Bevacizumab in Aggressive Pituitary Adenomas – Experience with 3 Patients

2020 ◽  
Author(s):  
Katharina Osterhage ◽  
Roman Rotermund ◽  
Michael Droste ◽  
Judith Dierlamm ◽  
Wolfgang Saeger ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Transsphenoidal Surgery ◽  
Pituitary Tumors ◽  
Considerable Effect ◽  
General Statement ◽  
Patient Deterioration ◽  
Short Period ◽  
Acth Secreting ◽  
Design And Methods ◽  
Current Stage

Abstract Objective To investigate bevacizumab as alternative treatment of aggressive pituitary adenomas after exhaustion of standard therapies. Design and Methods Retrospectively, 3 patients undergoing microscopic transsphenoidal surgery of aggressive pituitary adenomas from 2008 till 2018 that were treated with bevacizumab were identified. Development of disease and treatment were evaluated. Results Two patients suffered from ACTH-secreting adenomas, one from a non-functioning adenoma. All patients underwent multiple surgical, chemo- and radiotherapeutical approaches including temozolomide, showing favorable results in one patient. Deterioration of clinical condition in all patients led to an individual, palliative attempt of bevacizumab. Patients 1 and 2 showed a decrease of ACTH after first administrations, but therapy had to be ended shortly after due to a further deterioration of their condition. Patient 3 showed a stabilization of the disease for 18 months. Patients died 8, 15 and 7 years after initial diagnosis, respectively, and 2, 4, and 24 months after initiation of bevacizumab therapy, respectively. Conclusion The demonstrated results suggest a considerable effect of bevacizumab in aggressive pituitary adenomas. The advanced stage of disease in all three patients, the overall short period of administration and just one patient showing a clinical benefit do not allow a general statement on the effectiveness. At the current stage of clinical experience, an approach with bevacizumab can be considered as an individual palliative attempt of treatment, when standard treatments are exhausted. Our results underline the need for further studies to evaluate this drug as potential player in therapy resistant aggressive pituitary tumors.

scholarly journals Endoscopic endonasal transsphenoidal approach for pituitary adenomas: technical aspects and report of casuistic

2010 ◽  
Vol 68 (4) ◽  
pp. 608-612 ◽  
Author(s):  
Américo Rubens Leite dos Santos ◽  
Roberto Monteiro Fonseca Neto ◽  
José Carlos Esteves Veiga ◽  
José Viana Jr ◽  
Nilza Maria Scaliassi ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
Hormonal Control ◽  
Subtotal Resection ◽  
Endoscopic Endonasal ◽  
Technical Aspects ◽  
Transphenoidal Approach ◽  
Acth Secreting ◽  
Csf Leaks

OBJECTIVE: Analyse technical aspects, effectiveness and morbidity of the endoscopic endonasal transphenoidal approach for pituitary adenomas. METHOD: From January 2005 to September 2008, 30 consecutive patients underwent endoscopic endonasal resection of pituitary adenomas with a follow up from 3 to 36 months. Their medical charts were retrospectively analysed. RESULTS: There were 18 women and 12 men, mean age 44 years (range 17-65 yr). Among the 30 patients, 23 had macroadenomas and 7 microadenomas. Twelve patients had non-functioning tumors, 9 had ACTH-secreting tumors, 8 had GH-secreting tumors and 1 prolactinoma. Complete resection and hormonal control was achieved in all microadenomas. Macroadenomas were completely removed in 6 patients, subtotal resection in 6 and partial resection in 11. Three patients had diabetes insipidus and 5 had CSF leaks treated with lumbar drainage. CONCLUSION: The endonasal endoscopic approach for pituitary tumors is effective and has low morbidity.

scholarly journals Angiogenesis in Pituitary Adenomas and the Normal Pituitary Gland

2000 ◽  
Vol 85 (3) ◽  
pp. 1159-1162 ◽  
Author(s):  
Helen E. Turner ◽  
Zsusha Nagy ◽  
Kevin C. Gatter ◽  
Margaret M. Esiri ◽  
Adrian L. Harris ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Pituitary Adenomas ◽  
Anterior Pituitary ◽  
Pituitary Tumors ◽  
Anterior Pituitary Gland ◽  
Ulex Europaeus ◽  
Normal Pituitary Gland ◽  
Ulex Europaeus Agglutinin I ◽  
Acth Secreting ◽  
Tumor Types

Abstract Angiogenesis is essential for tumor growth beyond a few millimeters in diameter, and the intratumoral microvessel count that represents a measure of angiogenesis has been correlated with tumor behavior in a variety of different tumor types. To date no systematic study has assessed pituitary tumors of different secretory types, correlating vascular count with tumor size. The vascular densities of pituitary tumors and normal anterior pituitary were therefore assessed by counting vessels labeled using the vascular markers CD31 and ulex europaeus agglutinin I. One hundred and twelve surgically removed pituitary adenomas (30 GH-secreting, 25 prolactinomas, 15 ACTH-secreting, and 42 nonfunctioning tumors) were compared with 13 specimens of normal anterior pituitary gland. The vascular counts in the normal anterior pituitary gland were significantly higher (P < 0.05) than those in the tumors using both CD31 and ulex europaeus agglutinin I. In addition, microprolactinomas were significantly less vascular (P < 0.05) than macroprolactinomas, although there was no such difference between vascular densities of microadenomas and macroadenomas producing GH. ACTH-secreting tumors were, like microprolactinomas, of much lower vascular density than the normal pituitary and other secreting and nonsecreting tumor types. In marked contrast to other tumors, pituitary adenomas are less vascular than the normal pituitary gland, suggesting that there may be inhibitors of angiogenesis that play an important role in the behavior of these tumors.

Transsphenoidal extracapsular approach to pituitary tumors

1986 ◽  
Vol 64 (1) ◽  
pp. 16-20 ◽  
Author(s):  
Nobuo Hashimoto ◽  
Hajime Handa ◽  
Tatsuhito Yamagami
Keyword(s):  
Pituitary Adenomas ◽  
Transsphenoidal Surgery ◽  
Pituitary Tumors ◽  
Hormonal Control ◽  
Arachnoid Membrane ◽  
Content Type ◽  
Tumor Capsule ◽  
Suprasellar Extension ◽  
Fine Print ◽  
Transsphenoidal Resection

✓ Two years' experience with an extracapsular transsphenoidal approach to pituitary adenomas is presented. Some pituitary tumors contain an inordinate amount of connective tissue that often makes transsphenoidal resection difficult. By opening the tumor capsule and adjacent arachnoid membrane, such tumors with suprasellar extension can be safely removed. In some cases of functioning adenoma, resection of the diaphragma sellae and adjacent arachnoid membrane results in hormonal control. Among 62 cases of transsphenoidal surgery for pituitary adenomas, eight cases required this procedure. The surgical procedure is described and the cases are summarized. The indication and limitations of this procedure are discussed.

scholarly journals Treatment options for Cushing disease after unsuccessful transsphenoidal surgery

2007 ◽  
Vol 23 (3) ◽  
pp. 1-7 ◽  
Author(s):  
James K. Liu ◽  
Maria Fleseriu ◽  
Johnny B. Delashaw ◽  
Ivan S. Ciric ◽  
William T. Couldwell ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Transsphenoidal Surgery ◽  
Treatment Options ◽  
Pituitary Tumors ◽  
Premature Death ◽  
Treatment Modalities ◽  
Definitive Treatment ◽  
Sustained Remission ◽  
Cushing Disease ◽  
Acth Secreting

✓Cushing disease is considered an aggressive pituitary endocrinopathy because of the devastating effects from untreated hypercortisolemia. Although they are histologically benign, these adrenocorticotropic hormone (ACTH)-secreting pituitary tumors are associated with significant morbidity and premature death. Currently, transsphenoidal surgery is the primary treatment of Cushing disease associated with an ACTH-secreting pituitary tumor, resulting in remission rates ranging from about 50 to 90%. Some patients, however, will not achieve sustained remission after transsphenoidal surgery and can exhibit persistent or recurrent Cushing disease that requires multimodal treatment to achieve remission. In these patients, options for treatment include repeat transsphenoidal resection, radiation therapy (including conventional fractionated radiation therapy and stereotactic radiosurgery), and medical therapy. Despite undergoing multiple treatment modalities, some patients may ultimately require bilateral adrenalectomy for definitive treatment to eliminate hypercortisolemia associated with Cushing disease. In this article, the authors review the treatment options for patients who have persistent or recurrent Cushing disease after unsuccessful transsphenoidal surgery. The indications, current results reported in the literature, and complications of each treatment modality are discussed.

scholarly journals Microscopic Transsphenoidal Resection of Pituitary Adenomas With Conchal Sphenoid Sinus: a Report of Three Cases

2020 ◽  
Author(s):  
Jianhe Zhang ◽  
Shousen Wang
Keyword(s):  
Pituitary Adenomas ◽  
Transsphenoidal Surgery ◽  
Sphenoid Sinus ◽  
Pituitary Tumors ◽  
Absolute Contraindication ◽  
Neuronavigation System ◽  
Sellar Tumor ◽  
Sphenoid Sinuses ◽  
Transsphenoidal Resection

Abstract Object The present study aimed to investigate the methodology and characteristic of the microscopic transsphenoidal resection of pituitary adenomas with a conchal sphenoid sinus. Method Three patients with sellar tumor and non-pneumatized sphenoid sinuses received microscopic transsphenoidal surgery with help of neuronavigation system. Result The three conchal spenoid sinuses were accessed safely, total resction was achieved and no serious complication occurred. we found that pituitary tumors with conchal sphenoid sinus was more smaller and soft. Conclusion the presence of a conchal sphenoid sinus is not an absolute contraindication for employing the microscopic transsphenoidal route in the resction of pituitary adenomas with help of neuronavigation.

scholarly journals Magmas, a Gene Newly Identified as Overexpressed in Human and Mouse ACTH-Secreting Pituitary Adenomas, Protects Pituitary Cells from Apoptotic Stimuli

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4635-4642 ◽  
Author(s):  
Federico Tagliati ◽  
Erica Gentilin ◽  
Mattia Buratto ◽  
Daniela Molè ◽  
Ettore Ciro degli Uberti ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Mitochondrial Protein ◽  
Pituitary Tumors ◽  
Pituitary Cells ◽  
Subcellular Compartment ◽  
Adenoma Cell ◽  
Macrophage Colony ◽  
Reduced Rate ◽  
Acth Secreting

Pituitary tumors are mostly benign, being locally invasive in 5–35% of cases. Deregulation of several genes has been suggested as a possible alteration underlying the development and progression of pituitary tumors. We here report the identification of a cDNA, corresponding to Magmas gene (mitochondria-associated protein involved in granulocyte-macrophage colony-stimulating factor signal transduction), which is highly expressed in two different ACTH-secreting mouse pituitary adenoma cell lines as compared with normal pituitary as well as in two thirds of 64 examined pituitary adenomas as compared with human normal pituitary. Tim 16, the mitochondrial protein encoded by Magmas, was indeed expressed in a mouse ACTH-secreting pituitary adenoma cell line, AtT-20 D16v-F2 cells, in a subcellular compartment likely corresponding to mitochondria. Magmas silencing determined a reduced rate of DNA synthesis, an accumulation in G1 phase, and a concomitant decrease in S phase in At-T20 D16v-F2 cells. Moreover, Magmas-silenced cells displayed basal caspase 3/7 activity and DNA fragmentation levels similar to control cells, which both increased under proapoptotic stimuli. Our data demonstrate that Magmas is overexpressed in mouse and human ACTH-secreting pituitary adenomas. Moreover, our results show that Magmas protects pituitary cells from apoptosis, suggesting its possible involvement in neoplastic transformation.

Complication Rates after Endoscopic Transsphenoidal Surgery for ACTH-Secreting Pituitary Adenomas: A Comparative Analysis with GH and Nonfunctioning Adenomas

2021 ◽  
Author(s):  
Juan Á. Aibar-Durán ◽  
Michael Oladotun-Anka ◽  
Carlos Asencio-Cortés ◽  
Elena Valassi ◽  
Susan Webb ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Statistical Analysis ◽  
Diabetes Insipidus ◽  
Pituitary Adenomas ◽  
Transsphenoidal Surgery ◽  
Csf Leak ◽  
Complication Rates ◽  
Endoscopic Transsphenoidal Surgery ◽  
Number Of Patients ◽  
Acth Secreting

Abstract Objectives Some complications have been more frequently reported after surgery for adrenocorticotropin hormone (ACTH)-secreting pituitary adenomas. We compared complication rates in patients with ACTH-secreting pituitary adenomas with those in patients with growth hormone secreting pituitary adenomas (growth hormone [GH] group) and nonfunctioning adenomas (nonfunctioning group). Design A comparative three-group analysis was performed for all patients who had endoscopic transsphenoidal surgery for pituitary adenomas at our center between January 2011 and May 2019. Variables included demographics, preoperative clinical and radiological characteristics, and postoperative radiological and endocrinological outcomes. Complications were divided into four categories: endocrinological, neurosurgical, medical, and ENT (ear–nose–throat)-related complications. Univariate and multivariate statistical analysis were performed. Results A total of 111 patients with pituitary adenomas and a mean age of 53.7 years were included (25 ACTH, 35 GH, and 51 nonfunctioning adenomas). Overall, 28 patients had microadenomas (25.2%) and 83 had macroadenomas (74.8%). Univariate statistical analysis for complications between groups showed no differences in neurosurgical and medical complications. Transient diabetes insipidus and postsurgical bacterial sinusitis were the only variables more frequently seen in the ACTH group (p = 0.01 and 0.04, respectively). Multivariate analysis for transient diabetes insipidus showed no differences between groups (p = 0.58). Conclusion Complication rates were similar in all three adenoma groups, particularly concerning major infections, thrombotic events, postoperative cerebrospinal fluid (CSF) leak, and transient diabetes insipidus. Transient diabetes insipidus was related with adenoma size and intraoperative CSF leak. Despite postoperative bacterial sinusitis was statistically higher in the ACTH group, this data should be interpreted with caution given the low number of patients with this complication.

Adrenocorticotropin levels do not change during early recovery of transsphenoidal surgery for ACTH-secreting pituitary tumors

2001 ◽  
Vol 24 (2) ◽  
pp. 83-87 ◽  
Author(s):  
F. R. Pimentel-Filho ◽  
A. Cukiert ◽  
F. Miyashita ◽  
M. K. P. Huayllas ◽  
M. Knoepfelmacher ◽  
...  
Keyword(s):  
Transsphenoidal Surgery ◽  
Pituitary Tumors ◽  
Early Recovery ◽  
Acth Secreting

scholarly journals Recovery of Hypopituitarism after Neurosurgical Treatment of Pituitary Adenomas

1999 ◽  
Vol 84 (10) ◽  
pp. 3696-3700 ◽  
Author(s):  
Susan M. Webb ◽  
Mercedes Rigla ◽  
Anna Wägner ◽  
Bartolomé Oliver ◽  
Frederic Bartumeus
Keyword(s):  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
Postoperative Recovery ◽  
Pituitary Function ◽  
Pituitary Hormone ◽  
Substitution Therapy ◽  
Function Recovery ◽  
Neurosurgical Treatment ◽  
Initial Work ◽  
Acth Secreting

Abstract Surgery is the treatment of choice for many pituitary tumors; pituitary function may suffer after operation, but relief of pressure on the normal pituitary may also favor postoperative recovery of hypo-pituitarism. The aim of this study was to investigate the frequency of new appearance and recovery of hypopituitarism after neurosurgery and try to identify features associated with it. Pre- and postoperative anterior pituitary functions were investigated in 234 patients with pituitary adenomas (56 nonfunctioning, 71 PRL-secreting, 66 GH-secreting, 39 ACTH-secreting, 1 LH/FSH-secreting, and 1 TSH-secreting tumors). Eighty-eight new postoperative pituitary hypofunctions appeared in 52 patients (12 NF, 14 PRL-secreting, 15 GH-secreting, 10 ACTH-secreting, and 1 LH/FSH-secreting adenomas). They corresponded to 27% ACTH deficiencies (in 29 of the 107 patients with normal preoperative ACTH in whom postoperative evaluation was complete), 14.5% (15 of 103) new GH deficiencies, 10.5% (15 of 143; P < 0.0005, significantly less than ACTH deficiency) new TSH deficiencies, 16.5% (20 of 121) new gonadotropin deficiencies, and 13% (9 of 71) new PRL deficiencies. Preoperatively, 93 were deficient in at least 1 pituitary hormone; after surgery, 45 (48%) recovered between 1 and 3 hormones. The 2 patients with LH/FSH- and TSH-secreting macroadenomas did not recover pituitary function. Factors associated with a higher probability of postoperative pituitary function recovery were: no tumor rests on postoperative pituitary imaging (P = 0.001) and no neurosurgical (P = 0.001) or pathological evidence (P = 0.049) of an invasive nature. Tumor size did not differ significantly between those who did and those who did not recover pituitary function after surgery. Even if clear hypofunction is observed at initial work-up, patients should be reassessed after surgery without substitution therapy, because practically half the preoperative pituitary hormone deficiencies recover postoperatively, eliminating the need for life-long substitution therapy.

scholarly journals p27 variant and corticotropinoma susceptibility: a genetic and in vitro study

2014 ◽  
Vol 21 (3) ◽  
pp. 395-404 ◽  
Author(s):  
Tomoko Sekiya ◽  
Marcello D Bronstein ◽  
Katiuscia Benfini ◽  
Viviane C Longuini ◽  
Raquel S Jallad ◽  
...  
Keyword(s):  
Cell Line ◽  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
In Vitro Study ◽  
Mouse Cell ◽  
Endocrine Tumor ◽  
Endocrine Tumors ◽  
Parathyroid Adenomas ◽  
Acth Secreting

Abstract Germline mutations in p27kip1 are associated with increased susceptibility to multiple endocrine neoplasias (MEN) both in rats and humans; however, the potential role of common polymorphisms of this gene in endocrine tumor susceptibility and tumorigenesis remains mostly unrecognized. To assess the risk associated with polymorphism rs2066827 (p27-V109G), we genotyped a large cohort of Brazilian patients with sporadic endocrine tumors (pituitary adenomas, n=252; pheochromocytomas, n=125; medullary thyroid carcinoma, n=51; and parathyroid adenomas, n=19) and 885 population-matched healthy controls and determined the odds ratios and 95% CIs. Significant associations were found for the group of patients with pituitary adenomas (P=0.01), particularly for those with ACTH-secreting pituitary adenomas (P=0.005). In contrast, no association was found with GH-secreting pituitary tumors alone or with the sporadic counterpart of MEN2-component neoplasias. Our in vitro analyses revealed increased colony formation and cell growth rate for an AtT20 corticotropin mouse cell line overexpressing the p27-V109G variant compared with cells transfected with the WT p27. However, the genotypic effects in genetic and in vitro approaches were divergent. In accordance with our genetic data showing specificity for ACTH-secreting pituitary tissues, the overexpression of p27-V109G in a GH3 somatotropin rat cell line resulted in no difference compared with the WT. Pituitary tumors are one of the major clinical components of syndromes associated with the p27 pathogenic mutations MENX and MEN4. Our genetic and in vitro data indicate that the common polymorphism rs2066827 may play a role in corticotropinoma susceptibility and tumorigenesis through a molecular mechanism not fully understood thus far.

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