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William F Young

Publications and source records attributed to William F Young.

At least 37 records · Page 2Linked to original sources
PubMed2004

Malignant pheochromocytoma: current status and initiatives for future progress.

Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors that are usually benign, but which may also present as or develop into a malignancy. Predicting such behavior is notoriously difficult and there are currently no curative treatments for malignant tumors. This report follows from a workshop at the Banbury Conference Center, Cold Spring Harbor, New York, on the 16th-18th November 2003, held to review the state of science and to facilitate future progress in the diagnosis and treatment of malignant pheochromocytoma. The rarity of the tumor and the resulting fragmented nature of studies, typically involving small numbers of patients, represent limiting factors to the development of effective treatments and diagnostic or prognostic markers for malignant disease. Such development is being facilitated by the availability of new genomics-based tools, but for such approaches to succeed ultimately requires comprehensive clinical studies involving large numbers of patients, stringently collected clinical data and tumor samples, and interdisciplinary collaborations among multiple specialist centers. Nevertheless, the well-characterized hereditary basis and the unique functional nature of these neuroendocrine tumors provide a useful framework that offers advantages for establishing the pathways of tumorigenesis and malignancy. Such findings may have relevance for understanding the basis of other more common malignancies where similar frameworks are not available. As the relevant pathways leading to pheochromocytoma are established it should be possible to take advantage of the new generation of drugs being developed to target specific pathways in other malignancies. Again the success of this will require well-designed and coordinated multi-center studies.

Adrenal Gland Neoplasms↗
PubMed2003

Differential expression of galectin-3 in pituitary tumors.

Galectin-3 (Gal-3), a beta-galactoside-binding protein, has been implicated in a variety of biological functions, including cell proliferation and differentiation, tumor cell adhesion, angiogenesis, apoptosis, tumor progression, and metastasis. We investigated the role of Gal-3 in the development and progression of pituitary tumors. Immunohistochemical and Western blot analysis of normal and neoplastic human pituitaries showed that only lactotroph (PRL) and corticotroph (ACTH) hormone-producing cells and tumors expressed Gal-3. Gal-3 was present in 24 of 38 (63.2%) PRL adenomas, 5 of 6 (83.3%) PRL carcinomas, 19 of 41 (46.3) ACTH adenomas, and 7 of 8 (87.5%) ACTH carcinomas, but not in 112 other pituitary adenomas and carcinomas. Pituitary folliculo-stellate cells, which have macrophage-type functions in the anterior pituitary, also expressed Gal-3. Hyperplastic and neoplastic pituitaries from p27(Kip1) (p27)-null mice, which produce mainly ACTH, showed increased Gal-3 expression levels compared with control mice. Treatment with transforming growth factor beta1, which regulates pituitary cell proliferation, reduced Gal-3 as well as p27 expression levels in cultured HP75 pituitary cells and Gal-3 in cultured pituitary cells from p27-null mice, suggesting that p27 is not necessary for the inhibitory effects of transforming growth factor beta1 on the cell cycle in the pituitary. The role of Gal-3 in pituitary cell function was examined by RNA interference experiments. Inhibition of Gal-3 gene expression by RNA interference decreased HP75 cell proliferation and increased apoptosis. These results indicate that Gal-3 has an important role in pituitary cell proliferation and tumor progression.

Adenoma↗
PubMed2003

Primary aldosteronism - treatment options.

Diagnosis of primary aldosteronism results in either the surgical cure of hypertension or targeted pharmacotherapy. The two major subtypes of primary aldosteronism are unilateral aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism (IHA). Patients with APA usually are treated with unilateral adrenalectomy and patients with IHA are treated medically. The majority of patients with primary aldosteronism have the IHA subtype and require pharmacotherapy. Spironolactone has been the drug of choice to treat primary aldosteronism. However, it is not selective for the aldosterone receptor, and side effects include gynecomastia, erectile dysfunction and menstrual irregularity. Eplerenone is a new competitive and selective aldosterone receptor antagonist recently approved by the United States Food and Drug Administration for the treatment of hypertension. It lacks the side effects associated with spironolactone and will be the superior drug if it is shown to be as effective as spironolactone for the treatment of mineralocorticoid-dependent hypertension.

Humans↗
PubMed2003

Silent corticotroph carcinoma of the adenohypophysis: a report of five cases.

We report five silent corticotroph carcinomas of the pituitary gland. They represent 0.05% of adenohypophyseal tumors surgically treated at Mayo Clinic during a 20-year period and about 5% of all reported pituitary carcinomas. The patients (three females and two males), ranging in age from 26 to 58 years (mean 39 years, median 35 years) presented with symptoms of mass effect; none had Cushing's disease. All tumors were initially invasive macroadenomas, recurred locally, and metastasized, three outside the central nervous system. The follow-up period ranged from 2 to 23 years (mean 10.6 years). All patients died, four of disseminated tumor and one of myocardial infarction. Histologically, three of the primary lesions were indistinguishable from an ordinary benign adenoma. Two were initially diagnosed as atypical adenomas as they featured nuclear pleomorphism, prominent nucleoli, mitotic activity, high MIB-1 labeling indices, and p53 overexpression. For the purpose of comparison, 17 silent corticotroph adenomas were also investigated. In addition, the clinicopathologic features of the silent carcinomas were compared with those of a meta-analysis of published Cushing's disease-associated pituitary carcinomas. The silent adrenocorticotropin carcinomas showed a propensity for extraneural dissemination and an outcome similar to those of the Cushing's disease-associated carcinomas. The two patients with initial atypical tumors died with metastases outside the central nervous system at 2 and 4 years, whereas the three patients with tumors lacking atypia died 16, 18, and 23 years after initial sellar surgery.

Adult↗
PubMed2003

Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma.

Cushing's disease is caused by functional corticotroph adenomas of the pituitary, mostly noninvasive microadenomas. Classic Crooke's cells are nonneoplastic corticotrophs with cytoplasmic accumulation of cytokeratin filaments in response to glucocorticoid excess. Corticotroph adenomas exhibiting Crooke's change are rare and incompletely understood. We intend to define more clearly the clinicopathological features of Crooke's cell adenomas (CCA). Thirty-six CCAs were retrieved from the files of Mayo Clinic and from our (B.W.S., K.K.) consultation files. The number of informative cases varied for different criteria. Clinical follow-up was obtained in 31 cases. The 27 females and 9 males were 18 to 81 years of age (mean 46 years). At presentation, Cushing's disease was evident in 22/34 (65%); 81% were macroadenomas and 72% were invasive. All were initially treated by transsphenoidal resection. Twenty-five patients were followed for more than 1 year (mean 6.7 years). Of these, 15 (60%) developed recurrent tumor, and 6 (24%) had multiple recurrences. Lastly, 3 of these 25 patients (12%) died of tumor: 1 after multiple local recurrences and 2 from pituitary carcinoma. Compared with typical corticotroph adenomas, CCAs are aggressive. Most are functional adenomas occurring in middle-aged women and are invasive macroadenomas prone to recurrence. Morbidity and mortality rates are substantial. CCAs represent a distinct entity that should be separated from corticotroph adenomas without Crooke's hyaline change.

Adenoma↗
PubMed2003

Adrenal incidentaloma.

Adrenal incidentalomas are incidentally discovered adrenal masses greater than 1 cm in diameter that appear to be clinically nonfunctioning. They are detected during imaging procedures of the abdomen and chest (CT, MRI, and ultrasonography) for an unrelated condition or symptom complex. With the widespread escalation in the use of these imaging modalities and marked improvements in image resolution, the probability of finding an incidentaloma on cross-section imaging is rapidly approaching the 6% prevalence of previously reported autopsy studies. All incidentalomas greater than 1 cm should be evaluated for hormonal activity, including a 1-mg overnight dexamethasone suppression test, total 24-hour urinary metanephrines and fractionated catecholamines, and, in the hypertensive patient, a serum potassium level and plasma aldosterone concentration to plasma renin activity ratio. All hormonally active tumors should be removed. Hormonally inactive tumors are resected based on size, imaging phenotype, and interval growth. Percutaneous biopsies are generally unwarranted and are potentially dangerous. Laparoscopic adrenalectomy has become the surgical procedure of choice for most benign functioning and nonfunctioning tumors of the adrenal gland. Subclinical metabolic abnormalities associated with adrenal incidentalomas remain an area of intense clinical research.

Adrenal Gland Neoplasms↗
PubMed2003

Dysphagia, hoarseness, and unilateral true vocal fold motion impairment following anterior cervical diskectomy and fusion.

The charts of 100 patients who underwent anterior cervical diskectomy with fusion performed at our institution between January 1996 and February 1999 were reviewed. The incidences of hoarseness, dysphagia, and unilateral true vocal fold motion impairment were calculated. Univariate logistic regression was used to estimate the relationship of several patient and technical factors to the rates of occurrence of hoarseness and dysphagia. Patient age was found to be a significant predictor of postoperative dysphagia (p < .006), with an odds ratio of 1.113 (95% confidence limits, 1.04, 1.21) per year of age. Other factors studied were not found to be significant predictors. The overall incidence of these complications from the world literature was also calculated. The overall incidences of dysphagia, hoarseness, and unilateral true vocal fold motion impairment in the literature were calculated as 12.3%, 4.9%, and 1.4%, respectively. We conclude that dysphagia, hoarseness, and unilateral vocal fold motion impairment continue to remain significant complications of anterior cervical diskectomy with fusion. Older patients may be at higher risk for dysphagia.

Adult↗
PubMed2003

Minireview: primary aldosteronism--changing concepts in diagnosis and treatment.

Primary aldosteronism affects 5-13% of patients with hypertension. Patients with hypertension and hypokalemia and most patients with treatment-resistant hypertension should undergo screening for primary aldosteronism with a plasma aldosterone concentration to plasma renin activity ratio. A high plasma aldosterone concentration to plasma renin activity ratio is a positive screening test result, a finding that warrants confirmatory testing. For those patients that want to pursue a surgical cure, the accurate distinction between the subtypes (unilateral vs. bilateral adrenal disease) of primary aldosteronism is a critical step. The subtype evaluation may require one or more tests, the first of which is imaging the adrenal glands with computed tomography, followed by selective use of adrenal venous sampling. Because of the deleterious cardiovascular effects of aldosterone, normalization of circulating aldosterone or aldosterone receptor blockade should be part of the management plan for all patients with primary aldosteronism. Unilateral laparoscopic adrenalectomy is an excellent treatment option for patients with unilateral aldosterone-producing adenoma. Bilateral idiopathic hyperaldosteronism should be treated medically. In addition, aldosterone-producing adenoma patients may be treated medically if the medical treatment includes mineralocorticoid receptor blockade.

Humans↗
PubMed2003

A comparison of biochemical tests for pheochromocytoma: measurement of fractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholamines.

We compared the diagnostic efficacy of fractionated plasma metanephrine measurements to measurements of 24-h urinary total metanephrines and catecholamines in outpatients tested for pheochromocytoma at Mayo Clinic Rochester from January 1, 1999, until November 27, 2000. Catecholaminesecreting tumors were histologically proven. The sensitivity of fractionated plasma metanephrines was 97% (30 of 31 patients), compared with a sensitivity of 90% (28 of 31) for urinary total metanephrines and catecholamines (P = 0.63). The specificity of fractionated plasma metanephrines was 85% (221 of 261), compared with 98% (257 of 261; P < 0.001) for urinary measurements. The likelihood ratios for positive tests were 6.3 (95% confidence interval, 4.7 to 8.5) for fractionated plasma metanephrines and 58.9 (95% confidence interval, 22.1 to 156.9) for urinary total metanephrines and catecholamines. An adrenal pheochromocytoma was missed by urinary testing in two patients with familial syndromes and one asymptomatic patient with an incidentally discovered adrenal mass. An extra-adrenal paraganglioma was missed by plasma testing in one patient. In conclusion, measurements of 24-h urinary total metanephrines and catecholamines yield fewer false-positive results, an attribute preferred for testing low-risk patients, but fractionated plasma metanephrine measurements may be preferred in high-risk patients with familial endocrine syndromes.

Adolescent↗
PubMed2003

A model to determine workforce needs for endocrinologists in the United States until 2020.

The objective of this study was to define the workforce needs for the specialty of endocrinology, diabetes, and metabolism in the United States between 1999 and 2020. An interactive model of factors likely to influence the balance between the supply and demand of endocrinologists during the next 20 yr was constructed. The model used data from a wide range of sources and was developed under the guidance of a panel of experts derived from sponsoring organizations of endocrinologists. We determined current and projected numbers and demographics of endocrinologists in the United States workforce and the anticipated balance between supply and demand from 1999 to 2020. There were 3,623 adult endocrinologists in the workforce in 1999, of which 2,389 (66%) were in office-based practice. Their median age was 49 yr. Both total office visits and services performed by endocrinologists (particularly for diabetes) increased substantially during the 1990s. Waiting time for an initial appointment is presently longer for endocrinologists than for other physicians. Compared with a balanced, largely closed-staff health maintenance organization, the current national supply of endocrinologists is estimated to be 12% lower than demand. The number of endocrinologists entering the market has continuously fallen over the previous 5 yr, from 200 in 1995 to 171 in 1999. Even if this downward trend were abruptly stopped, the model predicts that demand will exceed supply from now until 2020. Whereas this gap narrows from 2000 to 2008 due to projected growth of managed care, it widens thereafter due to the aging of both the population and the endocrine workforce. Inclusion of other factors such as projected real income growth and increased prevalence of age-related endocrine disorders (e.g. diabetes and osteoporosis) further accentuates the deficit. If the number of endocrinologists entering the workforce remains at 1999 levels, demand will continue to exceed supply from now through 2020 for adult endocrinologists, and the gap will widen progressively from 2010 onward. The present analysis indicates that the number of endocrinologists entering the workforce will not be sufficient to meet future demand. These data suggest that steps should be taken to stop the ongoing decline in the number of endocrinologists in training and consideration should be given to actions designed to increase the number of endocrinologists in practice in the years ahead.

Aging↗
PubMed2003

A model to determine workforce needs for endocrinologists in the United States until 2020.

The objective of this study was to define the workforce needs for the specialty of Endocrinology, Diabetes, and Metabolism in the United States between 1999 and 2020. An interactive model of factors likely to influence the balance between the supply and demand of endocrinologists during the next 20 years was constructed. The model used data from a wide range of sources and was developed under the guidance of a panel of experts derived from sponsoring organizations of endocrinologists. We determined current and projected numbers and demographics of endocrinologists in the U.S. workforce and the anticipated balance between supply and demand from 1999 to 2020. There were 3,623 adult endocrinologists in the workforce in 1999, of which 2,389 (66%) were in office-based practice. Their median age was 49 years. Both total office visits and services performed by endocrinologists (particularly for diabetes) increased substantially during the 1990s. Waiting time for an initial appointment is presently longer for endocrinologists than for other physicians. Compared with a balanced, largely closed-staff health maintenance organization, the current national supply of endocrinologists is estimated to be 12% lower than demand. The number of endocrinologists entering the market has continuously fallen over the previous 5 years, from 200 in 1995 to 171 in 1999. Even if this downward trend were abruptly stopped, the model predicts that demand will exceed supply from now until 2020. While this gap narrows from 2000 to 2008 due to projected growth of managed care, it widens thereafter due to the aging of both the population and the endocrine workforce. Inclusion of other factors such as projected real income growth and increased prevalence of age-related endocrine disorders (e.g., diabetes and osteoporosis) further accentuates the deficit. If the number of endocrinologists entering the workforce remains at 1999 levels, demand will continue to exceed supply from now through 2020 for adult endocrinologists, and the gap will widen progressively from 2010 onward. The present analysis indicates that the number of endocrinologists entering the workforce will not be sufficient to meet future demand. These data suggest that steps should be taken to stop the ongoing decline in the number of endocrinologists in training and consideration should be given to actions designed to increase the number of endocrinologists in practice in the years ahead.

Endocrinology↗
PubMed2003

Gonadotropic pituitary carcinoma: HER-2/neu expression and gene amplification. Report of two cases.

The authors report on two gonadotropic carcinomas of the adenohypophysis that occurred in a55-year-old man (Case 1) and a 53-year-old woman (Case 2), with signs of mass effect and amenorrhea, respectively. Both lesions were macroadenomas. The tumor in Case 1 metastasized to dura mater, skull, nasal sinus, and larynx 2 years after patient presentation, whereas that in Case 2 spread to vertebral bodies and ribs after a 19-year latency. Histologically, the primary, recurrent, and metastatic lesions in Case 1 featured brisk mitotic activity and high MIB-1 levels as well as p53 labeling indices. Immunoreactivity for HER-2/neu was assessable only in rare neoplastic cells of the second recurrence and in 80% of cells of the dural metastasis. Low-level HER-2/neu gene amplification was evident in the recurrent tumors and metastasis. The sellar and metastatic tumors in Case 2 resembled benign gonadotropic adenoma with oncocytic change; p53 accumulation, HER-2/neu overexpression, and HER-2/neu gene amplification were not present. The results indicate that low-level amplification of the HER-2/neu gene might be associated with pituitary carcinomas in which more aggressive behavior is seen. Further studies are needed to determine whether HER-2/neu plays a role in the pathogenesis of pituitary carcinoma.

Brain Neoplasms↗
PubMed2003

Granular cell tumor of the sellar and suprasellar region: clinicopathologic study of 11 cases and literature review.

OBJECTIVE: To report a series of cases of surgically resected granular cell tumors in an attempt to better characterize their clinical presentation, imaging features, and treatment outcomes with attention to previously published literature. PATIENTS AND METHODS: This is a retrospective study of 11 patients with granular cell tumors. Information obtained from patients' medical records was supplemented by direct physician and patient telephone contact. RESULTS: The study group consisted of 9 women and 2 men, with a mean +/- SD age of 50 +/- 15 years (range, 26-73 years). Seven patients were symptomatic, 3 of whom presented with visual complaints. Four patients presented primarily with endocrine dysfunction (2) or headaches (2). The duration of symptoms varied from 1 to 12 months (mean +/- SD, 6.0 +/- 4.5 months). Formal visual field testing revealed bitemporal hemianopsia in 6 and a right-sided visual field deficit in 2. The tumor appeared as a well-defined, relatively homogeneously (6) or heterogeneously (1) enhancing suprasellar mass on contrast infusion. Tumor size varied from 1.5 to 6.0 cm (mean +/- SD, 3.1 +/- 1.6 cm). At surgery, the mass was noted to be firm and vascular, and in at least 3 patients these features prevented gross total resection. Only 1 patient who had undergone biopsy of his lesion received adjuvant radiation therapy. Follow-up was obtained in all but 1 patient. Nine of these 10 patients are alive and are either free of disease or have had no disease progression. Follow-up in these 9 patients varied from 1 to 16 years (mean +/- SD, 6.5 +/- 53 years). CONCLUSIONS: A granular cell tumor is generally a surprise finding in that it is seldom considered in the differential diagnosis of contrast-enhancing, demarcated sellar region masses. Granular cell tumors are benign and slow growing with no pronounced tendency for invasion or recurrence. Because of the indolent growth of granular cell tumors, the surgical goal of tumor decompression is a reasonable therapeutic approach.

Adult↗
PubMed2002

Stereotactic radiosurgery for patients with ACTH-producing pituitary adenomas after prior adrenalectomy.

PURPOSE: To review the results of stereotactic radiosurgery for patients with adrenocorticotropic hormone (ACTH)-producing pituitary adenomas after bilateral adrenalectomy. METHODS AND MATERIALS: Eleven patients with ACTH-producing pituitary adenomas after bilateral adrenalectomy underwent radiosurgery between 1990 and 1999. Nine patients had documented tumor growth, hyperpigmentation, and elevated ACTH levels (median 920 ng/mL) at the time of radiosurgery. Five of these patients had tumor enlargement despite prior fractionated radiotherapy (median dose 50 Gy). Two patients were treated prophylactically within 1 month of their adrenalectomies to prevent future tumor growth. The median follow-up was 37 months (range 22-74). RESULTS: Tumor growth control was achieved in 9 patients (82%); 2 patients had had continued tumor growth after radiosurgery. The ACTH levels decreased a median of 66% (range -99% to +27%); 4 patients had normal ACTH levels. Three patients had radiation-related complications, including diplopia (n = 2), ipsilateral blindness (n = 1), testosterone/growth hormone deficiency (n = 1), and asymptomatic temporal lobe radiation necrosis (n = 1): all had received prior radiotherapy. One patient who had undergone three prior resections and radiotherapy died 59 months after radiosurgery despite two additional attempts at tumor resection. CONCLUSION: Although our experience is limited, it appears that radiosurgery provides tumor control for most patients with ACTH-producing pituitary adenomas who have undergone bilateral adrenalectomy.

Adenoma↗
PubMed2002

Transient blindness after lumbar epidural steroid injection: a case report and literature review.

STUDY DESIGN: A case report of transient blindness after lumbar epidural steroids is presented. OBJECTIVE: To report the diagnosis and treatment of a case of blindness after administration of lumbar epidural steroids. SUMMARY OF BACKGROUND DATA: Nine previous cases of blindness after lumbar epidural injection for back pain were identified. Retinal hemorrhages were identified on ophthalmologic examination in all cases. METHODS: The 1-year follow up evaluation of a 39-year-old male who sustained transient blindness after administration of lumbar epidural steroids is reported. RESULTS: At 1 year, the patient had significant return of vision, but it did not improve back to baseline. CONCLUSIONS: Transient blindness is a rare complication of lumbar epidural injection. The pathophysiology and prevention of this rare entity is reviewed.

Adult↗