Incidentalomas o no incidentalomas: ¿cuál es la relevancia de los adenomas hipofisarios en el adulto? / Incidentalomas or Non-Incidentalomas: What is the Relevance of Pituitary Adenomas in the Adult?

Introducción: desde el punto de vista anatómico, los adenomas hipofisarios (AH) se observan en el 10% de la población. Son en su mayoría pequeños y no funcionantes. La mayoría de los incidentalomas descubiertos en estudios de imágenes con alta resolución pedidos en situaciones clínicas frecuentes, como el traumatismo craneoencefálico, el accidente cerebrovascular y las demencias, corresponden a AH indolentes. Nos preguntamos cuál es la relevancia clínica de los adenomas hipofisarios. Desarrollo: los AH clínicamente relevantes son tumores en su mayoría benignos que conllevan, en diferentes proporciones, aumento en la morbilidad y/o mortalidad de los pacientes por mecanismos relacionados con la hipersecreción hormonal, la insuficiencia hormonal y/o los efectos de masa ocupante. La prevalencia de los AH clínicamente relevantes es mayor de la que se suponía hace 20 años. Afecta aproximadamente a 1/1000 habitantes. Los más prevalentes son los prolactinomas y los adenomas no funcionantes. La acromegalia, la enfermedad de Cushing y los tumores agresivos se traducen en pacientes complejos con mayor morbimortalidad. El diagnóstico temprano y el tratamiento multimodal proveen una razonable mejoría de la sobrevida. El estudio epidemiológico de los AH clínicamente relevantes es importante para la estimación del impacto en los sistemas de salud. Conclusiones: los estudios por imágenes de mejor resolución continuarán señalando incidentalomas hipofisarios. Una evaluación cuidadosa de los pacientes podrá identificar aquellos AH clínicamente relevantes. (AU)

Introduction: from the anatomical point of view, pituitary adenomas (HA) are observed in 10% of the population. They are mostly small and non-functioning. Most incidentalomas discovered in high-resolution imaging studies ordered in frequent clinical situations, such as head trauma, stroke and dementia, correspond to indolent HA. We wonder what is the clinical relevance of pituitary adenomas. Development: clinically relevant HAs are mostly benign tumors that lead, in different degrees, to an increased morbidity and/or mortality in patients by mechanisms related to hormone hypersecretion, hormone insufficiency and/or occupying mass effects. The prevalence of clinically relevant HA is higher from what was assumed 20 years ago. It affects approximately 1/1000 of the population. The most prevalent are prolactinomas and non-functioning adenomas. Acromegaly, Cushing's disease and aggressive tumors make for complex patients with increased morbidity and mortality. Early diagnosis and multimodal treatment provide a reasonable improvement in survival. Epidemiological study of clinically relevant HAs is important for estimating the impact on health systems. Conclusions: Higher-resolution imaging studies will continue to highlight pituitary incidentalomas. Careful evaluation of patients will identify clinically relevant HAs. (AU)

Plurihormonal PIT1-lineage pituitary neuroendocrine tumors: a clinicopathological study / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics of plurihormonal PIT1-lineage pituitary neuroendocrine tumors. Methods: Forty-eight plurihormonal PIT1-lineage tumors were collected between January 2018 and April 2022 from the pathological database of Sanbo Brain Hospital, Capital Medical University. The related clinical and imaging data were retrieved. H&E, immunohistochemical and special stains were performed. Results: Out of the 48 plurihormonal PIT1-lineage tumors included, 13 cases were mature PIT1-lineage tumors and 35 cases were immature PIT1-lineage tumors. There were some obvious clinicopathological differences between the two groups. Clinically, the mature plurihormonal PIT1-lineage tumor mostly had endocrine symptoms due to increased hormone production, while a small number of immature PIT1-lineage tumors had endocrine symptoms accompanied by low-level increased serum pituitary hormone; patients with the immature PIT1-lineage tumors were younger than the mature PIT1-lineage tumors; the immature PIT1-lineage tumors were larger in size and more likely invasive in imaging. Histopathologically, the mature PIT1-lineage tumors were composed of large eosinophilic cells with high proportion of growth hormone expression, while the immature PIT1-lineage tumors consisted of chromophobe cells with a relatively higher expression of prolactin; the mature PIT1-lineage tumors had consistently diffuse cytoplasmic positive staining for keratin, while the immature PIT1-lineage tumors had various expression for keratin; the immature PIT1-lineage tumors showed more mitotic figures and higher Ki-67 proliferation index; in addition, 25.0% (12/48) of PIT1-positive plurihormonal tumors showed abnormal positive staining for gonadotropin hormones. There was no significant difference in the progression-free survival between the two groups (P=0.648) by Kaplan-Meier analysis. Conclusions: Plurihormonal PIT1-lineage tumor belongs to a rare type of PIT1-lineage pituitary neuroendocrine tumors, most of which are of immature lineage. Clinically increased symptoms owing to pituitary hormone secretion, histopathologically increased number of eosinophilic tumor cells with high proportion of growth hormone expression, diffusely cytoplasmic keratin staining and low proliferative activity can help differentiate the mature plurihormonal PIT1-lineage tumors from the immature PIT1-lineage tumors. The immature PIT1-lineage tumors have more complicated clinicopathological characteristics.

Transsphenoidal surgery for prolactinomas in male patients: a retrospective study / 亚洲男科学杂志(英文版)

Male patients with prolactinomas usually present with typical hyperprolactinemia symptoms, including sexual dysfunction and infertility. However, clinical factors related to sexual dysfunction and surgical outcomes in these patients remain unclear. This study aimed to investigate the outcomes of male patients with prolactinomas after transsphenoidal surgery and the risk factors affecting sexual dysfunction. This study was conducted on 58 male patients who underwent transsphenoidal surgery for prolactinomas between May 2014 and December 2020 at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. We evaluated the sexual function of patients before and after surgery through International Index of Erectile Function-5 scores, libido, and frequency of morning erection. Of the 58 patients, 48 (82.8%) patients had sexual intercourse preoperatively. Among those 48 patients, 41 (85.4%) patients presented with erectile dysfunction. The preoperative International Index of Erectile Function-5 scores in patients with macroprolactinomas were significantly higher than those in patients with giant prolactinomas (17.63 ± 0.91 vs 13.28 ± 1.43; P = 0.01). Postoperatively, the incidence of erectile dysfunction was 47.9%, which was significantly lower than that preoperatively (85.4%; P = 0.01). Twenty-eight (68.3%) patients demonstrated an improvement in erectile dysfunction. Tumor size and invasiveness were significantly correlated with the improvement of erectile dysfunction. Preoperative testosterone <2.3 ng ml-1 was an independent predictor of improvement in erectile dysfunction. In conclusion, our results indicated that tumor size and invasiveness were important factors affecting the improvement of sexual dysfunction in male patients with prolactinoma. The preoperative testosterone level was an independent predictor related to the improvement of erectile dysfunction.

Pituicytoma: a clinicopathological analysis of twenty-one cases / 中华病理学杂志

Objective: To investigate the clinicopathological features and treatment strategies of pituicytoma. Methods: Twenty-one cases of pituicytoma were collected at the First Affiliated Hospital of Nanjing Medical University and Jinling Hospital, Nanjing, China from 2009 to 2020. The clinical data of 21 pituicytoma patients was retrospectively analyzed, and the relevant literature was reviewed. Results: Twenty-one patients aged 4 to 68 years, including 8 males and 13 females. All patients underwent surgical treatment. Histologically, the tumor was consisted almost entirely of elongate, bipolar spindle cells arranged in a fascicular or storiform pattern. Mitotic figures were rare. Immunohistochemically, tumor cells were diffusely positive for S-100 protein (21/21), vimentin (15/15) and TTF1 (14/14), while they were weakly or focally positive for GFAP (13/16) and EMA (6/12). CKpan was negative in all cases and Ki-67 proliferation index was low (<5%). Among the 18 patients with follow-up, all survived and 2 relapsed after surgery. Conclusions: Pituicytoma is a rare low-grade glioma of the sellar area. It is easily confused with other sellar tumors. Preoperative diagnosis is difficult. It needs to be confirmed by histopathology and immunohistochemistry. Microsurgery is the main treatment method at present.

Hereditary pituitary tumor syndromes: genetic and clinical aspects

ABSTRACT The pituitary gland is responsible for the synthesis and secretion of various hormones that play a key role in regulating endocrine function and homeostasis. Pituitary adenomas (PA) are benign epithelial tumors arising from the endocrine cells of the anterior pituitary gland. Clinically relevant PA are relatively common and they occur in 0.1% of the general population. They are mostly benign monoclonal neoplasms that arise from any of the five hormone-secreting cell types of the anterior pituitary gland. PA are categorized as either functioning or non-functioning, depending on whether or not they produce a hormonal hypersecretion syndrome. Both functioning and non-functioning adenomas can produce symptoms or signs resulting from compression of the optic chiasm or invasion of cavernous sinuses. Only 5% of PA occur within the context of hereditary syndromes with reasonably well-defined oncogenic mechanisms. The vast majority of PA are sporadic, and their etiopathogenesis remains largely unknown. Pituitary tumor oncogenesis involves several mechanisms that eventually lead to abnormal cell proliferation and dysregulated hormone production. Among these factors, we found inactivating mutations of tumor suppressor genes, activating mutation of oncogenes and the participation of hormonal signals coming from the hypothalamus, all resulting in cell-cycle regulation abnormalities. In this review, we summarize the clinical and pathophysiological aspects of the different hereditary pituitary tumor syndromes.

Effect of lncRNA HULC knockdown on rat secreting pituitary adenoma GH3 cells

Pituitary adenoma is one of the most common tumors in the neuroendocrine system. This study investigated the effects of long non-coding RNAs (lncRNAs) highly up-regulated in liver cancer (HULC) on rat secreting pituitary adenoma GH3 cell viability, migration, invasion, apoptosis, and hormone secretion, as well as the underlying potential mechanisms. Cell transfection and qRT-PCR were used to change and measure the expression levels of HULC, miR-130b, and FOXM1. Cell viability, migration, invasion, and apoptosis were assessed using trypan blue staining assay, MTT assay, two-chamber transwell assay, Guava Nexin assay, and western blotting. The concentrations of prolactin (PRL) and growth hormone (GH) in culture supernatant of GH3 cells were assessed using ELISA. The targeting relationship between miR-130b and FOXM1 was verified using dual luciferase activity. Finally, the expression levels of key factors involved in PI3K/AKT/mTOR and JAK1/STAT3 pathways were evaluated using western blotting. We found that HULC was highly expressed in GH3 cells. Overexpression of HULC promoted GH3 cell viability, migration, invasion, PRL and GH secretion, as well as activated PI3K/AKT/mTOR and JAK1/STAT3 pathways. Knockdown of HULC had opposite effects and induced cell apoptosis. HULC negatively regulated the expression of miR-130b, and miR-130b participated in the effects of HULC on GH3 cells. FOXM1 was a target gene of miR-130b, which was involved in the regulation of GH3 cell viability, migration, invasion, and apoptosis, as well as PI3K/AKT/mTOR and JAK1/STAT3 pathways. In conclusion, HULC tumor-promoting roles in secreting pituitary adenoma might be via down-regulating miR-130b, up-regulating FOXM1, and activating PI3K/AKT/mTOR and JAK1/STAT3 pathways.

Tumores hipofisarios, casuística de Anatomía Patológica / Pituitary tumors: anatomopathological reports

This study examines a description of pituitary tumors considering an anatomopathological casuistic. The study of the tumors of the Central Nervous System (CNS) include the pituitary gland, located in the sella turcica. The pathology of the sellar region is represented by the adenomas, tumors of slow development with or without endocrine secretion, that usually involve the population of young adults. The aim of this report, was to describe the casuistic of the " J. Fernandez Hospital" between the years 2000 through 2017. A retrospective review was performed and 234 samples of the sellar region were processed. Mean age was 42 years with a range of 17 to 77 years. Sex distribution was 57% women and 43 % men. Of these, 77% of the cases resulted adenomas. The conclusions obtained in the study are detailed.

Recurrent Pituicytoma in a Pediatric Patient: A Case Report

Pituicytoma is a rare tumor that arises from the glial cells of the neurohypophysis. For a long time, it was believed that pituicytomas only appeared in adults. Currently, at least three cases of this entity occurring in children have been reported in the literature. The aim of the present report is to describe the case of a 5-year-old girl who presented to the emergency department with visual disturbances, and the diagnosis was a recurrent pituicytoma. Therefore, the clinical presentation, the radiological features of the tumor, and the corresponding surgical management are described. Additionally, a brief review of the management of this unusual entity was performed.

O pituicitoma é um tumor raro que surge das células gliais da neurohipófise. Durante muito tempo, acreditou-se que os pituicitomas só aparecessem em adultos. Atualmente, pelo menos três casos desta entidade ocorrendo em crianças foram relatados na literatura. O objetivo do presente artigo é descrever o caso de uma menina de 5 anos que chegou à emergência com distúrbios visuais, e o diagnóstico foi um pituicitoma recorrente. A apresentação clínica, as características radiológicas do tumor, e o correspondente manejo cirúrgico foram, portanto, descritos. Além disso, foi realizada uma breve revisão do tratamento desta entidade incomum.

Presentación atípica de un prolactinoma gigante en un adolescente de 15 años / Atypical presentation of a giant prolactinoma in a 15-year-old boy

El prolactinoma gigante es un adenoma pituitario poco frecuente caracterizado por su gran invasión local. Se reporta el caso de un varón de 15 años de edad con dolor retroocular izquierdo y exoftalmos ipsilateral de 4 meses de evolución secundario a un tumor en la base del cráneo que invadía la órbita. Los estudios hormonales revelaron prolactina sérica de 6913,7 ng/ml (valor normal < 20), que confirmó el diagnóstico de prolactinoma gigante. El paciente inició un tratamiento con el agonista dopaminérgico cabergolina en dosis crecientes. Luego de 7 meses de seguimiento, la prolactina había descendido a 349,8 ng/ml y el volumen del tumor se redujo un 70%, sin efectos adversos al tratamiento. El paciente se encontraba asintomático y había reiniciado la pubertad. La rápida remisión de los síntomas sin necesidad de tratamientos invasores subraya la importancia de considerar el diagnóstico de prolactinoma entre los posibles diagnósticos diferenciales de tumor de la base del cráneo.

Giant prolactinomas are rare pituitary adenomas characterized by their great local invasion. In this paper, we report a 15-year-old male with left retro-ocular pain and ipsilateral exophthalmos of 4 months of evolution, secondary to a tumour in the base of the skull that invaded the orbit. Hormonal studies revealed serum prolactin of 6913,7 ng/ml (normal value < 20), confirming the diagnosis of giant prolactinoma. The patient started treatment with the dopaminergic agonist cabergoline in increasing doses. After 7 months of follow-up the prolactin had decreased to 349.8 ng/ml and the tumor volume was reduced by 70%, without presenting adverse effects to the treatment. The patient was asymptomatic and had restarted puberty. The rapid remission of symptoms without the need for invasive treatments underlines the importance of considering the diagnosis of prolactinoma among the possible differential diagnoses of tumor of the skull base.

Study of major genetic factors involved in pituitary tumorigenesis and their impact on clinical and biological characteristics of sporadic somatotropinomas and non-functioning pituitary adenomas

Genetic and functional aberrations of guanine nucleotide-binding protein, alpha stimulating (GNAS), aryl hydrocarbon receptor interacting protein (AIP), and pituitary tumor transforming gene (PTTG) are among the most prominent events in pituitary tumorigenesis. A cohort of Brazilian patients with somatotropinomas (n=41) and non-functioning pituitary adenomas (NFPA, n=21) from a single tertiary-referral center were evaluated for GNAS and AIP mutations and gene expression of AIP and PTTG. Results were compared to the clinical and biological (Ki67 and p53 expression) characteristics of tumors and their response to therapy, if applicable. Genetic analysis revealed that 27% of somatotropinomas and 4.8% of NFPA harbored GNAS mutations (P=0.05). However, no differences were observed in clinical characteristics, tumor extension, response to somatostatin analog therapy, hormonal/surgical remission rates, Ki67 index, and p53 expression between mutated and non-mutated somatotropinomas patients. PTTG overexpression (RQ mean=10.6, min=4.39, max=11.9) and AIP underexpression (RQ mean=0.56, min=0.46-max=0.92) were found in virtually all cases without a statistically significant relationship with clinical and biological tumor features. No patients exhibited somatic or germline pathogenic AIP mutations. In conclusion, mutations in GNAS and abnormal PTTG and AIP expression had no impact on tumor features and treatment outcomes in this cohort. Our data support some previous studies and point to the need for further investigations, probably involving epigenetic and transcriptome analysis, to improve our understanding of pituitary tumor behavior.

Tumores selares: grosor de la capa de fibras nerviosas en tomografía de coherencia óptica de papila como factor pronóstico de recuperación visual postoperatoria / Sellar tumors: peripapillary retinal nerve fiber layer thickness on optical coherence tomography as prognosis of postoperatory visual recovery

Purpose: To establish the prognostic value of the retinal nerve fiber layer thickness measured at Optical Coherence Tomography (OCT) as a predictor of visual function posterior to resection of sellar tumors. Material and Methods: Descriptive, retrospective study in patients undergoing microscopic transsphenoidal resection of sellar tumors with preoperative ophthalmologic evaluation (evaluation by specialist, 24-2 Sita Standard visual field (24-2 SS VF) and optic nerve head Stratus OCT) and postoperative (evaluation by specialist and 24-2 SS VF). Minimum follow-up was 3 months. For statistical analysis, Spearman and Pearson's Correlation Coefficient and linear regression was used. Results: A total of 18 patients were included. In the preoperative evaluation, patients had logMAR average Snellen visual acuity (VA) of 0.70 (0.15 logMAR, 0-4.0), an average mean deviation (MD) of -9.25 dB (0.4 to -30.4 dB) and a average retinal nerve fiber layer thickness of 83.7 microns (45.24 to 115.37). Postoperative evaluation of patients showed an Snellenaverage VA of 0.78 (0.1 logMAR, 0-1.3) and MD of 5.58 dB (2.31 -32.39 dB). A positive correlation (r = 0.51) between average retinal nerve fiber layer thickness and postoperative MD, less probably to improved in VF and VA with thicknesses below 80 microns. Conclusion: A nerve fiber layer thickness on optic nerve head Stratus OCT below 80 microns correlated with poorer visual function improvement in patients undergoing transsphenoidal resection surgery of sellar tumors.

Propósito: Establecer el valor pronóstico del grosor peripapilar de la capa de fibras de las células ganglionares (CFCG) cuantificado a la Tomografía de Coherencia Óptica (OCT) como factor pronóstico visual posterior a la resección de tumores selares. Material y Método: Estudio descriptivo, retrospectivo en pacientes sometidos a resección transesfenoidal microscópica de tumores selares con evaluación oftalmológica preoperatoria (evaluación por especialista, campo visual 24 Sita Standard (CV 24-2 SS) y OCT Stratus de papila) y postoperatoria (evaluación por especialista y CV 24-2 SS). El seguimiento mínimo fue de 3 meses. Para el análisis estadístico se utilizó el coeficiente de correlación de Pearson y Spearman, y regresión lineal. Resultados principales: Se incluyó un total de 18 pacientes. En la evaluación prequirúrgica los pacientes presentaron agudeza visual (AV) promedio de 0,70 en Snellen (0,15 en logMAR, rango 0-4 logMAR), una desviación media (DM) promedio de -9,25 dB (0,4 a -30,4 dB) y un grosor de CFCG de 83.7 μm promedio (45,24 a 115,37 μm). En la evaluación postoperatoria los pacientes presentaron AVpromedio de 0,78 Snellen (0,1 logMAR, rango 0-1,3) y una DMpromedio de -5,58 dB (2,31, -32,39 dB). Se encontró una correlación positiva (r2 = 0,51) entre el grosor de CFCG y la DM postoperatoria, con tendencia a la menor mejoría del CV y AV con grosores bajo 80 μm. Conclusión: Una capa de fibras nerviosas bajo 80 μm al OCT Stratus se correlacionó con menor mejoría visual postoperatoria en pacientes sometidos a cirugia transesfenoidal de tumores selares.

Manifestaciones neuroftalmológicas en enfermedades neuroendocrinas / Neurophthalmological findings in neuroendocrine diseases

La neuroftalmología es considerada una especialidad frontera por su vínculo con otras múltiples especialidades médicas, clínicas y quirúrgicas. Los tumores de hipófisis son de tal importancia desde el punto de vista neuroftalmológico que son tratados separadamente en casi todos los textos de la especialidad. El objetivo de la presente revisión es aproximarnos, sobre la base de los conocimientos actuales, a los hallazgos neuroftalmológicos de algunas enfermedades neuroendocrinas, haciendo hincapié en dos temas fundamentales: los adenomas hipofisarios y el síndrome de neoplasias endocrinas múltiples, y demostrar además el importante papel del neuroftalmólogo en estas dos entidades. Quedan aquí evidenciadas las variadas manifestaciones neuroftalmológicas de estas entidades neuroendocrinas, el importante cometido del oftalmólogo en el diagnóstico y el ulterior seguimiento de los pacientes con adenomas hipofisarios, así como lo decisiva que puede resultar su actuación en la identificación de los hallazgos asociados al síndrome de neoplasias endocrinas múltiples tipo 2 B(AU)

Neurophthalmology is considerate frontier speciality because of their relationships with many other medical and surgical specialities. Pituitary tumors are so important from neuro-ophthalmological point of view that they appear as special chapter in text books. Our objective in the present review is to refer the neurophthalmological finfings in two main entities: pituitary adenomas and multiple endocrine neoplasia syndromes and to establish the important role of neuro-ophthalmologist in those neuroendocrine conditions. It was proved the diversity of neurophthalmological findings in neuroendocrine entities, the important role of ophthalmologist in diagnosis and pursuance of patients with pituitary adenomas and its peremptory role in screening finding associated to 2 B type multiple endocrine neoplasia syndrome(AU)

Prolactinomas may have unusual presentations resulting from massive extrasellar tumor extension / Prolactinomas podem ter apresentações incomuns resultantes de maciça extensão tumoral extrasselar

ABSTRACT The purpose of this case series is to report eight patients with giant prolactinomas emphasizing presentations and a treatment complication. The study group included six men and two women. The median age was 29 years (18–54 years); median serum prolactin level was 4,562 ng/ml (1,543–18,690 ng/ml); three patients (37.5%) had panhypopituitarism; median tumor diameter was 50 mm (41–60 mm). Five patients (62.5%) had visual field defects and three had improvement during treatment; six patients (75%) reached prolactin normalization, with a median time of 10.5 months (7–84 months) and median dose of 2.0 mg/week (1.0 to 3.0 mg/week). One patient presented as a true incidentaloma. One patient presented a cerebrospinal fluid leakage during medical treatment and refused surgery, however this resolved with conservative measures. This case series illustrate a rare subtype of macroprolactinomas, the importance of considering unusual presentations at the diagnosis, the effectiveness of pharmacological treatment and its possible complications.

RESUMO O objetivo desta série de casos é relatar oito pacientes com prolactinomas gigantes enfatizando as formas de apresentação e uma complicação do tratamento. O estudo incluiu seis homens e duas mulheres. A mediana de idade foi 29 anos (18–54); e dos níveis de prolactina foi 4.562 ng/ml (1.543–18.690); três pacientes (37,5%) apresentaram pan-hipopituitarismo; a mediana do máximo diâmetro tumoral foi 50 mm (41–60 mm). Cinco pacientes (62,5%) apresentaram alterações no campo visual e três tiveram melhora durante o tratamento; seis pacientes (75%) alcançaram normalização da prolactina em 10,5 meses (7–84) com dose mediana de cabergolina de 2,0 mg / semana (1,0 a 3,0). Um paciente se apresentou como um verdadeiro incidentaloma. Um paciente apresentou uma fistula liquórica durante o tratamento medicamentoso e recusou correção cirúrgica. No entanto a fistula foi resolvida com medidas conservadoras. Esta série de casos ilustra um subtipo raro de macroprolactinomas, a importância de considerar apresentações incomuns no diagnóstico, a eficácia do tratamento farmacológico e suas possíveis complicações.

Pituitary macroadenoma: analysis of intercarotid artery distance compared to controls / Macroadenoma de hipófise: análise da distância intercarotídea comparada a controles

ABSTRACT Objective To evaluate the intercarotid distance (ICD) of patients with pituitary macroadenoma and compare to heatlhy controls. Method We retrospectively reviewed contrast-enhanced MRI images from twenty consecutive patients diagnosed with non-functioning pituitary macroadenoma, measured the ICD at two different levels (petrous segment – ICD1 and horizontal cavernous segment – ICD2) and compared to twenty paired controls. Results There was no statistically significant difference of the mean ICD1 between the groups and subgroups. For the ICD2 there was statistically significant difference between the case and controls. However, there was no significant difference between the patients with smaller adenomas and the controls. In contrast, the patients with giant adenomas showed statistically significantly higher ICD2 than the controls. Conclusion The ICD at the horizontal segment of the cavernous carotid tends to be wider in patients with giant pituitary adenomas than in healthy individuals or patients with smaller adenomas.

RESUMO Objetivo Avaliar a distância intercarotídea (DIC) de pacientes com macroadenoma de hipófise e comparar com controles saudáveis. Método Foram analisados retrospectivamente imagens de ressonância magnética com contraste de vinte pacientes consecutivos com diagnóstico de macroadenoma hipofisário não-funcionante, medidas as DIC em dois níveis diferentes (segmento petroso – DIC1 e segmento cavernoso horizontal – DIC2) e comparados com vinte controles pareados. Resultados Não houve diferença estatisticamente significativa da DIC1 média entre os grupos e subgrupos. Para a DIC2 houve diferença estatisticamente significativa entre os casos e controles. No entanto, não houve diferença significativa entre os doentes com adenomas menores e os controles. Entretanto, os pacientes com adenomas gigantes tiveram estatisticamente significativamente DIC2 que os controlos. Conclusão A DIC no segmento horizontal da carótida cavernoso, tende a ser mais larga em doentes com adenomas hipofisários gigantes do que em indivíduos saudáveis ou de pacientes com adenomas menores.

Prolactinomas: evolution after menopause

ABSTRACT Objetive The aim was to assess the evolution of tumor size and prolactin (PRL) levels in patients with micro and macroprolactinomas diagnosed and treated with dopamine agonists during fertile age, and the effects of suspension of drugs after menopause. Retrospective study, 29 patients with prolactinomas, 22 microadenomas and 7 macroadenomas, diagnosed during their fertile age were studied in their menopause; treatment was stopped in this period. Age at menopause was 49 ± 3.6 years. The average time of treatment was 135 ± 79 months. The time of follow-up after treatment suspension was 4 to 192 months. Results Pre-treatment PRL levels in micro and macroadenomas were 119 ± 57 ng/mL and 258 ± 225 ng/mL, respectively. During menopause after treatment suspension, and at the latest follow-up: in microadenomas PRL levels were 23 ± 13 ng/mL and 16 ± 5.7 ng/mL, respectively; in macroadenomas, PRL levels were 20 ± 6.6 ng/mL 5t5and 25 ± 18 ng/mL, respectively. In menopause after treatment suspension, the microadenomas had disappeared in 9/22 and had decreased in 13/22. In the group of patients whose tumor had decreased, in the latest follow-up, tumors disappeared in 7/13 and remained unchanged in 6/13. In macroadenomas, after treatment suspension 3/7 had disappeared, 3/7 decreased and 1/7 remained unchanged. In the latest control in the 3 patients whose tumor decreased, disappeared in 1/3, decreased in 1/3 and there was no change in the remaining. Conclusions Normal PRL levels and sustained reduction or disappearance of adenomas were achieved in most of patients, probably due to the decrease of estrogen levels. Dopamine agonists might be stopped after menopause in patients with prolactinomas.

Surgical treatment of non-functioning pituitary macroadenomas by the endoscopic endonasal approach in the elderly / Tratamento cirúrgico dos macroadenomas não secretores de hipófise por via endoscópica endonasal em idosos

Over the past three decades, surgical series of elderly patients treated for pituitary adenomas have been published, all of which used the microscopic transsphenoidal or transcranial approach. The objective of this study was to retrospectively analyze the surgical results of our first 25 elderly patients with non-functioning pituitary macroadenoma (NFPM) operated by the endoscopic endonasal approach (EEA). Preoperative visual loss was found in 92.8% of the cases, and 70.8% experienced visual improvement following surgery. Preoperative pituitary dysfunction was found in 69.2% of the cases and postoperative pituitary recovery occurred in 22.2% of them. Mean hospital stay was 6.7 days. The results of this study suggest that surgery remains the first line of treatment for NFPM in the elderly. Because age alone is not a barrier for surgery, patients should be selected for surgical treatment based on their symptoms and clinical condition, as defined by comorbidities.

Nas últimas três décadas, foram publicadas casuísticas de pacientes idosos operados por adenomas de hipófise, nas quais foram utilizadas as vias transcraniana ou transesfenoidal microcirúrgicas. O objetivo deste estudo foi analisar retrospectivamente os resultados dos nossos primeiros 25 pacientes idosos com macroadenomas não secretores de hipófise, operados pela via endoscópica endonasal. O déficit visual pré-operatório foi encontrado em 92,8% dos casos e 70,8% apresentaram melhora da visão depois da cirurgia. O hipopituitarismo pré-operatório foi encontrado em 69,2% dos casos e a sua recuperação ocorreu em 22,2% destes casos. A estadia hospitalar média foi de 6,7 dias. Este estudo sugere que a cirurgia permanece como o tratamento de primeira escolha para pacientes idosos com macroadenomas não secretores de hipófise e a idade por si só não é contraindicação para cirurgia.

Pituitary macroadenoma presenting as a nasal tumor: case report / Macroadenoma hipofisário, apresentando-se como um tumor nasal: relato de caso

CONTEXT: Pituitary macroadenomas are rare intracranial tumors. In a few cases, they may present aggressive behavior and invade the sphenoid sinus and nasal cavity, causing unusual symptoms. In this paper, we report an atypical case of pituitary adenoma presenting as a nasal mass. CASE REPORT: The patient was a 44-year-old woman who had had amenorrhea and galactorrhea for ten months, with associated nasal obstruction, macroglossia and acromegaly. Both growth hormone and prolactin levels were increased. Magnetic resonance imaging showed a large mass originating from the lower surface of the pituitary gland, associated with sella turcica erosion and tumor extension through the sphenoid sinus and nasal cavity. Histopathological analysis demonstrated a chromophobe pituitary adenoma with densely packed rounded epithelial cells, with some atypias and rare mitotic figures. There was no evidence of metastases. CONCLUSION: Macroadenoma invading the nasal cavity is a rare condition and few similar cases have been reported in the literature. This study contributes towards showing that tumor extension to the sphenoid sinus and nasopharynx needs to be considered and investigated in order to make an early diagnosis when atypical symptoms like nasal obstruction are present. .

CONTEXTO: Macroadenomas hipofisários são tumores intracraniais raros. Em alguns casos, podem apresentar comportamento agressivo e invadir o seio esfenoidal e a cavidade nasal, causando sintomas não usuais. Neste relato de caso, descrevemos um caso atípico de adenoma hipofisário manifestando-se como uma massa nasal. RELATO DE CASO: A paciente de 44 anos, do sexo feminino, apresentava amenorreia e galactorreia por 10 meses associando-se a obstrução nasal, macroglossia e acromegalia. Os níveis do hormônio de crescimento e de prolactina apresentaram-se aumentados. Ressonância magnética mostrou uma grande massa originada da superfície inferior da glândula hipofisária associada com erosão da sela túrcica e extensão do tumor através do seio esfenoidal e cavidade nasal. Análise histopatológica demonstrou adenoma hipofisário cromófobo com células epiteliais arrendondadas densamente agrupadas com algumas atipias e escassas figuras de mitose. Não houve evidências de metástase. CONCLUSÃO: O macroadenoma invasivo para a cavidade nasal é uma condição rara e há poucos relatos similares descritos na literatura. Este trabalho contribui para mostrar que, na presença de sintomas atípicos como a obstrução nasal, a extensão para o seio esfenoidal e para a nasofaringe deve ser considerada e investigada para um diagnóstico precoce. .

Aggressive pituitary lesion with a remarkably high Ki-67 / Lesão pituitária agressiva com Ki-67 notavelmente elevado

The uncommon aggressive pituitary tumors are named carcinomas when metastases are detected, either in the central nervous system and/or systemically. Some cases are associated with hormonal overproduction, but most are diagnosed because of local symptoms. These neoplasias are generally refractory to current treatments. A 51 year-old woman presented sudden onset of headache, left arm paresis and left facial hypoesthesia. Computed tomography scan and magnetic resonance imaging revealed a pituitary tumor invading the left sphenoidal and cavernous sinuses. Laboratory data excluded hormonal hypersecretion. The patient underwent transsphenoidal surgery and histological findings showed a neoplasia with Ki-67 estimated at 75%. Medical imaging excluded both a primary occult tumor and central nervous system or systemic dissemination. Three weeks postoperatively, neurological condition worsened, with new onset of ataxia, bilateral ptosis, ophthalmoplegia and an increase in the size of the lesion, leading to surgical intervention by craniotomy, followed by only a few sessions of radiotherapy, because of severe disease progression. Patient died nearly 2 months after the initial manifestations. This case illustrates the aggressiveness of some pituitary lesions, the limited efficacy of current treatment modalities such as surgery or radiotherapy and the pitfalls of the current pituitary tumors classification. To our knowledge, this case corresponds to one of the most aggressive pituitary neoplasms reported so far, with a very high Ki-67 index (75%) and short survival (2 months). Ki-67 index could be of prognostic value in pituitary tumors. Pituitary tumors World Health Organization (WHO) classification could be revisited.

Os raros tumores pituitários agressivos são chamados carcinomas quando são detectadas metástases, sejam sistêmicas e/ou em sistema nervoso central. Alguns casos estão associados com superprodução de hormônio, mas a maioria é diagnosticada em função dos sintomas locais. Essas neoplasias são geralmente refratárias aos tratamentos atuais. Uma mulher com 51 anos de idade apresentou dor de cabeça de início súbito, paralisia de braço esquerdo e hipoestesia facial esquerda. A tomografia e a ressonância magnética revelaram um tumor pituitário invadindo os seios esfenoidal e cavernoso esquerdos. Os dados laboratoriais excluíram hipersecreção hormonal. A paciente foi submetida à cirurgia transesfenoidal, e os achados histológicos mostraram uma neoplasia com Ki-67 estimado em 75%. As imagens excluíram tanto um tumor oculto primário quanto disseminação sistêmica ou do sistema nervoso central. Três semanas após a cirurgia, a condição neurológica apresentou piora com início de ataxia, ptose bilateral, oftalmoplegia e aumento do tamanho da lesão, levando à intervenção cirúrgica por craniotomia, seguida por apenas algumas sessões de radioterapia devido à progressão grave da doença. A paciente veio a óbito depois de quase dois meses das manifestações iniciais. O caso ilustra a agressividade de algumas lesões pituitárias, a eficácia limitada das modalidades atuais de tratamento, como a cirurgia ou a radioterapia, e as limitações da classificação atual de tumores pituitários. Até onde sabemos, esse caso corresponde a uma das neoplasias pituitárias mais agressivas descritas até hoje, com um nível muito alto de Ki-67 (75%) e sobrevida curta (2 meses). O nível de Ki-67 pode ser de valor prognóstico em tumores pituitários. A classificação da Organização Mundial da Saúde (OMS) para tumores pituitários deveria ser revisitada.

Clinicopathologic Analysis of Pituitary Adenoma: A Single Institute Experience

Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent.

Physical activities in daily life and functional capacity compared to disease activity control in acromegalic patients: impact in self-reported quality of life / Avaliação da atividade física na prática de vida diária comparada com o nível de atividade da doença em pacientes acromegálicos: impacto na percepção da qualidade de vida

OBJECTIVE: To evaluate the quality of life and its association with daily physical activity and disease control in acromegalic patients. SUBJECTS AND METHODS: A cross-sectional, case series study, composed of 42 patients recruited from the Neuroendocrinology Unit of the University Hospital of Brasilia. Level of physical activity was accessed by the International Physical Activity Questionnaire (IPAQ 6-short-form), which evaluates the weekly time spent on physical activity of moderate to vigorous intensity in different contexts of life. Quality of life was evaluated by The Medical Outcome Study Questionnaire Short Form (SF-36). Data was compared to growth hormone (GH) and insulin-like growth factor (IGF-1) levels. Students' t test and Fisher test were used, p < 0.05, SPSS 17.0. RESULTS: Twenty-two women, aged 51.33 ± 14.33 and 20 men, aged 46.2 ± 13.18 were evaluated. Arthralgia was present in 83% of cases. In men, the most common sites of pain were the knees (73%), spine (47% lumbar, and 53% thoracic and cervical segments), hands and wrists (40%). Higher scores on SF-36 were observed in patients with intermediate or high levels of physical activity, in the domains social functioning (75 CI 57.3-92.6), general health (75.5 CI 60.4-90.5), mental health (70 CI 57.8-82.1). CONCLUSIONS: In this study, the presence and severity of physical disability and pain were not associated with initial GH and IGF-1 levels or time of exposure to GH excess. However, the patients considered controlled, with normal a normal age-adjusted IGF-1, presented higher scores in SF-36, in physical and emotional domains, compared with patients with persistent hypersomatotrophism. These findings suggest benefits of metabolic control in self-reported quality of life.

OBJETIVO: Avaliar a qualidade de vida e sua associação com a prática de vida diária e controle metabólico em pacientes portadores de acromegalia. SUJEITOS E MÉTODOS: Estudo seccional de série de casos, composto por 42 pacientes recrutados na Unidade de Neuroendocrinologia do Hospital Universitário de Brasília. O nível de atividade física foi estimado pelo Questionário Internacional de Atividade Física (IPAQ-6), que avalia o tempo gasto semanalmente em atividades físicas que variam de intensidade em diferentes contextos de vida. A qualidade de vida foi avaliada pelo questionário SF-36. Os dados obtidos foram comparados aos níveis de hormônio do crescimento (GH) e fator de crescimento semelhante à insulina (IGF-1). Os testes t Students e Fisher foram aplicados e p < 0,05 foram considerados significativos, SPSS 17.0. RESULTADOS: Avaliaram-se 22 mulheres com idades de 51,33 ± 14,33 e 20 homens com idades de 46,2 ±13,18. Artralgia foi relatada em 83% dos pacientes. Em homens, os sítios de dor mais comuns foram os joelhos (73%), coluna vertebral (47% lombar, 53% segmentos torácico e cervical), mãos e quadris (40%). Os maiores escores no SF-36 foram observados em pacientes com níveis intermediário ou alto de atividade física, sobretudo nos domínios social (75 CI 57,3-92,6), saúde geral (75,5 CI 60,4-90,5), saúde mental (70 CI 57,8-82,1). CONCLUSÕES: A presença e a severidade do prejuízo no desempenho físico e dor não se associaram com Gh e IGF-1 no diagnóstico, tempo de exposição prévio à doença. Todavia, pacientes considerados controlados apresentaram melhores escores nos domínios físico e emocional, comparados com pacientes com hipersomatotrofismo persistente. Tais achados sugerem benefícios do controle metabólico na qualidade de vida.