Dopamina D2/metabolismo , Adolescente , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Los adenomas hipofisarios son tumores cerebrales benignos considerados como el tercer grupo de lesiones intracraneales en frecuencia tras los meningiomas y los gliomas. El tratamiento de esta patología puede ser clínico o quirúrgico, dependiendo del tipo de tumor. El tratamiento quirúrgico puede ser realizado por dos vías: transcraneal o transesfenoidal, la misma que puede ser por abordaje sublabial, transeptal o transnasal con uso de microscopio o endoscopio. Los resultados posquirúrgicos son objetivables a través de la revisión de historias clínicas para valorar sintomatología, niveles hormonales prequirúrgicos y posquirúrgicos, complicaciones para evidenciar los resultados de esta técnica. Objetivos: Determinar los resultados del tratamiento quirúrgico por vía transesfenoidal utilizando abordaje transnasal endoscópico y transeptal microscópico en pacientes con adenomas hipofisarios. Metodología: Estudio descriptivo, retrospectivo, observacional, en el que se analizan 25 pacientes, que fueron hospitalizados para intervención neuroquirúrgica en el periodo comprendido entre enero 2014 a junio 2016 del Hospital Teodoro Maldonado Carbo. Resultados: Se analizaron 25 pacientes que fueron intervenidos por adenoma hipofisario por vía transesfenoidal, de los cuales 14 fueron mujeres y 11 varones. El rango de edad estuvo comprendido entre 13 y 79 años, con una media de 50 años. Según la clasificación por su tamaño, 3 pacientes presentaron microadenoma y 22 macroadenoma; 7 pacientes con adenoma hipofisario funcionante y 18 pacientes con adenoma hipofisario no funcionante. El 60 % de pacientes tuvo mejoría en la visión. En los adenomas hipofisarios funcionantes los niveles hormonales disminuyeron en 6 pacientes y en 1 paciente incrementó. Las complicaciones posquirúrgicas se presentaron en 6 pacientes, que representan un 24 % de pacientes; 2 presentaron fístula de líquido cefalorraquídeo, 2 pacientes empeoraron su sintomatología visual, 1 paciente desarrolló diabetes insípida y 1 paciente falleció en el posquirúrgico mediato. Conclusiones: El procedimiento transesfenoidal sea transeptal micróscopica o transnasal endoscópica son abordajes eficaces para el tratamiento quirúrgico de los pacientes con adenoma hipofisario.
Pituitary adenomas are benign brain tumors considered the third group of intracranial lesions in frequency after meningiomas and gliomas. The treatment of this pathology may be clinical or surgical depending on the type of tumor. Surgical treatment can be performed by 2-way transcranial or transsphenoidal, which can be by sublabial, transseptal or transnasal approach using a microscope or endoscope. The postoperative results are objectivable through the review of clinical histories to evaluate symptoms, pre-surgical and postsurgical hormone levels, complications to evidence the results of this technique. Objectives: To determine the results of transsphenoidal surgical treatment using transnasal endoscopic and microscopic transeptal approach in patients with pituitary adenomas. Methodology: A descriptive, retrospective, observational study in which 25 patients were analyzed, who were hospitalized for neurosurgical intervention in the period between 2014 and June 2016 of the Hospital Teodoro Maldonado Carbo. Results: We analyzed 25 patients who underwent transsphenoidal pituitary adenoma, 14 of whom were women and 11 men. The age range was between 13 and 79 years, with an average of 50 years. According to the classification by their size 3 patients presented microadenoma and 22 macroadenoma; 7 patients with functioning pituitary adenoma and 18 patients with nonfunctioning pituitary adenoma. Sixty percent of patients had improvement in vision. In functional pituitary adenomas, hormonal levels decreased in 6 patients and in 1 patient increase. Postoperative complications were presented in 6 patients representing 24% of patients, 2 had cerebrospinal fluid fistula, 2 patients worsened their visual symptomatology, 1 patient developed diabetes insipidus and 1 patient died in the postoperative period. Conclusions: The transsphenoidal procedure is transosseous or endoscopic transnasal micróscopica are effective approaches for the surgical treatment of patients with pituitary adenoma.
Assuntos
Humanos , Patologia Cirúrgica , Neoplasias Encefálicas , Adenoma Hipofisário Secretor de ACT , Patologia Clínica , Glioma , MeningiomaRESUMO
OBJECTIVES: To define the incidence and risk factors of postoperative sodium alterations in pediatric patients undergoing transsphenoidal surgery (TSS) for adrenocorticotropic hormone and growth hormone secreting pituitary adenomas. STUDY DESIGN: We retrospectively reviewed 160 patients ≤18 years of age who had TSS for pituitary adenomas at our institution from 1999 to 2017. Variables included daily serum sodium through postoperative day 10, urine specific gravity, and medications administered. We examined associations between sex, repeat surgery, manipulation of the posterior pituitary (PP), tumor invasion into the PP, tumor type and size, cerebrospinal fluid (CSF) leak, lumbar drain insertion, body mass index, puberty, and development of diabetes insipidus (DI) or syndrome of inappropriate antidiuretic hormone secretion (SIADH). RESULTS: Mean age was 12.9 ± 3.4 years (female = 81). Patients had adrenocorticotropic hormone (150/160) and growth hormone (10/160) producing adenomas. Forty-two (26%) patients developed DI. Among the 37 of 160 who required desmopressin acutely, 13 of 37 required it long term. Risk of long-term need for desmopressin was significantly higher in patients who had CSF leak 9 of 48 (P = .003), lumbar drain 6 of 30 (P = .019), manipulation 11 of 50 (P < .001), or invasion 4 of 15 (P = .022) of the PP. Sixty patients developed hyponatremia, 19 because of SIADH, 39 to hypotonic fluids and 2 to cerebral salt wasting syndrome. Patients with SIADH were placed on fluid restriction; 1 received salt tablets. CONCLUSIONS: Among 160 children who underwent TSS for pituitary adenomas, the incidence of DI and SIADH after TSS was 26% and 14%, respectively. Combined risk factors for DI and/or SIADH include female sex, manipulation of and/or tumor invasion into the PP, and CSF leak or lumbar drain. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00001595 and NCT00060541.
Assuntos
Adenoma Hipofisário Secretor de ACT/cirurgia , Adenoma/cirurgia , Diabetes Insípido/etiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Hiponatremia/etiologia , Complicações Pós-Operatórias/etiologia , Adolescente , Criança , Pré-Escolar , Diabetes Insípido/epidemiologia , Feminino , Humanos , Hiponatremia/epidemiologia , Incidência , Masculino , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Osso Esfenoide/cirurgiaRESUMO
Objetivo: determinar o perfil epidemiológico e clínico de pacientes com acromegalia no Estado de Alagoas. Métodos: trata-se de um estudo descritivo, observacional, que foi realizado na Farmácia de Medicamentos Excepcionais do Estado de Alagoas, abrangendo 12 pacientes com acromegalia dessa instituição, correspondendo a 85% dos acromegálicos do Estado de Alagoas. Resultados: dos 12 pacientes estudados, a média de idade foi de 50,8 +/- 12,1 anos e, no momento do diagnóstico, uma média de idade de 44,5 +/- 11,6 anos. Foram realizados exames de imagem em 91,6% dos pacientes, em que se evidenciou macroademona hipofisário no momento do diagnóstico. A octreotida foi o medicamento principal, utilizado em 92% dos pacientes. Conclusão: O estudo corrobora, em boa parte dos dados, a literatura atual e revela a necessidade de maior precocidade de diagnóstico e início de terapêutica adequada, evitando o surgimento de comorbidades e complicações típicas da doença. (AU)
Objective: to determine the clinical and epidemiological profile of patients with acromegaly in the state of Alagoas. Method: This is a descriptive and observational study, which was held at the Exceptional Drug Pharmacy of the State of Alagoas. This study included 12 patients with acromegaly of this institution, corresponding to 85% of acromegaly in the State of Alagoas. Results: The mean age of the patients was 50.8 +/- 12.1 year and the mean age at diagnosis was 44.5 +/- 11, 6 years. Medical imaging exams were performed in 91.7% of patients, showing pituitary macroadenoma at the moment of diagnosis. Octreotide was the main medication, used in 91,7% of patients. Conclusion: The study corroborates, in most of the data, the current literature and reveals the need for earlier diagnosis and appropriate therapy, which avoids the appearance of typical comorbidities and complications of this disease. (AU)
Assuntos
Acromegalia , Hormônio do Crescimento , Adenoma Hipofisário Secretor de ACTRESUMO
La hiperprolactinemia es uno de los trastornos neuroendocrinológicos más frecuentes; la causa común de la hiperprolactinemia es la presencia de un adenoma hipofisario productor de prolactina o prolactinoma. El país cuenta con escasa referencia bibliográfica sobre la patología presentada, por lo que resulta importante realizar la exposición de este caso. Objetivo: documentar el abordaje de hiperprolactinemia en el país. Caso clínico: paciente femenina de 22 años, con antecedentes familiares de macroprolactinoma; se presenta con historia de amenorrea de 6 años y caída de cabello de 2 años de evolución; prurito intenso en ambas mamas con predominio en la areola derecha desde hace 1 año; alteraciones en los niveles de prolactina presentando valores de 33.5ng/mL y ultrasonografía abdominal ausente de anormalidades. Tratada con cabergolina, sin éxito evidente en el tratamiento. Conclusión: en pacientes con hiperprolactinemia, su abordaje debe hacerse de manera ordenada, integral, secuencial y detallada con el fin de descartar previo al tratamiento, situaciones que secundariamente elevan los valores de prolactina. Esto lo demuestra el caso expuesto donde se integran diferentes pruebas clínicas y laboratoriales para descartar la etiología de la hiperprolactinemia en el país...(AU)
Assuntos
Humanos , Feminino , Adulto , Adenoma Hipofisário Secretor de ACT , Doenças do Sistema Endócrino , Hiperprolactinemia , Prolactinoma/complicaçõesRESUMO
La resonancia magnética constituye el examen ideal en pacientes con presunción clínica de tumores en la región selar, pues no emite radiaciones ionizantes y debido a su visión multiplanar y discriminación tisular, posibilita adoptar una conducta terapéutica adecuada y un seguimiento sin riesgos en estos casos. Se describen las imágenes obtenidas con esa técnica sobre los principales tumores selares, correspondientes a macroadenomas hipofisarios, meningioma intraselar, craneofaringioma supraselar y como caso interesante perteneciente a esta región: el cordoma del clivus, por poseer en la actualidad mejores posibilidades diagnósticas que en décadas anteriores
Magnetic resonance constitutes the ideal exam in patients with clinical presumption of tumors in the selar region, because it doesn't emit ionizing radiations and due to its multiplanar vision and tissular discrimination, it facilitates the adoption of an appropriate therapeutic behavior and a follow up without risks in these cases. The images obtained with that technique on the main selar tumors are described, corresponding to hypophysary macroadenomas, intraselar meningioma, supraselar craneopharyngioma and as an interesting case belonging to this region: the clivus chordoma, for having better diagnostic possibilities at the present time than in previous decades
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Hipofisárias/diagnóstico por imagem , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Craniofaringioma , Adenoma Hipofisário Secretor de ACT , MeningiomaRESUMO
Although it is a rare condition, the accurate diagnosis and treatment of Cushing's disease is important due to its higher morbidity and mortality compared to the general population, which is attributed to cardiovascular diseases, diabetes mellitus and infections. Screening for hypercortisolism is recommended for patients who present multiple and progressive clinical signs and symptoms, especially those who are considered to be more specific to Cushing's syndrome, abnormal findings relative to age (e.g., spinal osteoporosis and high blood pressure in young patients), weight gain associated with reduced growth rate in the pediatric population and for those with adrenal incidentalomas. Routine screening is not recommended for other groups of patients, such as those with obesity or diabetes mellitus. Magnetic resonance imaging (MRI) of the pituitary, the corticotropin-releasing hormone (CRH) test and the high-dose dexamethasone suppression test are the main tests for the differential diagnosis of ACTH-dependent Cushing's syndrome. Bilateral and simultaneous petrosal sinus sampling is the gold standard method and is performed when the triad of initial tests is inconclusive, doubtful or conflicting. The aim of this article is to provide information on the early detection and establishment of a proper diagnosis of Cushing's disease, recommending follow-up of these patients at experienced referral centers. Arch Endocrinol Metab. 2016;60(3):267-86.
Assuntos
Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma/diagnóstico , Consenso , Síndrome de Cushing/diagnóstico , Adenoma Hipofisário Secretor de ACT/complicações , Adenoma/complicações , Brasil , Cromatografia Líquida de Alta Pressão , Síndrome de Cushing/etiologia , Dexametasona , Diagnóstico Diferencial , Glucocorticoides , Humanos , Hidrocortisona/sangue , Imageamento por Ressonância MagnéticaRESUMO
ABSTRACT Although it is a rare condition, the accurate diagnosis and treatment of Cushing’s disease is important due to its higher morbidity and mortality compared to the general population, which is attributed to cardiovascular diseases, diabetes mellitus and infections. Screening for hypercortisolism is recommended for patients who present multiple and progressive clinical signs and symptoms, especially those who are considered to be more specific to Cushing’s syndrome, abnormal findings relative to age (e.g., spinal osteoporosis and high blood pressure in young patients), weight gain associated with reduced growth rate in the pediatric population and for those with adrenal incidentalomas. Routine screening is not recommended for other groups of patients, such as those with obesity or diabetes mellitus. Magnetic resonance imaging (MRI) of the pituitary, the corticotropin-releasing hormone (CRH) test and the high-dose dexamethasone suppression test are the main tests for the differential diagnosis of ACTH-dependent Cushing’s syndrome. Bilateral and simultaneous petrosal sinus sampling is the gold standard method and is performed when the triad of initial tests is inconclusive, doubtful or conflicting. The aim of this article is to provide information on the early detection and establishment of a proper diagnosis of Cushing’s disease, recommending follow-up of these patients at experienced referral centers. Arch Endocrinol Metab. 2016;60(3):267-86.
Assuntos
Humanos , Adenoma/diagnóstico , Síndrome de Cushing/diagnóstico , Consenso , Adenoma Hipofisário Secretor de ACT/diagnóstico , Brasil , Dexametasona , Hidrocortisona/sangue , Imageamento por Ressonância Magnética , Adenoma/complicações , Cromatografia Líquida de Alta Pressão , Síndrome de Cushing/etiologia , Diagnóstico Diferencial , Adenoma Hipofisário Secretor de ACT/complicações , GlucocorticoidesRESUMO
Silent corticotroph adenomas (SCA) are pituitary adenomas inmunoreactive to ACTH without hormonal overproduction and they form the 3 percent of the pituitary adenomas. Unlike the ademonas that cause the Cushings disease, frequently the SCA are aggressive macroademonas and their clinical expressions are the compromise of nearby structures with or without pituitary apoplexy. Frequently, the treatment chosen is a surgical procedure, albeit the total resection difficulties. The SCA are not diagnosed until an anatomopathological and immunohistochemical study is carried out. In this document, a case study of a woman diagnosed with a clinically silent macrocorticotroph adenomadiscovered by a third nerve palsy is explained.