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OBJECTIVE: To identify key recommendations for maximizing the efficiency and efficacy of perioperative care in transsphenoidal pituitary surgery. METHODS: The authors performed a comprehensive literature search of Enhanced Recovery After Surgery protocols implemented for patients undergoing transsphenoidal adenomectomy (TSA); individual recommendations were abstracted, and the evidence base thoroughly reviewed. RESULTS: The authors identified 19 individual recommendations pertinent to the care of patients undergoing TSA, which were subdivided into preoperative (n=6), intraoperative (n=6), and postoperative (n=7) interventions. Key factors recommended for minimizing length of stay, preventing readmission, and improving patient outcomes included comprehensive patient education, multidisciplinary evaluation, avoidance of routine lumbar drain placement and nasal packing, and rigorous postoperative monitoring of pituitary function and salt-water imbalances. The overall level of evidence for 7/19 (37%) implemented recommendations was found to be low, suggesting a need for continued research in this patient population. CONCLUSION: Several key interventions should be considered in the development of Enhanced Recovery After Surgery protocols for TSA, which may aid in further decreasing length of stay and promoting positive patient outcomes.
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Recuperação Pós-Cirúrgica Melhorada , Doenças da Hipófise , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/cirurgia , Hipófise/cirurgia , Assistência Perioperatória , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologiaRESUMO
In this case report, the clinical presentation of an inflammatory orbitopathy seen following treatment with ipilimumab is described. After 3 rounds of ipilimumab (10 mg/kg) treatment for Stage III metastatic melanoma, the subject of this case report developed acute eye pain and proptosis. At initial presentation, she had marked proptosis and diffuse severe ophthalmoparesis. After treatment with high-dose steroids, over a period of 6 months, the symptoms gradually resolved fully. Although the condition may mimic thyroid-associated orbitopathy, imaging and laboratory features suggest that the orbitopathy associated with ipilimumab is not a secondary effect of thyroid dysfunction but a distinct inflammatory condition. The authors conclude that immune-related side effects can occur with biologic agents used to treat malignancies and these side-effects can involve the eye. This case illustrates the occurrence of an inflammatory orbitopathy associated with ipilimumab treatment.
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Anticorpos Monoclonais/efeitos adversos , Inflamação/induzido quimicamente , Melanoma/tratamento farmacológico , Órbita/diagnóstico por imagem , Doenças Orbitárias/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Anticorpos Monoclonais/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Inflamação/diagnóstico , Ipilimumab , Imageamento por Ressonância Magnética , Melanoma/diagnóstico , Melanoma/secundário , Doenças Orbitárias/diagnóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/secundário , Ultrassonografia , Melanoma Maligno CutâneoRESUMO
OBJECTIVE: The prevalence of clinically silent corticotroph macroadenomas is unknown. Our aim was to determine the prevalence of clinically silent corticotroph macroadenomas among all pituitary macroadenomas. DESIGN: Patients scheduled to have transsphenoidal surgery for any sellar mass were prospectively evaluated clinically and biochemically. PATIENTS: Adults who were scheduled for transsphenoidal surgery for a sellar mass at a single academic medical centre. MEASUREMENTS: Patients were assessed clinically prior to surgery and graded as having typical, mild or no Cushingoid features. They were assessed biochemically by plasma ACTH and 24-h urine free cortisol (UFC). Excised tissue was examined histologically, and pituitary macroadenomas, examined by immunohistochemistry. Patients with corticotroph macroadenomas were classified as clinically silent if they exhibited no Cushingoid features but had elevated plasma ACTH and/or 24-h UFC. They were classified as totally silent if they exhibited neither Cushingoid features nor elevated plasma ACTH or 24-h UFC. RESULTS: Of 124 patients who had pathologically confirmed pituitary macroadenomas, 20 (16%) had corticotroph macroadenomas. Eight (40%) of these were clinically silent, in that they had no Cushingoid features but could be identified biochemically by elevated plasma ACTH (seven) and/or 24-h UFC (three). Five (25%) were totally silent. CONCLUSIONS: A substantial minority (16%) of pituitary macroadenomas treated surgically are corticotroph adenomas. Of these, 40% are clinically silent but can be recognized by elevated plasma ACTH and/or 24-h UFC. Recognizing these adenomas may influence the surgical approach and provide a marker by which to follow the response to treatment.
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Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma Hipofisário Secretor de ACT/epidemiologia , Hormônio Adrenocorticotrópico/sangue , Adulto , Feminino , Humanos , Hidrocortisona/análise , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/patologia , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/cirurgia , PrevalênciaRESUMO
Background/Objective: Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis is a rare small vessel vasculitis that can cause pituitary hypophysitis. Hypophysitis is difficult to treat, often requiring high doses of glucocorticoids with frequent flaring as glucocorticoids are tapered. We present a case of ANCA vasculitis involving the pituitary gland successfully treated with rituximab. Case Report: Fifty-one-year-old woman developed progressive frontal headaches, congestion, and epistaxis. Sinus computed tomography scan showed pituitary enlargement and chronic mucosal disease. Pituitary magnetic resonance imaging (MRI) confirmed a diffusely enlarged pituitary with a thickened pituitary stalk. Serologic evaluation revealed elevated inflammatory markers, positive perinuclear ANCA (p-ANCA), and an elevated serum anti-proteinase 3 (anti-PR3) antibody. The patient underwent pituitary biopsy, which showed adenohypophysitis with dense lymphoplasmacytic infiltration, some arranged perivascularly, compatible with involvement of the pituitary gland by ANCA vasculitis. The patient began rituximab and reported resolution of daily headaches, congestion, and epistaxis. Pituitary MRI scan 6 months after rituximab showed reduction in pituitary gland size and stalk thickening. Discussion: ANCA vasculitis is a rare etiology of pituitary hypophysitis, which can present a diagnostic and therapeutic challenge. Pituitary involvement of ANCA vasculitis can be identified through p-ANCA or cytoplasmic ANCA (c-ANCA) and biopsy of the involved tissue. Rituximab, a monoclonal antibody against CD20, has been successfully used to treat ANCA vasculitis and in this case, led to clinical improvements and reduction in the size of the pituitary gland. Conclusion: Pituitary biopsy enabled confirmation of ANCA hypophysitis and facilitated treatment with a steroid-sparing agent.
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Background: Sheehan syndrome (SS) is a rare complication of severe postpartum hemorrhage or hypotension during the processes of labor and delivery that results in ischemic pituitary infarction and necrosis. In this case report, we describe an unusual presentation of SS without inciting factors. Case Presentation: A 30-year-old multiparous woman presented 2 hours after a normal spontaneous vaginal delivery with a profound severe headache, and subsequent agalactia, dry skin, and mood changes. She was managed conservatively until 10 months postdelivery when she complained of persistent symptoms including amenorrhea. A brain magnetic resonance (MR) with pituitary imaging revealed findings consistent with SS. The patient's symptoms improved and ultimately resolved after levothyroxine, estrogen replacement therapy, and hydrocortisone were instituted. Conclusions: SS can present without recognized inciting factors. During the initial phase, women may present with profound headache and/or visual disturbances warranting neurological evaluation. A high index of suspicion and a brain MR with pituitary imaging should prompt early consideration of SS to aid in the diagnosis.
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BACKGROUND: Surgical resection is the primary treatment for nonfunctional (NF) pituitary adenomas, but gross-total resection is difficult to achieve in all cases. NF adenomas overexpress folate receptor alpha (FRα). OBJECTIVE: To test the hypothesis that we could target FRα for highly sensitive and specific intraoperative detection of NF adenomas using near-infrared (NIR) imaging. METHODS: Fourteen patients with NF pituitary adenoma were infused with the folate analog NIR dye OTL38 preoperatively. NIR fluorescence signal-to-background ratio (SBR) was recorded for each tumor during resection of the adenomas. Extent of surgery was not modified based on the presence or absence of fluorescence. Immunohistochemistry was performed to assess FRα expression in all specimens. Magnetic resonance imaging (MRI) was performed postoperatively to assess residual neoplasm. RESULTS: Nine adenomas overexpressed FRα and fluoresced with a NIR SBR of 3.2 ± 0.52, whereas the 5 non-FRα-overexpressing adenomas fluoresced with an SBR of 1.5 ± 0.21. Linear regression demonstrated a significant correlation between intraoperative SBR and the FRα expression (P-value < .001). Analysis of 14 margin samples revealed that the surgeon's impression of the tissue had 83% sensitivity, 100% specificity, 100% positive predictive value, and 89% negative predictive value, while NIR fluorescence had 100% for all values. NIR fluorescence accurately predicted postoperative MRI results in 78% of FRα-overexpressing patients. CONCLUSION: Preoperative injection of folate-tagged NIR dye provides strong signal and visualization of NF pituitary adenomas. It is 100% sensitive and specific for detecting margin neoplasm and can predict postoperative MRI findings. Our results suggest that NIR fluorescence may be superior to white-light visualization alone and may improve resection rates in NF pituitary adenomas.
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Adenoma/cirurgia , Receptor 1 de Folato/metabolismo , Imagem Óptica/métodos , Neoplasias Hipofisárias/cirurgia , Adenoma/diagnóstico por imagem , Adenoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluorescência , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/metabolismo , Adulto JovemRESUMO
OBJECTIVE Pituitary adenomas account for approximately 10% of intracranial tumors and have an estimated prevalence of 15%-20% in the general US population. Resection is the primary treatment for pituitary adenomas, and the transsphenoidal approach remains the most common. The greatest challenge with pituitary adenomas is that 20% of patients develop tumor recurrence. Current approaches to reduce recurrence, such as intraoperative MRI, are costly, associated with high false-positive rates, and not recommended. Pituitary adenomas are known to overexpress folate receptor alpha (FRα), and it was hypothesized that OTL38, a folate analog conjugated to a near-infrared (NIR) fluorescent dye, could provide real-time intraoperative visual contrast of the tumor versus the surrounding nonneoplastic tissues. The preliminary results of this novel clinical trial are presented. METHODS Nineteen adult patients who presented with pituitary adenoma were enrolled. Patients were infused with OTL38 2-4 hours prior to surgery. A 4-mm endoscope with both visible and NIR light capabilities was used to visualize the pituitary adenoma and its margins in real time during surgery. The signal-to-background ratio (SBR) was recorded for each tumor and surrounding tissues at various endoscope-to-sella distances. Immunohistochemical analysis was performed to assess the FRα expression levels in all specimens and classify patients as having either high or low FRα expression. RESULTS Data from 15 patients (4 with null cell adenomas, 1 clinically silent gonadotroph, 1 totally silent somatotroph, 5 with a corticotroph, 3 with somatotrophs, and 1 somatocorticotroph) were analyzed in this preliminary analysis. Four patients were excluded for technical considerations. Intraoperative NIR imaging delineated the main tumors in all 15 patients with an average SBR of 1.9 ± 0.70. The FRα expression level of the adenomas and endoscope-to-sella distance had statistically significant impacts on the fluorescent SBRs. Additional considerations included adenoma functional status and time from OTL38 injection. SBRs were 3.0 ± 0.29 for tumors with high FRα expression (n = 3) and 1.6 ± 0.43 for tumors with low FRα expression (n = 12; p < 0.05). In 3 patients with immunohistochemistry-confirmed FRα overexpression (2 patients with null cell adenoma and 1 patient with clinically silent gonadotroph), intraoperative NIR imaging demonstrated perfect classification of the tumor margins with 100% sensitivity and 100% specificity. In addition, for these 3 patients, intraoperative residual fluorescence predicted postoperative MRI results with perfect concordance. CONCLUSIONS Pituitary adenomas and their margins can be intraoperatively visualized with the preoperative injection of OTL38, a folate analog conjugated to NIR dye. Tumor-to-background contrast is most pronounced in adenomas that overexpress FRα. Intraoperative SBR at the appropriate endoscope-to-sella distance can predict adenoma FRα expression status in real time. This work suggests that for adenomas with high FRα expression, it may be possible to identify margins and to predict postoperative MRI findings.
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Adenoma/metabolismo , Adenoma/cirurgia , Receptor 1 de Folato/biossíntese , Procedimentos Neurocirúrgicos/métodos , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/cirurgia , Cirurgia Assistida por Computador/métodos , Adenoma/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Corantes Fluorescentes , Humanos , Raios Infravermelhos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/diagnóstico por imagem , Estudos Prospectivos , Seio EsfenoidalRESUMO
BACKGROUND: Ipilimumab, a humanized CLTA-4 antibody is a standard therapy in the treatment of advanced melanoma. While ipilimumab provides an overall survival benefit to patients, it can be associated with immune related adverse events (IrAEs). CASE PRESENTATION: Here we describe a patient treated with ipilimumab who experienced known IrAEs, including hypophysitis, as well as a profound vision loss due to optic neuritis. There are rare reports of optic neuritis occurring as an adverse event associated with ipilimumab treatment. Furthermore, the patient experienced multiple complications from high dose steroids used to manage his IrAEs. CONCLUSIONS: This case highlights the need for recognition of atypical immune mediated processes associated with newer checkpoint inhibitor therapies including ipilimumab.
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Antineoplásicos Imunológicos/efeitos adversos , Ipilimumab/efeitos adversos , Melanoma/complicações , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia , Doença Aguda , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores , Encéfalo/patologia , Antígeno CTLA-4/antagonistas & inibidores , Angiofluoresceinografia , Humanos , Ipilimumab/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Melanoma/tratamento farmacológico , Melanoma/patologia , Pessoa de Meia-Idade , Terapia de Alvo Molecular/efeitos adversos , Metástase Neoplásica , Nervo Óptico/patologia , Testes VisuaisAssuntos
Hipertireoidismo/complicações , Hipertireoidismo/terapia , Antitireóideos/uso terapêutico , Ansiedade/etiologia , Ablação por Cateter , Causas de Morte , Disfunção Erétil/etiologia , Feminino , Humanos , Hipertireoidismo/sangue , Hipertireoidismo/epidemiologia , Masculino , Osteoporose/etiologia , Hormônios Tireóideos/sangue , Tireoidectomia , Resultado do TratamentoRESUMO
PURPOSE: To examine whether the use of C-arm computed tomography (CT) during adrenal vein sampling improves the technical success rate of the procedure. MATERIALS AND METHODS: Nine consecutive patients with suspected primary hyperaldosteronism underwent standard adrenal vein sampling that included cortisol stimulation. The procedure was augmented with multiplanar C-arm CT images reconstructed from data acquired during a 180 degrees C-arm rotation. Whenever C-arm CT images showed the sampling catheter to be in the wrong position, the catheter was repositioned. Cortisol response was correlated to C-arm CT findings. RESULTS: All patients had successful and diagnostic adrenal vein sampling. C-arm CT showed sampling catheter malposition in two patients (22%). Repeat C-arm CT after repositioning showed proper catheter location. Cortisol stimulation results and C-arm CT findings were concordant in 100% of cases. CONCLUSIONS: C-arm CT is reliable in confirming the location of sampling catheters during adrenal vein sampling. If the 100% concordance between cortisol stimulation and C-arm CT findings is found in larger groups, the technical success rate may approach 100%. Cortisol stimulation may become obsolete and repeat procedures unnecessary, with significant time and cost savings.