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Biomedical subjects

William F Young

Publications and source records attributed to William F Young.

At least 19 recordsLinked to original sources
PubMed2007

Cervical spondylotic myelopathy: a brief review of its pathophysiology, clinical course, and diagnosis.

Degenerative disease of the cervical spine commonly occurs in the natural process of aging. This can lead to compression of the spinal cord and symptomatic myelopathy. We review the pathophysiological factors that lead to myelopathy and the controversial natural history of untreated myelopathy. Signs and symptoms at presentation, examination findings, differential diagnosis, and diagnostic studies are also discussed.

Cervical Vertebrae↗
PubMed2006

Primary aldosteronism: diagnostic and treatment strategies.

Primary aldosteronism is caused by bilateral idiopathic hyperplasia in approximately two-thirds of cases and aldosterone-producing adenoma in one-third. Most patients with primary aldosteronism are normokalemic. In the clinical setting of normokalemic hypertension, patients who have resistant hypertension and hypertensive patients with a family history atypical for polygenic hypertension should be tested for primary aldosteronism. The ratio of plasma aldosterone concentration to plasma renin activity has been generally accepted as a first-line case-finding test. If a patient has an increased ratio, autonomous aldosterone production must be confirmed with an aldosterone suppression test. Once primary aldosteronism is confirmed, the subtype needs to be determined to guide treatment. The initial test in subtype evaluation is CT imaging of the adrenal glands. If surgical treatment is considered, adrenal vein sampling is the most accurate method for distinguishing between unilateral and bilateral adrenal aldosterone production. Optimal treatment for aldosterone-producing adenoma or unilateral hyperplasia is unilateral laparoscopic adrenalectomy. The idiopathic bilateral hyperplasia and glucocorticoid-remediable aldosteronism subtypes should be treated pharmacologically. All patients treated pharmacologically should receive a mineralocorticoid receptor antagonist, a drug type that has been shown to block the toxic effects of aldosterone on nonepithelial tissues.

Adenoma↗
PubMed2006

Functioning paraganglioma and gastrointestinal stromal tumor of the jejunum in three women: syndrome or coincidence.

Functioning paraganglioma and gastrointestinal stromal tumor (GIST) are uncommon tumors that occur mostly in a sporadic and isolated form, occasionally as components of multiple neoplasia syndromes, either separately or together. Separately, they occur in several inherited syndromes including multiple endocrine neoplasia 2, and the GIST, lentigines, and mast cell tumor syndrome. Together, they are variably prominent components of three syndromes: the familial paraganglioma and gastric GIST syndrome, neurofibromatosis type 1, and the Carney triad. The two former conditions are inherited as autosomal dominant traits; the latter does not appear to be inherited and affects young women predominantly. This article reports the nonfamilial occurrence of functioning paraganglioma and GIST of the jejunum in 3 women, 1 young (22 years) at initial presentation. The occurrences were unexpected because of the infrequency of the tumors. The neoplasms, respectively, did not show germline SDHA, SDHB, SDHC, and SDHD, and KIT mutations associated with familial paraganglioma and familial GIST. The paraganglioma-jejunal GIST combination may be the harbinger of a rare genetic syndrome, a variant of the Carney triad or the paraganglioma-gastric stromal sarcoma syndrome, or be coincidental.

Adult↗
PubMed2006

Paragangliomas: clinical overview.

Paragangliomas are rare tumors that arise from extra-adrenal paraganglia. The effective diagnosis and management of the paraganglioma patient involves the close collaboration of endocrinologists, endocrine surgeons, anesthesiologists, geneticists, laboratory specialists, radiologists, oncologists, and pathologists. Paragangliomas are diagnosed in the following clinical settings: signs and symptoms related to catecholamine hypersecretion, mass effect symptoms (e.g., with head and neck paragangliomas), incidental finding on imaging, or family screening for hereditary paraganglioma. Paragangliomas that hypersecrete catecholamines may cause signs and symptoms identical to those in patients with hyperfunctioning adrenal pheochromocytoma. When a catecholamine-secreting tumor is suspected in a patient because of paroxysmal symptoms, biochemical documentation of catecholamine and fractionated metanephrine hypersecretion should precede any form of imaging study. Catecholamine-secreting paragangliomas are found where chromaffin tissue is located (e.g., along the para-aortic sympathetic chain, or within the organs of Zuckerkandl at the origin of the inferior mesenteric artery, the wall of the urinary bladder, and the sympathetic chain in the neck or mediastinum). As many as 50% of paragangliomas are hereditary and may be associated with familial paraganglioma, neurofibromatosis Type 1, von Hippel-Lindau disease, the Carney triad, and, rarely, with multiple endocrine neoplasia Type 2. Genetic testing should be considered in all patients with paraganglioma. The treatment of choice for paraganglioma is surgical resection; most tumors are benign and can be excised totally. Following surgical cure, annual biochemical testing assesses for metastatic disease, tumor recurrence or delayed appearance of multiple primary tumors.

Adult↗
PubMed2006

Pathobiology of pituitary adenomas and carcinomas.

OBJECTIVE: To examine relationships between pituitary tumors and lesion size, invasiveness, resectability, deoxyribonucleic acid ploidy, cell cycle profile, mitotic activity, and immunoreactivity for MIB-1, proliferating cell nuclear antigen (PCNA), p27Kip1, and p53. PATIENTS AND METHODS: One hundred fifty-three adenomas of most pathological subtypes, including 20 medically treated and prolactin and growth hormone-containing tumors, as well as 10 premetastatic tumors and 13 pituitary carcinomas, were studied. RESULTS: Significant (P < 0.05) differences were noted between functional versus nonfunctional adenomas (percent aneuploidy, percent S phase, p27Kip1 labeling indices [LI], male sex, tumor size, and frequency of visual disturbance); Cushing's versus silent adrenocorticotropin adenomas (percent hypertetraploidy, p53 LI, tumor size, visual disturbance, and resectability); untreated versus medically treated prolactin cell adenomas (MIB-1 LI, p53 LI, and resectability); untreated versus medically treated growth hormone-containing adenomas (percent diploidy, percent S phase, MIB-1 LI, p53 LI, and p27 LI); untreated prolactin cell adenomas versus premetastatic tumors (percent hypertetraploidy, PCNA LI, p53 LI, invasiveness, and resectability); untreated growth hormone-containing adenomas versus premetastatic tumors (percent diploidy, percent S phase, PCNA LI, p53 LI, invasiveness, and resectability); Cushing's adenomas versus premetastatic tumors (percent diploidy, percent hypertetraploidy, percent S phase, MIB-1 LI, p53 LI, tumor size, invasiveness, visual disturbance, and resectability); Nelson's adenomas versus premetastatic tumors (p53 LI, tumor size, invasiveness, and resectability); silent adenomas as a whole versus nonfunctional adenomas (percent nondiploid, percent S phase, invasiveness, and respectability); silent adrenocorticotropin adenomas I and II versus silent adenoma Subtype III (invasiveness); silent adrenocorticotropin adenoma Subtypes I and II versus premetastatic tumors (MIB-1 LI and invasiveness); silent adenoma Subtype III versus premetastatic tumors (PCNA and p53 LI); and premetastatic tumors versus metastatic pituitary carcinomas (MIB-1 LI). CONCLUSION: Only trends toward differences were noted between Cushing's versus Nelson's adenomas and between prolactinomas of reproductive female patients versus those of menopausal female patients and male patients. Too few "atypical adenomas" were encountered to permit their comparison with premetastatic tumors, but our results suggest that most pituitary carcinomas arise by malignant transformation from adenomas.

Adolescent↗
PubMed2006

Pheochromocytoma and paraganglioma in children: a review of medical and surgical management at a tertiary care center.

OBJECTIVE: The aim of this study was to review our institutional experience managing pheochromocytomas and paragangliomas in children. METHODS: A retrospective chart review of the Mayo Clinic database from 1975 to 2005 identified 30 patients < 18 years of age with histologically confirmed pheochromocytoma or paraganglioma. RESULTS: There were 12 patients with pheochromocytomas and 18 with paragangliomas. The most common presenting symptoms were hypertension (64%), palpitation (53%), headache (47%), and mass-related effects (30%). Nine patients (30%) had a genetic mutation or documented family history of pheochromocytoma or paraganglioma. Fourteen patients (47%) had malignant disease, whereas 16 (53%) had benign disease. Logistic analysis showed that statistically significant risk factors for malignancy were (1) paraganglioma, (2) apparently sporadic, as opposed to familial, pheochromocytoma or paraganglioma, and (3) tumor size of > 6 cm. Surgical resection was performed for 28 patients (93%), with perioperative mortality and major morbidity rates of 0% and 10%, respectively. Resection achieved symptomatic relief for 25 patients (83%). All patients with benign disease appeared cured after resection. For patients with malignant disease, the 5- and 10-year disease-specific survival rates were 78% and 31%, respectively, and the mean survival time was 157 +/- 32 months. CONCLUSIONS: The incidence of malignant pheochromocytoma/paraganglioma was high in children (47%), particularly those with apparently sporadic disease, paraganglioma, and tumor diameters of > 6 cm. Patients with a known genetic mutation or familial pheochromocytoma/paraganglioma were more likely to achieve resection with negative microscopic margins and had improved disease-specific mortality rates. Surgical resection remains the treatment of choice for pheochromocytoma and paraganglioma.

Adolescent↗
PubMed2005

Measurement of fractionated plasma metanephrines for exclusion of pheochromocytoma: Can specificity be improved by adjustment for age?

BACKGROUND: Biochemical testing for pheochromocytoma by measurement of fractionated plasma metanephrines is limited by false positive rates of up to 18% in people without known genetic predisposition to the disease. The plasma normetanephrine fraction is responsible for most false positives and plasma normetanephrine increases with age. The objective of this study was to determine if we could improve the specificity of fractionated plasma measurements, by statistically adjusting for age. METHODS: An age-adjusted metanephrine score was derived using logistic regression from 343 subjects (including 33 people with pheochromocytoma) who underwent fractionated plasma metanephrine measurements as part of investigations for suspected pheochromocytoma at Mayo Clinic Rochester (derivation set). The performance of the age-adjusted score was validated in a dataset of 158 subjects (including patients 23 with pheochromocytoma) that underwent measurements of fractionated plasma metanephrines at Mayo Clinic the following year (validation dataset). None of the participants in the validation dataset had known genetic predisposition to pheochromocytoma. RESULTS: The sensitivity of the age-adjusted metanephrine score was the same as that of traditional interpretation of fractionated plasma metanephrine measurements, yielding a sensitivity of 100% (23/23, 95% confidence interval [CI] 85.7%, 100%). However, the false positive rate with traditional interpretation of fractionated plasma metanephrine measurements was 16.3% (22/135, 95% CI, 11.0%, 23.4%) and that of the age-adjusted score was significantly lower at 3.0% (4/135, 95% CI, 1.2%, 7.4%) (p < 0.001 using McNemar's test). CONCLUSION: An adjustment for age in the interpretation of results of fractionated plasma metanephrines may significantly decrease false positives when using this test to exclude sporadic pheochromocytoma. Such improvements in false positive rate may result in savings of expenditures related to confirmatory imaging.

Journal Article↗
PubMed2005

Elective spinal surgery in asymptomatic HIV-seropositive persons: perioperative complications and outcomes.

STUDY DESIGN: This is a retrospective study consisting of medical records review and evaluation of pertinent radiographs. OBJECTIVES: In this study, complications and outcomes are reviewed in a series of HIV-positive patients undergoing spinal surgery. Surgery was performed for conditions that were unrelated to HIV infection. METHODS: From the period 1996 to 2000, we identified 10 seropositive patients who underwent spinal procedures for conditions that did not arise as a complication of HIV infection. A retrospective review was done, which included inpatient and out patient records. RESULTS: A total of 6 women and 5 men who were HIV-positive underwent spinal surgery during the time period reviewed. Surgery was performed for a variety of conditions, including lumbar disc herniaition, degenerative disc disease, cervical disc herniation, spinal fractures, and Arnold-Chiari malformation. The mean CD4 count was 279 cells/mm3 before surgery. All patients had at least 6 months of conservative management before surgery, except in the case of those who had spinal fractures. Two patients sustained postoperative complications: 1 patient developed a superficial wound infection, which was successfully treated with antibiotics, and 1 patient experienced prolonged fever (7 days) after surgery, which resolved without a clear diagnosis. All patients were improved after surgery (mean follow-up, 29.3 months) CONCLUSIONS: Many physicians have held a nihilistic approach, when it comes to the treatment of HIV-positive persons. However, our results in this small series of patients suggest that spinal surgery may be appropriate and can be performed with acceptable outcomes in selected patients.

Adult↗
PubMed2005

Laparoscopic adrenalectomy for patients who have Cushing's syndrome.

Laparoscopic adrenalectomy is one of the most significant advances in the past 20 years for treating adrenal disorders. When compared with open adrenalectomy, laparoscopic adrenalectomy is equally safe, effective, and curative; it is more successful in shortening hospitalization and convalescence and has less long-term morbidity. The laparoscopic approach is the procedure of choice for the surgical management of cortisol-producing adenomas and for patients who have corticotropin (ACTH)-dependent Cushing's syndrome for whom surgery failed to remove the source of ACTH. The keys to successful laparoscopic adrenalectomy are appropriate patient selection, knowledge of anatomy, delicate tissue handling, meticulous hemostasis, and experience with the technique of laparoscopic adrenalectomy.

Adrenalectomy↗
PubMed2005

Pituitary carcinoma: a clinicopathological review.

Pituitary carcinomas are rare tumors; less than 100 well-documented cases have been reported to date. Such tumors are aggressive and associated with a high mortality rate. The molecular events leading to the development of pituitary carcinomas are largely unknown. Recent studies have only begun to shed light on the probable mechanisms of tumor initiation and progression. A review of the clinicopathological and molecular genetic characteristics of pituitary carcinomas is presented.

Adenoma↗
PubMed2004

A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma.

BACKGROUND: Fractionated plasma metanephrine measurements are commonly used in biochemical testing in search of pheochromocytoma. METHODS: We aimed to critically appraise the diagnostic efficacy of fractionated plasma free metanephrine measurements in detecting pheochromocytoma. Nine electronic databases, meeting abstracts, and the Science Citation Index were searched and supplemented with previously unpublished data. Methodologic and reporting quality was independently assessed by two endocrinologists using a checklist developed by the Standards for Reporting of Diagnostic Studies Accuracy Group and data were independently abstracted. RESULTS: Limitations in methodologic quality were noted in all studies. In all subjects (including those with genetic predisposition): the sensitivities for detection of pheochromocytoma were 96%-100% (95% CI ranged from 82% to 100%), whereas the specificities were 85%-100% (95% CI ranged from 78% to 100%). Statistical heterogeneity was noted upon pooling positive likelihood ratios when those with predisposition to disease were included (p < 0.001). However, upon pooling the positive or negative likelihood ratios for patients with sporadic pheochromocytoma (n = 191) or those at risk for sporadic pheochromocytoma (n = 718), no statistical heterogeneity was noted (p = 0.4). For sporadic subjects, the pooled positive likelihood ratio was 5.77 (95% CI = 4.90, 6.81) and the pooled negative likelihood ratio was 0.02 (95% CI = 0.01, 0.07). CONCLUSION: Negative plasma fractionated free metanephrine measurements are effective in ruling out pheochromocytoma. However, a positive test result only moderately increases suspicion of disease, particularly when screening for sporadic pheochromocytoma.

Journal Article↗
PubMed2004

Role for adrenal venous sampling in primary aldosteronism.

BACKGROUND: The aim of this study was to determine the effect of adrenal venous sampling (AVS) on the management of patients with primary aldosteronism. METHODS: From September 1990 through October 2003, 203 patients with primary aldosteronism (mean age, 53 years; range, 17-80; 163 men) were selected prospectively for AVS on the basis of degree of aldosterone excess, age, desire for surgical treatment, and computed tomographic (CT) findings. RESULTS: Both adrenal veins were catheterized in 194 patients (95.6%). Notable among the 110 patients (56.7%) with unilateral aldosterone hypersecretion were 24 (41.4%) of 58 patients with normal adrenal CT findings, 24 (51.1%) of 47 with unilateral micronodule (< or =10 mm) apparent on CT (7 had unilateral aldosterone hypersecretion from the contralateral adrenal), 21 (65.6%) of 32 with unilateral macronodule (>10 mm) apparent on CT (1 had unilateral aldosterone hypersecretion from the contralateral adrenal), 16 (48.5%) of 33 with bilateral micronodules, and 2 (33%) of 6 with bilateral macronodules. CONCLUSIONS: On the basis of CT findings alone, 42 patients (21.7%) would have been incorrectly excluded as candidates for adrenalectomy, and 48 (24.7%) might have had unnecessary or inappropriate adrenalectomy. AVS is an essential diagnostic step in most patients to distinguish between unilateral and bilateral adrenal aldosterone hypersecretion.

Adolescent↗
PubMed2004

Internal jugular vein sampling in adrenocorticotropic hormone-dependent Cushing's syndrome: a comparison with inferior petrosal sinus sampling.

OBJECTIVE: Distinguishing between pituitary-dependent Cushing's syndrome (CS) and occult ectopic ACTH syndrome can be extremely difficult. Bilateral inferior petrosal sinus sampling has been shown to have the highest diagnostic accuracy in this subtype evaluation. Internal jugular vein sampling (IJVS) has been reported as a potentially safer invasive alternative, but data are limited. Our objective was to compare the sensitivity and specificity of bilateral IJVS and bilateral inferior petrosal sinus sampling (IPSS) in patients with ACTH-dependent CS. DESIGN: We prospectively collected blood samples from the inferior petrosal sinus and internal jugular vein of consecutive patients with ACTH-dependent CS. PATIENTS: The study group included 35 patients: 32 with pituitary-dependent CS (positive immunohistochemical findings for ACTH pituitary tumour or biochemical cure after pituitary surgery) and three with histologically proven ectopic ACTH syndrome. MEASUREMENTS: Inferior petrosal sinus sampling and bilateral IJVS were performed simultaneously before and after administration of corticotropin-releasing hormone (CRH), and ratios of central-to-peripheral ACTH concentrations were calculated. RESULTS: The basal IJVS central-to-peripheral ACTH ratios were diagnostic for pituitary-dependent CS (> 2) in 15 patients (46.9%), as were basal inferior petrosal sinus sampling central-to-peripheral ACTH ratios in 29 patients (90.6%). The post-CRH IJVS central-to-peripheral ACTH ratios were diagnostic for pituitary-dependent disease (> 3) in 24 patients (75%), as were post-CRH inferior petrosal sinus sampling central-to-peripheral ACTH ratios in 28 patients (87.5%). In the three patients with ectopic ACTH CS, the IJVS and inferior petrosal sinus sampling pre- and post-CRH ACTH ratios were correctly negative. The overall sensitivity of combined pre- or post-CRH was 81.3% for IJVS and 93.8% for inferior petrosal sinus sampling. Because of the difference between mean ratios in the two techniques, new criteria for IJVS were mathematically calculated: a pre-CRH central-to-peripheral ACTH ratio of 1.59 and a post-CRH central-to-peripheral ACTH ratio of 2.47 maximized sensitivity and specificity when both of these are equally taken into consideration. CONCLUSION: In conclusion, IJVS is not superior to inferior petrosal sinus sampling for establishing the cause of ACTH-dependent CS. When new criteria of basal (> 1.6) and post-CRH (> 2.5) central-to-peripheral ACTH gradients were applied to ACTH ratios from IJVS, the sensitivity of this test was maximized. However, confirmatory inferior petrosal sinus sampling is recommended when there is a lack of a central-to-peripheral ACTH gradient and when there is only a gradient above the cut-off on basal (pre-CRH) sampling.

ACTH Syndrome, Ectopic↗
PubMed2004

The economic implications of three biochemical screening algorithms for pheochromocytoma.

Pheochromocytoma is a rare, life-threatening condition. Using a modeling technique, we studied the economic implications of detection strategies for pheochromocytoma (third-party payer perspective). The diagnostic efficacy of biochemical tests was based on Mayo Clinic Rochester data. In all hypothetical algorithms, positive biochemical tests were followed by abdominal computerized tomography and, if negative, metaiodobenzylguanidine scintigraphy. In each hypothetical algorithm, imaging would be indicated after positive biochemical testing as follows: algorithm A, fractionated plasma metanephrine measurements above the laboratory reference range; or algorithm B, abnormal measurements of 24-h urinary total metanephrines or catecholamines. In algorithm C, subjects with fractions of plasma metanephrine at or above 0.5 nmol/liter or normetanephrine at or above 1.80 nmol/liter would undergo imaging, whereas those with values between the reference range and these cutoffs would undergo 24-h urinary measurements (total metanephrines and fractionated catecholamines) and be imaged if positive. We determined that, if 100,000 hypertensive patients (including 500 patients with pheochromocytoma) were tested, algorithm A (measurement of fractionated plasma metanephrines alone) would detect 489 pheochromocytoma patients at a cost of 56.6 million dollars, whereas B (24-h urinary measurements) would detect 457 pheochromocytoma patients for 39.5 million dollars, and C (combination of measurements of fractionated plasma metanephrines and urines) would detect 478 patients for 28.6 million dollars. None of the screening strategies for pheochromocytoma described are affordable if implemented on a routine basis in extremely low-risk patients. However, algorithm C may be the least costly, and at a reasonable level of sensitivity, for subjects in whom the suspicion of disease is moderate.

Adrenal Gland Neoplasms↗
PubMed2004

Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents.

Primary aldosteronism (PA) is a common form of endocrine hypertension previously believed to account for less than 1% of hypertensive patients. Hypokalemia was considered a prerequisite for pursuing diagnostic tests for PA. Recent studies applying the plasma aldosterone/plasma renin activity ratio (ARR) as a screening test have reported a higher prevalence. This study is a retrospective evaluation of the diagnosis of PA from clinical centers in five continents before and after the widespread use of the ARR as a screening test. The application of this strategy to a greater number of hypertensives led to a 5- to 15-fold increase in the identification of patients affected by PA. Only a small proportion of patients (between 9 and 37%) were hypokalemic. The annual detection rate of aldosterone-producing adenoma (APA) increased in all centers (by 1.3-6.3 times) after the wide application of ARR. Aldosterone-producing adenomas constituted a much higher proportion of patients with PA in the four centers that employed adrenal venous sampling (28-50%) than in the center that did not (9%). In conclusion, the wide use of the ARR as a screening test in hypertensive patients led to a marked increase in the detection rate of PA.

Aldosterone↗