William F Young

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

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Publications (182)901.68 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Context: Although adrenal vein sampling (AVS) is the standard method to distinguish unilateral from bilateral forms of primary aldosteronism (PA), it is an invasive and technically difficult procedure. (11)C-metomidate (MTO)-positron emission tomography (PET) was reported as a potential replacement for AVS. However, MTO has low selectivity for CYP11B2 over CYP11B1. Objective: This study aimed to determine the selectivity of (18)F-CDP2230, a new imaging agent, for CYP11B2 over CYP11B1 and determine whether the biodistribution profile of (18)F-CDP2230 is favorable for imaging CYP11B2. Methods: The half maximal inhibitory concentration (IC50) of CDP2230 for the enzymatic activities of CYP11B2 and CYP11B1 was determined using cells with stable expression of either enzyme. In vitro autoradiography (ARG) of human adrenal sections with aldosterone-producing adenomas was performed to confirm the specific binding ability of (18)F-CDP2230 to CYP11B2-expressing regions. Furthermore, PET and magnetic resonance imaging (MRI) were performed to evaluate the biodistribution of (18)F-CDP2230 in rats. Results: Although CDP2230 showed a significantly lower affinity for CYP11B2 and CYP11B1 than did metomidate analogues, its selectivity for CYP11B2 over CYP11B1 was higher than that of metomidate analogues. In vitro ARG revealed that the binding of (18)F-CDP2230 to CYP11B2-expressing regions in the adrenal gland was more specific than that of (123)I-IMTO. Moreover, the biodistribution study showed that (18)F-CDP2230 accumulated in adrenal glands with low background uptake. Conclusions: Our study showed a high selectivity of (18)F-CDP2230 for CYP11B2 over CYP11B1 with a favorable biodistribution for imaging CYP11B2. (18)F-CDP2230 is a promising imaging agent for detecting unilateral subtypes of PA.
    No preview · Article · Jan 2016 · The Journal of Clinical Endocrinology and Metabolism
  • James C. Andrews · Scott M. Thompson · William F. Young
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    ABSTRACT: A technique to facilitate blood sampling from the right adrenal vein is described. Between May 2012 and February 2015, 148 adrenal vein sampling (AVS) procedures were attempted. In 72 procedures, a simple 5-F end-hole catheter was employed. In 76, a coaxial guide wire technique was used when blood could not be aspirated, whereby a 0.018-inch guide wire was passed through the catheter and into a branch of the right adrenal vein and the sample was drawn around the wire by using a side-arm adaptor. Successful sampling was achieved in 71 of the 72 catheter-only procedures (98.6%) and in 75 of the 76 coaxial wire-assisted procedures (98.7%). This simple technique may eliminate the need for multiple catheter exchanges during AVS.
    No preview · Article · Dec 2015
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    ABSTRACT: Patients with multiple endocrine neoplasia type 1 (MEN1) are commonly evaluated for clinical manifestations of this syndrome with the rationale that early diagnosis and adequate treatment will result in improved survival and quality of life. Thymic and bronchial carcinoid tumors are uncommon but important manifestation of MEN1. Current practice guidelines recommend evaluation with computed tomography or magnetic resonance imaging scan of the chest every 2-3 years to detect these neoplasms. However, the certainty that patients will be better off (increased survival or quality of life) as a result of this case detection strategy is based on evidence at moderate-high risk of bias that yields only imprecise results of indirect relevance to these patients. In order to improve the care that patients with MEN1 receive, coordinated efforts from different stakeholders are required so that large, prospective, multicenter studies evaluating patient important outcomes are carried out. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · Clinical Endocrinology
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    ABSTRACT: Very low quality (VLQ) evidence translates into very low confidence in the balance of risk and benefits based on the estimates drawn from the body of evidence. Consequently, this assessment highlights gaps in the research evidence, i.e. knowledge gaps, for important clinical questions. In this way, expert guideline panels identify priority knowledge gaps that, arguably, should inform the research agenda and prioritize scarce research economical resources. The extent to which the research agenda reflects the knowledge gaps identified in clinical practice guidelines is unknown. A systematic evaluation of the Endocrine Society (ES) clinical practice guidelines portfolio from 2008 to 2014 was conducted with the objectives to identify (1) recommendations in the ES clinical practice guidelines based on VLQ evidence reflecting knowledge gaps in endocrinology, and (2) active research designed to address these gaps by searching the clinical trial registry, clinicaltrials.gov, using terms describing patients (diseases), interventions, comparison, and outcomes. In 25 ES guidelines, we found 660 recommendations, of which 131 (20 %) were supported by VLQ evidence. Clinical trialists are attempting to answer 28 (21 %) of these knowledge gaps by performing 69 clinical trials. The research enterprise is addressing one in five knowledge gaps identified in clinical practice recommendations in endocrinology. These findings suggest an inefficiency in the allocation of very scarce research economical resources. Linking the research agenda to evidence gaps in clinical practice guidelines may improve both the efficiency of the research enterprise and the translation of evidence into more confident clinical practice.
    Full-text · Article · Aug 2015 · BMC Medicine
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    ABSTRACT: The clinical features of thymic carcinoid (TC) and bronchial carcinoid (BC) tumors as part of multiple endocrine neoplasia type 1 (MEN1) have been rarely described and their importance in clinical practice is debated. The objective of this study was to describe the clinical presentation and outcome of this uncommon manifestation of MEN1 in a tertiary care center setting. We present the clinical features of patients with MEN1 and either TC or BC evaluated at the Mayo Clinic from 1977 to 2013. A total of 348 patients with MEN1 were evaluated and the prevalence of TC was 2.0 % (n = 7) and of BC 4.9 % (n = 17). The majority of the patients with BC were men (61 %) diagnosed on routine screening (77 %) and BC was not the confirmed cause of death in any patient. In contrast, TC patients were all men and during follow-up 43 % died due to TC complications. We conclude that TC and BC tumors are uncommon, but important components of MEN1. BC were most commonly diagnosed during routine screening and associated with an indolent course. TC were predominantly seen in men and associated with a more aggressive behavior.
    No preview · Article · Jun 2015 · Hormones and Cancer
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    ABSTRACT: Objective Report the prevalence of parathyroid carcinoma (PC) in patients with multiple endocrine neoplasia type 1 (MEN1) and review of the literature.Background Primary hyperparathyroidism (PHP) is the most common manifestation of MEN1. The occurrence of PC in patients with MEN1 is rare and the literature regarding the clinical manifestations – including the prevalence of the disease – is scarce.ContextSingle tertiary care center experience from 1977 to 2013.DesignElectronic search of the medical records to identify a cohort of patients with MEN1. Literature review based on current case reports.PatientsSingle case of PC in a cohort of 348 patients with MEN1. Ten cases of PC in patients with MEN1 reported in the literature.MeasurementClinical features of PC in patients with MEN1.ResultsThe prevalence of PC in 348 patients with MEN1 was found to be 0.28% (95% CI, 0 - 1.4%). Based on the current published cases of PC in patients with MEN1, 54.5% were women, mean age at diagnosis was 48.3 years, and the serum PTH concentrations at least 4 times the upper limit of the reference range in 73% of the cases.ConclusionPC in patients with MEN 1 is rare with a prevalence of 0.28% and the clinical features are similar to PC in patients without MEN1.This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2014 · Clinical Endocrinology
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    ABSTRACT: Context: The most common feature of multiple endocrine neoplasia type 1 (MEN1) is primary hyperparathyroidism (PHP), which occurs in approximately 95% of MEN1 patients. Approximately 40-60% of patients with MEN1 develop recurrent hypercalcemia within 10-12 years after their initial parathyroid surgery and the successful management of recurrent PHP is challenging. Objective: This study sought to evaluate the safety and efficacy of percutaneous ethanol ablation (PEA) for the treatment of recurrent PHP in patients with MEN1. DESIGN, SETTING, PATIENTS, INTERVENTION, OUTCOME MEASURED: We performed an electronic search to identify patients with a billing code for MEN1 who were seen at Mayo Clinic between 1977 and 2013. Patients with recurrent PHP who underwent PEA were identified and their clinical information was collected. We performed t test analyses to compare mean values. Results: Thirty-seven patients underwent 80 PEA treatments that included 123 sessions of ethanol administration. Twenty-one patients were women (56.8%) and the mean age at diagnosis of PHP was 33.8 years. The mean preprocedure calcium level was 10.7 mg/dl ± 0.57 (SD) and the mean postprocedure calcium level was 9.6 mg/dl ± 0.76 (P < .01). In 14 treatments (18.9%) the postprocedure calcium was greater than 10.1 mg/dl. Postprocedure hypocalcemia occurred in six treatments (8.1%). Normocalcemia was achieved in 54 of the treatment episodes (73%) and the mean duration of normocalcemia was 24.8 months. PEA was safe with transient hoarseness occurring in four of the treatments (5%). Conclusion: The treatment of recurrent PHP in patients with MEN1 represents a challenge that is associated with increased morbidity. PEA is an effective treatment option for achieving normocalcemia in the majority of the patients with MEN1. PEA is associated with low rates of hypocalcemia and no permanent complications.
    No preview · Article · Oct 2014 · Journal of Clinical Endocrinology & Metabolism
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    ABSTRACT: Neuroendocrine (NE) tumors commonly afflict patients with multiple endocrine neoplasia type 1 (MEN1). It is thought that patients with MEN1 have improved survival compared with individuals with analogous lesions. The role of metastasectomy of NE tumors in MEN1 patients is not clearly defined. A review of MEN1 patients undergoing surgery for NE tumors from 1994 to 2010 at a single tertiary care center was performed. Tumor function, the extent of metastasis, R0 resection, and survival were analyzed. We identified 30 patients who underwent resection including synchronous and metachronous metastasectomy. Synchronous metastases were identified in 19 patients (63%), whereas 11 (37%) had metachronous disease. R0 resection was achieved in 93% of patients. Estimated 10-year survival is 86.4% (95% confidence interval, 60% to 100%) with no factors predictive of overall survival. The disease-free interval at 1, 5, and 10 years was 89%, 50%, and 19%, respectively, with recurrence occurring at a median of 5.4 years (95% confidence interval, 77.7% to 100%). Synchronous metastasis (P = .0072; hazard ratio [HR], 3.4) and nonfunctioning tumors (P = .014; HR, 3.3) were more likely to recur, whereas age (P = .09; HR, 1.5), gender (P = .49; HR, 1.3), and the site of metastasis (P = .81; HR, 1.1) did not influence recurrence. Patients with MEN1 benefit from resection of metastatic NE disease. Despite a high recurrence rate, survival and disease-free interval is favorable vs patients without MEN1. Copyright © 2014 Elsevier Inc. All rights reserved.
    No preview · Article · Sep 2014 · The American Journal of Surgery
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    ABSTRACT: Introduction: Metastatic adrenocortical carcinoma (ACC) is rapidly fatal, with few options for treatment. Patients with metachronous recurrence may benefit from surgical resection. The survival benefit in patients with hematogenous metastasis at initial presentation is unknown. Methods: A review of all patients undergoing surgery (European Network for the Study of Adrenal Tumors) stage IV ACC between January 2000 and December 2012 from two referral centers was performed. Kaplan-Meier estimates were analyzed for disease-free and overall survival (OS). Results: We identified 27 patients undergoing surgery for stage IV ACC. Metastases were present in the lung (19), liver (11), and brain (1). A complete resection (R0) was achieved in 11 patients. The median OS was improved in patients undergoing R0 versus R2 resection (860 vs. 390 days; p = 0.02). The 1- and 2-year OS was also improved in patients undergoing R0 versus R2 resection (69.9 %, 46.9 % vs. 53.0 %, 22.1 %; p = 0.02). Patients undergoing neoadjuvant therapy (eight patients) had a trend towards improved survival at 1, 2, and 5 years versus no neoadjuvant therapy (18 patients) [83.3 %, 62.5 %, 41.7 % vs. 56.8 %, 26.6 %, 8.9 %; p = 0.1]. Adjuvant therapy was associated with improved recurrence-free survival at 6 months and 1 year (67 %, 33 % vs. 40 %, 20 %; p = 0.04) but not improved OS (p = 0.63). Sex (p = 0.13), age (p = 0.95), and location of metastasis (lung, p = 0.51; liver, p = 0.67) did not correlate with OS after operative intervention. Symptoms of hormonal excess improved in 86 % of patients. Conclusion: Operative intervention, especially when an R0 resection can be achieved, following systemic therapy may improve outcomes, including OS, in select patients with stage IV ACC. Response to neoadjuvant chemotherapy may be of use in defining which patients may benefit from surgical intervention. Adjuvant therapy was associated with decreased recurrence but did not improve OS.
    No preview · Article · Aug 2014 · Annals of Surgical Oncology
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    ABSTRACT: Objective: The aim was to formulate clinical practice guidelines for pheochromocytoma and paraganglioma (PPGL). Participants: The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), seven experts in the field, and a methodologist. The authors received no corporate funding or remuneration. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, European Society of Endocrinology, and Americal Association for Clinical Chemistry reviewed drafts of the guidelines. Conclusions: The Task Force recommends that initial biochemical testing for PPGLs should include measurements of plasma free or urinary fractionated metanephrines. Consideration should be given to preanalytical factors leading to false-positive or false-negative results. All positive results require follow-up. Computed tomography is suggested for initial imaging, but magnetic resonance is a better option in patients with metastatic disease or when radiation exposure must be limited. (123)I-metaiodobenzylguanidine scintigraphy is a useful imaging modality for metastatic PPGLs. We recommend consideration of genetic testing in all patients, with testing by accredited laboratories. Patients with paraganglioma should be tested for SDHx mutations, and those with metastatic disease for SDHB mutations. All patients with functional PPGLs should undergo preoperative blockade to prevent perioperative complications. Preparation should include a high-sodium diet and fluid intake to prevent postoperative hypotension. We recommend minimally invasive adrenalectomy for most pheochromocytomas with open resection for most paragangliomas. Partial adrenalectomy is an option for selected patients. Lifelong follow-up is suggested to detect recurrent or metastatic disease. We suggest personalized management with evaluation and treatment by multidisciplinary teams with appropriate expertise to ensure favorable outcomes.
    Full-text · Article · Jun 2014 · Journal of Clinical Endocrinology & Metabolism
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    ABSTRACT: The original 4 patients with Cushing syndrome who underwent bilateral adrenalectomy for primary pigmented nodular adrenocortical disease were followed up for an average of 31 years to determine whether they or any of their primary relatives had developed Carney complex or its components. None had. Three of the patients were alive and well; the fourth had died of an unrelated condition. All the adrenal glands contained multiple small, black or brown cortical nodules, up to 4 mm in diameter. The extracapsular extension of the micronodules was limited to the immediate pericapsular adipose tissue and was not considered evidence of low-grade malignancy. Immunocytochemically, the nodules were positive for synaptophysin, inhibin-A, and melan A and negative for vimentin and CD56. Ki-67 antibody stained the cytoplasm of cells in the micronodules but not that of the atrophic cortical cells. The 4 patients had the PRKAR1A deletion that has been associated with the isolated form of primary pigmented nodular adrenocortical disease.
    No preview · Article · May 2014 · The American journal of surgical pathology
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    ABSTRACT: Context: The accurate distinction between unilateral and bilateral adrenal disease in patients with primary aldosteronism (PA) guides surgical management. Adrenal venous sampling (AVS), the criterion standard localization procedure, is not readily available at many centers throughout the world. Objective: To determine factors most consistent with surgically curable PA. Design: A retrospective observational study Setting: Mayo Clinic, Rochester, a tertiary referral center Patients: All patients who underwent unilateral adrenalectomy for treatment of PA between January 1993 and December 2011. Intervention: Unilateral adrenalectomy Main outcome measures: Variables associated with prediction of unilateral disease Results: Over 19 years, 263 patients underwent unilateral adrenalectomy for the treatment of PA. Long-term postoperative follow-up was obtained in 143 patients (54.4%). The overall effective cure rate of PA was 95.5% in those patients sent for adrenalectomy for presumptive unilateral disease. In patients with cured PA, defined as resolution of autonomous aldosterone secretion, hypertension was cured in 53 (41.7%) and improved in 59 (46.5%) patients. PA was not cured with unilateral adrenalectomy in 6 (4.2%) patients. Adrenal imaging and AVS were concordant to the surgically documented side in 58.6% and 97.1% of the patients, respectively. Although there was no statistically significant difference in mean age between the inaccurate versus the accurate adrenal imaging group, we found that the minimum age in the former was 35.1 years. Conclusions: Using adrenal imaging and AVS, the effective surgical cure rate for PA was 95.5%. Although the overall accuracy of CT or MRI in detecting unilateral adrenal disease was poor at 58.6%, adrenal imaging performed well in those patients less than 35 years of age.
    No preview · Article · May 2014 · The Journal of Clinical Endocrinology and Metabolism
  • Qinghua Guo · William F. Young · Dana Erickson · Bradley Erickson
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    ABSTRACT: PurposeThe distinction between corticotropin (ACTH)-producing pituitary adenomas and occult ectopic ACTH neoplasms is a challenge and frequently complicated by the detection of nonfunctioning pituitary adenomas on dynamic magnetic resonance imaging (DMRI). Herein, we explored quantitative differences in DMRI measures from ACTH-producing pituitary adenomas.Materials and Methods Fifty-five patients with pathology confirmed ACTH-producing and 44 with nonfunctioning pituitary adenomas were analyzed in this retrospective pilot study. The intensities of adenomas and of adjacent pituitary tissue were measured by drawing a region of interest. Time–intensity curves were then constructed and quantitative analysis included: enhancement time, enhancement peak, and pre-peak slope (PPS). Multivariable logistic analysis and receiver operating characteristic curves (ROC) were used to evaluate the parameters.ResultsQuantitative analysis showed that tumor PPS in ACTH-producing adenomas was markedly lower than that in nonfunctioning adenomas (P=0.0042) and that, the PPS of the adjacent pituitary gland were not different (P=0.2441). The PPS was > 3.0 in 59.1% of nonfunctioning adenomas and ≤ 3.0 in 69.1% of ACTH-producing adenomas (P=0.0049). Logistic analysis revealed lower tumor PPS levels (P=0.0123, OR 1.24, 95% CI: 1.05-1.52) were associated with ACTH-producing adenomas. The optimal PPS cutoff determined by ROC analysis was 2.89, with a sensitivity of 69% and specificity of 70%. No significant difference was found between the two groups in enhancement time or enhancement peak.Conclusion Enhancement parameters in DMRI can help distinguishing ACTH-producing from nonfunctioning pituitary adenomas, which could be useful in the differential diagnosis between ACTH-producing pituitary adenomas and ectopic ACTH syndrome complicated with nonfunctioning pituitary adenoma.This article is protected by copyright. All rights reserved.
    No preview · Article · May 2014 · Clinical Endocrinology
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    Preview · Article · Apr 2014 · Hypertension
  • Paolo Pozzilli · Andrea Lenzi · Bart L Clarke · William F Young
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    ABSTRACT: This chapter presents key information on the definition, pathogenesis, presenting symptoms, laboratory findings, imaging results, and treatment of selected disorders affecting the pancreas, in particular “the endocrine pancreas.” We also report on two common disease conditions of the exocrine pancreas (acute pancreatitis and chronic pancreatitis) and endocrine pancreas diseases: diabetes and its chronic complications - cardiovascular disease, skin diseases, diabetic foot, distal symmetric polyneuropathy, diabetic nephropathy, and diabetic retinopathy; and also insulinoma. The images selected highlight the commonest features of these various disorders, as well as unusual presentations not seen frequently.
    No preview · Article · Jan 2014
  • Paolo Pozzilli · Andrea Lenzi · Bart L Clarke · William F Young
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    ABSTRACT: • Malignant conditions: testicular and ovarian cancer • Genetic conditions: Klinefelter and Turner syndromes • Anatomical and functional disorders: Cryptorchidism, gynecomastia, male infertility, varicocele, ovarian cyst, amenorrhea, hyperandrogenism in women, polycystic ovary syndrome
    No preview · Article · Jan 2014
  • Paolo Pozzilli · Andrea Lenzi · Bart L Clarke · William F Young
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    ABSTRACT: This chapter presents key information on the definitions, pathogenesis, symptomatology, laboratory findings, imaging results, and treatment for selected endocrine disorders affecting bone and mineral metabolism. The disorders included are the common diseases of postmenopausal osteoporosis and primary hyperparathyroidism, and rarer diseases including hypoparathyroidism, pseudohypoparathyroidism, Paget's disease of bone, osteomalacia, chronic kidney disease, fibrous dysplasia, selected sclerosing bone disorders, tumoral calcinosis, osteogenesis imperfecta, and several other rare skeletal disorders. The images selected highlight the commonest features of these various disorders, as well as unusual presentations not seen frequently.
    No preview · Article · Jan 2014
  • Paolo Pozzilli · Andrea Lenzi · Bart L Clarke · William F Young
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    ABSTRACT: This chapter presents the clinical picture and key information for a miscellanea of interesting mucocutaneous manifestations of endocrine disorders. The images selected highlight the commonest features of these various disorders.
    No preview · Article · Jan 2014
  • Paolo Pozzilli · Andrea Lenzi · Bart L Clarke · William F Young
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    ABSTRACT: This chapter presents key information on the definition, pathogenesis, presenting symptoms, laboratory findings, imaging results, and treatment of selected endocrine disorders affecting thyroid. The disorders included are common diseases of thyroid gland divided into autoimmune disorders or thyroiditis: Hashimoto's thyroiditis (chronic autoimmune thyroiditis), Graves' disease (Basedow's disease), subacute thyroiditis (de Quervain's thyroiditis) and “nodular diseases”, benign thyroid nodules, and thyroid cancer. The images selected highlight the commonest features of these various disorders.
    No preview · Article · Jan 2014
  • Paolo Pozzilli · Andrea Lenzi · Bart L Clarke · William F Young
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    ABSTRACT: This chapter presents key information on the definitions, pathogenesis, symptomatology, laboratory findings, imaging, and treatment for selected pituitary disorders. The disorders that are highlighted include craniopharyngioma, hypothalamic dysgerminoma, growth hormone-secreting pituitary tumor, prolactin-secreting pituitary tumor, corticotropin-secreting pituitary tumor, Nelson syndrome, clinically nonfunctioning pituitary tumors, primary pituitary carcinoma, pituitary cyst, nontumorous lesions of the pituitary gland and pituitary stalk, pituitary apoplexy, and tumors metastatic to the pituitary. The images selected highlight the key findings on physical examination and computed imaging.
    No preview · Article · Jan 2014

Publication Stats

8k Citations
901.68 Total Impact Points

Institutions

  • 1988-2015
    • Mayo Clinic - Rochester
      • • Department of Internal Medicine
      • • Department of Laboratory Medicine & Pathology
      • • Department of Hypertension
      Рочестер, Minnesota, United States
  • 2003-2014
    • Mayo Foundation for Medical Education and Research
      • Mayo Medical School
      Рочестер, Michigan, United States
    • Wayne State University
      Detroit, Michigan, United States
    • McMaster University
      Hamilton, Ontario, Canada
  • 2007
    • Fort Wayne Metals
      Fort Wayne, Indiana, United States
  • 2006
    • Umeå University
      • Department of Public Health and Clinical Medicine
      Umeå, Vaesterbotten, Sweden
  • 1994-2005
    • Temple University
      • • Department of Neurosurgery
      • • Department of Physiology
      Filadelfia, Pennsylvania, United States
  • 2004
    • Pontifical Catholic University of Chile
      CiudadSantiago, Santiago Metropolitan, Chile
  • 2002
    • University of Pittsburgh
      • Department of Otolaryngology
      Pittsburgh, Pennsylvania, United States
  • 2001
    • Ninewells Hospital
      • Department of Surgery
      Dundee, Scotland, United Kingdom
  • 1992-2000
    • University of Toronto
      • Laboratory Medicine Program
      Toronto, Ontario, Canada
    • St. Michael's Hospital
      • Department of Surgery
      Toronto, Ontario, Canada