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1.
J Vet Intern Med ; 38(1): 351-357, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37916616

RESUMO

Pituitary-dependent hypersomatotropism is rarely diagnosed in dogs and surgical treatment is not reported. A 6-year-10-month male neutered Patterdale Terrier presented with polyuria, polydipsia, progressive pharyngeal stertor, excessive hair growth and widened facial features and paws. Serum insulin-like growth factor-1 concentration via radioimmunoassay was consistent with hypersomatotropism (1783 ng/mL). A pituitary mass was identified on magnetic resonance and computed tomography imaging. Six weeks later, glucosuria, starved hyperglycemia and serum fructosamine above the reference range (467.6 µmol/L, RI 177-314) were documented, consistent with diabetes mellitus. Transsphenoidal hypophysectomy was performed under general anesthesia without complications. Pituitary histopathology identified an acidophil neoplasm, with positive immunostaining for growth hormone. Postoperatively, there was rapid resolution of clinical, biochemical and morphologic changes of hypersomatotropism with persistence of diabetes mellitus. This case demonstrates successful resolution of hypersomatotropism with ongoing diabetes mellitus in a dog after surgical treatment by transsphenoidal hypophysectomy.


Assuntos
Acromegalia , Adenoma , Diabetes Mellitus , Doenças do Cão , Adenoma Hipofisário Secretor de Hormônio do Crescimento , Neoplasias Hipofisárias , Cães , Masculino , Animais , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/veterinária , Hipofisectomia/veterinária , Hipofisectomia/métodos , Acromegalia/veterinária , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/veterinária , Diabetes Mellitus/veterinária , Adenoma/complicações , Adenoma/cirurgia , Adenoma/veterinária , Doenças do Cão/cirurgia , Doenças do Cão/diagnóstico
2.
Vet Surg ; 52(1): 69-80, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36416123

RESUMO

OBJECTIVE: To characterize the clinical features, neurological examination findings, diagnostic imaging results, histopathological findings, and outcome following transsphenoidal hypophysectomy (TSH) in dogs with nonfunctional sellar masses (NFSM). STUDY DESIGN: Multi-institutional retrospective study. METHODS: Medical records of dogs that underwent TSH for a NFSM were reviewed for clinical signs, physical and neurological examination findings, diagnostic imaging results, endocrine testing, surgery reports, and outcome. Magnetic resonance (MR) imaging was rereviewed, and tumors were classified using the previously described system according to pituitary tumor extension and vascular involvement. Owners of dogs that survived to discharge were contacted. RESULTS: The majority of dogs presented for mentation change (12/15). The mean pituitary to brain ratio (P/B ratio) was 1.05 (0.6-1.4). Eight dogs had a tumor imaging classification of 5B. Eleven dogs were diagnosed with a nonfunctional pituitary adenoma (NFPA). Perioperative mortality was 33% (5/15). The median survival for all dogs was 232 days (0-1658). When dogs that did not survive to discharge were excluded, the median survival time was 708 days. Seven of 10 dogs that survived the perioperative period received adjunctive therapy. Owner assessment of outcome was excellent (6/7) to good (1/7). CONCLUSION: The common presenting complaint for dogs with large NFSM causing mass effect was mentation changes. Dogs with NFPA that survived to discharge and received adjunctive therapy had good to excellent outcomes. CLINICAL SIGNIFICANCE: Transsphenoidal debulking with adjunctive therapy can be considered for the treatment of NFSM causing clinical signs of mass effect in dogs. Successful long-term outcomes are possible.


Assuntos
Doenças do Cão , Neoplasias Hipofisárias , Cães , Animais , Hipofisectomia/veterinária , Hipofisectomia/efeitos adversos , Hipofisectomia/métodos , Estudos Retrospectivos , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Hipófise/patologia , Hipófise/cirurgia , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/veterinária , Neoplasias Hipofisárias/patologia , Tireotropina , Resultado do Tratamento
3.
J Small Anim Pract ; 64(2): 111-117, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36335913

RESUMO

An 8.0-kg 8-year-old male dachshund was presented for surgical treatment of suspected pituitary-dependent hyperadrenocorticism with portal vein thrombosis. Advanced diagnostic imaging revealed a thrombus in the splenic and portal veins. For the portal vein thrombus, CT angiography showed an enhanced timing delay in the lateral right and caudate liver lobes. Blood tests showed a marked increase in the liver panel, including total bile acid. Brain MRI revealed a pituitary mass, suggesting pituitary-dependent hyperadrenocorticism. The mass was completely resected. The preoperative antithrombotic therapy of rivaroxaban (0.66 mg/kg, PO, once per day) and clopidogrel sulphate (1.66 mg/kg, PO, once per day) was continued postoperatively. Six months after resection of the pituitary mass, the thrombus had disappeared. Further studies are required to prove a causal association between the disappearance of the thrombus and the treatments provided.


Assuntos
Hiperfunção Adrenocortical , Doenças do Cão , Trombose , Masculino , Cães , Animais , Hipofisectomia/veterinária , Hipofisectomia/efeitos adversos , Hipofisectomia/métodos , Trombose/diagnóstico por imagem , Trombose/cirurgia , Trombose/veterinária , Fígado , Veia Porta , Hiperfunção Adrenocortical/cirurgia , Hiperfunção Adrenocortical/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/tratamento farmacológico , Doenças do Cão/cirurgia
4.
Neuro Endocrinol Lett ; 43(5): 265-269, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36584403

RESUMO

OBJECTIVES: Hypophysectomy is a method used in analgesia in patients with painful bone metastases. The pain relief after this procedure is not pathophysiologically fully understood. In only a few studies Leksell gamma knife (LGK) was used for radiosurgical hypophysectomy. In our study, we performed the LGK hypophysectomy in patients with intractable cancer-related pain due to bone metastases and evaluated the impact of this method on pain relief. METHODS: From 1994 to 2020 we enrolled 20 patients with the diagnosis of disseminated carcinoma. All patients underwent radiosurgical hypophysectomy on LGK. The maximum dose was 150-200Gy. The dose to the optic pathway was 9,8Gy on average. RESULTS: Six patients died before the first follow-up and we did not receive any posttreatment information from 4 patients. In all the rest 10 evaluated patients pain relief was achieved (0-50% of pre-procedural pain). The hypophysectomy effect lasted for the rest of their lives (the mean follow-up period was 12,6 months). In three patients we observed hormonal disbalance - hypocortisolism and diabetes insipidus with good response to substitutional therapy, one patient developed a temporary abducens nerve palsy. No other adverse events were observed. CONCLUSION: Our results suggest that the LGK hypophysectomy is an effective and safe procedure to reduce cancer-related intractable pain, especially in bone metastases of hormonally dependent tumors.


Assuntos
Dor do Câncer , Neoplasias , Dor Intratável , Radiocirurgia , Humanos , Hipofisectomia/métodos , Dor do Câncer/etiologia , Dor do Câncer/cirurgia , Dor Intratável/etiologia , Dor Intratável/cirurgia , Radiocirurgia/métodos
5.
Prensa méd. argent ; 108(3): 165-189, 20220000. tab, fig, graf
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1373279

RESUMO

Introducción. Los adenomas gigantes de hipófisis (AGHs) son aquellos tumores con un diámetro máximo ≥4 cm en cualquier dirección, representando del 5% al 14% del total de los adenomas que se tratan quirúrgicamente. Su manejo terapéutico es desafiante ya que, debido a su extensión hacia otras estructuras cerebrales,está asociado a un riesgo mayor de complicaciones quirúrgicas, con una menor tasa de resección total. El objetivo de este trabajo fue evaluar el impacto de la cirugía endoscópica transesfenoidal en AGHs, analizando las variables asociadas a resultados visuales, endocrinológicos y según el grado de resección. Pacientes y Métodos. Se evaluó en 44 pacientes con AGHs(diámetro ≥4 cm y/o volumen ≥10 ml) la presentación visual, endocrinológica e imágenes. Se analizaron estadísticamente resultados visuales, endocrinológicos, grado de resección y complicaciones quirúrgicas. Resultados. Edad promedio de 48.8 años, 24 mujeres y 20 hombres. Presentación: déficit del campo visual (93.1%), hipopituitarismo (61.3%), cefalea (54.5%). Diámetro, volumen y extensión supraselar promedios: 4.8 cm, 20.3 ml, 1.8 cm, respectivamente. Campo visual: mejoría: 83.3%, sin cambios: 9.5%, mayormente en síntomas bilaterales (p<0.0001). Desmejoríavisual: 0%. En resección total: mayor posibilidad de mejoría visual (p=0.040). Buenos resultados endocrinológicos: 85.7%. Tasa de resección total: 52.3%. Resección subtotal: más frecuente con invasión del seno cavernoso (p=0.014). Sin diferencias en el grado de resección según diámetro, volumen, extensión supraselar, forma ni aspecto. Hipopituitarismo: 4.2%. Diabetes insípida: 9.5%, asociada a mayor diámetro (p=0.038) o extensión supraselar (p=0.010) y aspecto sólido (p=0.023). Fístula de LCR: 7.1%. Conclusión. La resección total puede lograrse en la mitad de los casos, siendo la limitante principal el grado de invasión del seno cavernoso y no el aspecto morfológico del AGH per se. Aun así, los resultados visuales y endocrinológicos son muy buenos. En resecciones incompletas se logra el control de la enfermedad mediante tratamientos complementarios


Introduction. Giant pituitary adenomas (sGAs) are those tumors with a maximum diame- ter ≥4 cm in any direction, representing 5% to 14% of all adenomas that are treated surgi- cally. Its therapeutic management is challenging since, due to its extension to other brain structures, it is associated with a higher risk of surgical complications, with a lower rate of total resection. Te objective of this work was to evaluate the impact of transsphenoidal endoscopic surgery on AGHs, analyzing the variables associated with visual and endocri- nological results and according to the degree of resection. Patients and Methods. Visual, endocrinological and imaging presentation were evaluated in 44 patients with sHAA (dia- meter ≥4 cm and/or volume ≥10 ml). Visual and endocrinological results, degree of resection and surgical complications were statistically analyzed. Results. Average age of 48.8 years, 24 women and 20 men. Presentation: visual field deficit (93.1%), hypopituitarism (61.3%), headache (54.5%). Average diameter, volume and suprasellar extension: 4.8 cm, 20.3 ml, 1.8 cm, respectively. Visual field: improvement: 83.3%, no changes: 9.5%, mostly in bilate- ral symptoms (p<0.0001). Visual impairment: 0%. In total resection: greater possibility of visual improvement (p=0.040). Good endocrinological results: 85.7%. Total resection rate: 52.3%. Subtotal resection: more frequent with invasion of the cavernous sinus (p=0.014). No differences in the degree of resection according to diameter, volume, suprasellar exten- sion, shape or appearance. Hypopituitarism: 4.2%. Diabetes insipidus: 9.5%, associated with greater diameter (p=0.038) or suprasellar extension (p=0.010) and solid appearance (p=0.023). CSF fistula: 7.1%. Conclusion. Total resection can be achieved in half of the cases, the main limitation being the degree of invasion of the cavernous sinus and not the morphological appearance of the HGA per se. Even so, the visual and endocrinological results are very good. In incomplete resections, disease control is achieved through com- plementary treatments


Assuntos
Humanos , Hipófise/patologia , Complicações Pós-Operatórias , Adenoma/patologia , Distribuição de Qui-Quadrado , Endoscopia/métodos , Liberação de Cirurgia , Margens de Excisão , Hipofisectomia/métodos
6.
Am J Vet Res ; 83(5): 465-472, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35175933

RESUMO

OBJECTIVE: To assess the accuracy of transsphenoidal hypophysectomy using 3-D printed patient-specific guides (3D-PSGs) in small-breed dogs. ANIMALS: Heads obtained from the cadavers of 19 small-breed dogs (ex vivo portion of study) and 3 healthy adult (3 to 4 years) purpose-bred Beagles with a median body weight of 9.2 kg. PROCEDURES: In the ex vivo study, CT images of the cadavers were collected. The position, width, and length of the pituitary fossa and the pilot hole (insertion angle and place) were measured. Using PSGs, 19 pilot holes were made for the pituitary gland fossa, and CT was performed to assess the position accuracy. In the in vivo study, 3 surgical windows from the pilot holes were made using PSGs. Repeated CT and MRI were performed to evaluate the safeness and effectiveness of PSGs, followed by necropsy. RESULTS: In the ex vivo study, the median (interquartile range) difference between the pre- and postoperative insertion angles was 2° (0° to 3.5°) and the median deviation of the pilot hole was 0.46 mm (0 to 1.58 mm). In the in vivo study, the surrounding structures were not damaged, and favorable outcomes were evident in terms of the shape, size, and position of the surgical window. CLINICAL RELEVANCE: 3D-PSGs provided a safe and effective surgical window for transsphenoidal hypophysectomy. Our findings emphasized the applicability of PSGs in brain surgery, in terms of accuracy and effectiveness.


Assuntos
Doenças do Cão , Hipofisectomia , Animais , Cadáver , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Cães , Hipofisectomia/métodos , Hipofisectomia/veterinária , Hipófise/diagnóstico por imagem , Hipófise/cirurgia , Impressão Tridimensional
7.
J Endocrinol Invest ; 45(3): 629-637, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34699044

RESUMO

PURPOSE: Dynamic testing represents the mainstay in the differential diagnosis of ACTH-dependent Cushing's syndrome. However, in case of undetectable or detectable lesion < 6 mm on MRI, bilateral inferior petrosal sinus sampling (BIPSS) is suggested by current guidelines. Aim of this study was to analyze the performance of CRH, desmopressin and high-dose dexamethasone suppression test (HDDST) in the differential diagnosis of ACTH-dependent Cushing's syndrome as well as the impact of invasive and noninvasive tests on surgical outcome in patients affected by Cushing's disease (CD). METHODS: Retrospective analysis on 148 patients with CD and 26 patients with ectopic ACTH syndrome. RESULTS: Among CD patients, negative MRI/lesion < 6 mm was detected in 97 patients (Group A); 29 had a 6-10 mm lesion (Group B) and 22 a macroadenoma (Group C). A positive response to CRH test, HDSST and desmopressin test was recorded in 89.4%, 91·4% and 70.1% of cases, respectively. Concordant positive response to both CRH/HDDST and CRH/desmopressin tests showed a positive predictive value of 100% for the diagnosis of CD. Among Group A patients with concordant CRH test and HDDST, no difference in surgical outcome was found between patients who performed BIPSS and those who did not (66.6% vs 70.4%, p = 0.78). CONCLUSIONS: CRH, desmopressin test and HDDST have high accuracy in the differential diagnosis of ACTH-dependent CS. In patients with microadenoma < 6 mm or non-visible lesion, a concordant positive response to noninvasive tests seems sufficient to diagnose CD, irrespective of MRI finding. In these patients, BIPSS should be reserved to discordant tests.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Síndrome de Cushing/diagnóstico , Imageamento por Ressonância Magnética/métodos , Amostragem do Seio Petroso/métodos , Hipersecreção Hipofisária de ACTH , Testes de Função Hipofisária/métodos , Neoplasias Hipofisárias , Adulto , Síndrome de Cushing/epidemiologia , Diagnóstico Diferencial , Técnicas de Diagnóstico Endócrino , Feminino , Humanos , Hipofisectomia/métodos , Hipofisectomia/estatística & dados numéricos , Itália/epidemiologia , Masculino , Hipersecreção Hipofisária de ACTH/sangue , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/epidemiologia , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos
8.
J Endocrinol Invest ; 45(3): 617-627, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34655038

RESUMO

OBJECTS: Cushing's disease (CD) is the most common cause of ACTH-dependent hypercortisolism in children age ≥ 7. The utility of bilateral inferior petrosal sinus sampling (BIPSS), an important test in adults, is less defined in children. We present a case series of children with ACTH-dependent hypercortisolemia and review the literature to assess the utility of BIPSS in the diagnosis and localization of CD. METHODS: We performed an IRB-approved chart review of patients aged ≤ 18 with ACTH-dependent hypercortisolism at MGH between 2000 and 2019 and collected clinical, laboratory, radiographic, BIPSS, surgical, and outcomes data. RESULTS: In our cohort (n = 21), BIPSS had a sensitivity of 93% and specificity of 100% for diagnosis of CD. Compared to surgery, successful BIPSS correctly predicted adenoma laterality in 69% of cases vs. 70% by MRI. Among patients with lesions ≥ 4 mm (n = 9), BIPSS correctly lateralized in 50% vs. 100% by MRI. In patients with subtle lesions (< 4 mm, n = 7), BIPSS correctly lateralized in 80% vs. 71% by MRI. In patients (n = 4) with CD and negative MRIs, BIPSS correctly lateralized in 75% cases. Surgical cure was achieved in 90% of patients and 95% of patients had long-term disease control. CONCLUSIONS: In our cohort (n = 21; n = 20 CD, n = 1 ectopic ACTH secretion), BIPSS was sensitive and specific for the diagnosis of CD. Compared to MRI, BIPSS was not additionally helpful for lateralization in patients with lesions ≥ 4 mm on MRI. BIPSS was helpful in guiding surgical exploration and achieving immediate postoperative remission among patients with subtle and negative MRI findings.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Hipofisectomia/métodos , Amostragem do Seio Petroso/métodos , Hipersecreção Hipofisária de ACTH , Neoplasias Hipofisárias , Adolescente , Índice de Massa Corporal , Feminino , Humanos , Hidrocortisona/urina , Imageamento por Ressonância Magnética/métodos , Masculino , Hipersecreção Hipofisária de ACTH/sangue , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/patologia , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Indução de Remissão/métodos , Reprodutibilidade dos Testes , Tempo , Resultado do Tratamento
9.
J Endocrinol Invest ; 45(1): 9-16, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34115342

RESUMO

OBJECTIVE: Patients with Cushing's syndrome (CS) are at high risk of venous thromboembolism related to a hypercoagulability due to procoagulant imbalance. However, whether these alterations are reversible after disease remission is still unclear. The endogenous thrombin potential (ETP) measured with and without the addition of thrombomodulin provides a global representation of coagulation and previous data confirmed hypercoagulable profile in patients with active hypercortisolism. Aim of this study was to assess the short- and long-term modification of ETP in patients with CS after disease remission. DESIGN AND METHODS: Nineteen patients with CS for whom surgical remission was achieved, were prospectively evaluated for clinical characteristics, cortisol secretion profile and ETP at different time points: (i) before surgical intervention; (ii) after 6 months and (iii) 5 years from the time of persistent remission. Nineteen healthy subjects matched for age and gender were also evaluated as control group. RESULTS: Before surgery, patients showed higher ETP-ratio (with/without thrombomodulin) than controls (0.62 ± 0.09-vs-0.56 ± 0.09, p = 0.034). No significant correlation between ETP-ratio and cortisol secretion was found. 6 months after remission, ETP-ratio was still significantly increased compared to controls (0.64 ± 0.09-vs-0.56 ± 0.09, p = 0.01), but was similar to baseline (0.64 ± 0.09-vs-0.62 ± 0.09, p = 0.87). At 5 years, ETP-ratio showed a significant decrease (0.55 ± 0.14-vs-0.62 ± 0.09, p = 0.02) and was comparable to controls (0.55 ± 0.14-vs-0.56 ± 0.09, p = 0.7). CONCLUSIONS: Plasma hypercoagulability detected in patients with active hypercortisolism persists at short-term evaluation and seems to be completely reversible after long-term remission of disease. These data, as part of a whole evaluation of thrombotic risk, can contribute to make appropriate therapeutic choice in these patients.


Assuntos
Testes de Coagulação Sanguínea/métodos , Síndrome de Cushing , Hidrocortisona/sangue , Trombina/análise , Trombofilia , Tromboembolia Venosa , Adrenalectomia/métodos , Adulto , Coagulação Sanguínea , Síndrome de Cushing/sangue , Síndrome de Cushing/complicações , Síndrome de Cushing/cirurgia , Feminino , Humanos , Hipofisectomia/métodos , Masculino , Período Pós-Operatório , Indução de Remissão , Medição de Risco/métodos , Trombofilia/sangue , Trombofilia/etiologia , Tempo , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
10.
J Endocrinol Invest ; 44(11): 2511-2520, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34128213

RESUMO

PURPOSE: Sinking of the diaphragma sellae (DS) may stretch the pituitary stalk, which in turn impairs neurohypophyseal function; thus, it may play a role in the development of postoperative hyponatremia. We aimed to assess the factors influencing the development of hyponatremia after transsphenoidal surgery (TSS) for pituitary adenomas and analyze the effect of DS sinking on hyponatremia. METHODS: After applying the inclusion and exclusion criteria, we retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. The pituitary gland was scanned using a 3.0-T magnetic resonance imaging, and sagittal and coronal images were acquired. We evaluated the following: preoperative and postoperative hypothalamus‒pituitary‒thyroid axis function, hypothalamus‒pituitary‒adrenal axis function, intra-operative cerebrospinal fluid leaks, diabetes insipidus, hyponatremia, time from the day of surgery to the day of discharge, and time of hyponatremia onset. RESULTS: Of the 460 patients who had microscopic TSS for pituitary adenoma, 83 experienced postoperative hyponatremia. Hyponatremia occurred approximately 5.25 days postoperatively and persisted for 5.54 days. The lowest average blood sodium level was 123.9 mEq/L, which occurred at 7.49 days after surgery. Logistic regression analysis showed that the risk of hyponatremia was greater for patients with a significant DS sinking depth, a large pituitary stalk deviation angle difference, and a longer postoperative "measurable pituitary stalk". The difference in blood sodium levels between pre-TSS and 2 days post-TSS was also an independent predictor of postoperative hyponatremia onset. CONCLUSION: DS sinking plays an important role in predicting hyponatremia onset after TSS for pituitary adenomas.


Assuntos
Adenoma , Vazamento de Líquido Cefalorraquidiano , Diabetes Insípido , Hiponatremia , Hipofisectomia/efeitos adversos , Complicações Intraoperatórias/diagnóstico , Hipófise , Neoplasias Hipofisárias , Complicações Pós-Operatórias , Adenoma/patologia , Adenoma/cirurgia , Vazamento de Líquido Cefalorraquidiano/diagnóstico , Vazamento de Líquido Cefalorraquidiano/etiologia , Diabetes Insípido/diagnóstico , Diabetes Insípido/etiologia , Feminino , Humanos , Hiponatremia/diagnóstico , Hiponatremia/etiologia , Hiponatremia/terapia , Hipofisectomia/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Hipófise/diagnóstico por imagem , Hipófise/patologia , Hipófise/cirurgia , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Prognóstico , Medição de Risco , Fatores de Risco , Sódio/sangue
11.
J Endocrinol Invest ; 44(12): 2621-2633, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33847973

RESUMO

CONTEXT: Although consensus guidelines recommend dopamine agonists (DAs) as the first-line approach in prolactinomas, some patients may opt instead for upfront surgery, with the goal of minimizing the need for continuation of DAs over the long term. While this approach can be recommended in selected patients with a microprolactinoma, the indication for upfront surgery in macroprolactinomas remains controversial, with limited long-term data in large cohorts. We aimed at elucidating whether first-line surgery is equally safe and effective for patients with micro- or macroprolactinomas not extending beyond the median carotid line (i.e., Knosp grade ≤ 1). METHODOLOGY: Retrospective study of patients with prolactinomas Knosp grade ≤ 1 treated with upfront surgery. The primary endpoint was patients' dependence on DAs at last follow-up. The secondary endpoint was postoperative complications. Independent risk factors for long-term dependence on DAs were analyzed. RESULTS: A microadenoma was noted in 45 patients (52%) and a macroadenoma in 41 (48%), with 17 (20%) harboring a Knosp grade 1 prolactinoma. Median follow-up was 80 months. First-line surgery resulted in long-term remission in 31 patients (72%) with a microprolactinoma and in 18 patients (45%) with a macroprolactinoma (p = 0.02). DA therapy was ultimately required in 11 patients (24%) with microadenomas vs. 20 (49%) with macroadenomas (p = 0.03). As for the latter, DA was required in 13 patients (76%) with Knosp grade 1 macroadenomas vs. 7 patients (29%) with Knosp grade 0 macroadenomas (p = 0.004). There was no mortality, and morbidity was minimal. Knosp grade 1 prolactinomas (OR 7.3, 95% CI 1.4-37.7, p = 0.02) but not adenoma size (i.e., macroprolactinomas) were an independent predictor of long-term dependence on DAs. CONCLUSIONS: First-line surgery in patients with microprolactinomas or macroprolactinomas Knosp grade 0 resulted in a good chance of non-dependency on DA therapy. However, in patients with prolactinomas Knosp grade 1, first-line surgery cannot be recommended, as adjuvant DA therapy after surgery is required in the majority of them over the long term.


Assuntos
Agonistas de Dopamina , Hipofisectomia , Invasividade Neoplásica/diagnóstico , Neoplasias Hipofisárias , Complicações Pós-Operatórias , Prolactinoma , Seio Cavernoso/patologia , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/efeitos adversos , Duração da Terapia , Feminino , Humanos , Hipofisectomia/efeitos adversos , Hipofisectomia/métodos , Hipofisectomia/estatística & dados numéricos , Imuno-Histoquímica , Efeitos Adversos de Longa Duração/diagnóstico , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Prolactinoma/tratamento farmacológico , Prolactinoma/patologia , Prolactinoma/cirurgia , Risco Ajustado/métodos , Carga Tumoral
12.
World Neurosurg ; 148: e275-e281, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33412326

RESUMO

OBJECTIVE: Cushing disease (CD) is a rare clinical disease in which brain structural and function are impaired as the result of excessive cortisol. However, little is known whether rich-club organization changes in patients with CD, as visualized on resting-state magnetic resonance imaging (fMRI), can reverse to normal conditions after transsphenoidal surgery (TSS). In this study, we aimed to investigate whether the functional connectivity of rich-club organization is affected and whether any abnormal changes may reverse after TSS. METHODS: In this study, 38 patients with active CD, 33 with patients with CD in remission, and 41 age-, sex-, and education-matched healthy control participants underwent resting-state fMRI. Brain functional connectivity was constructed based on fMRI and rich club was calculated with graph theory approach. We constructed the functional brain networks for all participants and calculated rich-club connectivity based on fMRI. RESULTS: We identified left precuneus, right precuneus, left middle cingulum, right middle cingulum, right inferior temporal, right middle temporal, right lingual, right postcentral, right middle occipital, and right precentral regions as rich club nodes. Compared with healthy control participants, rich-club connectivity was significantly lower in patients with active CD (P < 0.001). Moreover, abnormal rich-club connectivity improved to normal after TSS. CONCLUSIONS: Our results show rich-club organization was disrupted in patients with active CD with excessive cortisol production. TSS can reverse abnormal rich-club connectivity. Rich club may be a new indicator to investigate the outcomes of TSS and to increase our understanding of the effect of excessive cortisol on brain functional connectivity in patients with CD.


Assuntos
Adenoma Hipofisário Secretor de ACT/cirurgia , Conectoma , Substância Cinzenta/patologia , Hipersecreção Hipofisária de ACTH/fisiopatologia , Neoplasias Hipofisárias/cirurgia , Adenoma Hipofisário Secretor de ACT/complicações , Adolescente , Adulto , Mapeamento Encefálico , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Hidrocortisona/sangue , Hipofisectomia/métodos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Neuroimagem , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Hipersecreção Hipofisária de ACTH/patologia , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/complicações , Indução de Remissão , Osso Esfenoide/cirurgia , Adulto Jovem
13.
Surg Radiol Anat ; 43(2): 211-218, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32975638

RESUMO

PURPOSE: Intercavernous sinuses (ICSs) are physiological communications between the cavernous sinuses. The ICSs run between the endosteal and meningeal layers of the dura mater of the sella turcica. Whereas the anterior and posterior ICSs have been frequently described, the inferior ICS (iICS) has been less well studied in the literature; however, poor awareness of the ICS's anatomy can lead to serious problems during transsphenoidal, transsellar surgery. The objective of the present anatomical study was to describe the iICS in detail. METHODS: The study was carried out over a 6-month period in a university hospital's anatomy laboratory, using brains extracted from human cadavers. The brains were injected with colored neoprene latex and dissected to study the iICS (presence or absence, shape, diameter, length, distance between inferior and anterior ICSs, distance between inferior and posterior ICSs, relationships, and boundaries). RESULTS: Seventeen cadaveric specimens were studied, and an iICS was found in all cases (100%). The shape was variously plexiform (47.1%), filiform (35.3%), or punctiform (17.6%). The mean ± standard deviation diameter and length of the iICS were 3.75 ± 2.90 mm and 11.92 ± 2.96 mm, respectively. The mean iICS-anterior ICS and iICS-posterior ICS distances were 5.36 ± 1.99 mm and 7.03 ± 2.28 mm, respectively. CONCLUSION: The iICS has been poorly described in the literature. However, damage to the iICS during transsphenoidal, transsellar surgery could lead to serious vascular complications. A precise radiological assessment appears to be essential for a safe surgical approach.


Assuntos
Adenoma/cirurgia , Perda Sanguínea Cirúrgica/prevenção & controle , Seio Cavernoso/anatomia & histologia , Neoplasias Hipofisárias/cirurgia , Sela Túrcica/anatomia & histologia , Adenoma/diagnóstico , Adenoma/patologia , Adulto , Cadáver , Seio Cavernoso/diagnóstico por imagem , Seio Cavernoso/cirurgia , Feminino , Humanos , Hipofisectomia/efeitos adversos , Hipofisectomia/métodos , Imageamento por Ressonância Magnética , Microcirurgia/efeitos adversos , Microcirurgia/métodos , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Cirurgia Endoscópica por Orifício Natural/métodos , Hipófise/diagnóstico por imagem , Hipófise/patologia , Hipófise/cirurgia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/patologia , Sela Túrcica/diagnóstico por imagem , Sela Túrcica/cirurgia
14.
Acta Orthop Traumatol Turc ; 54(5): 561-564, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33155569

RESUMO

Growth hormone secreting pituitary tumor or gigantism has not been previously reported to be associated with rapid progression of scoliosis in the literature. However, there are some reports indicating scoliosis can be worsened by growth hormone therapy in children and adolescents. A 19-year-old boy was referred to our institution for the treatment of a right thoracolumbar scoliosis. The Cobb angle had worsened from 29° to 83° over two years' duration. He attained puberty at the age of 13. He had a previous history of slipped upper femoral epiphysis (SUFE), which was operated in 2015, with no clinical features of gigantism. Preoperative assessment was performed. He was diagnosed with growth hormone secreting pituitary macroadenoma by magnetic resonance imaging with a high serum level of insulin-like growth factor-I (IGF-I). Computed tomography (CT) of the pancreas showed a pancreatic endocrine tumor. The patient was later diagnosed with multiple endocrine neoplasia type 1 (MEN 1). He underwent endoscopic endonasal excision of the pituitary mass and distal pancreatectomy. This case indicates that growth hormone secreting pituitary macroadenoma could result in rapid progression of scoliosis.


Assuntos
Adenoma , Hipofisectomia/métodos , Hipopituitarismo , Insulinoma , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , Neoplasias Pancreáticas , Neoplasias Hipofisárias , Escoliose , Tomografia Computadorizada por Raios X/métodos , Adenoma/sangue , Adenoma/patologia , Adenoma/fisiopatologia , Adenoma/cirurgia , Humanos , Hipopituitarismo/diagnóstico , Hipopituitarismo/etiologia , Hipopituitarismo/terapia , Fator de Crescimento Insulin-Like I/análise , Insulinoma/patologia , Insulinoma/cirurgia , Imageamento por Ressonância Magnética/métodos , Masculino , Pancreatectomia/métodos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Administração dos Cuidados ao Paciente/métodos , Hipófise/diagnóstico por imagem , Hipófise/cirurgia , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/fisiopatologia , Neoplasias Hipofisárias/cirurgia , Radiografia/métodos , Escoliose/diagnóstico por imagem , Escoliose/etiologia , Adulto Jovem
15.
BMJ Case Rep ; 13(6)2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32606131

RESUMO

A 57-year-old woman presented with severe lethargy, dizziness and nausea 1 week after transsphenoidal resection of a growth hormone secreting pituitary adenoma. She was found to have severe hyponatremia of 115 mmol/L. Importantly, she was neurologically intact and clinically euvolaemic. Her fluid intake was restricted and her sodium levels increased to 131 mmol/L over 4 days. She made a full recovery.She was diagnosed with isolated second-phase diabetes insipidus, a state of symptomatic hypoosmolar hyponatremia that usually occurs 7-10 days after transsphenoidal surgery. The sodium levels improve with fluid restriction.


Assuntos
Adenoma/cirurgia , Água Potável , Hiponatremia , Hipofisectomia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias , Desequilíbrio Hidroeletrolítico/terapia , Adenoma/metabolismo , Adenoma/patologia , Dietoterapia/métodos , Tontura/diagnóstico , Tontura/etiologia , Feminino , Humanos , Hiponatremia/sangue , Hiponatremia/etiologia , Hiponatremia/fisiopatologia , Hiponatremia/terapia , Hipofisectomia/efeitos adversos , Hipofisectomia/métodos , Letargia/diagnóstico , Letargia/etiologia , Pessoa de Meia-Idade , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapia , Osso Esfenoide/cirurgia , Resultado do Tratamento
16.
BMJ Case Rep ; 13(6)2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32532912

RESUMO

A 60-year-old man presented with right third nerve palsy and headaches. Neuroimaging showed a pituitary lesion. There was evidence of rapid enlargement on interval scans, invasion of the cavernous sinus and displacement of the pituitary stalk. He subsequently developed anterior hypopituitarism. CT thorax, abdomen and pelvis did not show any evidence of malignancy. This was thought to be an aggressive pituitary macroadenoma but histology post-trans-sphenoidal surgery surprisingly showed metastasis from an undiagnosed prostate primary. His prostate specific antigen was raised and MRI pelvis confirmed locally advanced prostate cancer.


Assuntos
Adenocarcinoma , Hipofisectomia/métodos , Hipófise , Neoplasias Hipofisárias , Neoplasias da Próstata , Adenocarcinoma/patologia , Adenocarcinoma/fisiopatologia , Adenocarcinoma/cirurgia , Biópsia/métodos , Cefaleia/diagnóstico , Cefaleia/etiologia , Humanos , Hipopituitarismo/diagnóstico , Hipopituitarismo/etiologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neuroimagem/métodos , Doenças do Nervo Oculomotor/diagnóstico , Doenças do Nervo Oculomotor/etiologia , Hipófise/diagnóstico por imagem , Hipófise/cirurgia , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/fisiopatologia , Neoplasias Hipofisárias/secundário , Neoplasias Hipofisárias/cirurgia , Antígeno Prostático Específico/análise , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Radioterapia/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
17.
Clin Neurol Neurosurg ; 196: 106000, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32574965

RESUMO

OBJECTIVES: The inferior intercavernous sinus is located below the pituitary gland in the sella turcica. Its presence has been controversial among anatomists because it is not always found on radiological imaging or during cadaveric dissections; however, it is becoming a better-known structure in the neurosurgical and radiological fields, specifically with respect to transsphenoidal surgery. Therefore, the present study was performed to better elucidate this structure at the skull base. PATIENTS AND METHODS: Fifty adult, latex injected cadavers underwent dissection. The presence or absence of the inferior cavernous sinus was evaluated and when present, measurements of its width and length were made. Its connections with other intradural venous sinuses were also documented. RESULTS: An inferior intercavernous sinus was identified in 26 % of specimens. In all specimens, it communicated with the left and right cavernous sinus. The average width and length were 3 mm and 9.5 mm, respectively. In the sagittal plane, the inferior intercavernous sinus was positioned anteriorly in 31 %, at the nadir of the sella turcica in 38 %, and slightly posterior to the nadir of the sella turcica in 31 %. In two specimens (15.4 %), the sinus was plexiform in its shape. In one specimen a diploic vein connected the basilar venous plexus to the inferior intercavernous sinus on its deep surface. CONCLUSION: An improved understanding of the variable anatomy of the inferior intercavernous sinus is important in pathological, surgical, and radiological cases.


Assuntos
Seio Cavernoso/anatomia & histologia , Craniotomia/métodos , Hipofisectomia/métodos , Hipófise/cirurgia , Sela Túrcica/anatomia & histologia , Osso Esfenoide/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cadáver , Seio Cavernoso/diagnóstico por imagem , Seio Cavernoso/embriologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipófise/anatomia & histologia , Hipófise/irrigação sanguínea , Hipófise/diagnóstico por imagem , Sela Túrcica/diagnóstico por imagem
18.
JAMA Otolaryngol Head Neck Surg ; 146(7): 621-629, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32379292

RESUMO

Importance: Iatrogenic olfactory dysfunction after endoscopic transsphenoidal hypophysectomy (ETSH) is an overlooked complication without elucidated risk factors. Objective: To assess the independent prognostic role of demographic, comorbidity, cephalometric, intraoperative, histological, and postoperative parameters in patient-reported postoperative olfactory dysfunction, and to explore the association between anatomical measurements of the skull base and sinonasal cavity and postoperative olfactory dysfunction. Design, Setting, and Participants: This retrospective cohort study in a tertiary care medical center enrolled consecutive patients with primary sellar lesions who underwent ETSH between January 1, 2015, and January 31, 2019. Patients were excluded if they underwent multiple sinonasal surgical procedures, presented with a sellar malignant neoplasm, required an expanded transsphenoidal approach, had nasal polyposis or a neurodegenerative disease, or sustained traumatic brain injury. After undergoing medical record review and telephone screening, patients were asked to participate in a 3-item telephone survey. Main Outcomes and Measures: The primary outcome was the Clinical Global Impressions change in smell rating, a validated transitional patient-reported outcome measure. Patients rated their change in smell before and after ETSH on a 7-point Likert scale, with the following response options: (1) much better, (2) somewhat better, (3) slightly better, (4) neither better nor worse, (5) slightly worse, (6) somewhat worse, or (7) much worse. Responses of slightly worse, somewhat worse, and much worse were surrogates for postoperative olfactory dysfunction status. Patient medical records, preoperative imaging scans, operative notes, and pathology reports were reviewed. Results: Of the 147 patients (mean [SD] age, 54 [15] years; 79 women [54%]) who responded to the telephone survey, 42 (29%) reported olfactory dysfunction after ETSH. Median (interquartile range [IQR]) time between the ETSH completion and survey response was 31.1 (21-43) months. On multivariable analysis, abdominal fat grafting (adjusted relative risk [aRR], 2.95; 95% CI, 1.89-4.60) was associated with postoperative olfactory dysfunction, whereas smoking history (aRR, 1.54; 95% CI, 0.95-2.51) demonstrated a clinically meaningful but imprecise effect size. A more obtuse angle between the planum sphenoidale and face of the sella turcica on sagittal imaging was protective (aRR, 0.98; 95% CI, 0.96-0.99). Increased number of months after the ETSH was associated with patient-reported normosmia (aRR, 0.93; 95% CI, 0.91-0.95). In contrast, other comorbidities; intraoperative variables such as turbinate resection, nasoseptal flap, and mucosal or bone grafting; histological variables such as pathology and proliferative index; and postoperative variables such as adjuvant radiotherapy were not associated with postoperative olfactory dysfunction. Conclusions and Relevance: This study found that abdominal fat grafting, acute skull base angle, and smoking history appeared to be clinically significant risk factors for patient-reported postoperative olfactory dysfunction. Increased time after ETSH may be associated with better olfactory outcomes.


Assuntos
Hipofisectomia/efeitos adversos , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Transtornos do Olfato/etiologia , Sela Túrcica/cirurgia , Gordura Abdominal/transplante , Variação Anatômica , Doenças do Sistema Nervoso Central/diagnóstico por imagem , Doenças do Sistema Nervoso Central/patologia , Doenças do Sistema Nervoso Central/cirurgia , Cefalometria , Feminino , Humanos , Hipofisectomia/métodos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/anatomia & histologia , Cavidade Nasal/diagnóstico por imagem , Cirurgia Endoscópica por Orifício Natural/métodos , Medidas de Resultados Relatados pelo Paciente , Complicações Pós-Operatórias , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco , Sela Túrcica/anatomia & histologia , Sela Túrcica/diagnóstico por imagem , Base do Crânio/anatomia & histologia , Base do Crânio/diagnóstico por imagem , Fumar/efeitos adversos
19.
World Neurosurg ; 133: e211-e217, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31493596

RESUMO

BACKGROUND: Craniopharyngiomas show a high recurrence rate despite their pathologically benign nature. Thus, we analyzed the clinical features to elucidate the prognostic factors for the recurrence of craniopharyngiomas in adults with long-term follow-up. METHODS: This retrospective study reviewed and analyzed the preoperative features, surgical results, and tumor recurrence of patients who underwent an operation at a single institution from 2004 to 2013. RESULTS: This study analyzed the results of 64 consecutive adult patients, and the median follow-up period was 83.5 months (range 9-163 months). Ten patients had a history of surgery, whereas 4 had a history of adjuvant radiation. Retrochiasmatic tumors (n = 51, 79.7%) were more common than prechiasmatic tumors. Operations were performed via the transcranial approach in 31 (48.4%) patients and transsphenoidal approach in 33. Gross total removal was achieved in 44 (68.8%) patients, and the transsphenoidal approach showed a greater gross total removal rate than the transcranial approach did (97.0% vs. 38.7%, P < 0.001). Adjuvant radiotherapy was performed in 8 patients, and radiosurgery was performed in 2. Recurrence was identified in 25 (39.1%) patients in 45.0 months of the median time to recurrence. The overall actuarial 5- and 7-year progression-free survival rates were 71.8% and 63.6%, respectively. Multivariate analysis revealed that supra- and subdiaphragmatic tumor locations and subtotal removal were risk factors for long-term tumor recurrence. CONCLUSIONS: The long-term recurrence rate of craniopharyngiomas was high; therefore, long-term regular follow-up is mandatory. Adjuvant irradiation for remnant tumors showed a long-term tumor control rate comparable to that of completely removed tumors.


Assuntos
Craniofaringioma/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Hipofisárias/epidemiologia , Adulto , Idoso , Terapia Combinada , Craniofaringioma/complicações , Craniofaringioma/radioterapia , Craniofaringioma/cirurgia , Feminino , Seguimentos , Humanos , Hidrocefalia/etiologia , Hipofisectomia/métodos , Hipopituitarismo/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/radioterapia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias , Prognóstico , Intervalo Livre de Progressão , Radiocirurgia , Radioterapia Adjuvante , Estudos Retrospectivos , Transtornos da Visão/etiologia
20.
Clin Endocrinol (Oxf) ; 92(2): 89-97, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31715012

RESUMO

The clinical course of pituitary adenoma can be highly variable. Aggressive pituitary tumours may require multimodal therapy with multiple operations. Even standard pituitary adenomas exhibit relatively high long-term recurrence rates and delayed intervention is often required. The indications for revision surgery in the endoscopic era are expanding for both functioning and nonfunctioning tumours, including access to the cavernous sinus and intracranial compartments. Although revision surgery can be challenging, it has been demonstrated to be both safe and effective. The question of the use of early radiotherapy in pituitary adenoma remains controversial. Our increasing understanding of pituitary tumour biology facilitates individualized treatment and surveillance protocols, with early intervention in high-risk adenoma subtypes. In this review, we discuss the treatment options for recurring pituitary tumours and focus on the role of revision surgery.


Assuntos
Adenoma/cirurgia , Hipofisectomia/métodos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Hipofisárias/cirurgia , Reoperação/métodos , Adenoma/patologia , Seio Cavernoso/patologia , Seio Cavernoso/cirurgia , Terapia Combinada , Humanos , Neoplasias Hipofisárias/patologia , Fatores de Tempo
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