105 results on '"Vance, M. L."'
Search Results
2. Guidelines for Acromegaly Management: An Update
- Author
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Melmed, S, Colao, A, Barkan, A, Molitch, M, Grossman, A B., Kleinberg, D, Clemmons, D, Chanson, P, Laws, E, Schlechte, J, Vance, M L., Ho, K, and Giustina, A
- Published
- 2009
3. Treatment of Adrenocorticotropin-Dependent Cushingʼs Syndrome: A Consensus Statement
- Author
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Biller, B M. K., Grossman, A B., Stewart, P M., Melmed, S, Bertagna, X, Bertherat, J, Buchfelder, M, Colao, A, Hermus, A R., Hofland, L J., Klibanski, A, Lacroix, A, Lindsay, J R., Newell-Price, J, Nieman, L K., Petersenn, S, Sonino, N, Stalla, G K., Swearingen, B, Vance, M L., Wass, J A. H., and Boscaro, M
- Published
- 2008
4. Trattamento a lungo termine dell’acromegalia mediante pegvisomant, un antagonista del recettore dell’ormone della crescita
- Author
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van der Lely, A. J., Hutson, R. K., Trainer, P. J., Besser, G. M., Barkan, A. L., Katznelson, L., Kilbanski, A., Herman-Bonert, V., Melmed, S., Vance, M. L., Freda, P. U., Stewart, P. M., Friend, K. E., Clemmons, D. R., Johannsson, G., Stavrou, S., Cook, D. M., Phillips, L. S., Strasburger, C. J., Hacker, S., Zib, K. A., Davis, R. J., Scarlett, J. A., Thorner, M. O., Colao, Annamaria, Ciccarelli, Antonio, Pivonello, Rosario, and Lombardi, Gaetano
- Published
- 2002
- Full Text
- View/download PDF
5. Diagnosis and Complications of Cushing’s Syndrome: A Consensus Statement
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Arnaldi, G, Angeli, A, Atkinson, A B., Bertagna, X, Cavagnini, F, Chrousos, G P., Fava, G A., Findling, J W., Gaillard, R C., Grossman, A B., Kola, B, Lacroix, A, Mancini, T, Mantero, F, Newell-Price, J, Nieman, L K., Sonino, N, Vance, M L., Giustina, A, and Boscaro, M
- Published
- 2003
6. The Pharmacokinetic and Pharmacodynamic Characteristics of a Long-Acting Growth Hormone (GH) Preparation (Nutropin Depot) in GH-Deficient Adults
- Author
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Cook, D M., Biller, B M. K., Vance, M L., Hoffman, A R., Phillips, L S., Ford, K M., Benziger, D P., Illeperuma, A, Blethen, S L., Attie, K M., Dao, L N., Reimann, J D., and Fielder, P J.
- Published
- 2002
7. Guidelines for Acromegaly Management
- Author
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Melmed, S, Casanueva, F F., Cavagnini, F, Chanson, P, Frohman, L, Grossman, A, Ho, K, Kleinberg, D, Lamberts, S, Laws, E, Lombardi, G, Vance, M L., WERDER, K Von, Wass, J, and Giustina, A
- Published
- 2002
8. Surgical Management of GH-Secreting Pituitary Adenomas: An Outcome Study Using Modern Remission Criteria
- Author
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Kreutzer, J, Vance, M L, Lopes, M B. S, and Laws, E R, Jr.
- Published
- 2001
9. Estrogen Receptors in Prolactinomas: A Clinico-Pathological study
- Author
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Kaptain, G. J., Simmons, N. E., Alden, T. D., Lopes, M. B., Vance, M. L., and Laws, E. R.
- Published
- 1999
10. Confronto tra chirurgia endoscopica e microchirurgia transsfenoidale per l’acromegalia: risultati in una serie parallela di pazienti usando i moderni criteri di remissione
- Author
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Starke, R. M., Raper, D. M. S., Payne, S. C., Vance, M. L., Oldfield, E. H., Jane, J. A., and Cozzi, Renato
- Published
- 2013
- Full Text
- View/download PDF
11. La chirurgia endoscopica transfenoidale per l’acromegalia: remissione usando criteri moderni, complicanze e fattori predittivi dell’outcome
- Author
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Jane, Jr., J. A., Starke, R. M., Elzoghby, M. A., Reames, D. L., Payne, S. C., Thorner, M. O., Marshall, J. C., Laws, Jr, E. R., Vance, M. L., and Cozzi, Renato
- Published
- 2011
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12. Treatment of prolactin-secreting pituitary macroadenomas with the long-acting non-ergot dopamine agonist CV 205-502.
- Author
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Vance, Mary Lee, Lipper, Maurice, Klibanski, Anne, Biller, Beverly M.K., Samaan, Naguib A., Molitch, Mark E., Vance, M L, Lipper, M, Klibanski, A, Biller, B M, Samaan, N A, and Molitch, M E
- Subjects
DOPAMINE agonists ,PITUITARY diseases ,ADENOMA ,COMPARATIVE studies ,IMPOTENCE ,MAGNETIC resonance imaging ,RESEARCH methodology ,MEDICAL cooperation ,MENSTRUAL cycle ,PITUITARY tumors ,PROLACTIN ,PSYCHOANALYTIC interpretation ,QUINOLINE ,RESEARCH ,RESEARCH funding ,EVALUATION research ,DOPAMINE agents - Abstract
Study Objective: Evaluation of the effects of an experimental long-acting non-ergot dopamine agonist, CV 205-502, on serum prolactin, tumor size, gonadal function, visual abnormalities, and tolerability in patients with macroprolactinomas.Design: Prospective, unblinded, dose escalation as needed.Setting: Four university medical centers; patients referred for treatment.Patients: Twenty-six hyperprolactinemic patients (prolactin greater than 150 micrograms/L) with a pituitary macroadenoma were treated for 24 weeks with CV 205-502 given once daily.Measurements and Main Results: Serum prolactin was measured at regular intervals. Prolactin levels decreased in all patients during treatment (mean pretreatment level, 2051.7 +/- 1077 micrograms/L [+/- SE]; 24 weeks, 39.0 +/- 11.3 micrograms/L; P = 0.0001); normal prolactin levels were achieved in 15 (58%). Tumor size decreased in 21 of 26 patients and ranged from 6% to 67% (mean, 19.2% +/- 3.4%). Onset or return of regular menses occurred in 11 of 15 premenopausal women, accompanied by an increase in estradiol concentrations (pretreatment, 186.5 +/- 25.0 pmol/L; on treatment, 690.9 +/- 104.3 pmol/L; P = 0.0003). Serum testosterone increased in 6 of 8 men; sexual function improved in 5 of 7 with pretreatment abnormalities. Two patients with reversible visual abnormalities improved within 2 weeks of starting treatment. Side effects occurred in 11 patients and abated over 1 to 2 weeks or after the dose was reduced. There was no evidence of toxicity as indicated by serial serum chemistries, liver function tests, hematologic profiles, thyroxine levels, and electrocardiogram studies.Conclusions: CV 205-502 reverses hyperprolactinemia and promotes reduction in tumor size with reversal of visual abnormalities and restoration of gonadal function in most patients. This compound will probably be useful in treating prolactinomas. [ABSTRACT FROM AUTHOR]- Published
- 1990
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13. Drugs five years later. Bromocriptine.
- Author
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Vance, M L, Evans, W S, and Thorner, M O
- Abstract
Bromocriptine, a specific dopamine receptor agonist, has been used for the treatment of various hyperprolactinemic conditions and as adjunctive therapy for acromegaly (with or without concomitant hyperprolactinemia) and Parkinson's disease. Bromocriptine is extremely effective in suppressing prolactin secretion regardless of the cause, in restoring gonadal function and fertility, and in decreasing the size of prolactin-secreting pituitary tumors. Most patients with acromegaly have clinical improvement with this drug. When bromocriptine is added to a regimen of levodopa or carbidopa, patients with Parkinson's disease frequently have additional clinical improvement and, in most patients, the levodopa or carbidopa dose can be reduced. Withdrawal of bromocriptine therapy is associated in most patients with reversal of its beneficial effects--return of hyperprolactinemia, return of excess growth hormone secretion, and exacerbation of Parkinson's disease. [ABSTRACT FROM AUTHOR]
- Published
- 1984
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14. Growth-hormone-releasing hormone: a clinical update.
- Author
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Vance, Mary Lee, Thorner, Michael O., Vance, M L, and Thorner, M O
- Subjects
GROWTH hormone releasing factor ,PITUITARY hormone releasing factors - Abstract
Presents information on growth-hormone-releasing hormone (GHRH). Information on the regulation of growth hormone secretion; Discussion of the therapeutic use of GHRH; Details of the therapeutic trials of GHRH.
- Published
- 1986
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15. Effects of an Oral Ghrelin Mimetic on Body Composition and Clinical Outcomes in Healthy Older Adults.
- Author
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Nass, R., Pezzoli, S. S., Oliveri, M. C., Patrie, J. T., Harrell Jr., F. E., Clasey, J. L., Heymsfield, S. B., Bach, M. A., Vance, M. L., and Thorner, M. O.
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INTERNAL medicine - Abstract
An abstract of the study "Effects of an Oral Ghrelin Mimetic on Body Composition and Clinical Outcomes in Healthy Older Adults. A Randomized Trial," by R. Nass and colleagues is presented.
- Published
- 2008
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16. PERIOPERATIVE ACTH CHANGES PREDICT OUTCOME DURING TRANSSPHENOIDAL MICROSURGERY FOR CUSHING'S DISEASE.
- Author
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Pajewski, T. N., Vance, M. L., Jaeger, J. M., and Laws Jr., E. R.
- Published
- 1997
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17. Consensus statement: medical management of acromegaly.
- Author
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Melmed S, Casanueva F, Cavagnini F, Chanson P, Frohman LA, Gaillard R, Ghigo E, Ho K, Jaquet P, Kleinberg D, Lamberts S, Laws E, Lombardi G, Sheppard MC, Thorner M, Vance ML, Wass JA, and Giustina A
- Subjects
- Acromegaly drug therapy, Acromegaly radiotherapy, Acromegaly surgery, Dopamine Agonists therapeutic use, Female, Human Growth Hormone analogs & derivatives, Human Growth Hormone blood, Human Growth Hormone therapeutic use, Humans, Insulin-Like Growth Factor I analysis, Male, Somatostatin analogs & derivatives, Somatostatin therapeutic use, Acromegaly therapy
- Abstract
In November 2003, the Pituitary Society and the European Neuroendocrine Association sponsored a consensus workshop in Seville to address challenging issues in the medical management of acromegaly. Participants comprised 70 endocrinologists and neurosurgeons with international expertise in managing patients with acromegaly. All participants participated in the workshop proceedings, and the final document written by the scientific committee reflects the consensus opinion of the interactive deliberations. The meeting was supported by an unrestricted educational grant from Ipsen. No pharmaceutical representatives participated in the program planning or in the scientific deliberations.
- Published
- 2005
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18. Cushing's disease resulting from pituitary corticotrophic microadenoma. Treatment results from transsphenoidal microsurgery and gamma knife radiosurgery.
- Author
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Laws ER, Reitmeyer M, Thapar K, and Vance ML
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- Adenoma etiology, Adenoma metabolism, Cushing Syndrome etiology, Female, Humans, Hydrocortisone metabolism, Hypopituitarism etiology, Magnetic Resonance Imaging, Male, Phenotype, Pituitary Neoplasms etiology, Pituitary Neoplasms metabolism, Pituitary-Adrenal System physiopathology, Postoperative Complications, Remission Induction, Salvage Therapy, Treatment Outcome, Adenoma surgery, Cushing Syndrome surgery, Hypophysectomy methods, Pituitary Neoplasms surgery, Radiosurgery adverse effects
- Abstract
Cushing's disease and its associated clinical syndrome reflect the effects of excess cortisol on the individual. The cause of Cushing's disease is ordinarily an ACTH-secreting benign pituitary adenoma. The diagnosis of Cushing's disease is established by sophisticated endocrine testing and comprehensive imaging studies. Because of the devastating effects of excess cortisol, therapy that provides prompt and effective normalization of serum cortisol is essential. Currently this goal is best achieved by transsphenoidal microsurgery. This paper reviews the clinical presentation, laboratory analysis, surgical management and outcome in patients with Cushing's disease.
- Published
- 2002
19. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist.
- Author
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van der Lely AJ, Hutson RK, Trainer PJ, Besser GM, Barkan AL, Katznelson L, Klibanski A, Herman-Bonert V, Melmed S, Vance ML, Freda PU, Stewart PM, Friend KE, Clemmons DR, Johannsson G, Stavrou S, Cook DM, Phillips LS, Strasburger CJ, Hackett S, Zib KA, Davis RJ, Scarlett JA, and Thorner MO
- Subjects
- Adult, Blood Glucose drug effects, Cohort Studies, Drug Administration Schedule, Female, Growth Hormone blood, Human Growth Hormone analogs & derivatives, Humans, Insulin blood, Insulin-Like Growth Factor I metabolism, Male, Middle Aged, Acromegaly drug therapy, Receptors, Somatotropin antagonists & inhibitors, Receptors, Somatotropin therapeutic use
- Abstract
Background: Pegvisomant is a new growth hormone receptor antagonist that improves symptoms and normalises insulin-like growth factor-1 (IGF-1) in a high proportion of patients with acromegaly treated for up to 12 weeks. We assessed the effects of pegvisomant in 160 patients with acromegaly treated for an average of 425 days., Methods: Treatment efficacy was assessed by measuring changes in tumour volume by magnetic resonance imaging, and serum growth hormone and IGF-1 concentrations in 152 patients who received pegvisomant by daily subcutaneous injection for up to 18 months. The safety analysis included 160 patients some of whom received weekly injections and are excluded from the efficacy analysis., Findings: Mean serum IGF-1 concentrations fell by at least 50%: 467 mg/L (SE 24), 526 mg/L (29), and 523 mg/L (40) in patients treated for 6, 12 and 18 months, respectively (p<0.001), whereas growth hormone increased by 12.5 mg/L (2.1), 12.5 mg/L (3.0), and 14.2 mg/L (5.7) (p<0.001). Of the patients treated for 12 months or more, 87 of 90 (97%) achieved a normal serum IGF-1 concentration. In patients withdrawn from pegvisomant (n=45), serum growth hormone concentrations were 8.0 mg/L (2.5) at baseline, rose to 15.2 mg/L (2.4) on drug, and fell back within 30 days of withdrawal to 8.3 mg/L (2.7). Antibodies to growth hormone were detected in 27 (16.9%) of patients, but no tachyphylaxis was seen. Serum insulin and glucose concentrations were significantly decreased (p<0.05). Two patients experienced progressive growth of their pituitary tumours, and two other patients had increased alanine and asparate aminotransferase concentrations requiring withdrawal from treatment. Mean pituitary tumour volume in 131 patients followed for a mean of 11.46 months (0.70) decreased by 0.033 cm(3) (0.057; p=0.353)., Interpretation: Pegvisomant is an effective medical treatment for acromegaly.
- Published
- 2001
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20. Hypogonadism in patients with acromegaly: data from the multi-centre acromegaly registry pilot study.
- Author
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Katznelson L, Kleinberg D, Vance ML, Stavrou S, Pulaski KJ, Schoenfeld DA, Hayden DL, Wright ME, Woodburn CJ, and Klibanski A
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- Acromegaly blood, Adenoma blood, Adult, Databases, Factual, Female, Growth Hormone blood, Humans, Hypogonadism blood, Male, Middle Aged, Pilot Projects, Pituitary Neoplasms blood, Prevalence, Prolactin blood, Registries, Retrospective Studies, Acromegaly etiology, Adenoma complications, Hypogonadism etiology, Pituitary Neoplasms complications
- Abstract
Objective: Because acromegaly is an uncommon disorder, epidemiological data regarding the demographics of the disease such as the prevalence of hypogonadism have been limited. In order to derive clinical and epidemiological information, including underlying hormonal factors, regarding hypogonadism in patients with acromegaly, we performed a pilot study designed to develop a multi-centre acromegaly patient registry., Design and Measurements: Medical records of patients with acromegaly seen between 1976 and 1996 at three Institutions were reviewed, and data were entered into a database using a secure internet website. Hypogonadism was defined as amenorrhoea in women and testosterone deficiency in men. Subanalysis was performed in patients with microadenomas and women less than 50 years of age, to include women of reproductive age., Results: Information was available on 363 patients, of whom 54% were women. The mean age at diagnosis was 41 +/- 13 years. In subjects less than 50 years of age, hypogonadism was present in 59%. Hyperprolactinaemia was present in 45% and 21% of hypogonadal and eugonadal patients of reproductive age, respectively (P = 0.0003). GH levels were higher in patients with hypogonadism (P = 0.03). In patients < 50 years of age with microadenomas, hypogonadism was present in nine of the 22 (41%) patients, including 55% of the women and 27% of the men (P = ns). Hyperprolactinaemia was present in three of the 10 and four of the 14 of microadenoma patients with hypogonadism and eugonadism, respectively., Conclusion: We developed a web-based acromegaly patient registry and used it to show that hypogonadism is a frequent consequence of acromegaly, even in patients with microadenomas, who are not at risk from hypopituitarism due to local mass effects. We also demonstrated that prolactin and GH hypersecretion contribute to the pathogenesis of hypogonadism in acromegaly, and that hypogonadism may occur in microadenoma patients even in the absence of hyperprolactinaemia.
- Published
- 2001
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21. Double pituitary lesions in three patients with Cushing's disease.
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Meij BP, Lopes MB, Vance ML, Thorner MO, and Laws ER Jr
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- Adenoma diagnosis, Adenoma surgery, Adult, Cushing Syndrome diagnosis, Cushing Syndrome surgery, Female, Humans, Immunohistochemistry, Magnetic Resonance Imaging, Male, Microscopy, Electron, Pituitary Neoplasms diagnosis, Pituitary Neoplasms surgery, Adenoma pathology, Cushing Syndrome pathology, Pituitary Neoplasms pathology
- Abstract
Double pituitary adenomas are rare in surgical specimens and the most common clinical feature in reported patients has been acromegaly. We report 3 cases of double pituitary lesions in patients who presented with Cushing's disease. In a 22-year-old man (case 1) with delayed puberty and low testosterone levels, mild hyperprolactinemia was diagnosed and treated with dopamine agonist therapy that reduced the prolactin (PRL) levels to normal. Over a 1-year period Cushing's disease developed gradually and was confirmed with classical endocrine testing. In a 27-year-old woman (case 2) who initially presented with severe depression and morbid obesity there was a gradual onset of Cushing's disease; initially she had minimally elevated serum PRL. In a 33-year-old woman (case 3) there was a 2-year history of Cushing's disease characterized by hirsutism, hypertension and weight gain; serum PRL was normal. Magnetic resonance imaging in all 3 patients revealed a microadenoma that was successfully removed by transsphenoidal pituitary surgery. Histology and immunocytochemistry in case 1 and case 3 revealed a corticotroph cell adenoma and a PRL cell adenoma in separate areas of the pituitary. In case 3 the PRL cell adenoma was "silent" but in case 1 the PRL cell adenoma may have been the cause of the mild hyperprolactinemia. In case 2 nodular corticotroph hyperplasia was the cause of Cushing's disease and a "silent" PRL cell adenoma was also identified. We conclude from these cases and a literature review that double pituitary lesions may occur in patients with Cushing's disease. The corticotroph part of the double lesion may consist of a corticotroph cell adenoma or, as reported in this study, of corticotroph nodular hyperplasia. The counterpart of the double lesion may consist either of a "silent" PRL cell adenoma or a functional PRL cell adenoma causing hyperprolactinemia.
- Published
- 2000
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22. Radiosurgery for Cushing's disease after failed transsphenoidal surgery.
- Author
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Sheehan JM, Vance ML, Sheehan JP, Ellegala DB, and Laws ER Jr
- Subjects
- Adenoma diagnosis, Adolescent, Adult, Aged, Female, Humans, Hydrocortisone urine, Hypopituitarism etiology, Magnetic Resonance Imaging, Male, Middle Aged, Pituitary Neoplasms diagnosis, Postoperative Complications, Reoperation, Retrospective Studies, Sphenoid Bone surgery, Treatment Failure, Adenoma surgery, Cushing Syndrome surgery, Pituitary Neoplasms surgery, Radiosurgery
- Abstract
Object: Although transsphenoidal surgery has become the standard of care for Cushing's disease, it is often unsuccessful in normalizing cortisol production. In this study the authors investigate the safety and efficacy of gamma knife radiosurgery (GKRS) for Cushing's disease after failed transsphenoidal surgery., Methods: The records of all patients who underwent GKRS at the authors' institution after unsuccessful transsphenoidal surgery for Cushing's disease were retrospectively reviewed. Successful treatment was considered a normal or below-normal 24-hour urinary free cortisol (UFC) level. Records were also evaluated for relapse, new-onset endocrine deficiencies, interval change in tumor size, and visual complications. Forty-three patients underwent 44 gamma knife procedures with follow up ranging from 18 to 113 months (mean 39.1, median 44 months). Normal 24-hour UFC levels were achieved in 27 patients (63%) at an average time from treatment of 12.1 months (range 3-48 months). Three patients had a recurrence of Cushing's disease at 19, 37, and 38 months, respectively, after radiosurgery. New endocrine deficiencies were noted in seven patients (16%). Follow-up magnetic resonance images obtained in 33 patients revealed a decrease in tumor size in 24, no change in nine, and an increase in size in none of the patients. One patient developed a quadrantanopsia 14 months after radiosurgery despite having received a dose of only 0.7 Gy to the optic tract., Conclusions: Gamma knife radiosurgery appears to be safe and effective for the treatment of Cushing's disease refractory to pituitary surgery. Delayed recurrences and new hormone deficiencies may occur, indicating the necessity for regular long-term follow up.
- Published
- 2000
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23. Conventional radiotherapy for pituitary tumors.
- Author
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Laws ER Jr and Vance ML
- Subjects
- Adenoma surgery, Humans, Pituitary Neoplasms surgery, Adenoma radiotherapy, Pituitary Irradiation, Pituitary Neoplasms radiotherapy, Radiosurgery
- Abstract
Radiosurgery for pituitary adenomas is clearly attaining a more prominent position in the spectrum of management of these lesions. It is our belief that improvements in radiosurgical technology can significantly enhance the outcome for patients with these lesions.
- Published
- 2000
24. Clinical and reimbursement issues in growth hormone use in adults.
- Author
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Biller BM, Vance ML, Kleinberg DL, Cook DM, and Gordon T
- Subjects
- Growth Disorders economics, Growth Hormone economics, Hormone Replacement Therapy economics, Humans, Managed Care Programs economics, Adult, Growth Disorders drug therapy, Growth Hormone administration & dosage, Insurance Coverage
- Abstract
Data published in the past decade have demonstrated that adults who are deficient in growth hormone (GH) experience deleterious clinical consequences without treatment. In 1996, the Food and Drug Administration approved the use of GH in adults who were GH deficient as a result of hypothalamic or pituitary disease. However, there are other conditions in adults for which GH treatment has also been approved (acquired immune deficiency syndrome [AIDS]-related wasting) or for which it is being considered, such as aging, catabolic states, and cardiomyopathy. Clinical issues revolve around the rationale for treatment; the diagnostic evaluation; the effects of GH therapy on body composition, bone density, lipids, and cardiac function; and appropriate dosing and follow up. Clearly, the use of GH in adults raises reimbursement issues as well. In this article, Dr. Beverly M.K. Biller provides an overview of the rationale for the treatment of adult-onset GH deficiency and reviews its etiology and clinical features as well as reimbursement and utilization issues related to treatment. Dr. Mary Lee Vance discusses various assays and criteria used in the diagnostic evaluation of the patient with adult-onset GH deficiency. Dr. David L. Kleinberg focuses on the effects of GH therapy on body composition, bone density, lipid profiles, and cardiac function, as well as on reimbursement issues regarding body composition studies. To complete the clinical portion of this session, Dr. David M. Cook addresses dosing and follow up. To address economic implications, Dr. Terry Gordon provides the payer's perspective on the diagnosis and treatment of adult-onset GH deficiency.
- Published
- 2000
25. The reliability and validity of the impact on lifestyle questionnaire in patients with acromegaly.
- Author
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Lenderking WR, Zacker C, Katznelson L, Vance ML, Hossain S, Tafesse E, Guacaneme AO, and Pashos CL
- Abstract
Objectives: Treatments for acromegaly, a growth hormone disorder, can be burdensome to patients, often requiring multiple self-administered injections daily. We developed the Impact on Lifestyle Questionnaire (ILQ) to measure the impact on patient's lifestyle imposed by the burden of injectable treatments for acromegaly. The primary objective of this study was to establish the reliability and validity of the ILQ., Methods: The ILQ consists of the SF-12 and 30 additional questions. Thirty-four patients, from two sites, completed the ILQ and scales measuring related concepts. Fourteen patients also completed a retest survey 4 weeks later. Survey sample data were combined with ILQ data from another 56 patients with acromegaly for a factor analysis. Reliability was assessed with Cronbach's alpha and test-retest. Zero-order correlations were examined between ILQ subscales and symptoms, depression, SF-12 mental and physical components, a measure of self-care burden, appraisal of illness, and single-item measures of quality of life and satisfaction., Results: The preconceived subscale structure was supported by factor analysis. These factors were internally consistent and stable over time. Good convergent validity was demonstrated between the Burden and Disruption scales with other measures of the burden of treatment. Patients indicated that they were generally compliant with therapy, and that treatment was not particularly burdensome or disruptive. Results based on the ILQ were consistent with other scales and qualitative responses., Conclusions: The ILQ has three subscales, Burden, Lifestyle Disruption, and Compliance, that are reliable and demonstrate preliminary evidence of construct validity.
- Published
- 2000
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26. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.
- Author
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Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der Lely AJ, Dimaraki EV, Stewart PM, Friend KE, Vance ML, Besser GM, Scarlett JA, Thorner MO, Parkinson C, Klibanski A, Powell JS, Barkan AL, Sheppard MC, Malsonado M, Rose DR, Clemmons DR, Johannsson G, Bengtsson BA, Stavrou S, Kleinberg DL, Cook DM, Phillips LS, Bidlingmaier M, Strasburger CJ, Hackett S, Zib K, Bennett WF, and Davis RJ
- Subjects
- Acromegaly blood, Adenoma drug therapy, Adenoma pathology, Adult, Autoantibodies blood, Double-Blind Method, Female, Human Growth Hormone adverse effects, Human Growth Hormone blood, Human Growth Hormone immunology, Human Growth Hormone therapeutic use, Humans, Insulin-Like Growth Factor I metabolism, Male, Middle Aged, Pituitary Neoplasms drug therapy, Pituitary Neoplasms pathology, Acromegaly drug therapy, Human Growth Hormone analogs & derivatives, Receptors, Somatotropin antagonists & inhibitors
- Abstract
Background: Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone., Methods: We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly., Results: The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups., Conclusions: On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.
- Published
- 2000
- Full Text
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27. Transsphenoidal surgery for Cushing's disease: outcome in patients with a normal magnetic resonance imaging scan.
- Author
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Semple PL, Vance ML, Findling J, and Laws ER Jr
- Subjects
- Adenoma surgery, Adult, Aged, Female, Humans, Hypophysectomy, Male, Middle Aged, Neurosurgery methods, Petrosal Sinus Sampling, Pituitary Neoplasms surgery, Postoperative Complications, Sphenoid Bone surgery, Treatment Outcome, Cushing Syndrome diagnosis, Cushing Syndrome surgery, Magnetic Resonance Imaging, Pituitary Gland pathology
- Abstract
Objective: Transsphenoidal surgery for Cushing's disease from a pituitary adenoma is an effective and safe treatment. Definitive preoperative diagnosis of Cushing's disease caused by a pituitary adenoma is often difficult, particularly in patients with normal imaging studies and a normal sella turcica. We present the outcome of transsphenoidal surgery in patients with presumed Cushing's disease and a normal pituitary magnetic resonance imaging scan., Methods: Between January 1992 and December 1997, 105 patients underwent transsphenoidal surgery for Cushing's disease at our institution. The criteria for inclusion in this study were clinical and biochemical studies strongly suggestive of Cushing's disease, a normal magnetic resonance imaging scan with normal sella and sellar contents, no previous pituitary surgery, and transsphenoidal surgery performed at this institution. Eighteen patients fulfilled these criteria, and their results were analyzed retrospectively., Results: The average age of the patients was 47.8 years; there were 13 women and 5 men. Inferior petrosal sinus sampling with and without corticotropin-releasing hormone stimulation was performed in 16 patients with correct localization of the lesion in 13 (81%). During surgery, the surgeon identified and removed 17 pituitary tumors; 15 patients had selective adenomectomies, one had a hemihypophysectomy, and two had total hypophysectomies. Thirteen discrete adrenocorticotropic hormone-secreting adenomas were proven histologically, and one pituitary gland had diffuse involvement with tumor. Complications occurred in five patients. Sixteen patients who were followed up for an average of 21.6 months had sustained remission, 12 of whom were profoundly hypocortisolemic immediately after surgery., Conclusion: In patients with Cushing's disease and a normal magnetic resonance imaging scan, an experienced surgeon can perform transsphenoidal surgery resulting in effective removal of very small microadenomas, with clinical and biochemical remission in the majority. Inferior petrosal sinus sampling is helpful in localizing the adenoma.
- Published
- 2000
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28. Pituitary surgery for the management of acromegaly.
- Author
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Laws ER, Vance ML, and Thapar K
- Subjects
- Acromegaly pathology, Acromegaly surgery, Humans, Pituitary Gland pathology, Radiosurgery, Acromegaly therapy, Endocrine Surgical Procedures adverse effects, Pituitary Gland surgery
- Abstract
Active acromegaly is almost always the result of a benign growth hormone (GH)-secreting adenoma of the pituitary gland. Because the same pituitary stem cell can produce both GH and prolactin (PRL), many acromegalic patients also have hyperprolactinemia. The advantages of surgical excision of pituitary adenomas associated with acromegaly include: (1) prompt decrease in GH; (2) reliable and immediate relief of the mass effect from the tumor (decompression of the optic nerves and chiasm), and (3) the opportunity to obtain tumor tissue for characterization and investigative study. Currently, more than 97% of operations for removal of pituitary tumors associated with acromegaly are done using the transsphenoidal approach rather than craniotomy. Technical advances to make the surgery safer continue to evolve, and include endoscopic approaches, computer-guided image-based intraoperative visualization, and intraoperative magnetic resonance imaging. Criteria for satisfactory remission of acromegaly after surgery are the same as those used for medical management. They include normal insulin-like growth factor (IGF)-I and suppression of GH to undetectable levels (<1.0 ng/ml) during an oral glucose tolerance test (OGTT). Data from a recent series of 86 patients operated upon for acromegaly at the University of Virginia and followed for more than 1 year have been reviewed. In patients receiving surgery as the initial procedure, 67% had a normal IGF-I, and 52% suppressed to <1.0 ng/ml in an OGTT. There was one true recurrence of disease diagnosed 81 months after surgery. Results are best in patients with noninvasive microadenomas. Gamma knife radiosurgery has been a valuable adjunct in those patients who fail to achieve postoperative remission. Pathological evaluation of the tumors revealed that 16% expressed GH only, 25% stained for GH and glycoprotein hormones (follicle stimulating hormone, thyroid hormone, thyroid stimulating hormone, alpha-subunit), 21% for GH and PRL, and 33% for GH, PRL and glycoprotein hormones. There was one acidophil stem cell tumor and 10% had the mammosomatotroph subtype. This contemporary series was free of mortality or serious complications. One patient had a transient cerebrospinal fluid leak and 3 developed transient SIADH with hyponatremia. Surgical treatment remains an important aspect of the combined management of patients with acromegaly., (Copyright 2000 S. Karger AG, Basel)
- Published
- 2000
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29. Growth hormone therapy in adults and children.
- Author
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Vance ML and Mauras N
- Subjects
- Adult, Child, HIV Wasting Syndrome drug therapy, Human Growth Hormone adverse effects, Humans, Kidney Failure, Chronic drug therapy, Turner Syndrome drug therapy, Growth Disorders drug therapy, Human Growth Hormone deficiency, Human Growth Hormone therapeutic use
- Published
- 1999
- Full Text
- View/download PDF
30. Radiosurgery for pituitary tumors and craniopharyngiomas.
- Author
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Laws ER Jr and Vance ML
- Subjects
- Brain Injuries etiology, Brain Injuries prevention & control, Craniopharyngioma radiotherapy, Humans, Patient Selection, Pituitary Neoplasms radiotherapy, Radiation Dosage, Radiation Injuries etiology, Radiation Injuries prevention & control, Radiosurgery standards, Radiotherapy adverse effects, Radiotherapy standards, Remission Induction, Retrospective Studies, Treatment Outcome, Craniopharyngioma surgery, Pituitary Neoplasms surgery, Radiosurgery methods
- Abstract
Standard techniques of conventional radiation therapy have been used for many years to treat pituitary adenomas and craniopharyngiomas. These techniques are not always effective and carry with them morbidity in the form of damage to the normal pituitary gland, damage to the hypothalamus, the potential of damage to the visual system and to intellectual functions of the brain and a small but real risk of the development of secondary malignancies. In an effort to avoid these complications and to provide more effective adjunctive radiation therapy, techniques of stereotactic delivery of high-dose radiation to the pituitary region have been developed, known as radiosurgery. The history of the development of radiosurgery and its application to pituitary problems are recounted in this article, as are a number of the controversies that currently exist and need to be considered as these modalities of stereotactic radiosurgery are applied more frequently and to better effect in the future.
- Published
- 1999
31. Endocrinological evaluation of acromegaly.
- Author
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Vance ML
- Subjects
- Adenoma surgery, Adult, Age Factors, Aged, Female, Follow-Up Studies, Glucose, Humans, Immunoradiometric Assay, Luminescent Measurements, Male, Middle Aged, Pituitary Neoplasms surgery, Remission Induction, Sex Factors, Treatment Outcome, Acromegaly surgery, Human Growth Hormone blood, Insulin-Like Growth Factor I analysis
- Published
- 1998
- Full Text
- View/download PDF
32. Octreotide as primary therapy for acromegaly.
- Author
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Newman CB, Melmed S, George A, Torigian D, Duhaney M, Snyder P, Young W, Klibanski A, Molitch ME, Gagel R, Sheeler L, Cook D, Malarkey W, Jackson I, Vance ML, Barkan A, Frohman L, and Kleinberg DL
- Subjects
- Acromegaly blood, Acromegaly surgery, Adenoma drug therapy, Adenoma pathology, Adenoma surgery, Adult, Aged, Double-Blind Method, Female, Human Growth Hormone blood, Humans, Insulin-Like Growth Factor I metabolism, Kinetics, Male, Middle Aged, Octreotide administration & dosage, Pituitary Neoplasms drug therapy, Pituitary Neoplasms pathology, Pituitary Neoplasms surgery, Placebos, Acromegaly drug therapy, Antineoplastic Agents, Hormonal therapeutic use, Octreotide therapeutic use
- Abstract
The effects of octreotide (up to 5 yr) as primary treatment in 26 patients with acromegaly were compared with those in 81 patients with acromegaly who received octreotide as secondary or adjunctive therapy after previous surgery and/or pituitary radiation. These patients were part of a multicenter study that took place between 1989-1995. The study was divided into 3 phases beginning with a 1-month placebo-controlled treatment period followed by a 1-month washout period. In the second phase, patients were randomized to treatment with either 100 or 250 micrograms octreotide, sc, every 8 h for 6 months. Octreotide was then discontinued for 1 month and reinitiated at the lower dose for a total mean treatment duration of 39 months. The dose was titrated by each investigator to improve each patient's individual response, which included improvement in symptoms and signs of acromegaly as well as reduction of GH and insulin-like growth factor I (IGF-I) into the normal range. In the second phase of the study, in which patients were randomized to either 100 or 250 micrograms octreotide, three times daily, mean integrated GH and IGF-I concentrations after 3 and 6 months were equivalent in the primary and secondary treatment groups. During long term open label treatment, mean GH fell from 32.7 +/- 5.2 to 6.0 +/- 1.7 micrograms/L 2 h after octreotide injection in the primary therapy group and remained suppressed for a mean period of 24 months (range, 3-60 months). The mean final daily dose was 777 micrograms. In the patients receiving secondary treatment, mean GH fell from 30.2 +/- 7.6 to 5.6 +/- 1.1 micrograms/L after 3 months and remained suppressed for the remainder of the study (average dose, 635 micrograms daily). Mean IGF-I concentrations fell from 5.2 +/- 0.5 x 10(3) U/L (primary treatment group) and 4.7 +/- 0.4 x 10(3) U/L (secondary treatment group) to a mean of 2.2 +/- 0.3 x 10(3) U/L in both groups after 3 months of open label treatment and remained suppressed. IGF-I was reduced into the normal range during at least half of the study visits in 68% of the primary treatment group and in 62% of the secondary treatment group. Patients whose GH levels fell to at least 2 SD below the baseline mean GH were considered responders. There was no significant difference in the percentage of responders in the primary and secondary treatment groups (70% vs. 61%), nor was there a statistical difference in the mean GH concentrations between the groups. Symptoms of headache, increased perspiration, fatigue, and joint pain were reported at baseline by 46%, 73%, 69%, and 85%, respectively, of patients in the primary therapy group and improved during 3 yr of octreotide treatment in 50-100%. Similarly, these acromegaly-related symptoms were reported by 62%, 58%, 78%, and 60% of patients in the secondary therapy group, and improvement was noted in 62-88%. Pituitary magnetic resonance imaging scans were available in 13 of 26 patients in the primary treatment group before and after 6 months of octreotide treatment. Tumor shrinkage was observed in 6 of 13 patients, with reduction in tumor volume greater than 25% in only 3. Of 6 patients with documented tumor shrinkage, IGF-I was reduced into the normal range in 4 patients. Of the 7 remaining patients in whom tumor shrinkage was less than 10%, IGF-I was reduced into the normal range in 4 patients. Of the 7 remaining patients in whom tumor shrinkage was less than 10%, IGF-I was reduced into the normal range in 5 patients. The degree of tumor shrinkage did not correlate with the percent reduction in IGF-I or GH. In summary, octreotide was equally effective in 26 previously untreated acromegalic patients (primary treatment group) and 81 patients previously treated with either surgery or pituitary radiation (secondary treatment group). These observations call into question the current practice of surgical resection of all newly diagnosed GH-secreting pituitary adenomas regardless of the likelihood of cure. (AB
- Published
- 1998
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33. Primary fibrosarcoma of the sella unrelated to previous radiation therapy.
- Author
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Lopes MB, Lanzino G, Cloft HJ, Winston DC, Vance ML, and Laws ER Jr
- Subjects
- Diagnosis, Differential, Female, Fibrosarcoma diagnosis, Fibrosarcoma etiology, Fibrosarcoma ultrastructure, Humans, Magnetic Resonance Imaging, Microscopy, Electron, Middle Aged, Neoplasms, Radiation-Induced diagnosis, Neoplasms, Second Primary diagnosis, Pituitary Neoplasms diagnosis, Pituitary Neoplasms ultrastructure, Fibrosarcoma pathology, Pituitary Neoplasms pathology, Sella Turcica
- Abstract
Fibrosarcomas involving the sella turcica are rare lesions and, when encountered, have been associated with previous radiation of a pituitary adenoma. Although primary intracranial fibrosarcomas are well recognized, no case of primary fibrosarcoma of the sella turcica has been reported to date. We describe here a patient who presented with a 2-month history of headache, visual disturbances, and diabetes insipidus. Her past medical history was unremarkable, with no radiation therapy. Magnetic resonance imaging revealed a sellar/suprasellar lesion that at surgery appeared firm in consistency. A radical removal of the mass was performed through a transsphenoidal approach. The patient recovered promptly from the operation and 2 weeks later, given the aggressive histologic appearance of the lesion, underwent gamma knife radiosurgery. Seven months after diagnosis, the patient presented with local tumor recurrence. A subtotal surgical resection was performed, and additional postsurgical treatment is still under consideration. Although most often related to previous radiation of the pituitary gland, primary fibrosarcomas can occur in the sella. This possibility should be suspected in the differential diagnosis of sellar masses that lack the classical characteristics of the much more common pituitary adenomas.
- Published
- 1998
34. Pheochromocytoma in von Hippel-Lindau disease: clinical presentation and mutation analysis in a large, multigenerational kindred.
- Author
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Atuk NO, Stolle C, Owen JA Jr, Carpenter JT, and Vance ML
- Subjects
- Adenoma epidemiology, Adenoma genetics, Adolescent, Adrenal Gland Neoplasms diagnosis, Adrenal Gland Neoplasms epidemiology, Adrenal Gland Neoplasms therapy, Adult, Age of Onset, Aged, Carcinoma, Renal Cell epidemiology, Carcinoma, Renal Cell genetics, Catecholamines urine, Child, Child, Preschool, Female, Hemangioma epidemiology, Hemangioma genetics, Humans, Infant, Kidney Neoplasms epidemiology, Kidney Neoplasms genetics, Male, Middle Aged, Pancreatic Neoplasms epidemiology, Pancreatic Neoplasms genetics, Pedigree, Phenotype, Pheochromocytoma diagnosis, Pheochromocytoma epidemiology, Pheochromocytoma therapy, Retinal Neoplasms epidemiology, Retinal Neoplasms genetics, Risk Factors, Sensitivity and Specificity, Adrenal Gland Neoplasms genetics, Pheochromocytoma genetics, Point Mutation, von Hippel-Lindau Disease complications, von Hippel-Lindau Disease genetics
- Abstract
The clinical presentation and characterization of the mutation in members of a large kindred with von Hippel-Lindau disease (VHLD) and pheochromocytoma were examined. Twenty-five proven cases of VHLD occurring in four generations of a large kindred have been followed since 1964, and pheochromocytoma has occurred in 17. Symptoms of pheochromocytoma developed at an early age, on average at 12.5 +/- 1.3 yr, and definitive diagnosis and treatment of pheochromocytoma occurred at 19.9 +/- 2.6 yr. Significantly higher urine catecholamine concentrations were observed in younger patients than in older ones. Mutation analysis was performed in 14 family members, and a new mutation in the VHLD gene was identified in 11; this mutation is a G to T change at nucleotide 658 that results in the substitution of a serine for an alanine residue at position 149 of the polypeptide chain. Seven of the 11 patients with the mutation have VHLD; four, all 10 yr old or less, are asymptomatic and have no evidence of disease, but are at high risk for developing VHLD. These children are being followed closely for clinical and biochemical manifestations. The characterization of this new mutation has permitted identification of family members who are likely to develop VHLD.
- Published
- 1998
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35. The Gordon Wilson Lecture. Growth hormone replacement in adults and other uses.
- Author
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Vance ML
- Subjects
- Adult, Aged, Body Composition drug effects, Child, Clinical Trials as Topic, Female, Growth Hormone-Releasing Hormone administration & dosage, Human Growth Hormone deficiency, Human Growth Hormone metabolism, Humans, Hypothalamic Diseases drug therapy, Male, Middle Aged, Pituitary Diseases drug therapy, Human Growth Hormone therapeutic use
- Abstract
The modern era of growth hormone research began in 1981 with the characterization and synthesis of the primary stimulator of GH synthesis and secretion, growth hormone releasing hormone. Discovery of this peptide and studies in human adults and children resulted in unraveling the complex nature of the regulation of GH secretion. Discovery of regulatory mechanisms has permitted a greater understanding of normal and abnormal growth hormone physiology. The use of growth hormone therapeutically as replacement in GH deficient adults is in its medical infancy, but preliminary studies indicate a beneficial effect on body composition, serum lipid concentrations, bone mineral density, muscle strength, and exercise endurance. These studies over the past decade resulted in Food and Drug Administration approval of GH for replacement in adults with hypothalamic or pituitary disease. It remains to be determined whether or not chronic GH replacement will have beneficial effects on morbidity and mortality. The use of growth hormone in other areas such as aging, catabolic illness, obesity, diabetes, and muscular disorders is under active investigation and risks and benefits remain to be determined.
- Published
- 1998
36. The empty sella.
- Author
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Vance ML
- Subjects
- Empty Sella Syndrome drug therapy, Empty Sella Syndrome physiopathology, Empty Sella Syndrome surgery, Hormones therapeutic use, Humans, Empty Sella Syndrome therapy
- Published
- 1997
37. Nonfunctioning pituitary adenoma.
- Author
-
Vance ML
- Subjects
- Adenoma radiotherapy, Adenoma surgery, Humans, Pituitary Neoplasms radiotherapy, Pituitary Neoplasms surgery, Adenoma therapy, Pituitary Neoplasms therapy
- Published
- 1997
38. Bromocriptine therapy for prolactin-secreting pituitary adenomas.
- Author
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Laws ER Jr, Thorner MO, and Vance ML
- Abstract
An effective systematic approach for the management of prolactin-secreting pituitary adenomas is described. This methodology has stood the test of time and has been modified in accordance with experience. The primary goals are to obtain satisfactory control of the tumor and to avoid undesirable side effects related to dopamine agonist-based therapeutic agents.
- Published
- 1996
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39. Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline.
- Author
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Biller BM, Molitch ME, Vance ML, Cannistraro KB, Davis KR, Simons JA, Schoenfelder JR, and Klibanski A
- Subjects
- Adolescent, Adult, Aged, Cabergoline, Dopamine Agonists therapeutic use, Ergolines adverse effects, Female, Follow-Up Studies, Gonads physiopathology, Humans, Male, Middle Aged, Pituitary Neoplasms physiopathology, Prolactin blood, Visual Fields drug effects, Adenoma drug therapy, Adenoma metabolism, Ergolines therapeutic use, Pituitary Neoplasms drug therapy, Pituitary Neoplasms metabolism, Prolactin metabolism
- Abstract
Dopamine agonist administration is the primary therapy for macroprolactinomas, but bromocriptine is the only agent approved in the United States. Its use is limited by a high incidence of side effects, a short duration of action, and a lack of effectiveness in some patients. Cabergoline is a long-acting dopamine agonist specific for the D2 receptor that is more effective and better tolerated than bromocriptine in women with microadenomas or idiopathic hyperprolactinemia. However, experience with cabergoline in the treatment of patients with macroadenomas is limited. We report the first study of chronic administration of cabergoline conducted exclusively in patients with macroprolactinomas. Fifteen patients (8 women, 7 men) ages 18-76 yr were studied in an open-label 48-week dose escalation trial of cabergoline administered once per week. Eleven patients had received prior therapy with other dopamine agonists. Mean prolactin (PRL) levels decreased by 93.6%, and normal levels were attained in 73% of patients at doses of 0.5-3.0 mg per week. Three of five patients who had failed to normalize PRL on prior dopamine agonists achieved normal levels. Gonadal function was restored in all hypogonadal men and in 75% of premenopausal women with amenorrhea. Tumor size decreased in 11 of the 15 patients. Side effects were minimal. Of the 5 patients who had experienced side effects in prior dopamine agonists, 4 had none on cabergoline, and the fifth had milder symptoms. During two further years of follow up, the improvement in PRL levels, gonadal function, and tumor size has persisted during cabergoline administration, and three patients have experienced a further decline in PRL and/or tumor size. This study demonstrates the effectiveness and minimal side effects of once-weekly cabergoline for treatment of macroprolactinomas.
- Published
- 1996
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40. Nutrition, body composition, physical activity and growth hormone secretion.
- Author
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Vance ML
- Subjects
- Adult, Humans, Body Composition physiology, Exercise physiology, Human Growth Hormone metabolism, Nutritional Physiological Phenomena physiology
- Abstract
Determinants of GH secretion in adults are multifactorial. Of all of the influences on GH secretion, it is highly probable that the two more influential factors are age and body composition: older age and increased adiposity are negative influences on GH release. Although aging per se is immutable, body composition can be modified by appropriate diet and exercise.
- Published
- 1996
41. Fasting as a metabolic stress paradigm selectively amplifies cortisol secretory burst mass and delays the time of maximal nyctohemeral cortisol concentrations in healthy men.
- Author
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Bergendahl M, Vance ML, Iranmanesh A, Thorner MO, and Veldhuis JD
- Subjects
- Adult, Dehydroepiandrosterone analogs & derivatives, Dehydroepiandrosterone blood, Dehydroepiandrosterone Sulfate, Follicle Stimulating Hormone blood, Growth Hormone blood, Humans, Hydrocortisone blood, Luteinizing Hormone blood, Male, Metabolic Clearance Rate, Prolactin blood, Testosterone blood, Thyrotropin blood, Circadian Rhythm, Fasting physiology, Hydrocortisone metabolism
- Abstract
Serum cortisol concentrations are increased in fasted or malnourished human subjects. The dynamic mechanisms underlying this adaptive response have been investigated in eight normal men by analyzing serum cortisol concentrations measured in blood obtained at 5-min intervals over 24 h on a control (fed) day and on the fifth day of a fast (water only) assigned in randomized order. A multiple parameter deconvolution method was used to simultaneously resolve endogenous cortisol secretion and half-life. Five days of fasting induced a 1.8-fold increase in the 24-h endogenous cortisol production rate (fed, 2504 +/- 308; fasted, 4528 +/- 488 nmol/L distribution volume; P < 0.006). This enhanced cortisol production rate was accounted for by a 1.6-fold increase in the mass of cortisol secreted per burst (fed, 115 +/- 12.1; fasted, 183 +/- 17.3 nmol/L; P < 0.02). Cortisol secretory event amplitudes (maximal rates of cortisol release attained within a burst) increased in seven of eight men, and mean secretory burst durations remained unchanged by fasting. Moreover, the number of computer-resolved cortisol secretory bursts per 24 h (fed, 22 +/- 1.4; fasted, 25 +/- 2.0; P = NS) and the interburst interval (fed, 65 +/- 4.0; fasted, 57 +/- 4.4 min) did not change significantly during a 5-day fast. The calculated half-life of endogenous cortisol was not significantly altered by fasting (fed, 108 +/- 9.7; fasted, 129 +/- 11 min). There was no significant change in the nyctohemeral pattern of varying adrenocortical secretory burst frequency in response to fasting. However, the mean (mesor) mass of glucocorticoid secreted per burst over 24 h rose significantly in response to fasting. In addition, by cosinor analysis, maximal serum cortisol concentrations occurred (95% confidence intervals) between 0930-1334 h in the fed state and between 1116-1612 h in the fasted state (P < 0.04). Fasting augmented the mesor (average value about which the diurnal rhythm oscillates; P < 0.0008 compared with fed state) and the amplitude (P < 0.04) of the 24-h serum cortisol concentration profile. Linear regression analysis disclosed a significant inverse relationship between mean serum cortisol and GH concentrations in fasted men (r = -0.76; P < 0.02). In conclusion, the present data indicate that starvation-induced enhancement of cortisol secretion in young healthy men is mediated by an increased glucocorticoid secretory burst mass, rather than changes in secretory burst frequency or duration or in cortisol half-life. In addition, fasting modifies the diurnal secretory pattern of cortisol by delaying maximal serum concentrations to the early afternoon. The inverse relationship between serum cortisol and GH responses to fasting suggests differential regulation of the corticotropic and somatotropic axis by the metabolic stress of fasting and/or feedback interactions between these two axes when they are both activated.
- Published
- 1996
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42. Neuroendocrine regulation of growth hormone secretion.
- Author
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Thorner MO, Hartman ML, Vance ML, Pezzoli SS, and Ampleford EJ
- Subjects
- Animals, Growth Hormone physiology, Humans, Periodicity, Growth Hormone metabolism, Neurosecretory Systems physiology
- Abstract
Growth hormone (GH) secretion is controlled by many factors, including stage of development, age, gonadal steroids, body composition, nutritional state, time of day and whether the subject is asleep or awake. Understanding regulation of GH secretion is important since this hormone regulates not only growth, but also the partitioning of nutrients and body composition. There is increasing evidence that there is a basic ultradian rhythm of GH secretion. The NSF Center studies will be facilitated by 3 major efforts: (a) improvement of sensitivity of GH assays to permit accurate description of GH pulses; (b) use of biomathematical models to objectively determine GH pulse characteristics, as well as calculation of secretion rates to facilitate the study of the relationship between neural controls and GH secretion; and (c) use of the tau mutant hamster and the new mouse mutant animal models. By manipulation of the endogenous circadian clock in these animal models it will be possible to study the relationship between endogenous circadian systems and ultradian GH rhythms.
- Published
- 1995
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- View/download PDF
43. Circulating dihydroxyphenylglycol and norepinephrine concentrations during sympathetic nervous system activation in patients with pheochromocytoma.
- Author
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Atuk NO, Hanks JB, Weltman J, Bogdonoff DL, Boyd DG, and Vance ML
- Subjects
- Adolescent, Adult, Blood Pressure, Child, Exercise physiology, Female, Heart Rate, Humans, Male, Methoxyhydroxyphenylglycol blood, Supine Position, Adrenal Gland Neoplasms physiopathology, Methoxyhydroxyphenylglycol analogs & derivatives, Norepinephrine blood, Pheochromocytoma physiopathology, Sympathetic Nervous System physiopathology
- Abstract
Although increased plasma norepinephrine (NE) concentrations mediate vasoconstriction during episodic hypertension and hypertensive crises in patients with pheochromocytoma (Pheo), the precise origin of this circulating NE (tumor or sympathetic nerves) is not known. Dihydroxyphenylglycol (DHPG), a deaminated metabolite of NE, is formed principally in sympathetic nerve endings. Under basal conditions, plasma NE and DHPG concentrations correlate closely, and during sympathetic nervous system activation, both plasma NE and DHPG concentrations increase. This observation suggests that plasma DHPG concentrations may reflect the source of circulating NE (tumor or sympathetic nerves) during hypertensive episodes in patients with Pheo. Plasma NE and DHPG concentrations were measured simultaneously, and the NE/DHPG ratio was calculated in seven patients with Pheo during 20 min of sympathetic nervous system activation (treadmill exercise) before and after surgical resection of the tumor. Age- and sex-matched normal subjects were also studied. Exercise resulted in a significant increase in plasma NE and DHPG concentrations in patients with Pheo and in normal subjects (Pheo: basal NE, 1827 +/- 639; peak NE, 3016 +/- 769 pg/mL (P = 0.02); normal subjects: basal NE, 266 +/- 27; peak NE, 1166 +/- 197 pg/mL (P = 0.01); Pheo: basal DHPG, 1521 +/- 280; peak DHPG, 2313 +/- 252 pg/mL (P = 0.007); normal subjects: basal DHPG, 870 +/- 50; peak DHPG, 1630 +/- 180 pg/mL (P = 0.01)]. The NE/DHPG ratio increased with exercise in normal subjects (basal, 0.30 +/- 0.02; peak, 0.83 +/- 12; P = 0.005), but did not change in patients with Pheo (basal, 1.22 +/- 0.32; peak, 1.54 +/- 0.27). Exercise also increased plasma NE and DHPG concentrations and the NE/DHPG ratio in five patients studied after surgical resection of the tumor. Systolic blood pressure and heart rate increased significantly during exercise in all three study groups. The increase in plasma NE and HDPG concentrations during exercise-induced sympathetic nervous system stimulation in patients with Pheo is similar to that in normal subjects and may indicate that the sympathetic nervous system plays an important role in the pathogenesis of hypertension and hypertensive crises in patients with Pheo.
- Published
- 1994
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44. Enhanced basal and disorderly growth hormone secretion distinguish acromegalic from normal pulsatile growth hormone release.
- Author
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Hartman ML, Pincus SM, Johnson ML, Matthews DH, Faunt LM, Vance ML, Thorner MO, and Veldhuis JD
- Subjects
- Acromegaly blood, Adult, Analysis of Variance, Eating, Fasting, Female, Growth Hormone blood, Humans, Male, Middle Aged, Reference Values, Sex Factors, Statistics as Topic methods, Acromegaly physiopathology, Circadian Rhythm, Growth Hormone metabolism
- Abstract
Pulses of growth hormone (GH) release in acromegaly may arise from hypothalamic regulation or from random events intrinsic to adenomatous tissue. To distinguish between these possibilities, serum GH concentrations were measured at 5-min intervals for 24 h in acromegalic men and women with active (n = 19) and inactive (n = 9) disease and in normal young adults in the fed (n = 20) and fasted (n = 16) states. Daily GH secretion rates, calculated by deconvolution analysis, were greater in patients with active acromegaly than in fed (P < 0.05) but not fasted normal subjects. Significant basal (nonpulsatile) GH secretion was present in virtually all active acromegalics but not those in remission or in fed and fasted normal subjects. A recently introduced scale- and model-independent statistic, approximate entropy (ApEn), was used to test for regularity (orderliness) in the GH data. All but one acromegalic had ApEn values greater than the absolute range in normal subjects, indicating reduced orderliness of GH release; ApEn distinguished acromegalic from normal GH secretion (fed, P < 10(-12); fasted, P < 10(-7)) with high sensitivity (95%) and specificity (100%). Acromegalics in remission had ApEn scores larger than those of normal subjects (P < 0.0001) but smaller than those of active acromegalics (P < 0.001). The coefficient of variation of successive incremental changes in GH concentrations was significantly lower in acromegalics than in normal subjects (P < 0.001). Fourier analysis in acromegalics revealed reduced fractional amplitudes compared to normal subjects (P < 0.05). We conclude that GH secretion in acromegaly is highly irregular with disorderly release accompanying significant basal secretion.
- Published
- 1994
- Full Text
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45. Hypopituitarism.
- Author
-
Vance ML
- Subjects
- Humans, Hypopituitarism diagnosis, Hypopituitarism etiology, Hypopituitarism therapy
- Published
- 1994
- Full Text
- View/download PDF
46. Nonfunctioning pituitary adenoma.
- Author
-
Vance ML
- Subjects
- Adenoma drug therapy, Adenoma radiotherapy, Adenoma surgery, Bromocriptine therapeutic use, Dopamine Agonists therapeutic use, Humans, Pituitary Neoplasms drug therapy, Pituitary Neoplasms radiotherapy, Pituitary Neoplasms surgery, Adenoma therapy, Pituitary Neoplasms therapy
- Published
- 1994
47. Growth and the child with diabetes mellitus.
- Author
-
Clarke WL, Vance ML, and Rogol AD
- Subjects
- Adolescent, Carrier Proteins metabolism, Child, Female, Growth Hormone blood, Growth Hormone metabolism, Humans, Insulin-Like Growth Factor I metabolism, Male, Menarche, Puberty, Diabetes Mellitus, Type 1 drug therapy, Diabetes Mellitus, Type 1 physiopathology, Growth, Insulin therapeutic use
- Published
- 1993
- Full Text
- View/download PDF
48. Metabolic status and growth hormone secretion in man.
- Author
-
Vance ML
- Subjects
- Adult, Aging metabolism, Body Composition drug effects, Female, Gonadal Steroid Hormones physiology, Growth Hormone pharmacology, Humans, Male, Metabolism, Middle Aged, Nutritional Physiological Phenomena, Growth Hormone metabolism
- Abstract
The metabolic state influences GH secretion and, in turn, GH secretion influences overall body metabolism. While these are distinct physiological entities, separation of these interrelated phenomena should be considered artificial since the overall result is an organism which retains functional capacity in the setting of a variety of circumstances.
- Published
- 1993
- Full Text
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49. Amplitude suppression of the pulsatile mode of immunoradiometric luteinizing hormone release in fasting-induced hypoandrogenemia in normal men.
- Author
-
Veldhuis JD, Iranmanesh A, Evans WS, Lizarralde G, Thorner MO, and Vance ML
- Subjects
- Adult, Circadian Rhythm, Humans, Immunoradiometric Assay, Luteinizing Hormone metabolism, Male, Pituitary Gland, Anterior metabolism, Pulsatile Flow, Reference Values, Time Factors, Androgens blood, Fasting, Luteinizing Hormone blood
- Abstract
In the male rodent and primate, fasting or severe caloric restriction significantly decreases serum testosterone concentrations, putatively via inducing secondary hypogonadotrophism. To clarify this presumptive pathophysiology, we have used: 1) a high sensitivity immunoradiometric assay, which correlates well with an in vitro Leydig cell bioassay of LH; 2) blood sampling every 5 min for 24 h basally and every 10 min for 3 h after GnRH injection before and after a 5-day (water only) fast in eight healthy young men; and 3) deconvolution analysis to evaluate in vivo LH secretory burst frequency, amplitude, duration, and mass, and LH half-life simultaneously. We documented a 50% fall in serum total and free testosterone concentrations, and a 30% decrease in 24-h mean serum LH concentrations (viz., fed 3.0 +/- 0.47 vs. fasted 2.1 +/- 0.39 U/L, P = 0.043). Deconvolution analysis revealed preservation of LH secretory pulse frequency (fed 12.9 +/- 0.48 vs. fasted 12.6 +/- 0.78 secretory bursts/day, P = NS) during fasting-induced hypogonadotropism. The duration of computer-resolved LH secretory bursts, the interburst interval, and the calculated endogenous half-life of LH also did not change, whereas LH secretory burst mass declined significantly; viz. from 28 +/- 5 in the fed to 14 +/- 3.2 U/L of distribution volume/day in the fasted state (P = 0.034). In contrast, LH release after a 10 micrograms pulse of GnRH iv was enhanced during fasting in seven of the eight men. Fasting also decreased mean (24 h) serum TSH and PRL, increased cortisol, dehydroepiandrosterone sulfate and GH, and did not affect FSH concentrations or the radioiodinated albumen distribution space. In summary, in young men 5 days of nutrient deprivation selectively attenuates the mass of LH secreted per burst without altering LH secretory event frequency or LH half-life. We infer that decreased LH release per burst is due to decreased hypothalamic GnRH impulse strength, since LH release induced by a submaximally effective pulse of exogenous GnRH is amplified rather than attenuated.
- Published
- 1993
- Full Text
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50. Growth hormone and cortisol secretion in patients with burn injury.
- Author
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Jeffries MK and Vance ML
- Subjects
- Adult, Body Surface Area, Female, Growth Hormone blood, Growth Hormone urine, Hospitalization, Humans, Hydrocortisone blood, Hydrocortisone urine, Male, Middle Aged, Prospective Studies, Burns metabolism, Growth Hormone metabolism, Hydrocortisone metabolism, Insulin-Like Growth Factor I metabolism
- Abstract
A prospective study of growth hormone, insulin-like growth factor (IGF-1), and cortisol secretion was undertaken in six adults with burn injury. Serum concentrations of growth hormone and IGF-1 were low in all patients during the first 2 weeks of hospitalization. The mean growth hormone level was 4.35 +/- 0.83 micrograms/L on day 1 and 1.70 +/- 0.50 micrograms/L on day 13. The mean serum concentration of IGF-1, which reflects overall growth hormone secretion, was 0.43 +/- 0.09 U/ml on day 1 and 0.61 +/- 0.11 U/ml on day 13; these values are distinctly low. After 3 to 4 weeks, IGF-1 concentrations increased to the mid-normal range, whereas growth hormone values did not change. Morning plasma cortisol concentrations were modestly elevated; however, urine free cortisol concentrations, which reflect total cortisol secretion, were elevated 2 to 28 times above normal values at the time of admission (mean, 443.5 +/- 323.7 nmol/L). Urinary free cortisol concentrations remained elevated after 2 weeks (mean, 230.5 +/- 94.5 nmol/L). Patients with burn injury have inappropriately low growth hormone secretion and IGF-1 production in spite of the stress of the injury and more than adequate nutritional therapy.
- Published
- 1992
- Full Text
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