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Edward H. Oldfield - One of the best experts on this subject based on the ideXlab platform.
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the history of pituitary surgery for Cushing Disease historical vignette
Journal of Neurosurgery, 2012Co-Authors: Edward H. Oldfield, Russell R. Lonser, Gautam U. MehtaAbstract:Although he never performed a pituitary operation for the Disease, Harvey Cushing was the first to describe and treat patients with Cushing Disease (CD). Other surgeons at the time were reluctant to operate on the pituitary due to the normal sella on skull radiographs in CD and the unclear etiology of the disorder. To better define and understand factors influencing the history of pituitary surgery for CD, the authors analyzed historical texts related to CD biology, diagnosis, and treatment. Cushing's monograph on basophilic pituitary adenomas and cortisol excess appeared in 1932. One year later in 1933, Alfred Pattison performed the first successful pituitary operation for CD by implanting radon seeds in the sella. Resection of a pituitary adenoma for CD was attempted 1 month later in 1933 by Howard Naffziger, resulting in only transient improvement that corresponded to the lack of tumor in the resected tissue. Soon thereafter, Susman in 1935 and Costello in 1936 described pituitary basophilic adenomas a...
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The history of pituitary surgery for Cushing Disease: Historical vignette
Journal of neurosurgery, 2011Co-Authors: Gautam U. Mehta, Russell R. Lonser, Edward H. OldfieldAbstract:Although he never performed a pituitary operation for the Disease, Harvey Cushing was the first to describe and treat patients with Cushing Disease (CD). Other surgeons at the time were reluctant to operate on the pituitary due to the normal sella on skull radiographs in CD and the unclear etiology of the disorder. To better define and understand factors influencing the history of pituitary surgery for CD, the authors analyzed historical texts related to CD biology, diagnosis, and treatment. Cushing's monograph on basophilic pituitary adenomas and cortisol excess appeared in 1932. One year later in 1933, Alfred Pattison performed the first successful pituitary operation for CD by implanting radon seeds in the sella. Resection of a pituitary adenoma for CD was attempted 1 month later in 1933 by Howard Naffziger, resulting in only transient improvement that corresponded to the lack of tumor in the resected tissue. Soon thereafter, Susman in 1935 and Costello in 1936 described pituitary basophilic adenomas at autopsy in patients without premorbid endocrinopathy. They concluded that the adrenal gland was the cause of CD, which resulted in a 3-decade abandonment of pituitary surgery for CD. Jules Hardy in 1963 used the operating microscope to perform the first selective removal of an adrenocorticotropic hormone (ACTH)-secreting microadenoma, which established a pituitary cause and defined the modern treatment of CD. Subsequent reports by Hardy, Laws, and Wilson resulted in widespread acceptance of pituitary surgery for CD. Initial reluctance to operate on the pituitary for CD was multifaceted and included general uncertainty surrounding the etiology of Cushing syndrome as well as a lack of early surgical success, both due to the small size of ACTH-secreting adenomas. Selective removal of ACTH-secreting adenomas identified the source of CD and ended the delay in acceptance of pituitary surgery for CD.
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Prospective evaluation of the characteristics and incidence of adenoma-associated dural invasion in Cushing Disease.
Journal of neurosurgery, 2011Co-Authors: Russell R. Lonser, Alexander Ksendzovsky, Joshua J. Wind, Alexander O. Vortmeyer, Edward H. OldfieldAbstract: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)...
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outcome of using the histological pseudocapsule as a surgical capsule in Cushing Disease
Journal of Neurosurgery, 2009Co-Authors: Jay Jagannathan, Alexander O. Vortmeyer, Rene Smith, Hetty L Devroom, Constantine A Stratakis, Lynnette K Nieman, Edward H. OldfieldAbstract:Object Many patients with Cushing Disease still have active or recurrent Disease after pituitary surgery. The histological pseudocapsule of a pituitary adenoma is a layer of compressed normal anterior lobe that surrounds the adenoma and can be used during surgery to identify and guide removal of the tumor. In this study the authors examined the results of using the pseudocapsule as a surgical capsule in the resection of adenomas in patients with Cushing Disease. Methods The authors reviewed a prospective database of data obtained in patients with Cushing Disease who underwent surgery. The analysis included all cases in which a lesion was identified during surgery and in which the lesion was believed to be confined to the pituitary gland in patients with Cushing Disease between January 1990 and March 2007. Since the objective was to determine the success of using the pseudocapsule as a surgical capsule, patients with invasive tumors and patients in whom no lesion was identified during surgery—challenging c...
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an assessment of petrosal sinus sampling for localization of pituitary microadenomas in children with Cushing Disease
The Journal of Clinical Endocrinology and Metabolism, 2006Co-Authors: Dalia L Batista, Margaret F. Keil, Edward H. Oldfield, Monia Gennari, Jehan Riar, Richard Chang, Constantine A StratakisAbstract:CONTEXT: Pituitary adenomas in Cushing Disease (CD) are usually small and difficult to visualize. Bilateral inferior petrosal venous sampling (BIPSS) before and after ovine CRH stimulation is reserved for patients who have ACTH-dependent Cushing syndrome and negative magnetic resonance imaging (MRI) or positive MRI but inconsistent biochemical data. OBJECTIVE: The objective of the study was to evaluate the usefulness of BIPSS as a tool for localization of a pituitary adenoma in children with CD. DESIGN: The study was a retrospective review of the records of 141 children who were admitted for evaluation of CD from 1982 to 2004. SETTING: The study was conducted at a tertiary care center. INTERVENTIONS AND OUTCOME MEASURES: Lateralization of ACTH secretion during BIPSS was compared with MRI and surgical findings for the localization of a microadenoma. RESULTS: A total of 94 patients, 49 males and 45 females with an age range of 5.3 to 18.7 yr (13 +/- 3.2 yr), underwent BIPSS. Localization of a microadenoma by BIPSS agreed with surgical location in only 58% of the cases (95% confidence interval, 43-66). The combined use of information from the MRI and inferior petrosal venous sampling did not predict the location of the tumor more frequently than MRI alone (P > 0.1), which in this study localized a lesion in 39% of the patients (95% confidence interval, 28-50). The procedure was completed successfully in all patients, and no serious complications were recorded. CONCLUSIONS: Although BIPSS was safe and well tolerated in an experienced center, lateralization of the ACTH gradient during BIPSS was a poor predictor of the site of the adenoma in children with CD.
Prashant Chittiboina - One of the best experts on this subject based on the ideXlab platform.
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children with men1 gene mutations may present first and at a young age with Cushing Disease
Clinical Endocrinology, 2018Co-Authors: Angeliki Makri, Amit Tirosh, Prashant Chittiboina, Margaret F. Keil, Maria Belen Bonella, Laura C Hernandezramirez, Gabriella Paluch, Carolina Saldarriaga, Stephen J. MarxAbstract:Objective Cushing Disease (CD) is a rare entity caused by ACTH-secreting pituitary tumours, leading to prolonged hypercortisolism. Most cases are sporadic but can rarely occur in the context of familial predisposition, due to germline mutations in genes such as MEN1, leading to multiple endocrine neoplasia type 1, MEN1. We have reported previously that CD can be the first and only presenting manifestation of MEN1. In this report, we describe a cohort of paediatric patients who presented with CD as the first manifestation of MEN1. Materials and methods A retrospective analysis of paediatric patients admitted to the National Institutes of Health (NIH) Clinical Center for evaluation of hypercortisolism, between 1997 and 2017. MEN1 was diagnosed on a clinical, familial and/or genetic basis. Results Of a total of 238 children with CD, six patients were subsequently diagnosed with MEN1, three males and three females with a mean age at diagnosis of CD at 13.4 ± 2.9 years. Five of the six patients had familial MEN1 and one patient was a sporadic case. Additional manifestations of MEN1 included primary hyperparathyroidism in three patients and hyperprolactinemia in two patients. Discussion This report describes a paediatric patient population with MEN1 in whom CD was the initial manifestation, confirming a previous observation that paediatric patients with MEN1 may present first with an ACTH-producing adenoma. Therefore, germline MEN1 mutations should be sought in paediatric CD and tested for when there is a suggestive family history and/or other manifestations.
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histone deacetylase inhibitor saha is a promising treatment of Cushing Disease
The Journal of Clinical Endocrinology and Metabolism, 2017Co-Authors: Gregoire P Chatain, Alejandro Bugarini, Xiang Wang, Dragan Maric, Stuart Walbridge, Zhengping Zhuang, Prashant ChittiboinaAbstract:Context Remission failure following transsphenoidal surgery in Cushing Disease (CD) from pituitary corticotroph tumors (CtTs) remains clinically challenging. Histone deacetylase inhibitors (HDACis) are antitumor drugs approved for clinical use, with the potential to affect adrenocorticotropin hormone (ACTH) hypersecretion by inhibiting pro-opiomelanocortin (POMC) transcription. Objective Testing the efficacy of suberoylanilide hydroxamic acid (SAHA) on human and murine ACTH-secreting tumor (AtT-20) cells. Design Cell viability, ACTH secretion (enzyme-linked immunosorbent assay), apoptosis, and gene expression profile were investigated on AtT-20 cells. In vivo efficacy was examined in an athymic nude mouse AtT-20 xenograft model. SAHA efficacy against human-derived corticotroph tumor (hCtT) (n = 8) was tested in vitro. Setting National Institutes of Health. Intervention SAHA (0.5 to 8 µM). Main Outcome Measures AtT-20 and hCtT cell survival, in vitro/invivo ACTH measurements. Results SAHA (1 µM) reduced AtT-20 viability to 75% at 24 hours, 43% at 48 hours (analysis of variance; P = 0.002). Apoptosis was confirmed with elevated BAX/Bcl2 ratio and FACS. Intriguingly, early (3-hour) significant decline (70%; P < 0.0001) of secreted ACTH and diminished POMC transcription was observed with SAHA (1 µM). Microarray analysis revealed a direct association between liver X receptor alpha (LXRα) and POMC expression. Accordingly, SAHA reduced LXRα in AtT-20 cells but not in normal murine corticotrophs. Xenografted nude-mice tumor involution (126 ± 33/160 ± 35 vs 337 ± 49 mm3; P = 0.0005) was observed with 5-day intraperitoneal SAHA, with reversal of elevated ACTH (P < 0.0001). SAHA did not affect serum ACTH in nontumor mice. Lastly, we confirmed that SAHA (1 µM/24 h) decreased hCtT survival (78.92%; P = 0.0007) and ACTH secretion (83.64%; P = 0.03). Conclusion Our findings demonstrate SAHA's efficacy in reducing survival and ACTH secretion in AtT-20 and hCtT cells, providing a potential intervention for recurrent/unremitting CD.
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Somatic USP8 Gene Mutations Are a Common Cause of Pediatric Cushing Disease.
The Journal of Clinical Endocrinology & Metabolism, 2017Co-Authors: Fabio R. Faucz, Nikolaos Settas, Anna Angelousi, Amit Tirosh, Christina Tatsi, Annabel Berthon, Laura C. Hernández-ramírez, Ricardo G. Correa, Georgios Z. Papadakis, Prashant ChittiboinaAbstract:Context Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have been recently identified as the most common genetic alteration in patients with Cushing Disease (CD). However, the frequency of these mutations in the pediatric population has not been extensively assessed. Objective We investigated the status of the USP8 gene at the somatic level in a cohort of pediatric patients with corticotroph adenomas. Design and methods The USP8 gene was fully sequenced in both germline and tumor DNA samples from 42 pediatric patients with CD. Clinical, biochemical, and imaging data were compared between patients with and without somatic USP8 mutations. Results Five different USP8 mutations (three missense, one frameshift, and one in-frame deletion) were identified in 13 patients (31%), all of them located in exon 14 at the previously described mutational hotspot, affecting the 14-3-3 binding motif of the protein. Patients with somatic mutations were older at Disease presentation [mean 5.1 ± 2.1 standard deviation (SD) vs 13.1 ± 3.6 years, P = 0.03]. Levels of urinary free cortisol, midnight serum cortisol, and adrenocorticotropic hormone, as well as tumor size and frequency of invasion of the cavernous sinus, were not significantly different between the two groups. However, patients harboring somatic USP8 mutations had a higher likelihood of recurrence compared with patients without mutations (46.2% vs 10.3%, P = 0.009). Conclusion Somatic USP8 gene mutations are a common cause of pediatric CD. Patients harboring a somatic mutation had a higher likelihood of tumor recurrence, highlighting the potential importance of this molecular defect for the Disease prognosis and the development of targeted therapeutic options.
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Cushing Disease in a patient with multiple endocrine neoplasia type 2B
Elsevier, 2017Co-Authors: Kannan Kasturi, Prashant Chittiboina, Constantine A Stratakis, Lucas Fernandes, Martha Quezado, Mary Eid, Leigh Marcus, Mark Rappaport, Brigitte Widemann, Maya LodishAbstract:Context: Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing Disease is a rare cause of endogenous hypercortisolism in children. Case description: We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene. Following thyroidectomy, he was initiated on Vandetanib, a tyrosine kinase inhibitor, and has since had stable Disease over the last 5 years. Conclusions: Our patient is the first individual with MEN2B to be described with Cushing Disease. The RET oncogene may play a role in pituitary tumorigenesis; alternatively, the coexistence of these two entities may represent an extremely rare coincidence. Keywords: Hypercortisolemia, Neuroendocrine tumor, Genetic syndrome, RE
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high resolution18f fluorodeoxyglucose positron emission tomography and magnetic resonance imaging for pituitary adenoma detection in Cushing Disease
Journal of Neurosurgery, 2015Co-Authors: Prashant Chittiboina, Blake K Montgomery, Corina Millo, Peter Herscovitch, Russell R. LonserAbstract:OBJECT High-resolution PET (hrPET) performed using a high-resolution research tomograph is reported as having a resolution of 2 mm and could be used to detect corticotroph adenomas through uptake of18F-fluorodeoxyglucose (18F-FDG). To determine the sensitivity of this imaging modality, the authors compared18F-FDG hrPET and MRI detection of pituitary adenomas in Cushing Disease (CD). METHODS Consecutive patients with CD who underwent preoperative18F-FDG hrPET and MRI (spin echo [SE] and spoiled gradient recalled [SPGR] sequences) were prospectively analyzed. Standardized uptake values (SUVs) were calculated from hrPET and were compared with MRI findings. Imaging findings were correlated to operative and histological findings. RESULTS Ten patients (7 females and 3 males) were included (mean age 30.8 ± 19.3 years; range 11–59 years). MRI revealed a pituitary adenoma in 4 patients (40% of patients) on SE and 7 patients (70%) on SPGR sequences.18F-FDG hrPET demonstrated increased18F-FDG uptake consistent with ...
Constantine A Stratakis - One of the best experts on this subject based on the ideXlab platform.
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recovery of hypothalamic pituitary adrenal axis in pediatric Cushing Disease
Clinical Endocrinology, 2020Co-Authors: Christina Tatsi, Meg Keil, Megan L Neely, Chelsi Flippo, Mariaeleni Bompou, Constantine A StratakisAbstract:Objectives The postoperative period of Cushing Disease (CD) is complicated by a phase of adrenal insufficiency (AI). Factors that influence the duration of AI and its prognostic significance for CD recurrence in children have not been extensively studied. We investigated whether clinical or biochemical factors contribute to the duration of AI, and the correlation of the recovery process with the risk for recurrence. Design Patients with pediatric-onset CD who were followed up for at least 3 months after transsphenoidal surgery (TSS) (n=130) were included in the study. Multivariable Cox proportional hazards analysis was used to assess the association of biochemical and clinical factors with duration of AI. Results Overall, 102 patients recovered adrenal function during their follow-up. Median time to recovery was 12.7 months [95%Confidence Intervals (CI): 12.2-13.4]. On multivariable analysis, clinical (age, gender, Disease duration, puberty stage, BMI z-score, tumor size, invasion of the cavernous sinus, year of surgery) and biochemical (midnight cortisol, morning ACTH) factors did not correlate with the time to recovery, except for increase of recovery time noted with increase of urinary free cortisol (UFC) [Hazard Ratio (HR):0.94, 95%CI:0.89-0.99]. Among patients who eventually recovered adrenal function, the risk for CD recurrence was associated with the time to recovery (HR:0.86, 95%CI:0.75-0.99). Conclusions Recovery of adrenal function in patients with CD after TSS may not be associated with most clinical and biochemical factors in the preoperative period except for total cortisol excretion, as evidenced by the correlation with UFC. Earlier recovery is associated with higher risk for recurrence, which has implications for the patients' follow up and counseling.
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Cushing Disease in a patient with nonbullous congenital ichthyosiform erythroderma lessons in avoiding glucocorticoids in ichthyosis
Journal of Pediatric Endocrinology and Metabolism, 2019Co-Authors: Iris R Hartley, Maya B. Lodish, Julia Costa Beber Nunes, Constantine A StratakisAbstract:Nonbullous congenital ichthyosis erythroderma (CIE) is an autosomal recessive disorder of ineffective keratinization. We present a unique case of a 16-year-old female with CIE who developed Cushing Disease (CD) at age 13 with concomitant worsening of her skin Disease. After transsphenoidal resection of her pituitary adenoma, she had both resolution of her Cushing symptoms and significantly milder skin manifestations of her CIE. To the best of our knowledge, this is the first reported case of a patient with both CD and CIE, one that is important in demonstrating the role of glucocorticoids in this disorder.
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Cushing Disease in a patient with multiple endocrine neoplasia type 2B
Elsevier, 2017Co-Authors: Kannan Kasturi, Prashant Chittiboina, Constantine A Stratakis, Lucas Fernandes, Martha Quezado, Mary Eid, Leigh Marcus, Mark Rappaport, Brigitte Widemann, Maya LodishAbstract:Context: Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing Disease is a rare cause of endogenous hypercortisolism in children. Case description: We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene. Following thyroidectomy, he was initiated on Vandetanib, a tyrosine kinase inhibitor, and has since had stable Disease over the last 5 years. Conclusions: Our patient is the first individual with MEN2B to be described with Cushing Disease. The RET oncogene may play a role in pituitary tumorigenesis; alternatively, the coexistence of these two entities may represent an extremely rare coincidence. Keywords: Hypercortisolemia, Neuroendocrine tumor, Genetic syndrome, RE
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outcome of using the histological pseudocapsule as a surgical capsule in Cushing Disease
Journal of Neurosurgery, 2009Co-Authors: Jay Jagannathan, Alexander O. Vortmeyer, Rene Smith, Hetty L Devroom, Constantine A Stratakis, Lynnette K Nieman, Edward H. OldfieldAbstract:Object Many patients with Cushing Disease still have active or recurrent Disease after pituitary surgery. The histological pseudocapsule of a pituitary adenoma is a layer of compressed normal anterior lobe that surrounds the adenoma and can be used during surgery to identify and guide removal of the tumor. In this study the authors examined the results of using the pseudocapsule as a surgical capsule in the resection of adenomas in patients with Cushing Disease. Methods The authors reviewed a prospective database of data obtained in patients with Cushing Disease who underwent surgery. The analysis included all cases in which a lesion was identified during surgery and in which the lesion was believed to be confined to the pituitary gland in patients with Cushing Disease between January 1990 and March 2007. Since the objective was to determine the success of using the pseudocapsule as a surgical capsule, patients with invasive tumors and patients in whom no lesion was identified during surgery—challenging c...
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role of brg1 and hdac2 in gr trans repression of the pituitary pomc gene and misexpression in Cushing Disease
Genes & Development, 2006Co-Authors: Steve Bilodeau, Constantine A Stratakis, Dalia L Batista, Dominique Figarellabranger, Thierry Brue, Sophie Vallettekasic, Yves Gauthier, Andre Lacroix, J M Hanson, B P MeijAbstract:Negative feedback regulation of the proopiomelanocortin (POMC) gene by the glucocorticoid (Gc) receptor (GR) is a critical feature of the hypothalamo-pituitary-adrenal axis, and it is in part exerted by trans-repression between GR and the orphan nuclear receptors related to NGFI-B. We now show that Brg1, the ATPase subunit of the Swi/Snf complex, is essential for this trans-repression and that Brg1 is required in vivo to stabilize interactions between GR and NGFI-B as well as between GR and HDAC2. Whereas Brg1 is constitutively present at the POMC promoter, recruitment of GR and HDAC2 is ligand-dependent and results in histone H4 deacetylation of the POMC locus. In addition, GR-dependent repression inhibits promoter clearance by RNA polymerase II. Thus, corecruitment of repressor and activator at the promoter and chromatin modification jointly contribute to trans-repression initiated by direct interactions between GR and NGFI-B. Loss of Brg1 or HDAC2 should therefore produce Gc resistance, and we show that approximately 50% of Gc-resistant human and dog corticotroph adenomas, which are the hallmark of Cushing Disease, are deficient in nuclear expression of either protein. In addition to providing a molecular basis for Gc resistance, these deficiencies may also contribute to the tumorigenic process.
Russell R. Lonser - One of the best experts on this subject based on the ideXlab platform.
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high resolution18f fluorodeoxyglucose positron emission tomography and magnetic resonance imaging for pituitary adenoma detection in Cushing Disease
Journal of Neurosurgery, 2015Co-Authors: Prashant Chittiboina, Blake K Montgomery, Corina Millo, Peter Herscovitch, Russell R. LonserAbstract:OBJECT High-resolution PET (hrPET) performed using a high-resolution research tomograph is reported as having a resolution of 2 mm and could be used to detect corticotroph adenomas through uptake of18F-fluorodeoxyglucose (18F-FDG). To determine the sensitivity of this imaging modality, the authors compared18F-FDG hrPET and MRI detection of pituitary adenomas in Cushing Disease (CD). METHODS Consecutive patients with CD who underwent preoperative18F-FDG hrPET and MRI (spin echo [SE] and spoiled gradient recalled [SPGR] sequences) were prospectively analyzed. Standardized uptake values (SUVs) were calculated from hrPET and were compared with MRI findings. Imaging findings were correlated to operative and histological findings. RESULTS Ten patients (7 females and 3 males) were included (mean age 30.8 ± 19.3 years; range 11–59 years). MRI revealed a pituitary adenoma in 4 patients (40% of patients) on SE and 7 patients (70%) on SPGR sequences.18F-FDG hrPET demonstrated increased18F-FDG uptake consistent with ...
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high resolution 18 f fluorodeoxyglucose positron emission tomography and magnetic resonance imaging for pituitary adenoma detection in Cushing Disease
Journal of Neurosurgery, 2015Co-Authors: Prashant Chittiboina, Blake K Montgomery, Corina Millo, Peter Herscovitch, Russell R. LonserAbstract:OBJECT High-resolution PET (hrPET) performed using a high-resolution research tomograph is reported as having a resolution of 2 mm and could be used to detect corticotroph adenomas through uptake of18F-fluorodeoxyglucose (18F-FDG). To determine the sensitivity of this imaging modality, the authors compared18F-FDG hrPET and MRI detection of pituitary adenomas in Cushing Disease (CD). METHODS Consecutive patients with CD who underwent preoperative18F-FDG hrPET and MRI (spin echo [SE] and spoiled gradient recalled [SPGR] sequences) were prospectively analyzed. Standardized uptake values (SUVs) were calculated from hrPET and were compared with MRI findings. Imaging findings were correlated to operative and histological findings. RESULTS Ten patients (7 females and 3 males) were included (mean age 30.8 ± 19.3 years; range 11–59 years). MRI revealed a pituitary adenoma in 4 patients (40% of patients) on SE and 7 patients (70%) on SPGR sequences.18F-FDG hrPET demonstrated increased18F-FDG uptake consistent with ...
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the history of pituitary surgery for Cushing Disease historical vignette
Journal of Neurosurgery, 2012Co-Authors: Edward H. Oldfield, Russell R. Lonser, Gautam U. MehtaAbstract:Although he never performed a pituitary operation for the Disease, Harvey Cushing was the first to describe and treat patients with Cushing Disease (CD). Other surgeons at the time were reluctant to operate on the pituitary due to the normal sella on skull radiographs in CD and the unclear etiology of the disorder. To better define and understand factors influencing the history of pituitary surgery for CD, the authors analyzed historical texts related to CD biology, diagnosis, and treatment. Cushing's monograph on basophilic pituitary adenomas and cortisol excess appeared in 1932. One year later in 1933, Alfred Pattison performed the first successful pituitary operation for CD by implanting radon seeds in the sella. Resection of a pituitary adenoma for CD was attempted 1 month later in 1933 by Howard Naffziger, resulting in only transient improvement that corresponded to the lack of tumor in the resected tissue. Soon thereafter, Susman in 1935 and Costello in 1936 described pituitary basophilic adenomas a...
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The history of pituitary surgery for Cushing Disease: Historical vignette
Journal of neurosurgery, 2011Co-Authors: Gautam U. Mehta, Russell R. Lonser, Edward H. OldfieldAbstract:Although he never performed a pituitary operation for the Disease, Harvey Cushing was the first to describe and treat patients with Cushing Disease (CD). Other surgeons at the time were reluctant to operate on the pituitary due to the normal sella on skull radiographs in CD and the unclear etiology of the disorder. To better define and understand factors influencing the history of pituitary surgery for CD, the authors analyzed historical texts related to CD biology, diagnosis, and treatment. Cushing's monograph on basophilic pituitary adenomas and cortisol excess appeared in 1932. One year later in 1933, Alfred Pattison performed the first successful pituitary operation for CD by implanting radon seeds in the sella. Resection of a pituitary adenoma for CD was attempted 1 month later in 1933 by Howard Naffziger, resulting in only transient improvement that corresponded to the lack of tumor in the resected tissue. Soon thereafter, Susman in 1935 and Costello in 1936 described pituitary basophilic adenomas at autopsy in patients without premorbid endocrinopathy. They concluded that the adrenal gland was the cause of CD, which resulted in a 3-decade abandonment of pituitary surgery for CD. Jules Hardy in 1963 used the operating microscope to perform the first selective removal of an adrenocorticotropic hormone (ACTH)-secreting microadenoma, which established a pituitary cause and defined the modern treatment of CD. Subsequent reports by Hardy, Laws, and Wilson resulted in widespread acceptance of pituitary surgery for CD. Initial reluctance to operate on the pituitary for CD was multifaceted and included general uncertainty surrounding the etiology of Cushing syndrome as well as a lack of early surgical success, both due to the small size of ACTH-secreting adenomas. Selective removal of ACTH-secreting adenomas identified the source of CD and ended the delay in acceptance of pituitary surgery for CD.
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Prospective evaluation of the characteristics and incidence of adenoma-associated dural invasion in Cushing Disease.
Journal of neurosurgery, 2011Co-Authors: Russell R. Lonser, Alexander Ksendzovsky, Joshua J. Wind, Alexander O. Vortmeyer, Edward H. OldfieldAbstract: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)...
Brooke Swearingen - One of the best experts on this subject based on the ideXlab platform.
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two synchronous pituitary adenomas causing Cushing Disease and acromegaly
AACE clinical case reports, 2019Co-Authors: Melanie Schorr, Anne Klibanski, Brooke Swearingen, Xun Zhang, Wenxiu Zhao, Parisa Abedi, Kate E Lines, Essa Te Hedleywhyte, Karen K Miller, Rajesh V ThakkerAbstract:ABSTRACT Objective: To report the first case of 2 synchronous pituitary adenomas, 1 corticotroph and 1 somatotroph, with distinct molecular lineages confirmed by differential hormone and S-100 prot...
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transsphenoidal surgery for Cushing Disease after nondiagnostic inferior petrosal sinus sampling
Neurosurgery, 2012Co-Authors: Sameer A Sheth, Matthew K Mian, Jonathan Neal, Nicholas A Tritos, Lisa B Nachtigall, Anne Klibanski, Beverly M K Biller, Brooke SwearingenAbstract:BACKGROUND: Inferior petrosal sinus sampling (IPSS) is a useful technique for confirming a pituitary source of adrenocorticotropic hormone (ACTH) overproduction in Cushing Disease. Uncertainty remains regarding the appropriate course of therapy when an ectopic tumor is predicted by IPSS but none can be found and in circumstances when the procedure cannot be successfully completed owing to technical or anatomic limitations. OBJECTIVE: To determine an appropriate course of action after nondiagnostic IPSS. METHODS: We reviewed 288 IPSS procedures in 283 patients between 1986 and 2010 at our center. An IPS:peripheral ACTH ratio ≥ 2 at baseline or ≥ 3 after corticotrophin-releasing hormone was considered predictive of a pituitary source of ACTH. A procedure was considered nondiagnostic if the procedure was successfully performed and the results predicted an ectopic source but none could be found despite extensive imaging or if the IPS could not be bilaterally cannulated because of technical difficulties or anatomic variants. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of IPSS for detecting a pituitary source in Cushing Disease were 94%, 50%, 98%, and 29%, respectively. We identified 3 categories of nondiagnostic IPSS comprising 44 of the total procedures. These patients underwent exploratory transsphenoidal surgery, and in 42 of these patients (95%), a pituitary source was surgically proven, with a remission rate of 83%. CONCLUSION: Transsphenoidal surgery should be considered in cases of ACTH-dependent Cushing Disease and noncentralized or technically unsuccessful IPSS without evidence of ectopic tumor.
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health care resource use and costs among patients with Cushing Disease
Endocrine Practice, 2011Co-Authors: Brooke Swearingen, Shihyin Chen, Sonia Pulgar, Beverly M K BillerAbstract:Objective: To assess health care costs associated with Cushing Disease and to determine changes in overall and comorbidity-related costs after surgical treatment.Methods: In this retrospective coho...
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management of Cushing Disease
Nature Reviews Endocrinology, 2011Co-Authors: Nicholas A Tritos, Beverly M K Biller, Brooke SwearingenAbstract:Cushing Disease is caused by a corticotroph tumor of the pituitary gland. Patients with Cushing Disease are usually treated with transsphenoidal surgery, as this approach leads to remission in 70-90% of cases and is associated with low morbidity when performed by experienced pituitary gland surgeons. Nonetheless, among patients in postoperative remission, the risk of recurrence of Cushing Disease could reach 20-25% at 10 years after surgery. Patients with persistent or recurrent Cushing Disease might, therefore, benefit from a second pituitary operation (which leads to remission in 50-70% of cases), radiation therapy to the pituitary gland or bilateral adrenalectomy. Remission after radiation therapy occurs in ∼85% of patients with Cushing Disease after a considerable latency period. Interim medical therapy is generally advisable after patients receive radiation therapy because of the long latency period. Bilateral adrenalectomy might be considered in patients who do not improve following transsphenoidal surgery, particularly patients who are very ill and require rapid control of hypercortisolism, or those wishing to avoid the risk of hypopituitarism associated with radiation therapy. Adrenalectomized patients require lifelong adrenal hormone replacement and are at risk of Nelson syndrome. The development of medical therapies with improved efficacy might influence the management of this challenging condition.
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long term mortality after transsphenoidal surgery for Cushing Disease
Annals of Internal Medicine, 1999Co-Authors: Brooke Swearingen, Anne Klibanski, Beverly M K Biller, Fred G Barker, Laurence Katznelson, Steven K Grinspoon, Nicholas T ZervasAbstract:Survival of patients treated for Cushing Disease with current management techniques between 1978 and 1996 was better than the poor survival historically associated with this disorder.
