Brooke Swearingen

Harvard University, Cambridge, Massachusetts, United States

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Publications (67)287.93 Total impact

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    ABSTRACT: Late-night salivary cortisol (LNSC) is well-validated in the diagnosis of Cushing's disease (CD). The accuracy of LNSC during follow-up of patients undergoing transsphenoidal surgery (TSS) has not been fully characterized. To examine the accuracy of LNSC in establishing remission and identifying recurrence in postoperative patients with CD. Retrospective study. Records of patients with CD who underwent TSS by a single neurosurgeon in our tertiary center (2005-2014) were analyzed (N=224). Patients were selected for further investigation (N=165) if there was at least one available LNSC test, obtained after TSS (either within 3 months or during long-term follow-up). Extracted data included demographic and clinical characteristics, magnetic resonance imaging (MRI) and laboratory data [morning serum cortisol, 24 hr urine free cortisol (UFC), LNSC]. Remission was defined as nadir morning serum cortisol <5 mcg/dl and nadir 24 hr UFC<23 mcg. Recurrence was considered definite if confirmed surgically or prompted radiotherapy. Surgical remission occurred in 89% of 89 patients with available LNSC data. LNSC, obtained within 3 months of TSS, established remission with 94% sensitivity and 80% specificity at a cutpoint of 1.9 nmol/l (AUC=0.90). At a median follow-up of 53.5 months, LNSC established recurrence (75% sensitivity and 95% specificity) at a cutpoint of 7.4 nmol/l (AUC=0.87), and 24 hr UFC established recurrence (68% sensitivity and 100% specificity) at a cutpoint of 1.6 fold above normal (AUC=0.82). LNSC may accurately establish remission after TSS and identify recurrence more accurately than 24 hr UFC during long-term follow-up.
    No preview · Article · Jul 2015 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Pituitary adenomas occur in up to 40% of patients with MEN-1, 10% of which are somatotropinomas. MEN-1 is reported in 3% of patients with pituitary adenomas, but limited data confirm this. The goal of this study was to evaluate the prevalence of MEN-1 in patients with acromegaly and determine if known MEN-1 mutations were associated. The records of 198 consecutive patients with acromegaly evaluated at our Center were reviewed. Twelve (6.06%) with MEN-1 were identified by one of the following: two or more MEN1-associated endocrine tumors, one MEN1-associated tumors and a first degree relative with MEN-1, or genetically proven MEN-1. Commercially available genetic testing for MEN-1 was performed in 9 consenting patients and tested for known MEN-1 mutations. Of these 12 patients (7F/5M), 11 had primary hyperparathyroidism; two had a neuroendocrine pancreatic tumor in addition to acromegaly. The mean age at diagnosis of acromegaly was 46.5±16 years. Four (33.3%) had family history of MEN-1 in a first degree relative. The mean random GH and IGF-1 index at the time of diagnosis of acromegaly was 9.6±7.1 ng/dl and 2.49±0.9 (x upper normal range), respectively. In 9 patients tested for known MEN-1 mutations all were negative. Seven (58.3%) had at least one cancer (4 with thyroid, one breast, one prostate and one cervical) compared to 14% cancer incidence in patients with acromegaly without MEN-1 (p <.0001). The prevalence of MEN-1 in patients with acromegaly was 6%, twice that previously reported in pituitary tumor series. Although negative genetic tests may be expected in up to 15% of MEN-1, the negative findings in all tested patients suggest that other mutations may explain the association of the MEN-1 phenotype in acromegaly. Furthermore, the phenotype of clinical MEN-1 in acromegaly may be associated with an increased risk of other malignancies. Key Words: MEN-1, Acromegaly,
    No preview · Conference Paper · Mar 2015

  • No preview · Conference Paper · Jan 2015
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    ABSTRACT: Purpose/Objective(s) This study evaluated the efficacy and toxicity of proton therapy for functional pituitary adenomas (FPAs). Methods and Materials We analyzed 165 patients with FPAs who were treated at a single institution with proton therapy between 1992 and 2012 and had at least 6 months of follow-up. All but 3 patients underwent prior resection, and 14 received prior photon irradiation. Proton stereotactic radiosurgery was used for 92% of patients, with a median dose of 20 Gy(RBE). The remainder received fractionated stereotactic proton therapy. Time to biochemical complete response (CR, defined as ≥3 months of normal laboratory values with no medical treatment), local control, and adverse effects are reported. Results With a median follow-up time of 4.3 years (range, 0.5-20.6 years) for 144 evaluable patients, the actuarial 3-year CR rate and the median time to CR were 54% and 32 months among 74 patients with Cushing disease (CD), 63% and 27 months among 8 patients with Nelson syndrome (NS), 26% and 62 months among 50 patients with acromegaly, and 22% and 60 months among 9 patients with prolactinomas, respectively. One of 3 patients with thyroid stimulating hormone—secreting tumors achieved CR. Actuarial time to CR was significantly shorter for corticotroph FPAs (CD/NS) compared with other subtypes (P=.001). At a median imaging follow-up time of 43 months, tumor control was 98% among 140 patients. The actuarial 3-year and 5-year rates of development of new hypopituitarism were 45% and 62%, and the median time to deficiency was 40 months. Larger radiosurgery target volume as a continuous variable was a significant predictor of hypopituitarism (adjusted hazard ratio 1.3, P=.004). Four patients had new-onset postradiosurgery seizures suspected to be related to generously defined target volumes. There were no radiation-induced tumors. Conclusions Proton irradiation is an effective treatment for FPAs, and hypopituitarism remains the primary adverse effect.
    Full-text · Article · Nov 2014 · International journal of radiation oncology, biology, physics

  • No preview · Article · Sep 2014 · International journal of radiation oncology, biology, physics
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    ABSTRACT: Warfarin-associated intracranial hemorrhage is associated with a high mortality rate. Ongoing coagulopathy increases the likelihood of hematoma expansion and can result in catastrophic hemorrhage if surgery is performed without reversal. The current standard of care for emergency reversal of warfarin is with fresh frozen plasma (FFP). In April 2013, the USA Food and Drug Administration approved a new reversal agent, 4-factor prothrombin complex concentrate (PCC), which has the potential to more rapidly correct coagulopathy. We sought to determine the feasibility and outcomes of using PCC for neurosurgical patients. A prospective, observational study of all patients undergoing coagulopathy reversal for intracranial hemorrhage from April 2013 to December 2013 at a single, tertiary care center was undertaken. Thirty three patients underwent emergent reversal of coagulopathy using either FFP or PCC at the discretion of the treating physician. Intracranial hemorrhage included subdural hematoma, intraparenchymal hematoma, and subarachnoid hemorrhage. FFP was used in 28 patients and PCC was used in five patients. International normalized ratio at presentation was similar between groups (FFP 2.9, PCC 3.1, p=0.89). The time to reversal was significantly shorter in the PCC group (FFP 256minutes, PCC 65minutes, p<0.05). When operations were performed, the time delay to perform operations was also significantly shorter in the PCC group (FFP 307minutes, PCC 159minutes, p<0.05). In this preliminary experience, PCC appears to provide a rapid reversal of coagulopathy. Normalization of coagulation parameters may prevent further intracranial hematoma expansion and facilitate rapid surgical evacuation, thereby improving neurological outcomes.
    No preview · Article · Jun 2014 · Journal of Clinical Neuroscience
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    ABSTRACT: Background: Pituitary apoplexy is an infrequent occurrence that can require timely treatment. The term "pituitary apoplexy" as used in the literature describes a heterogeneous spectrum. There is controversy about which subsets require urgent as opposed to elective surgical treatment or even medical treatment alone. We present a retrospective series of 109 consecutive cases of pituitary apoplexy from a single institution from 1992-2012 and develop a comprehensive classification system to analyze outcome. Methods: Surgical and endocrine consult databases were reviewed to analyze patterns of presentation, imaging, treatment, and outcomes. Results: Most of the patients in this series presented clinically with "classic" pituitary apoplexy (97%), had magnetic resonance imaging for evaluation (99%), underwent transsphenoidal surgery as their primary treatment (93%), and were found to have pituitary adenomas on histopathology (90%). We categorized patients into 5 grades based on clinical presentation. Tumor volume, cavernous sinus involvement, suprasellar extension, and need for ongoing endocrine replacement correlated with grade. Long-term endocrine replacement at follow-up was required in 62%-68% of patients with a higher grade compared with 0-23% of patients with a lower grade. Higher grade patients tended to undergo earlier surgery after symptom onset. Symptoms resolved or improved with treatment in 92%-100% of patients across all grades with good general outcomes for visual deficits and ocular motility problems, validating management decisions overall. Conclusions: We offer a simple yet comprehensive grading system to classify the clinical spectrum of pituitary apoplexy, which has implications for management, outcomes, and categorization for future studies.
    No preview · Article · Jun 2014 · World Neurosurgery
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    ABSTRACT: Implementation of intraoperative magnetic resonance imaging (iMRI) has been shown to optimize the extent of resection and safety of brain tumor surgery. In addition, iMRI can help account for the phenomenon of brain shift and can help to detect complications earlier than routine postoperative imaging, which can potentially improve patient outcome. The higher signal-to-noise ratio offered by 3 Tesla (T) iMRI compared with lower field strength systems is particularly advantageous. The purpose of this article is to review the imaging protocols, imaging findings, and technical considerations related to 3T iMRI. To maximize efficiency, iMRI sequences can be tailored to particular types of tumors and procedures, including nonenhancing brain tumor surgery, enhancing brain tumor surgery, transsphenoidal pituitary tumor surgery, and laser ablation. Unique imaging findings on iMRI include the presence of surgically induced enhancement, which can be a potential confounder for residual enhancing tumor, and hyperacute hemorrhage, which tends to have intermediate signal on T1-weighted sequences and high signal on T2-weighted sequences due to the presence of oxyhemoglobin. MR compatibility and radiofrequency shielding pose particularly stringent technical constraints at 3T and influence the design and usage of the surgical suite with iMRI. J. Magn. Reson. Imaging 2014;39:1357–1365. © 2013 Wiley Periodicals, Inc.
    Full-text · Article · Jun 2014 · Journal of Magnetic Resonance Imaging
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    ABSTRACT: Warfarin-associated intracranial hemorrhage is associated with a high mortality rate. Ongoing coagulopathy increases the likelihood of hematoma expansion and can result in catastrophic hemorrhage if surgery is performed without reversal. The current standard of care for emergency reversal of warfarin is with fresh frozen plasma (FFP). In April 2013, the USA Food and Drug Administration approved a new reversal agent, 4-factor prothrombin complex concentrate (PCC), which has the potential to more rapidly correct coagulopathy. We sought to determine the feasibility and outcomes of using PCC for neurosurgical patients. A prospective, observational study of all patients undergoing coagulopathy reversal for intracranial hemorrhage from April 2013 to December 2013 at a single, tertiary care center was undertaken. Thirty three patients underwent emergent reversal of coagulopathy using either FFP or PCC at the discretion of the treating physician. Intracranial hemorrhage included subdural hematoma, intraparenchymal hematoma, and subarachnoid hemorrhage. FFP was used in 28 patients and PCC was used in five patients. International normalized ratio at presentation was similar between groups (FFP 2.9, PCC 3.1, p = 0.89). The time to reversal was significantly shorter in the PCC group (FFP 256 minutes, PCC 65 minutes, p < 0.05). When operations were performed, the time delay to perform operations was also significantly shorter in the PCC group (FFP 307 minutes, PCC 159 minutes, p < 0.05). In this preliminary experience, PCC appears to provide a rapid reversal of coagulopathy. Normalization of coagulation parameters may prevent further intracranial hematoma expansion and facilitate rapid surgical evacuation, thereby improving neurological outcomes.
    No preview · Article · Jan 2014
  • Sameer A Sheth · Sarah K Bourne · Nicholas A Tritos · Brooke Swearingen
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    ABSTRACT: Cushing disease (CD) is caused by overproduction of adrenocorticotropin by a pituitary adenoma (or, rarely, carcinoma). The diagnosis of CD requires distinguishing it from other hypercortisolemic states with a thorough endocrine workup. CD remains a primarily surgical disease, with remission rates of 70% to 95% following microscopic or endoscopic transsphenoidal surgery.
    No preview · Article · Oct 2012 · Neurosurgery clinics of North America
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    ABSTRACT: Unlabelled: Patients with thyrotropin-secreting pituitary adenomas may present with mass effect, hypopituitarism, and/or hyperthyroidism. The spectrum of pathologic and clinical features of patients whose tumors demonstrate β-thyrotropin immunoreactivity (β-TSH IR) has not been characterized. To characterize the phenotype of patients with pituitary adenomas with positive β-TSH IR, we conducted a retrospective analysis of patient records of all adult patients (n = 1,223) undergoing pituitary surgery in our institution over one decade (1999-2009). The search identified 166 adults with tumors which had β-TSH IR. These patients were individually matched to 166 patients whose tumors revealed no β-TSH IR. Clinical, pathological, imaging and biochemical data were extracted. 332 patients, aged 51.4 ± 15.1 years [150 women (45 %) and 182 men (55 %)], with pituitary adenomas (mean tumor diameter ± SD: 22.7 ± 9.0 mm) were studied. The degree of β-TSH IR was associated with the presence of central hyperthyroidism (p < 0.0001) or goiter (p = 0.0217). Patients whose tumors expressed more extensive β-TSH IR were less likely to develop pituitary apoplexy than those without β-TSH IR (p = 0.0428). In addition, the degree of β-TSH IR correlated with the presence of immunoreactivity for β-FSH (p < 0.0001), β-LH (p < 0.0001), alpha subunit (p < 0.0001), and GH (p = 0.0036). Conclusions: Pituitary adenomas expressing β-TSH IR were more likely to demonstrate immunoreactivity for β-FSH, β-LH, GH or alpha subunit. Patients with such tumors were more likely to exhibit hyperthyroidism and goiter, but less likely to develop pituitary apoplexy than patients without β-TSH IR. These findings suggest that β-TSH IR is associated with specific phenotypic features in patients with pituitary adenomas.
    No preview · Article · Aug 2012 · Pituitary
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    ABSTRACT: Pituicytomas are rare neoplasms of the sellar region. We report a case of vision loss and a junctional scotoma in a 43-year-old woman caused by compression of the optic chiasm by a pituitary tumor. The morphological and immunohistochemical characteristics of the tumor were consistent with the diagnosis of pituicytoma. The tumor was debulked surgically, and the patient's vision improved.
    Full-text · Article · May 2012 · Case Reports in Ophthalmology
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    ABSTRACT: 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. To determine an appropriate course of action after nondiagnostic IPSS. 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. 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%. Transsphenoidal surgery should be considered in cases of ACTH-dependent Cushing disease and noncentralized or technically unsuccessful IPSS without evidence of ectopic tumor.
    No preview · Article · Feb 2012 · Neurosurgery
  • Brooke Swearingen
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    ABSTRACT: Transsphenoidal surgery has an important role in the management of pituitary tumors and remains the primary treatment for most adenomas, with the exception of prolactinomas. This update will review the recent neurosurgical literature; modifications to the traditional microscopic approach, including the potential utility of endoscopy and intraoperative magnetic resonance imaging, are discussed. The value of experienced surgical judgment and expertise remains clear, over and above the possible advantages of current technology. Preliminary data on the relative cost-effectiveness of surgery vs. medical treatment suggest that surgical approaches compare favorably. It will be important to incorporate future technological advances in surgical technique with new medical therapies in a combined multidisciplinary approach for improved treatment algorithms.
    No preview · Article · Feb 2012 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Both growth hormone (GH) excess and GH deficiency are associated with abnormalities in body composition and biomarkers of cardiovascular risk in patients with pituitary disorders. However, the effects of developing GH deficiency after definitive treatment of acromegaly are largely unknown. To determine whether development of GH deficiency after definitive therapy for acromegaly is associated with increased visceral adiposity and biomarkers of cardiovascular risk compared with GH sufficiency after definitive therapy for acromegaly. Cross-sectional. We studied three groups of subjects, all with a history of acromegaly (n = 76): subjects with subsequent GH deficiency (GHD; n = 31), subjects with subsequent GH sufficiency (GHS; n = 25) and subjects with active acromegaly (AA; n = 20). No study subjects were receiving somatostatin analogues, dopamine agonists or hGH. Body composition (by DXA), abdominal adipose tissue depots (by cross-sectional CT), total body water (by bioimpedance analysis) and carotid intima-media thickness (IMT) were measured. Fasting morning serum was collected for high-sensitivity C-reactive protein (hsCRP), lipids and lipoprotein levels. An oral glucose tolerance test was performed, and homoeostasis model of assessment-insulin resistance (HOMA-IR) was calculated. Abdominal visceral adipose tissue, total adipose tissue and total body fat were higher in subjects with GHD than GHS or AA (P < 0·05). Subcutaneous abdominal fat was higher, and fibrinogen and IMT were lower in GHD (but not GHS) than AA (P < 0·05). Patients with GHD had the highest hsCRP, followed by GHS, and hsCRP was lowest in AA (P < 0·05). Fasting glucose, 120-min glucose, fasting insulin, HOMA-IR and per cent total body water were lower in GHD and GHS than AA (P < 0·05). Triglycerides were higher in GHS than AA (P < 0·05). Lean body mass, mean arterial pressure, total cholesterol, HDL and LDL were comparable among groups. Development of GHD after definitive treatment of acromegaly may adversely affect body composition and inflammatory biomarkers of cardiovascular risk but does not appear to adversely affect glucose homoeostasis, lipids and lipoproteins, or other cardiovascular risk markers.
    No preview · Article · Feb 2012 · Clinical Endocrinology
  • Travis S. Tierney · Brooke Swearingen
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    ABSTRACT: Modern transsphenoidal surgery for Cushing’s disease is usually curative, achieving durable remission in 70–90% of cases. Comparison of remission and recurrence rates between series in the literature is difficult as many employ different remission criteria. Complication rates are low, but include hypopituitarism, diabetes insipidus, and CSF rhinorhhea. Improved remission rates can be obtained with early re-exploration after initial unsuccessful procedures, and reoperation remains an option after recurrence. This chapter reviews current surgical techniques, including microscopic and endoscopic approaches. KeywordsAdrenocorticotropic hormone-Hypercortisolemia-Hypophysectomy-Pituitary adenoma-Transsphenoidal surgery
    No preview · Chapter · Sep 2011
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    ABSTRACT: DLK1-MEG3 is an imprinted locus consisting of multiple maternally expressed noncoding RNA genes and paternally expressed protein-coding genes. The expression of maternally expressed gene 3 (MEG3) is selectively lost in clinically nonfunctioning adenomas (NFAs) of gonadotroph origin; however, expression status of other genes at this locus in human pituitary adenomas has not previously been reported. Using quantitative real-time RT-PCR, we evaluated expression of 24 genes from the DLK1-MEG3 locus in 44 human pituitary adenomas (25 NFAs, 7 ACTH-secreting, 7 GH-secreting, and 5 PRL-secreting adenomas) and 10 normal pituitaries. The effects on cell proliferation of five miRNAs whose expression was lost in NFAs were investigated by flow cytometry analysis. We found that 18 genes, including 13 miRNAs at the DLK1-MEG3 locus, were significantly down-regulated in human NFAs. In ACTH-secreting and PRL-secreting adenomas, 12 and 7 genes were significantly down-regulated, respectively; no genes were significantly down-regulated in GH-secreting tumors. One of the five miRNAs tested induced cell cycle arrest at the G2/M phase in PDFS cells derived from a human NFA. Our data indicate that the DLK1-MEG3 locus is silenced in NFAs. The growth suppression by miRNAs in PDFS cells is consistent with the hypothesis that the DLK1-MEG3 locus plays a tumor suppressor role in human NFAs.
    Full-text · Article · Aug 2011 · American Journal Of Pathology
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    B. Swearingen · N. Wu · S. Y. Chen · S. Pulgar · B. M. K. Biller

    Preview · Article · May 2011 · Value in Health
  • Brooke Swearingen · Ning Wu · Shih-Yin Chen · Sonia Pulgar · Beverly M K Biller
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    ABSTRACT: To assess health care costs associated with Cushing disease and to determine changes in overall and comorbidity-related costs after surgical treatment. In this retrospective cohort study, patients with Cushing disease were identified from insurance claims databases by International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for Cushing syndrome (255.0) and either benign pituitary adenomas (227.3) or hypophysectomy (07.6×) between 2004 and 2008. Each patient with Cushing disease was age- and sex-matched with 4 patients with nonfunctioning pituitary adenomas and 10 population control subjects. Comorbid conditions and annual direct health care costs were assessed within each calendar year. Postoperative changes in health care costs and comorbidity-related costs were compared between patients presumed to be in remission and those with presumed persistent disease. Of 877 identified patients with Cushing disease, 79% were female and the average age was 43.4 years. Hypertension, diabetes mellitus, and hyperlipidemia were more common among patients with Cushing disease than in patients with nonfunctioning pituitary adenomas or in control patients (P<.01). For every calendar year studied, patients with Cushing disease had significantly higher total health care costs (2008: $26 440 [Cushing disease] vs $13 708 [nonfunctioning pituitary adenomas] vs $5954 [population control], P<.01). Annual outpatient costs decreased significantly for patients in remission after surgery, and there was a trend towards improvement in overall disease-related costs with remission. A significant increase in postoperative health care costs was observed in those patients not in remission. Patients with Cushing disease had more comorbidities than patients with nonfunctioning pituitary adenomas or control patients and incurred significantly higher annual health care costs; these costs decreased after successful surgery and increased after unsuccessful surgery.
    No preview · Article · Feb 2011 · Endocrine Practice
  • Nicholas A Tritos · Beverly M K Biller · Brooke Swearingen
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    ABSTRACT: 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.
    No preview · Article · Feb 2011 · Nature Reviews Endocrinology

Publication Stats

3k Citations
287.93 Total Impact Points

Institutions

  • 2008-2014
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1990-2014
    • Massachusetts General Hospital
      • • Department of Neurosurgery
      • • Department of Pathology
      Boston, Massachusetts, United States
  • 1998-2006
    • Harvard Medical School
      Boston, Massachusetts, United States