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 Marked Response of a Hypermutated ACTH-Secreting Pituitary Carcinoma to Ipilimumab and Nivolumab

2018 ◽  
Vol 103 (10) ◽  
pp. 3925-3930 ◽  
Author(s):  
Andrew L Lin ◽  
Philip Jonsson ◽  
Viviane Tabar ◽  
T Jonathan Yang ◽  
John Cuaron ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Liver Metastasis ◽  
Effective Treatment ◽  
Somatic Hypermutation ◽  
Treatment Options ◽  
Pituitary Tumors ◽  
Pituitary Carcinoma ◽  
Tumor Resistance ◽  
Clinical Sequencing ◽  
Acth Secreting

Abstract Context Pituitary carcinoma is a rare and aggressive malignancy with a poor prognosis and few effective treatment options. Case A 35-year-old woman presented with an aggressive ACTH-secreting pituitary adenoma that initially responded to concurrent temozolomide and capecitabine prior to metastasizing to the liver. Following treatment with ipilimumab and nivolumab, the tumor volume of the dominant liver metastasis reduced by 92%, and the recurrent intracranial disease regressed by 59%. Simultaneously, her plasma ACTH level decreased from 45,550 pg/mL to 66 pg/mL. Molecular Evaluation Both prospective clinical sequencing with Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets and retrospective whole-exome sequencing were performed to characterize the molecular alterations in the chemotherapy-naive pituitary adenoma and the temozolomide-resistant liver metastasis. The liver metastasis harbored a somatic mutational burden consistent with alkylator-induced hypermutation that was absent from the treatment-naive tumor. Resistance to temozolomide treatment, acquisition of new oncogenic drivers, and subsequent sensitivity to immunotherapy may be attributed to hypermutation. Conclusion Combination treatment with ipilimumab and nivolumab may be an effective treatment in pituitary carcinoma. Clinical sequencing of pituitary tumors that have relapsed following treatment with conventional chemotherapy may identify the development of therapy-induced somatic hypermutation, which may be associated with treatment response to immunotherapy.

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 New developments in the medical treatment of Cushing's syndrome

2012 ◽  
Vol 19 (6) ◽  
pp. R205-R223 ◽  
Author(s):  
R van der Pas ◽  
W W de Herder ◽  
L J Hofland ◽  
R A Feelders
Keyword(s):  
Medical Treatment ◽  
Medical Therapy ◽  
Cushing’S Syndrome ◽  
Treatment Options ◽  
Cushing's Syndrome ◽  
Treatment Modalities ◽  
Primary Therapy ◽  
Ectopic Acth ◽  
Considerable Morbidity ◽  
Acth Secreting

Cushing's syndrome (CS) is a severe endocrine disorder characterized by chronic cortisol excess due to an ACTH-secreting pituitary adenoma, ectopic ACTH production, or a cortisol-producing adrenal neoplasia. Regardless of the underlying cause, untreated CS is associated with considerable morbidity and mortality. Surgery is the primary therapy for all causes of CS, but surgical failure and ineligibility of the patient to undergo surgery necessitate alternative treatment modalities. The role of medical therapy in CS has been limited because of lack of efficacy or intolerability. In recent years, however, new targets for medical therapy have been identified, both at the level of the pituitary gland (e.g. somatostatin, dopamine, and epidermal growth factor receptors) and the adrenal gland (ectopically expressed receptors in ACTH-independent macronodular adrenal hyperplasia). In this review, results of preclinical and clinical studies with drugs that exert their action through these molecular targets, as well as already established medical treatment options, will be discussed.

scholarly journals Thromboangiitis Obliterans (Buerger’s Disease)—Current Practices

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Abhishek Vijayakumar ◽  
Rahul Tiwari ◽  
Vinod Kumar Prabhuswamy
Keyword(s):  
Stem Cell ◽  
Disease Progression ◽  
Treatment Options ◽  
Vascular Diseases ◽  
Major Amputation ◽  
Walking Distance ◽  
Treatment Modalities ◽  
Definitive Treatment ◽  
Thromboangiitis Obliterans ◽  
Upper And Lower Extremities

Thromboangiitis obliterans (TAO) is a nonatherosclerotic, segmental inflammatory disease that most commonly affects the small and medium-sized arteries and veins in the upper and lower extremities. Cigarette smoking has been implicated as the main etiology of the disease. In eastern parts of the world TAO forms 40–60% of peripheral vascular diseases. Clinical features and angiographic finding are the basis of early diagnosis of TAO. Abstinence from smoking is the only definitive treatment to prevent disease progression. Medical management in form of aspirin, pentoxyfylline, cilostazol, and verapamil increase pain-free walking distance in intermittent claudication, but long term usage fails to prevent disease progression in patients who continue to smoke. Surgical treatment in form of revascularization, lumbar sympathectomy, omentopexy, and Ilizarov techniques help reduce pain and promote healing of trophic changes. Newer treatment modalities like spinal cord stimulation, prostacyclin, bosentan, VEGF, and stem cell therapy have shown promising results. Latest treatment options include peripheral mononuclear stem cell, and adipose tissue derived mononuclear stem cells have been shown to be effective in preventing disease progression, decrease major amputation rates, and improving quality of life.

Ectopic intracavernous sinus adrenocorticotropic hormone—secreting microadenoma: could this be a common cause of failed transsphenoidal surgery in Cushing disease?

2003 ◽  
Vol 98 (6) ◽  
pp. 1312-1317 ◽  
Author(s):  
Louis J. Kim ◽  
Jeffrey D. Klopfenstein ◽  
Ming Cheng ◽  
Murugasu Nagul ◽  
Stephen Coons ◽  
...  
Keyword(s):  
Transsphenoidal Surgery ◽  
Adrenocorticotropic Hormone ◽  
Sella Turcica ◽  
Cardiac Events ◽  
Cushing Disease ◽  
Rapid Reduction ◽  
Content Type ◽  
Negative Findings ◽  
Acth Secreting ◽  
Fine Print

✓ Despite diagnostic advances, it remains difficult to identify intrasellar and ectopic parasellar adrenocorticotropic hormone (ACTH)—secreting microadenomas. The authors present the case of a 61-year-old woman with Cushing disease in whom a significant central-to-peripheral and lateralized right-sided ACTH gradient was demonstrated on inferior petrosal sinus sampling; no discernible abnormality was seen on magnetic resonance imaging. She underwent transnasal transsphenoidal surgery. No tumor was found on sellar exploration and a total hypophysectomy was performed, yet her hypercortisolemia persisted. The patient died of cardiac events 17 days postsurgery. Autopsy revealed an isolated, right-sided, intracavernous ACTH-secreting adenoma with no intrasellar communication. This case represents the first failed transsphenoidal surgery for Cushing disease in which there is postmortem confirmation of a suspected intracavernous sinus lesion. It supports the hypothesis that Cushing disease associated with nondiagnostic imaging studies, a strong ACTH gradient on venography, and negative findings on sellar exploration may be caused by an ectopic intracavernous ACTH-secreting adenoma. There are no premortem means of confirming the presence of such lesions, but these tumors could underlie similar cases of failed surgery. Radiation therapy targeting the sella turcica and both cavernous sinuses, possibly supplemented with medical treatment, is suggested for similar patients in whom transsphenoidal hypophysectomy has failed. Adrenalectomy may also be appropriate if a rapid reduction in ACTH is necessary.

scholarly journals Glucocorticoid Receptor Antagonism Upregulates Somatostatin Receptor Subtype 2 Expression in ACTH-Producing Neuroendocrine Tumors: New Insight Based on the Selective Glucocorticoid Receptor Modulator Relacorilant

2022 ◽  
Vol 12 ◽  
Author(s):  
Rosario Pivonello ◽  
Pamela N. Munster ◽  
Massimo Terzolo ◽  
Rosario Ferrigno ◽  
Chiara Simeoli ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Neuroendocrine Tumors ◽  
Tumor Size ◽  
Somatostatin Receptor ◽  
Pituitary Tumors ◽  
Receptor Subtype ◽  
Cushing Disease ◽  
Ectopic Acth ◽  
Somatostatin Receptor Subtype 2 ◽  
Acth Secreting

Somatostatin exhibits an inhibitory effect on pituitary hormone secretion, including inhibition of growth hormone and adrenocorticotropic hormone (ACTH), and it can have antisecretory and antitumor effects on neuroendocrine tumors (NETs) that express somatostatin receptors. Although the precise mechanism remains unclear, the finding that glucocorticoids downregulate somatostatin receptor subtype 2 (SSTR2) expression has been used to explain the lack of efficacy of traditional SSTR2-targeting analogs in patients with ACTH-secreting NETs. Glucocorticoid receptor (GR) antagonism with mifepristone has been shown to reverse the glucocorticoid-induced downregulation of SSTR2; however, the effects of GR modulation on SSTR2 expression in ACTH-secreting NETs, particularly corticotroph pituitary tumors, are not well known. The current study presents new insight from in vitro data using the highly selective GR modulator relacorilant, showing that GR modulation can overcome dexamethasone-induced suppression of SSTR2 in the murine At-T20 cell line. Additional data presented from clinical case observations in patients with ACTH-secreting NETs suggest that upregulation of SSTR2 via GR modulation may re-sensitize tumors to endogenous somatostatin and/or somatostatin analogs. Clinical, laboratory, and imaging findings from 4 patients [2 ACTH-secreting bronchial tumors and 2 ACTH-secreting pituitary tumors (Cushing disease)] who were treated with relacorilant as part of two clinical studies (NCT02804750 and NCT02762981) are described. In the patients with ectopic ACTH secretion, SSTR2-based imaging (Octreoscan and 68Ga-DOTATATE positron emission tomography) performed before and after treatment with relacorilant showed increased radiotracer uptake by the tumor following treatment with relacorilant without change in tumor size at computed tomography. In the patients with Cushing disease who received relacorilant prior to scheduled pituitary surgery, magnetic resonance imaging after a 3-month course of relacorilant showed a reduction in tumor size. Based on these findings, we propose that GR modulation in patients with ACTH-secreting NETs upregulates previously suppressed SSTR2s, resulting in tumor-specific antisecretory and anti-proliferative effects. The effect of relacorilant on pituitary corticotroph tumors is being investigated in an ongoing phase 3 study (NCT03697109; EudraCT 2018-003096-35).

scholarly journals MicroRNAs Differentially Expressed in ACTH-Secreting Pituitary Tumors

2009 ◽  
Vol 94 (1) ◽  
pp. 320-323 ◽  
Author(s):  
Fernando Colbari Amaral ◽  
Natalia Torres ◽  
Fabiano Saggioro ◽  
Luciano Neder ◽  
Hélio Rubens Machado ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Tumor Size ◽  
Target Genes ◽  
Pituitary Tumors ◽  
Mirna Expression Profile ◽  
Fragile Sites ◽  
Cushing Disease ◽  
Small Noncoding Rnas ◽  
Mirna Genes ◽  
Acth Secreting

Abstract Context: MicroRNAs (miRNAs) are small noncoding RNAs, functioning as antisense regulators of gene expression by targeting mRNA and contributing to cancer development and progression. More than 50% of miRNA genes are located in cancer-associated genomic regions or in fragile sites of the genome. Objective: The aim of the study was to analyze the differential expression of let-7a, miR-15a, miR-16, miR-21, miR-141, miR-143, miR-145, and miR-150 in corticotropinomas and normal pituitary tissue and verify whether their profile of expression correlates with tumor size or remission after treatment. Material and Methods: ACTH-secreting pituitary tumor samples were obtained during transphenoidal surgery from patients with Cushing disease and normal pituitary tissues from autopsies. The relative expression of miRNAs was measured by real-time PCR using RNU44 and RNU49 as endogenous controls. Relative quantification of miRNA expression was calculated using the 2−ΔΔCt method. Results: We found underexpression of miR-145 (2.0-fold; P = 0.04), miR-21 (2.4-fold; P = 0.004), miR-141 (2.6-fold; P = 0.02), let-7a (3.3-fold; P = 0.003), miR-150 (3.8-fold; P = 0.04), miR-15a (4.5-fold; P = 0.03), miR-16 (5.0-fold; P = 0.004), and miR-143 (6.4-fold; P = 0.004) in ACTH-secreting pituitary tumors when compared to normal pituitary tissues. There were no differences between miRNA expression and tumor size as well as miRNA expression and ratio of remission after surgery, except in patients presenting lower miR-141 expression who showed a better chance of remission. Conclusion: Our results support the possibility that altered miRNA expression profile might be involved in corticotrophic tumorigenesis. However, the lack of knowledge about miRNA target genes postpones full understanding of the biological functions of down-regulated or up-regulated miRNAs in corticotropinomas.

scholarly journals Current Trends in the Management of Ballistic Fractures of the Hand and Wrist: Experiences of a High-Volume Level I Trauma Center

Hand ◽  
2017 ◽  
Vol 13 (2) ◽  
pp. 176-180 ◽  
Author(s):  
Paul A. Ghareeb ◽  
Charles Daly ◽  
Albert Liao ◽  
Diane Payne
Keyword(s):  
Trauma Center ◽  
Treatment Options ◽  
High Volume ◽  
Operative Intervention ◽  
Treatment Modalities ◽  
Definitive Treatment ◽  
Percutaneous Fixation ◽  
Low Velocity ◽  
Patient Demographics ◽  
Level I

Background: Ballistic fractures of the carpus and hand are routinely treated in large urban centers. These injuries can be challenging due to many factors. Various treatment options exist for these complicated injuries, but there are limited data available. This report analyzes patient demographics, treatments, and outcomes at a large urban trauma center. Methods: All ballistic fractures of the hand and wrist of the patients who presented to a single center from 2011 to 2014 were retrospectively reviewed. Patient demographics, injury mechanism, treatment modalities, and outcomes were analyzed. Results: Seventy-seven patients were identified; 70 were male, and 7 were female. Average age of the patients was 29.6 years. Seventy-five injuries were low velocity, whereas 2 were high velocity. Sixty-seven patients had fractures of a metacarpal or phalanx, whereas 4 had isolated carpal injuries. Six had combined carpal and metacarpal or phalanx fractures. Thirty-six patients had concomitant tendon, nerve, or vascular injuries requiring repair. Sixty-three patients underwent operative intervention, with the most common intervention being percutaneous fixation. Sixteen patients required secondary surgery. Eighteen complications were reported. Conclusions: The majority of patients in this report underwent early operative intervention with percutaneous fixation. Antibiotics were administered in almost all cases and can usually be discontinued within 24 hours after surgery. It is important to consider concomitant nerve, vascular, or tendon injuries requiring repair. We recommend early treatment of these injuries with debridement and stabilization. Due to lack of follow-up and patient noncompliance, early definitive treatment with primary bone grafting should be considered.

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 Prospective evaluation of the characteristics and incidence of adenoma-associated dural invasion in Cushing disease

2012 ◽  
Vol 116 (2) ◽  
pp. 272-279 ◽  
Author(s):  
Russell R. Lonser ◽  
Alexander Ksendzovsky ◽  
Joshua J. Wind ◽  
Alexander O. Vortmeyer ◽  
Edward H. Oldfield
Keyword(s):  
Mr Imaging ◽  
Cavernous Sinus ◽  
Significant Risk ◽  
Pituitary Tumors ◽  
Significant Risk Factor ◽  
Incomplete Resection ◽  
Cushing Disease ◽  
Cavernous Sinus Invasion ◽  
Sinus Wall ◽  
Acth Secreting

Object Dural invasion by adrenocorticotropic hormone (ACTH)-secreting adenomas is a significant risk factor for incomplete resection and recurrence in Cushing disease (CD). Since ACTH-producing adenomas are often the smallest of the various types of pituitary tumors at the time of resection, examining their invasion provides the best opportunity to identify the precise sites of early dural invasion by pituitary adenomas. To characterize the incidence and anatomical distribution of dural invasion by ACTH-secreting adenomas, the authors prospectively and systematically analyzed features of dural invasion in patients with CD. Methods The authors prospectively studied consecutive patients with CD undergoing the systematic removal of ACTH-secreting adenoma and histological analysis of the anterior sella dura as well as other sites of dural invasion that were evident at surgery. Clinical, imaging, histological, and operative findings were analyzed. Results Eighty-seven patients with CD (58 females and 29 males) were included in the study. Overall, dural invasion by an ACTH-positive adenoma was histologically confirmed in 30 patients (34%). Eighteen patients (60% of dural invasion cases, 21% of all patients) had evidence of cavernous sinus wall invasion (4 of these patients also had other contiguous sites of invasion), and 12 patients (40% of dural invasion cases) had invasion of the sella dura excluding the cavernous sinus wall. Eleven patients (13% all patients) had invasion of the routinely procured anterior sella dura specimen. Preoperative MR imaging revealed an adenoma in 64 patients (74%) but accurately predicted dural invasion in only 4 patients (22%) with cavernous sinus invasion and none of the patients with non–cavernous sinus invasion. Adenomas associated with dural invasion (mean ± SD, 10.9 ± 7.8 mm, range 2–37 mm) were significantly larger than those not associated with dural invasion (5.7 ± 2.1 mm, range 2.5–12 mm; p = 0.0006, Mann-Whitney test). Conclusions Dural invasion by ACTH-producing adenomas preferentially occurs laterally into the wall of the cavernous sinus. Preoperative MR imaging infrequently detects dural invasion, including cavernous sinus invasion. Invasion is directly associated with tumor size. To provide a biochemical cure and avoid recurrence after resection, identification and removal of invaded sella dura, including the medial cavernous sinus wall, are necessary.

Sign in / Sign up

Export Citation Format

Share Document